Regulations Amending Certain Regulations Made Under the Food and Drugs Act (Agile Licensing): SOR/2024-238

Canada Gazette, Part II, Volume 158, Number 26

Registration
SOR/2024-238 November 29, 2024

FOOD AND DRUGS ACT

P.C. 2024-1264 November 29, 2024

Her Excellency the Governor General in Council, on the recommendation of the Minister of Health, makes the annexed Regulations Amending Certain Regulations Made Under the Food and Drugs Act (Agile Licensing) under section 30footnote a of the Food and Drugs Act footnote b.

Regulations Amending Certain Regulations Made Under the Food and Drugs Act (Agile Licensing)

Food and Drug Regulations

1 Subsection A.01.015(2) of the Food and Drug Regulations footnote 1 is replaced by the following:

(2) The adequate directions for use required to be shown on the inner and outer labels of a drug under subparagraph C.01.004(1)(c)(iii) or paragraph C.04.009(2)(f) shall be in English and French if the drug is available for sale without prescription in an open self-selection area.

2 Paragraph A.01.048(d) of the Regulations is replaced by the following:

3 (1) Paragraph C.01.004(1)(a) of the Regulations is amended by adding “and” at the end of subparagraph (ii) and by repealing subparagraphs (iii) and (iv).

(2) Subsection C.01.004(5) of the Regulations is replaced by the following:

(5) Subsections (1) to (3) do not apply to a drug that is

4 Section C.01.011 of the Regulations is amended by adding the following after subsection (4):

(5) Subsection (4) does not apply in respect of new drugs, other than those listed in Schedule C to the Act.

5 Section C.01.014.1 of the Regulations is amended by adding the following after subsection (3):

(4) The Minister may request that a manufacturer of a drug for human use, other than a new drug, who has made an application under subsection (1) provide the Minister, within a period specified by the Minister that is reasonable in the circumstances, with a risk management plan for the drug that meets the requirements set out in section C.01.701, if the Minister has reasonable grounds to believe that

6 Subsection C.01.014.2(2) of the Regulations is replaced by the following:

(2) The Minister may refuse to issue the document if

7 (1) Subsection C.01.014.21(1.1) of the Regulations is replaced by the following:

(1.1) The Minister may, at any time, impose terms and conditions on a drug identification number assigned for a public health emergency drug or amend such terms and conditions if

(2) The definition designated COVID-19 drug in subsection C.01.014.21(3) of the Regulations is repealed.

(3) Subsection C.01.014.21(3) of the Regulations is amended by adding the following in alphabetical order:

public health emergency drug
has the same meaning as in section C.08.001.1. (drogue pour urgence de santé publique)

(4) Section C.01.014.21 of the Regulations is replaced by the following:

C.01.014.21 (1) The Minister may, at any time, impose terms and conditions on a drug identification number assigned for a drug or amend such terms and conditions after considering

(2) The Minister shall notify, in writing, the manufacturer who was issued a document under subsection C.01.014.2(1) that sets out the drug identification number, of any terms and conditions imposed on the drug identification number and of any amendment to those terms and conditions.

8 The Regulations are amended by adding the following after section C.01.625:

Risk Management Plans

C.01.700 For the purposes of sections C.01.703 and C.01.704, existing risk management plan means the most recent risk management plan for a drug that the drug’s manufacturer has provided to the Minister under these Regulations.

C.01.701 (1) A risk management plan for a drug that the drug’s manufacturer provides to the Minister under these Regulations must, taking into account the Canadian context, contain sufficient information to enable the Minister to identify and characterize the risks associated with the drug and to conclude that the plan, if implemented, would prevent or reduce those risks or address uncertainties associated with the drug and must include

(2) Despite paragraph (1)(f), for the purposes of subsection C.01.014.1(4), paragraph C.08.002(2)(p), subparagraph C.08.002.01(2)(b)(xi), paragraph C.08.002.1(2)(a.1) and subsection C.08.003(3.2), the manufacturer may initially provide the summary of the risk management plan in either English or French if the manufacturer then provides a summary of the plan in the other language before the document that sets out the drug identification number assigned for the drug is issued under subsection C.01.014.2(1) or the notice of compliance is issued under section C.08.004 or C.08.004.01.

C.01.702 (1) The Minister may request that the manufacturer of a drug for human use for which a drug identification number has been assigned and not been cancelled provide the Minister, within a period specified by the Minister that is reasonable in the circumstances, with a risk management plan for the drug that meets the requirements set out in section C.01.701, if

(2) The manufacturer must provide the risk management plan within the specified period.

C.01.703 In cases where there is already an existing risk management plan, the manufacturer of a drug for human use for which a drug identification number has been assigned and not been cancelled must, as soon as feasible, provide the Minister with an updated risk management plan for the drug that meets the requirements set out in section C.01.701 if

C.01.704 (1) In cases where there is already an existing risk management plan, the Minister may request that the manufacturer of a drug for human use for which a drug identification number has been assigned and not been cancelled provide the Minister, within a period specified by the Minister that is reasonable in the circumstances, with an updated risk management plan for the drug that meets the requirements set out in section C.01.701, if the Minister, on the basis of information obtained after the existing risk management plan was provided, has reasonable grounds to believe that

(2) The manufacturer must provide the updated risk management plan within the specified period.

9 Subsection C.01A.005(2) of the Regulations is replaced by the following:

(2) An application for an establishment licence that relates to one or more activities set out in Table I to section C.01A.008 that are to be carried out in respect of a category of drugs that is set out in Table II to that section and that includes a drug that is fabricated, sold or represented for use in relation to a condition described in the List of Conditions that Threaten Public Health, as defined in section C.08.001.1, may include a statement to that effect.

10 Subsection C.01A.006(1.1) of the Regulations is replaced by the following:

(1.1) An application to amend an establishment licence that relates to one or more activities set out in Table I to section C.01A.008 that are to be carried out in respect of a category of drugs that is set out in Table II to that section and that includes a drug that is fabricated, sold or represented for use in relation to a condition described in the List of Conditions that Threaten Public Health, as defined in section C.08.001.1, may include a statement to that effect.

11 Subsection C.01A.008(1.1) of the Regulations is replaced by the following:

(1.1) The Minister shall, in ascertaining whether they have received the information and material referred to in sections C.01A.005 to C.01A.007 in relation to an application referred to in subsection C.01A.005(2) or C.01A.006(1.1) that contains the statement referred to in the applicable subsection, also take into consideration the public health need related to the condition described in the List of Conditions that Threaten Public Health, as defined in section C.08.001.1.

(1.2) If an application for an establishment licence or to amend such a licence contains a statement referred to in subsection C.01A.005(2) or C.01A.006(1.1) that relates to a condition that is subsequently removed from the List of Conditions that Threaten Public Health, as defined in section C.08.001.1, the Minister may nonetheless issue or amend the licence on the basis of the application.

12 Section C.01A.012.1 of the Regulations is amended by adding the following after subsection (2):

(3) For greater certainty, the power in subsection (1) continues to apply in respect of an establishment licence until the licence is cancelled, even if the holder of the licence does not carry out activities in respect of the drug that formed the basis for the statement contained in the application that led to the issuance or amendment of the licence.

13 Paragraph C.01A.013(b) of the Regulations is replaced by the following:

14 Sections C.02.003 and C.02.003.1 of the Regulations are replaced by the following:

C.02.003 No distributor referred to in paragraph C.01A.003(b) and no importer shall sell a drug unless it has been fabricated, packaged/labelled, tested and stored, including during transportation, in accordance with the requirements set out in this Division.

C.02.003.1 No person shall sell a drug that they have fabricated, packaged/labelled, tested or stored unless they have fabricated, packaged/labelled, tested or stored the drug, including during transportation, in accordance with the requirements set out in this Division.

15 Section C.02.003.3 of the Regulations is replaced by the following:

C.02.003.3 No person shall use an active ingredient in the fabrication of a drug unless the ingredient has been fabricated, packaged/labelled, tested and stored, including during transportation, in accordance with the requirements set out in this Division.

16 Section C.02.006 of the Regulations is replaced by the following:

C.02.006 Every lot or batch of a drug shall be fabricated, packaged/labelled, tested and stored, including during transportation, under the supervision of personnel who, having regard to the duties and responsibilities involved, have had any technical, academic or other training that the Minister considers satisfactory in the interests of the health of the consumer or purchaser.

17 Subsection C.02.009(4) of the Regulations is replaced by the following:

(4) If any property of a raw material is subject to change during storage of the material, including during transportation, no lot or batch of that raw material shall be used in the fabrication of a drug after the lot or batch has been stored, including during transportation, unless the raw material is retested after an appropriate interval and meets the specifications for that material.

18 The heading before section C.02.013 of the Regulations is replaced by the following:

Quality Control

C.02.012.1 Every lot or batch of a drug shall be fabricated, packaged/labelled, tested and stored, including during transportation, in a manner that assures the quality of the drug.

19 Subsection C.02.019(4.1) of the Regulations is replaced by the following:

(4.1) Subsections (1) and (2) do not apply to a distributor or importer of a COVID-19 drug if the lot of the drug is the subject of a request made under subsection C.04.007(2).

20 (1) The portion of subsection C.02.020(1) of the French version of the Regulations before paragraph (a) and paragraph (a) are replaced by the following:

C.02.020 (1) Le manufacturier, l’emballeur-étiqueteur, le distributeur visé à l’alinéa C.01A.003b) et l’importateur conservent dans leurs locaux au Canada, pour chaque drogue qu’ils manufacturent, emballent-étiquettent, distribuent ou importent :

(2) Paragraphs C.02.020(1)(b) and (c) of the Regulations are replaced by the following:

21 (1) Subsection C.02.021(1) of the Regulations is replaced by the following:

C.02.021 (1) All records and evidence of the fabrication, packaging/labelling, finished product testing referred to in section C.02.018 and storage, including storage during transportation, of a drug in dosage form that are required to be maintained under this Division shall be retained for one year after the expiration date of the drug unless the relevant establishment licence specifies some other period.

(2) The portion of subsection C.02.021(2) of the Regulations before paragraph (a) is replaced by the following:

(2) Subject to subsection (4), all records and evidence of the fabrication, packaging/labelling, finished product testing referred to in section C.02.018 and storage, including during transportation, of an active ingredient that are required to be maintained under this Division shall be retained in respect of each lot or batch of the active ingredient for the following period unless the relevant establishment licence specifies some other period:

(3) Subsection C.02.021(3) of the Regulations is replaced by the following:

(3) Subject to subsection (4), all records and evidence of the raw material testing referred to in section C.02.009 and of the testing of packaging/labelling materials that are required to be maintained under this Division shall be retained for five years after the raw materials and packaging/labelling materials were last used in the fabrication or packaging/labelling of a drug unless the relevant establishment licence specifies some other period.

22 Section C.03.206 of the Regulations is replaced by the following:

C.03.206 Sections C.01.005 and C.04.009 do not apply to a component or kit.

23 Division 4 of Part C of the Regulations is replaced by the following:

DIVISION 4
Schedule D Drugs

Definitions

C.04.001 The following definitions apply in this Division.

biological source material
means
  • (a) biological material sourced or derived from humans;
  • (b) animals, including insects, or any biological material sourced or derived from them;
  • (c) plants or any biological material sourced or derived from them; or
  • (d) micro-organisms, including bacteria, viruses, fungi and bacteriophages, or any biological material sourced or derived from them. (matériel d’origine biologique)
drug
means a drug that is listed in Schedule D to the Act that is in dosage form or an active ingredient that can be used in the preparation of a drug listed in that Schedule. (drogue)
holder,
in respect of a drug identification number assigned for a drug, means the manufacturer to whom a document setting out the number was issued under subsection C.01.014.2(1). (titulaire)
Prohibitions on Sale

C.04.002 It is prohibited for a distributor or importer of a drug to sell the drug unless it has been fabricated, packaged/labelled and tested in accordance with this Division.

C.04.003 It is prohibited for a person to sell a drug that they have fabricated, packaged/labelled or tested unless they have fabricated, packaged/labelled or tested it, as the case may be, in accordance with this Division.

Biological Source Material

C.04.004 (1) It is prohibited for a person to use biological source material in the fabrication of a drug unless

(2) A person who uses biological source material in the fabrication of a drug must ensure that the material meets any specifications for the material that have been provided to the Minister in connection with the drug.

(3) A person who uses biological source material in the fabrication of a drug must retain any documents containing the information referred to in paragraph (1)(b) for a period that they determine after taking into account the following factors, but the period must end no earlier than five years after the day on which the biological source material was last used in the fabrication of the drug:

Prevention of Contamination

C.04.005 (1) Every person who fabricates a drug and every person who packages a drug in an immediate container must

(2) It is prohibited for a person to conduct laboratory procedures of a diagnostic nature in their premises unless the conduct of those procedures is segregated from the fabrication, packaging/labelling and testing of drugs.

Reference Preparations

C.04.006 Reference preparations that are used to test the purity or potency of a drug must allow for the control of the quality of the drug.

Lot Release

C.04.007 (1) In this section, suitable for sale, in respect of a lot of a drug, means that the lot has been fabricated, packaged/labelled and tested in accordance with these Regulations and in a manner that is consistent with information provided to the Minister regarding the quality and safety of the drug.

(2) The Minister may, for the purpose of assessing whether a lot of a drug in dosage form is suitable for sale, request that the following persons provide the Minister with any information, samples of the drug or its active ingredients, or material to be used to test the samples:

(3) It is prohibited for a person who is requested to provide information, samples or material under subsection (2), and any other person whom the Minister notifies of the request, to sell drugs from the lot to which the request relates unless the Minister notifies the person that the lot is suitable for sale.

Periodic Quality Reporting

C.04.008 The holder of the drug identification number for a drug in dosage form must, at the request of the Minister, provide the Minister, on an annual basis or at any longer interval specified by the Minister, with information regarding the quality of the drug and its active ingredients, including information regarding the consistency of the fabrication and packaging processes for the drug and the ingredients.

Labelling

C.04.009 (1) The principal display panel of both the inner and outer labels of a drug in dosage form must show

(2) The inner and outer labels of a drug in dosage form must show on any panel

(3) Paragraph (2)(f) does not apply if adequate directions for use of the drug must be displayed on the label in accordance with section C.01.004.02 or C.01.004.03.

(4) Despite paragraph (2)(g), if another provision of these Regulations requires that information referred to in that paragraph be shown on a particular panel of a label, the information must be shown on that panel.

(5) The outer label of a drug in dosage form must show on any panel

(6) The inner label requirements of these Regulations do not apply in respect of a drug in dosage form whose immediate container is too small to accommodate an inner label that meets those requirements if

(7) The expiration date referred to in paragraph (2)(e) and subparagraph (6)(a)(ix) may be omitted from the label of a drug that is to be stockpiled by the following entities for use in emergency situations if the date is communicated by an alternative means to the individuals who administer the drug:

Labelling — Prescription Drugs

C.04.010 (1) In the case of a drug in dosage form that is a prescription drug, the symbol “Pr” must be shown on

(2) Subsection (1) does not apply to a drug that is

24 (1) The definition designated COVID-19 drug in section C.08.001.1 of the Regulations is repealed.

(2) Section C.08.001.1 of the Regulations is amended by adding the following in alphabetical order:

List of Conditions that Threaten Public Health
means the List of Conditions that Threaten Public Health in Canada, published on the Government of Canada’s website, as amended from time to time; (Liste d’affections qui menacent la santé publique)
public health emergency drug
means a new drug for which the purpose and conditions of use recommended by the manufacturer relate to a condition that is described in the List of Conditions that Threaten Public Health; (drogue pour urgence de santé publique)

25 The Regulations are amended by adding the following after section C.08.001.1:

C.08.001.2 (1) The Minister may add a condition to the List of Conditions that Threaten Public Health only if the Minister has reasonable grounds to believe that

(2) However, the Minister may add COVID-19 to the List of Conditions that Threaten Public Health, even if the criteria set out in subsection (1) are not met with respect to COVID-19 at the time of the addition, as long as the Minister has reasonable grounds to believe that the addition is necessary to protect public health or safety.

C.08.001.3 If a condition that is on the List of Conditions that Threaten Public Health is removed from the list, a public health emergency drug that relates to that condition continues to be considered a public health emergency drug for the purposes of this Division if

26 (1) Paragraph C.08.002(2)(o) of the Regulations is replaced by the following:

(2) Subsection C.08.002(2) of the Regulations is amended by striking out “and” at the end of paragraph (n), by adding “and” at the end of paragraph (o) and by adding the following after paragraph (o):

(3) Subsections C.08.002(2.1) to (2.3) of the Regulations are replaced by the following:

(2.01) If clinical trial data that is included in a new drug submission under paragraph (2)(g) or (h) or (2.1)(b) is broken down by population subgroup in an application made to the European Medicines Agency or the United States Food and Drug Administration to authorize the sale of the new drug, the data must be broken down in the same manner in the new drug submission.

(2.1) A manufacturer may file, for a public health emergency drug, a new drug submission that does not meet the requirements set out in paragraphs (2)(g) and (h) if the submission contains

(2.2) A manufacturer may file, for a public health emergency drug for human use, a new drug submission that does not meet the requirements set out in paragraph (2)(j.1) if the submission contains a draft of every label to be used in connection with the drug, including any package insert and any document provided on request that sets out supplementary information on the use of the drug.

(2.3) If, at the time a new drug submission is filed for a public health emergency drug, the manufacturer is unable to provide the Minister with information or material that is referred to in any of paragraphs (2)(e) to (k), (m) and (n) and (2.1)(b) and subsection (2.2) — and, as applicable, the corresponding material referred to in paragraphs C.08.005.1(1)(b) to (d) — or any of that information or material is incomplete, the manufacturer must provide the Minister, at that time, with a plan that specifies how and when they will provide the Minister with the missing information or material.

(4) Subsection C.08.002(2.3) of the Regulations is replaced by the following:

(2.3) If, at the time a new drug submission is filed for a public health emergency drug, the manufacturer is unable to provide the Minister with information or material that is referred to in any of paragraphs (2)(e) to (k), (m), (n) and (p) and (2.1)(b) and subsection (2.2) — and, as applicable, the corresponding material referred to in paragraphs C.08.005.1(1)(b) to (d) — or any of that information or material is incomplete, the manufacturer must provide the Minister, at that time, with a plan that specifies how and when they will provide the Minister with the missing information or material.

(5) Subsections C.08.002(2.4) and (2.5) of the Regulations are replaced by the following:

(2.4) Subsections (2.1) to (2.3) apply only if

(2.5) Subsections (2.1) to (2.3) do not apply if a notice of compliance is being sought on the basis of a direct or indirect comparison between the new drug and another drug.

27 Paragraph C.08.002.01(2)(b) of the Regulations is amended by striking out “and” at the end of subparagraph (ix), by adding “and” at the end of subparagraph (x) and by adding the following after subparagraph (x):

28 Subsection C.08.002.1(2) of the Regulations is amended by adding the following after paragraph (a):

29 (1) Section C.08.003 of the Regulations is amended by adding the following after subsection (3):

(3.01) If clinical trial data that is included in a supplement to a new drug submission is broken down by population subgroup in an application made to the European Medicines Agency or the United States Food and Drug Administration to authorize the sale of the new drug, the data must be broken down in the same manner in the supplement.

(2) Section C.08.003 of the Regulations is amended by adding the following after subsection (3.1):

(3.2) A supplement to a submission referred to in subsection (1) for a new drug for human use shall contain

(3) Section C.08.003 of the Regulations is amended by adding the following after subsection (4):

(5) The manufacturer may file, for a public health emergency drug, a supplement to the new drug submission referred to in subsection (1) that does not contain all of the information and material that is required under subsection (3) if the supplement contains

(6) The manufacturer may file, for a public health emergency drug for human use, a supplement to the new drug submission referred to in subsection (1) that does not meet the requirements set out in subparagraph (3.1)(a)(ii) or (b)(ii) if the supplement contains a draft of every label to be used in connection with the drug, including any package insert and any document provided on request that sets out supplementary information on the use of the drug.

(7) If, at the time the manufacturer files, for a public health emergency drug, a supplement to the new drug submission referred to in subsection (1), the manufacturer is unable to provide the Minister with information or material that relates to any of the matters referred to in paragraphs (2)(d) to (h) and (5)(b) and subsection (6) — and, as applicable, the corresponding material referred to in paragraphs C.08.005.1(1)(b) to (d) — or if any of that information or material is incomplete, the manufacturer shall provide the Minister, at that time, with a plan that specifies how and when they will provide the Minister with the missing information or material.

(4) Subsection C.08.003(7) of the Regulations is replaced by the following:

(7) If, at the time the manufacturer files, for a public health emergency drug, a supplement to the new drug submission referred to in subsection (1), the manufacturer is unable to provide the Minister with information or material that relates to any of the matters referred to in paragraphs (2)(d) to (h), subsection (3.2), paragraph (5)(b) and subsection (6) — and, as applicable, the corresponding material referred to in paragraphs C.08.005.1(1)(b) to (d) — or if any of that information or material is incomplete, the manufacturer shall provide the Minister, at that time, with a plan that specifies how and when they will provide the Minister with the missing information or material.

(5) Section C.08.003 of the Regulations is amended by adding the following after subsection (7):

(8) Subsections (5) to (7) apply only if

(9) Subsections (5) to (7) do not apply if a notice of compliance in respect of the supplement is being sought on the basis of a direct or indirect comparison between the new drug and another drug.

30 Section C.08.003.1 of the Regulations is replaced by the following:

C.08.003.1 In examining a new drug submission, an extraordinary use new drug submission, an abbreviated new drug submission, an abbreviated extraordinary use new drug submission or a supplement to any of those submissions, the Minister may, for the purpose of assessing the safety and effectiveness of the new drug for which the submission or supplement was filed, examine

31 The Regulations are amended by adding the following after section C.08.003.1:

C.08.003.2 In cases where there are significant uncertainties respecting the evidence of the effectiveness of a new drug that was provided in a new drug submission or supplement to a new drug submission, the Minister may, in examining the submission or supplement, take into account whether terms and conditions that may be imposed or amended under section C.01.014.21 would enable the Minister to obtain additional information respecting the uncertainties if

32 The Regulations are amended by adding the following after C.08.003.2:

C.08.003.3 For greater certainty, the obligation of the manufacturer to provide a risk management plan referred to in paragraph C.08.002(2)(p), subparagraph C.08.002.01(2)(b)(xi) or paragraph C.08.002.1(2)(a.1) or C.08.003(3.2)(a) or an updated risk management plan referred to in paragraph C.08.003(3.2)(b) may arise at any time before the Minister issues a notice of compliance under section C.08.004 or C.08.004.01 or a notice under paragraph C.08.004(3)(b) or C.08.004.01(3)(b).

33 The heading before section C.08.009.01 of the Regulations is replaced by the following:

Pre-positioning of Public Health Emergency Drugs

34 Section C.08.009.01 of the Regulations is amended by adding the following in alphabetical order:

dosage form class
has the same meaning as in subsection C.01A.001(1). (classe de forme posologique)
fabricate
has the same meaning as in subsection C.01A.001(1). (manufacturer)
package/label
has the same meaning as in subsection C.01A.001(1). (emballer-étiqueter)

35 Section C.08.009.02 of the Regulations is replaced by the following:

C.08.009.02 Sections C.08.009.03 to C.08.009.05 apply in respect of a public health emergency drug if

36 Subsection C.08.009.03(1) of the Regulations is replaced by the following:

C.08.009.03 (1) The holder of an establishment licence may import a public health emergency drug if

37 Sections C.08.009.04 and C.08.009.05 of the Regulations are replaced by the following:

C.08.009.04 Sections A.01.040, C.01.004.1 and C.01A.006 and Divisions 2 to 4 of this Part, other than the following provisions, do not apply in respect of the importation of a public health emergency drug under section C.08.009.03 by the holder of an establishment licence:

C.08.009.05 Despite anything in these Regulations, the holder of an establishment licence may distribute a public health emergency drug that they have imported under section C.08.009.03 if

38 (1) Subsection C.08.011.2(2) of the Regulations is amended by adding the following after paragraph (c):

(2) Subsection C.08.011.2(2) of the Regulations is amended by adding “and” after paragraph (i), by striking out “and” after paragraph (j), and by repealing paragraph (k).

39 (1) Subsection C.10.001(5) of the Regulations is amended by adding the following after paragraph (c):

(2) Subsection C.10.001(5) of the Regulations is amended by adding “and” after paragraph (i), by striking out “and” after paragraph (j), and by repealing paragraph (k).

40 Subsection C.10.002(2) of the Regulations is amended by adding the following after paragraph (c):

Medical Devices Regulations

41 Subsections 36(2) to (4) of the Medical Devices Regulations footnote 2 are replaced by the following:

(2) The Minister may, at any time, impose terms and conditions on a medical device licence or amend such terms and conditions after considering

42 Section 37 of the Regulations is replaced by the following:

37 If the terms and conditions of a medical device licence for an in vitro diagnostic device require that tests be performed to ensure that the device continues to meet the applicable requirements set out in sections 10 to 20, no person shall sell a device from a lot of the in vitro diagnostic device unless

Regulations Amending the Food and Drug Regulations (Interim Order Respecting the Importation, Sale and Advertising of Drugs for Use in Relation to COVID-19)

43 Paragraph 20(e) of the Regulations Amending the Food and Drug Regulations (Interim Order Respecting the Importation, Sale and Advertising of Drugs for Use in Relation to COVID-19) footnote 3 is replaced by the following:

Transitional Provisions

44 Unless the context otherwise requires, the words and expressions used in sections 45 to 50 have the same meaning as in the Food and Drug Regulations.

45 (1) Terms and conditions imposed on a drug identification number under subsection C.01.014.21(1.1) of the Food and Drug Regulations, as that subsection read immediately before the day on which subsection 7(1) of these Regulations comes into force, that are in effect immediately before that day remain in effect until the day immediately before the day on which subsection 7(4) of these Regulations comes into force.

(2) Subsection C.01.014.21(1.1) of the Food and Drug Regulations, as that subsection read immediately before the day on which subsection 7(1) of these Regulations comes into force, continues to apply in respect of a designated COVID-19 drug, as defined in section C.08.001.1 of the Food and Drug Regulations as it read immediately before the day on which subsection 24(1) of these Regulations comes into force, until the day immediately before the day on which subsection 7(4) of these Regulations comes into force.

(3) For the purposes of subsection C.01.014.21(1.1) of the Food and Drug Regulations, if a condition is removed from the List of Conditions that Threaten Public Health, a public health emergency drug to which the condition relates continues to be considered a public health emergency drug until the day immediately before the day on which subsection 7(4) of these Regulations comes into force.

(4) Terms and conditions that have been imposed on a drug identification number and that are in effect immediately before the day on which subsection 7(4) of these Regulations comes into force remain in effect.

46 (1) For the purposes of paragraphs C.01.702(1)(a) and C.08.003(3.2)(a) of the Food and Drug Regulations, a risk management plan for the drug is considered to have not yet been provided in the following cases:

(2) The most recent version of the risk management plan for a drug that has been provided to the Minister before the day on which section 8 of these Regulations comes into force and in respect of which the Minister provided, either by that day or after it, an indication that the plan was acceptable is considered to be the existing risk management plan as defined in section C.01.700 of the Food and Drug Regulations.

47 If an application for an establishment licence or to amend such a licence contains — in accordance with subsection C.01A.005(2) or C.01A.006(1.1) of the Food and Drug Regulations, as those subsections read immediately before the day on which sections 9 and 10 of these Regulations come into force — a statement that refers to COVID-19 and the application is submitted to the Minister before that day, the Minister may, on or after that day, issue or amend the licence on the basis of the application.

48 If, on the day on which subsections 26(3) and (5) of these Regulations come into force the Minister has not yet issued a notice of compliance under section C.08.004 of the Food and Drug Regulations or a notice under paragraph C.08.004(3)(b) of those Regulations in respect of a new drug submission for a designated COVID-19 drug — as defined in section C.08.001.1 of the Food and Drug Regulations as that section read immediately before the day on which subsection 24(1) of these Regulations comes into force — that was filed in accordance with subsections C.08.002(2) to (2.5) and section C.08.005.1 of the Food and Drug Regulations, as those provisions read immediately before the day on which subsections 26(3) and (5) of these Regulations come into force, subsections C.08.002(2) to (2.5) of the Food and Drug Regulations, as those subsections read immediately before that day, continue to apply until one of the notices is issued.

49 (1) Subsection C.08.002(2.01) of the Food and Drug Regulations does not apply in respect of a new drug submission that is filed before the day on which that subsection comes into force.

(2) Subsection C.08.003(3.01) of the Food and Drug Regulations does not apply in respect of a supplement to a new drug submission if the supplement is filed before the day on which that subsection comes into force.

50 Any terms and conditions that, immediately before the day on which section 41 of these Regulations comes into force, are set out in a medical device licence referred to in subsection 36(1) of the Medical Devices Regulations are deemed to be imposed by the Minister under subsection 36(2) of the Medical Devices Regulations, as that subsection reads as of that day.

Coming into Force

51 (1) Subject to subsections (2) to (4), these Regulations come into force on the day on which they are published in the Canada Gazette, Part II.

(2) Sections 1 and 2, subsection 3(2), sections 19, 22 and 23, subsections 38(2) and 39(2) and section 43 come into force on July 1, 2025.

(3) Sections 5 and 6, subsection 7(4), section 8, subsections 26(2) and (4), sections 27 and 28, subsections 29(2) and (4), sections 31 and 32, subsection 45(4) and section 46 come into force on April 1, 2027.

(4) Sections 41, 42 and 50 come into force on January 1, 2026.

REGULATORY IMPACT ANALYSIS STATEMENT

(This statement is not part of the Regulations.)

Executive summary

Issues: The pace of innovation today means that drugs regulated under the Food and Drug Regulations (FDR) and medical devices regulated under the Medical Devices Regulations (MDR) are evolving more rapidly than the traditional regulatory frameworks that were designed to regulate them. In response, there has been a focus among regulators on introducing measures to enhance post-market oversight of drugs and medical devices. For many years, Health Canada has been actively engaging in legislative and regulatory modernization, and implementing certain policies to better protect the health and safety of people in Canada and improve international alignment while allowing for innovation. However, further regulatory amendments were required to provide a legal framework that better supports the Department’s policy practices and strengthens the safety oversight of drugs and devices throughout their lifecycle.

For example, many of the regulations specific to biologic drugs (biologics) were overly prescriptive, product-specific and did not reflect current science and technology. The removal of product-specific requirements for biologics also highlighted the need to clarify quality control requirements for good manufacturing practices (GMP) for all drugs.

Diverse population subgroups, such as women, racial and ethnic minorities, children and elderly people are often underrepresented in clinical trial data, impacting Health Canada’s ability to identify product risks and their different safety and effectiveness profiles between the subgroups.

Requirements also did not allow drug manufacturers to qualify limits for purity and potency that could be considered acceptable by Health Canada when a manufacturer’s standard is used that are different from those in publications listed under Schedule B of the Food and Drugs Act (the Act). Furthermore, manufacturers of certain drugs were required to indicate the standard on the label of their drug, which was a Canadian-specific requirement and at times created challenges for manufacturers due to limited space available.

Description: The Regulations Amending Certain Regulations Made Under the Food and Drugs Act (Agile Licensing) (the Regulations) amend the FDR and MDR to deliver on the Department’s modernization commitments and leverage long-standing policies and practices. They also take into consideration recent experience with regulatory agilities piloted during the COVID-19 pandemic through the interim orders and their transition to regulations. The Regulations are comprised of several distinct components that, once in force, will:

  • Enable the use of terms and conditions (T&Cs) on the drug identification number (DIN) of any drug;
  • Broaden the scope of use of T&Cs on Class II, III and IV medical device licences;
  • Require risk management plans (RMPs) for certain human drugs to manage risks and uncertainties;
  • Expand the flexibilities for COVID-19 drugs to other public health emergency drugs, including the option of a rolling review of the submission;
  • Clarify expectations that a drug be fabricated, packaged/labelled, tested and stored, including during transportation, in a manner that assures its quality;
  • Modernize requirements for biologics by repealing outdated requirements and replacing them with those that reflect current practices;
  • Clarify, in regulation, the authority to consider certain information obtained outside of a drug submission to support Health Canada’s examination of that submission;
  • Require manufacturers to submit clinical trial data broken down by different subgroups (disaggregated data) for certain drug submissions, as submitted to the United States Food and Drug Administration (USFDA) or the European Medicines Agency (EMA); and
  • Update requirements relating to the inclusion of drug standard information on labels and for manufacturers that use a manufacturer’s standard for their drug.

Rationale: Measures introduced as part of Heath Canada’s ongoing modernization efforts, including in the Regulations, support a drug and medical device framework that more effectively oversees regulated products over the entirety of their lifecycle. The amendments focus on innovation, international alignment, and further commitments set out in the Health and Biosciences: Targeted Regulatory Review – Regulatory Roadmap and the Agri-food and aquaculture sector: Targeted regulatory review, without lowering the standards of evidence required for approval.

More specifically, through the inclusion of T&Cs, the Regulations enable the Minister of Health (the Minister) to better manage risks and uncertainties with respect to drugs and medical devices, including for new products. Formalizing into regulation Health Canada’s longstanding practice with respect to RMPs supports on-market evaluation of information that could have an impact on the benefit-risk profile of certain human drugs. The Regulations also facilitate access to public health emergency drugs through, among other things, the option of a rolling review. It is worth noting that, as for all drugs, drugs subject to any of these measures can only be authorized for sale once all of the information required to assess their safety, effectiveness and quality is provided and found to be acceptable.

Product-specific requirements for biologics are replaced with broader, more flexible regulations that better address advancements in science and technology, and support current practice. Quality control requirements are also clarified to apply to all drugs to complement the amendments for biologics.

The Regulations also clarify the Minister’s authority to consider information and material obtained from sources other than the submission, to support the review of a new drug (i.e. drugs regulated under Part C, Division 8 of the FDR), consistent with current practice.

Furthermore, access to disaggregated data as submitted to the USFDA or the EMA incrementally enhances Health Canada’s ability to assess the safety and effectiveness of new drugs for human use in certain subgroups. This step toward promoting increased diversity in clinical trials underscores Health Canada’s continued commitment to address the growing evidence of potential health disparities for equity-seeking and rights-holding populations, such as women, racial and ethnic minorities, children and elderly people, due to their underrepresentation in clinical trials.

Finally, updating regulations related to manufacturer’s standards, as well as those that require the standard to be indicated on the drug label, addresses long-standing concerns from manufacturers that the previous requirements were not necessary to ensure the safety, effectiveness and quality of certain drugs.

Cost-benefit statement: The incremental costs for industry are estimated at $183 million (present value (PV)). It is expected to cost Health Canada $7 million (PV) to review and manage T&Cs and RMPs. As a result, the total anticipated cost of the Regulations is $190 million (PV) over a 10-year period, discounted at 7%.

The quantified benefits derived from the elimination of regulatory requirements around standards would benefit industry by a cost saving of $62 million (PV) over a 10-year period. The total anticipated net cost of the Regulations is $128 million (PV).

One-for-one rule and small business lens: The Regulations are an out for the purpose of the one-for-one rule as the anticipated administrative burden to the industry is estimated to be reduced by $24,728 (2012 dollars) annually, or $1,649 (2012 dollars) per business. The small business lens applies as there are approximately 225 small businesses in Canada that may be affected by these Regulations.

Issues

It is important that Health Canada’s regulatory framework support the introduction of promising new therapies and not inhibit innovation that could improve the health of people in Canada, while maintaining appropriate safety oversight. The previous regulations provided the Minister with limited abilities to compel manufacturers to take steps to manage the risks and uncertainties associated with a drug or medical device, which did not keep pace with rapid advancements in the science and technology used in the development of these products. While Health Canada implemented certain practices through policy to address these issues, there was a need to codify such practices and promote compliance through measures that provide transparency, predictability and consistency.

With regard to the fabrication, packaging/labelling, testing, storing and transportation of a drug, despite the FDR setting out requirements for the quality control department’s responsibilities with respect to methods and procedures, there was no clear requirement that such activities must be conducted in a way that maintains and assures the quality of the drug. One such example was the expectation set out in policy that drugs be stored, including during transportation, in a way that reduces the risk of exposure to temperatures outside of their approved storage conditions.

In addition, many of the provisions related to biologics did not reflect the current science and technology, and the ways in which the industry has evolved over the years. Many of the provisions were overly prescriptive, product-specific, and were no longer scientifically relevant. This presented a risk to the health and safety of people in Canada, which Health Canada addressed through flexible and outcome-based practices and policies.

When examining a drug submission, in order for the Minister to make the most informed decision about the authorization of the drug, the Minister may consider information that could come from sources other than the submission. Prior to these Regulations, the FDR did not clearly indicate that information other than that filed with the Minister could be considered during Health Canada’s examination and authorization of a new drug.

Additionally, the FDR did not previously have a requirement to provide disaggregated data to support the examination of certain submissions for new drugs. However, research and evidence suggest there can be different effectiveness and safety profiles for some drugs between diverse subgroups, including those that are frequently underrepresented in clinical trials (e.g. women, racial and ethnic minorities, children and elderly people). Receiving disaggregated data gives Health Canada the opportunity to better evaluate a drug’s safety and effectiveness within a given subgroup to determine if the drug poses an increased risk for that group.

Finally, where a manufacturer’s standard is used for certain drugs, the FDR did not allow the manufacturer to set limits for purity and potency that were different from those in the publications listed under Schedule B of the Act that could be considered acceptable to Health Canada. Manufacturers have indicated that this requirement has occasionally resulted in a drug being pulled off the market in Canada. Furthermore, certain Canadian-specific labelling requirements related to drug standards created challenges for some manufacturers due to limited space available on the label.

Background

The Minister of Health is responsible for regulatory activities related to the safety, effectiveness and quality of drugs and medical devices. The Minister’s authority is derived from the Act, and regulations made under it, including the FDR and the MDR.

For the purposes of this document, “drugs” refers to drugs for human and veterinary use regulated under the FDR, such as pharmaceuticals, biologics and radiopharmaceuticals, and does not include natural health products or biocides.

For several years, Health Canada has been actively engaging in legislative and regulatory modernization to support drug and medical device frameworks that effectively oversee regulated products over the entirety of their lifecycle. For example, in 2014, Parliament adopted Vanessa’s Law, which amended the Act to include regulation-making authorities for the purposes of gathering safety information for drugs and medical devices, as well as authorities that enable the Minister to take action in the event that a serious health risk is identified. Regulations made under the Vanessa’s Law authorities introduced measures that:

Further work on identifying and responding to regulatory irritants and roadblocks to innovation was conducted as part of the Health and Biosciences: Targeted Regulatory Review – Regulatory Roadmap and the Agri-food and aquaculture sector: Targeted regulatory review, and resulted in the launch of Health Canada’s Regulatory Innovation Agenda. Through these initiatives, Health Canada has committed to modernizing applicable regulations to ultimately deliver modern, flexible regulatory frameworks for drugs and medical devices.

Some of these flexibilities (T&Cs and rolling reviews) were piloted as part of the response to the COVID-19 pandemic through the following regulatory packages:

The Regulations are part of Health Canada’s Regulatory Innovation Agenda and contribute directly to the Government of Canada’s Biomanufacturing and Life Sciences Strategy, which recognizes the importance of the regulatory system as an enabler of the growth of the domestic biomanufacturing sector.

Terms and Conditions

T&Cs are obligations that the Minister may impose on the DIN of a drug or medical device licence to conduct an activity with respect to the drug or medical device to which the authorization applies. The main purpose of T&Cs is to optimize the benefits and manage risks and uncertainties associated with the drug or medical device, including by collecting additional information after it has been authorized. Health Canada has long recognized the value of such an approach. In 1998, the Notice of Compliance with Conditions (NOC/c) policy was introduced to enable manufacturers of certain human drugs – namely, those intended to treat a serious, life-threatening or severely debilitating disease or condition – to apply for an authorization to sell a drug based on promising evidence of clinical effectiveness from well-controlled and well-conducted clinical trials that demonstrates its use is reasonably likely to have the intended benefit. For example, a drug’s ability to reduce the size of a cancerous tumor -- a surrogate marker -- may be considered to be promising evidence of extended patient survival on that drug, i.e. the clinically relevant endpoint. This policy has allowed Health Canada to more effectively manage uncertainties related to risks and benefits and, as a result, facilitate earlier market access for potentially life-saving drugs when the manufacturer agrees to undertake further studies to confirm the effectiveness and monitor the safety of those drugs and provide that information to the Minister following its entry onto the Canadian market.

With respect to drugs, the FDR gives the Minister a broad power to impose or amend T&Cs on opioids and designated COVID-19 drugs. As for medical devices, when the MDR came into force in 1998, the Minister was granted the authority to impose or amend T&Cs related to testing on Class II, III and IV medical device licences. Further, broad T&Cs powers were included in interim orders related to the authorization of COVID-19 medical devices and also in subsequent amendments to Part 1.1 of the MDR for medical devices for an urgent public health need.

Risk Management Plans

An RMP summarizes the identified and potential risks and uncertainties related to a drug and the associated pharmacovigilance activities, as well as other measures, that the manufacturer intends to put in place to manage those risks and uncertainties.

Internationally, most regulators of human drugs including those in the European Union, the United Kingdom, and the United States have introduced legal requirements for RMPs or their equivalent. Since 2009, to better align with international practice, Health Canada has requested RMPs from manufacturers on a voluntary basis.footnote 4 In 2015, Health Canada published the Guidance Document - Submission of Risk Management Plans and Follow-up Commitments that formalized the practice of requesting RMPs for certain human drugs including:

Through policy, manufacturers were also expected to consider the Canadian context in the RMP by discussing factors that are applicable to the Canadian population and marketplace.

Rolling Reviews for COVID-19 drugs

The review of a standard drug submission begins following receipt of all the information required to establish the safety, effectiveness and quality of the drug, which is typically provided in a single transaction. The option of a “rolling review” allows Health Canada to begin its review of the submission before all of the required information has been provided. If certain conditions are met, such a submission may be filed with the requirement that the missing information must be provided and found to be acceptable before the drug can be authorized for sale. Because a rolling review allows Health Canada to begin the review of the submission earlier, it has the potential to make much-needed drugs available sooner.

Rolling reviews have been available for new drug submissions for designated COVID-19 drugs that do not make a comparison or reference to another drug as set out in the FDR, following making of the Regulations Amending the Food and Drugs Regulations (Interim Order Respecting the Importation, Sale and Advertising of Drugs for Use in Relation to COVID-19).

Assuring Drug Quality During Manufacturing

GMP is an internationally recognized quality assurance system used to ensure drugs are consistently fabricated, packaged/labelled, tested, imported, distributed and wholesaled. However, while it is expected that drugs, including both active ingredients and drugs in dosage form, are fabricated, packaged/labelled, tested and stored, including during transportation, in a manner that would assure their quality, this was not clearly stated in regulation.

Modernizing Requirements for Biologics

Biologics are manufactured and extracted from living tissue or organisms, some with modified genes. Their safety and effectiveness are highly dependent on their source materials (e.g. cells, living organisms) and auxiliary materials (e.g. additives used to supplement cell culture medium). In addition, biologics tend to be sterile, injectable solutions that treat serious or life-threatening conditions, and the risks related to these drugs can be equally serious or life-threatening.

Much of Part C, Division 4 of the FDR consisted of product-specific regulations for biologics that were introduced in the 1950s and 1960s to respond to issues of the day. As the number of biologics greatly increased over time, the regulations, which have historically been largely product-focused, did not keep pace with scientific advances.

Significant amendments were made in 1997 in order to amalgamate requirements for establishment licences for the manufacturing of pharmaceutical, biologic, and radiopharmaceutical drugs into Part C, Division 1A of the FDR. While these changes introduced GMP inspections related to the premises, personnel, process, and products, Health Canada also used information obtained on site to confirm the manufacturer’s ability to consistently produce a safe biologic and verify information provided in a drug submission filed by that manufacturer to meet the obligations under section 12 of the Act.

Information Considered to Support the Examination of Drug Submissions

In practice, Health Canada considers information and material from a variety of sources during the examination of a drug submission when assessing the safety, effectiveness and quality of the drug in order to make an informed decision about whether to authorize it for sale. Such sources include on-site evaluations and GMP inspections.

Disaggregated Clinical Trial Data for New Drug Submissions and Supplements to New Drug Submissions

Collection of disaggregated data about clinical trial participants is a key measure Health Canada can take to first assess and, if needed, address any discrepant risks and benefits of drugs in different population subgroups. Health Canada places importance on the development and conduct of inclusive clinical trials particularly for underrepresented populations. Drug submissions generally include some degree of disaggregated data; however, it is not always reflective of the entire patient population or broken down by subgroups like age, sex, race, and ethnicity.

Standards

Drug standards include tests, limits and methods of analysis that help to assure the quality of a drug. These standards can be prescribed in regulation, set out in pharmacopoeiasfootnote 5 listed under Schedule B of the Act or developed by the manufacturer. If a standard has not been prescribed in regulation, but it appears in a pharmacopoeia listed under Schedule B (e.g. the United States Pharmacopoeia), a manufacturer may use either the pharmacopoeial standard or their own manufacturer’s standard.

Where a manufacturer’s standard is used, the manufacturer is required to make available to the Minister, on request, details of that standard and of the tests, limits, and methods of analyses for the drug that are acceptable to the Department. Manufacturers of new drugs should routinely provide the Minister with this information (e.g. in a drug submission).

If a manufacturer’s standard is used, the regulations required that the drug meet the highest degree of purity and the least variation in potency for that drug found in any of the pharmacopoeias listed under Schedule B. This applied to all drugs, including active ingredients, regulated under Part C, Divisions 1, 3, 4 and 8 of the FDR throughout their lifecycle. This prescriptive requirement did not allow those manufacturers who use a manufacturer’s standard to have different limits for purity and potency than the most stringent listed under Schedule B, even if different limits would be qualified and acceptable to the Minister.

For certain drugs, the FDR required that the inner and outer label indicate if a standard prescribed in the FDR, under Schedule B of the Act, or a manufacturer’s standard was used. The inclusion of this information was a Canadian-specific requirement and at times created challenges for manufacturers due to the limited space available on the label.

Objectives

In order to improve the health and safety of people in Canada, the objectives of the Regulations are to strengthen Health Canada’s oversight of drugs and medical devices throughout their lifecycle, encourage innovation by facilitating access to advanced treatments and promising new therapies, and improve alignment with other trusted regulators, all while maintaining the existing high standards for authorization respecting safety, effectiveness, and quality.

Description

The Regulations introduce a number of targeted changes to the FDR and MDR that reflect Health Canada’s long-standing policies, regulatory initiatives introduced during the COVID-19 pandemic (e.g. interim orders and transition regulations), and further modernization commitments such as those made for drugs and medical devices under Vanessa’s Law.

Terms and Conditions – Drugs and Medical Devices (amendments to the FDR and MDR)

Amendments to the FDR allow the Minister to impose T&Cs on the DIN of any drug at the time the DIN is issued, or at any time later. T&Cs can also be amended (including removed) at any time and are enforceable under section 21.7 of the Act.

Previously, Part 1 of the MDR allowed the Minister to impose T&Cs related to testing on Class II, III and IV medical device licences to ensure that devices continued to meet applicable safety and effectiveness requirements under the MDR. The Minister was also able to amend T&Cs to take into account any new development with respect to the device. Amendments to Part 1 of the MDR broaden the scope of use of T&Cs as T&Cs powers are no longer limited to tests. T&Cs can also be imposed or amended (including removed) at any time and are enforceable under section 21.7 of the Act.

All drug and device submissions must satisfy all requirements under the FDR and MDR for an authorization, including containing the necessary information and data to establish the safety, effectiveness and quality of the drug or device to demonstrate a favorable benefit/risk profile. The overall objective of imposing T&Cs is to ensure the drug or device maintains a favorable benefit/risk profile throughout its lifecycle and that the drug or device continues to satisfy safety, effectiveness and quality requirements.

For example, T&Cs for a drug or device can be used to:

Before imposing or amending T&Cs in respect of a drug or device, the Minister would consider whether the T&Cs contribute to meeting the objectives of: managing uncertainties related to the benefits and risks; optimizing the benefits and managing the risks; identifying changes related to the benefits and risks; and in the case of a medical device, whether they would contribute to maintaining its safety and effectiveness.

Furthermore, the Minister must consider whether the T&Cs are technically feasible, whether there are less burdensome means of achieving those objectives, and whether they could be achieved through the application of existing requirements under the Act, the FDR, or the MDR, as the case may be.

Once the T&Cs for drugs are finalized, the Minister is required to notify the manufacturer.

Timing of the amendments related to T&Cs

At the time of publication of the Regulations in Canada Gazette, Part II, the Minister will have the ability to impose T&Cs on the DIN of a public health emergency drug (see below for more information), without needing to take into account any of the above-mentioned considerations. However, on April 1, 2027, the product-specific provisions related to T&Cs for opioids and public health emergency drugs will be repealed and the amendments related to T&Cs for all drugs, including the considerations, will come into force. The amendments respecting T&Cs for Class II, III and IV medical devices will come into force on January 1, 2026.

Transitional provisions ensure that at the time of coming into force of the various amendments related to T&Cs, any T&Cs already imposed will remain in effect.

Consideration of T&Cs prior to the issuance of a notice of compliance

When the amendments related to T&Cs for all drugs come into force on April 1, 2027, the NOC/c policy will be replaced by these amendments. As with drug submissions which previously qualified under the NOC/c policy, where there is promising evidence but still some significant uncertainties about the clinical effectiveness of the new drug, the Minister will have the ability to take into account whether T&Cs could address these uncertainties when determining whether to issue a notice of compliance for a new drug submission, or a supplement to a new drug submission.

This ability of the Minister will apply only to new drugs where there are significant uncertainties respecting the effectiveness of the new drug and where:

This ability of the Minister does not apply to abbreviated new drug submissions as they do not contain information about the clinical effectiveness of the drug.

This consideration of T&Cs by the Minister does not in any way change the requirements the submission must meet in order for the notice of compliance to be issued.

Risk Management Plans (amendments to the FDR)

The RMP-related amendments for certain drugs for human use reflect Health Canada’s long standing practice set out in the guidance document entitled Submission of Risk Management Plans and Follow-up Commitments (RMP Guidance). An RMP must contain sufficient information to enable the Minister to identify and characterize the risks associated with the drug and to conclude that the plan, if implemented, would prevent or reduce those risks or address uncertainties associated with the drug. The RMP must also take into account the Canadian context and contain a description of:

The amendments also clarify that the most recent RMP provided by the manufacturer to the Minister under the Regulations is considered to be the existing RMP.

The RMP must also contain a summary of the plan in English and in French. However, when the RMP is required as part of a DIN application or drug submission, the amendments allow the manufacturer to submit the summary in the second language later during the review but before assignment of the DIN or issuance of the notice of compliance.

Risk Management Plans required in new drug submissions and DIN applications

The Regulations require that an RMP must be included in a new drug submission or an abbreviated new drug submission if:

In the case of an application for a DIN, if either of the above conditions are met, the Minister may request that the manufacturer include an RMP in the application.

The Regulations also require that an RMP be included in all extraordinary use new drug submissions. However, for an abbreviated extraordinary use new drug submission, an RMP must only be included if the above conditions are met.

Risk Management Plans required in supplements to new drug submissions

If an RMP has not yet been provided to the Minister, the Regulations require that one be included in a supplement to a new drug submission, to an abbreviated new drug submission, to an extraordinary use new drug submission and to an abbreviated extraordinary use new drug submission, if:

Where there is an existing RMP, an updated one must be included in a supplement to any of the new drug submissions mentioned above if, compared to the existing plan, there are significant differences in:

Risk Management Plans required following authorization of a drug

Where an RMP has not yet been provided for a drug that is authorized for sale, the manufacturer is required to provide one upon request if the Minister has reasonable grounds to believe that:

Where there is an existing RMP for a drug that is authorized for sale, the manufacturer is required to provide the Minister with an updated one if:

The manufacturer is also required to provide an updated RMP upon request if the Minister has reasonable grounds to believe that:

Transitioning RMPs provided prior to coming into force

Transitional provisions clarify that the most recent version of the RMP provided under the RMP Guidance before the amendments come into force and for which the Minister has indicated to the manufacturer that it is acceptable, will be considered to be the existing RMP for the purposes of the Regulations. An indication of acceptability includes where a notice has been provided to the manufacturer indicating that the RMP is acceptable, or where the RMP was included as part of a drug submission for which a notice of compliance was issued.

The transitional provisions also clarify that an RMP that has not yet been provided to the Minister includes where no RMP was provided before the amendments come into force as well as where one was provided before the coming into force but where the Minister has not indicated to the manufacturer that it is acceptable.

However, the transitional provisions do not apply to an RMP provided before the amendments come into force and that is part of a submission under review at the time of coming into force. In such a case, the RMP must meet the requirements of the Regulations.

Public Health Emergency Drugs (amendments to FDR)

Regulatory flexibilities in the FDR respecting establishment licensing activities related to COVID-19 under Part C, Division 1A and the pre-positioning and market authorization of designated COVID-19 drugs under Part C, Division 8, are expanded to apply to any public health emergency drug in relation to a condition referred to on the List of Conditions that Threaten Public Health (the list), which is a list incorporated by reference. A public health emergency drug is defined as a new drug for which the purpose and conditions of use recommended by the manufacturer relate to a condition that is described on the list. Generally, in order to add a condition to the list, the Minister needs to have reasonable grounds to believe that the condition presents, or is the result of, a significant risk to public health in Canada, and immediate action is required to deal with the risk. However, in the case of COVID-19, this condition can be added to the list where the Minister has reasonable grounds to believe the addition is necessary to protect public health or safety. Given the continued emergence of variants of concern, this will ensure that people in Canada continue to have timely access to much-needed COVID-19 drugs. Once included, because the list is considered a regulation under the Interpretation Act, the Minister can amend it, including removing a condition at any time.

The introduction of a list incorporated by reference allows the Minister to respond to a public health emergency in a timely and flexible manner. The list will be developed, reviewed, maintained, and amended in accordance with the guiding principles set out in Health Canada’s Incorporation by Reference Policy.

The Regulations clarify that a public health emergency drug, for which the Minister has received a submission or establishment licence application, remains a public health emergency drug until the Minister has decided whether to authorize the drug for sale or issue the establishment licence.

Transitional provisions also allow the Minister to impose or amend T&Cs on the DIN of a public health emergency drug, including COVID-19 drugs (authorized before or after the Regulations come into force), even after the condition to which the drug relates has been removed from the list. Given the public health risk associated with conditions such as COVID-19 has been shown to fluctuate over time, these transitional provisions help ensure that drugs will be available to deal with such risks and that there is continued oversight once they are on the market.

The Regulations also expand the regulatory flexibilities afforded to new drug submissions for designated COVID-19 drugs to supplements to new drug submissions for any public health emergency drug. These flexibilities include the option of a rolling review (see below for details) and, in the case of a public health emergency drug for human use, the ability to provide drafts of every label to be used in connection with the new drug instead of label mock-ups.

As was the case for new drug submissions for designated COVID-19 drugs, in order to take advantage of these regulatory flexibilities, the purpose and conditions of use specified in the new drug submission, or supplement to it, must relate only to a condition described on the list. For a supplement to a new drug submission, this means that any other changes to the drug that the manufacturer would like to make, that do not relate to a condition on the list, must be included in a separate submission.

Furthermore, similar to new drug submissions for designated COVID-19 drugs, the flexibilities for public health emergency drugs are not available to new drug submissions or supplements to new drug submissions for generic drugs or biosimilars (subsequent entry drugs). This is because the FDR allows manufacturers of subsequent entry drugs to submit reduced data packages based on comparative studies with the innovator’s drug. For example, the option of a rolling review allows Health Canada to begin its review of available drug development data while later-stage clinical trials take place, which enables the Department to expedite the overall regulatory review process. Given that submissions for subsequent entry drugs do not provide these sorts of supporting clinical trial data, manufacturers of these drugs will remain in a position to meet applicable requirements under the FDR without the need for additional flexibilities.

The criteria for pre-positioning a designated COVID-19 drug are also expanded to include any public health emergency drug to allow a response to a condition referred to on the list. However, the Regulations only allow importation by the holder of a drug establishment licence if the public health emergency drug is the subject of a new drug submission, a supplement to a new drug submission, or an application made to a foreign regulator. The holder of the drug establishment licence must also be an authorized importer and the public health emergency drug must be within the same category of drugs as is authorized by the licence.

Rolling Reviews for Public Health Emergency Drugs

The option of a rolling review allows drug manufacturers to provide some but not all of the required information at the time of filing a submission. However, any missing information needed to assess the benefits and risks regarding the drug’s safety, effectiveness and quality must be provided within a reasonable time before the Minister can complete the examination of the submission and decide whether to authorize the drug. All other requirements under the FDR, such as record retention, would also apply to those submissions and drugs that are subject to a rolling review.

In order to allow Health Canada to begin the review of the new drug submission, the same minimum information requirements that applied to designated COVID-19 drugs subject to a rolling review also apply to new drug submissions for public health emergency drugs. All drug submissions subject to a rolling review must include, at the time they are filed, all of the information that is normally required respecting the formulation, medicinal ingredient, use, and dosage form of the drug for which approval is being sought. Any changes to this information over the course of the rolling review will not be accepted.

The filing date for a submission that is eligible for a rolling review would be the date that the submission is determined to be administratively complete by Health Canada (i.e. once all the elements and forms required for processing are completed and have been submitted). This date may differ from the date of receipt of the initial transaction, should the submission be considered to be administratively incomplete at that time. Once established, the filing date does not change, even though, in the case of a rolling review, the manufacturer provides Health Canada with missing information afterwards.

In addition to expanding the option for a rolling review of a new drug submission for a designated COVID-19 drug to any public health emergency drug, the Regulations also authorize the option of a rolling review for a supplement to a new drug submission for a public health emergency drug.

As was the case for the rolling review of a new drug submission for a designated COVID-19 drug, a plan must be included in a new drug submission or supplement to a new drug submission for a public health emergency drug, that specifies how and when the manufacturer will provide the missing information.

With respect to filing a supplement to a new drug submission for a public health emergency drug, the manufacturer is allowed to provide certain information and material, as applicable, on a rolling basis, including:

While the option of a rolling review for a supplement to a new drug submission for a public health emergency drug allows Health Canada to begin its review before all of the required information has been provided, a notice of compliance cannot be issued unless the Minister has received sufficient information and material to assess its safety, effectiveness and quality in relation to the matters that are different.

Assuring Drug Quality During Manufacturing (amendments to the FDR)

The Regulations clarify expectations that a drug must be fabricated, packaged/labelled, tested, and stored, including during transportation, in a manner that assures the drug’s quality.

This amendment is meant to apply to all licensed fabricators, packagers/labellers, testers, and wholesalers, as well as Canadian importers and distributors. It also works together with other requirements of Part C, Division 2 of the FDR and does not change the established expectations for all drugs. Furthermore, it supports the policy set out in the Guidelines for environmental control of drugs during storage and transportation (GUI-0069), which includes that drugs must be transported in a way that reduces the risk of exposure to temperatures outside of approved storage conditions.

In addition, all occurrences of the word “storage” or “stored” in Part C, Division 1A and 2 of the FDR are changed to clarify that storage includes storage during transportation. This reflects the current interpretation of the regulations.

Modernizing Requirements for Biologics (amendments to the FDR)

The modernization of Part C, Division 4 of the FDR removes outdated product-specific regulations for biologics, and replaces them with more general requirements that reflect the underlying safety purposes, as they are applied through guidance and practice. In this Division, “drug” means a drug that is listed in Schedule D to the Act that is in dosage form or an active ingredient that can be used in the preparation of a drug listed in that Schedule, also referred to as a “biologic” throughout this section of this document. The provisions that have been removed and replaced are the product-specific provisions spanning between C.04.050 and C.04.683. As a result, the definitions “date of manufacture” and “date of issue” are no longer required and therefore do not appear in the amended Division 4.

The modernization of Part C, Division 4 of the FDR will be implemented in a manner that minimizes impact on manufacturers of currently marketed biologics by recognizing and supporting current practices. More specifically, the amendments to the FDR do not change existing practices, including those with regards to lot release and on-site evaluations.

Controls over Manufacturing of Biologics

The Regulations reflect current practice and replace prescriptive requirements for biological starting materials and auxiliary materials used in the manufacturing of biologics with more flexible, outcome-based regulations that maintain an appropriate level of safety oversight. Biological source materials include biological raw materials, biological starting materials and auxiliary materials. The requirements regarding the fabrication and collection of biologics have been clarified to also apply to biological source materials. Previous regulations for controlling contamination of biologics have been generalized to ensure that production personnel do not contribute to the risk of contamination of the biological source materials by infectious agents. The Regulations also remove certain storage requirements as they are outdated, and the Department will instead rely on corresponding regulations under Part C, Division 2 (Good Manufacturing Practices) of the FDR.

Standards for Biologics

Individual standards for biologics, such as insulin, that were prescribed in Part C, Division 4 of the FDR were out of date with changes in science and as a result were no longer relied upon by manufacturers or Health Canada. The Regulations replace these prescribed standards with broader, more flexible requirements to allow the Department to continue to assess specifications provided by the manufacturer during the review of a drug submission. In addition, the Regulations require that reference preparations used to evaluate the purity or potency of a drug, as applicable, allow for the control of the quality of the product.

Lot Release of Biologics

Provisions supporting the lot release program have been amended to better support a risk-based, tiered approach, as per Guidance for Sponsors: Lot Release Program for Schedule D (Biologic) Drugs and current practice.

To manage risks associated with individual lots, the Regulations enable the Minister to ask for information, samples or other materials, as required, including for the purposes of conducting independent testing. Where a request has been made, no person is permitted to sell any drug from that lot until the Minister notifies them that the lot may be sold.

The Regulations also formalize and increase flexibility of the current discretionary practice of providing yearly biologic product reports. Periodic quality reporting characterizes the quality of the drug and its active ingredients, and the consistency of their fabrication and packaging processes over the period of time since the last report. The requirements include periodic quality reporting on an annual basis or longer as specified by the Minister.

Labelling of Biologics

The Regulations update some labelling requirements for biologics to reflect current practice, offer regulatory flexibility and increase alignment with labelling rules for non-Schedule D drugs in Part C, Division 1 of the FDR.

For example, the label of a biologic must include:

The Regulations also include labelling flexibilities for biologics. For example, for biologics that are sold to different levels of Canadian government for use in emergency situations, the expiry date can be omitted from the label provided it is communicated by other means. This is applicable to instances where the drug is anticipated to be stored for prolonged periods and the manufacturer’s long-term stability program is ongoing. The alternate means of indicating the expiry date must be readily available to the person administering the drug.

The Regulations also require that certain information appear on the inner label of a small container for biologics, for example: the drug’s brand name and proper name (if available), the drug’s common name (if there is no proper name), the DIN, the net quantity of the drug in the container.

In order to maintain alignment with existing plain language labelling requirements in Part C, Divisions 1 and 4 of the FDR, and to allow a biologic to be used safely and for the purposes for which it is intended, the qualifier “adequate” was reintroduced to the labelling requirements for directions for use.

The above labelling amendments are in line with current practices and, therefore, are not expected to impact approved labels.

Amendments are also made to Part A, Division 1 of the FDR to indicate that biologics available for sale without a prescription in an open self-selection area must include adequate directions for use in both English and French.

Information Considered to Support the Examination of Drug Submissions (amendments to the FDR)

In line with current practice, the amendments clarify the Minister’s authority to consider information or material that could be examined on a risk-based, case-by-case basis during Health Canada’s examination of a drug submission. The Minister can examine information and material:

The updated requirements do not change the manufacturer’s obligation to provide sufficient information to support the submission and are not intended to impact the potential application of any intellectual property requirements.

Disaggregated Clinical Trial Data for New Drug Submissions and Supplements to New Drug Submissions (amendments to the FDR)

The Regulations require manufacturers to submit clinical trial data that supports the safety and effectiveness of a drug, broken down into population subgroups for both new drug submissions and supplements to new drug submissions. This requirement only applies where the disaggregated data has already been submitted to the USFDA or the EMA. This is an important step as Health Canada moves forward with an incremental approach toward additional data disaggregation requirements to better understand how drugs work in diverse populations, including any potential differences in drug safety and effectiveness between groups.

Standards (amendments to the FDR)

Where a manufacturer uses a manufacturer’s standard for a new drug (i.e. a drug regulated under Part C, Division 8 of the FDR), the Regulations exempt them from having to meet the most stringent limits for purity and potency of all the Schedule B pharmacopoeias in which the active ingredient or drug appears. This allows those manufacturers who use a manufacturer’s standard to have different limits for purity and potency than the most stringent listed under Schedule B, that are acceptable to the Minister. This exemption does not apply to new drugs regulated under Schedule C (radiopharmaceutical drugs). Due to their unique characteristics Schedule C drugs must continue to meet the most stringent limits for purity and potency of all Schedule B pharmacopoeias when a manufacturer’s standard is used.

Manufacturers who use a manufacturer’s standard for drugs that are not new drugs will continue to be required to meet the most stringent limits for purity and potency of all the Schedule B pharmacopoeias.

For all drugs, other than those regulated under Part C, Divisions 3 and 4 (i.e. radiopharmaceuticals and biologics) of the FDR, the Regulations remove the requirement for the standard used for the drug to be indicated on the package label. Biologics, which were already exempt from having to indicate the standard used on the package label, will continue to be exempt, while radiopharmaceuticals will continue to be required to indicate the standard used on the package label.

Other Changes to the Regulations

Additional changes to improve alignment between the French and English languages have also been applied to the Regulations. These changes do not impact on the operation of the Regulations.

Coming into force

The following regulatory amendments, which prioritize burden reduction for industry and ensure that Health Canada is well positioned to address any future public health emergencies, come into force upon publication of the Regulations in Canada Gazette, Part II:

The following regulatory amendments require additional time to operationalize and will therefore have a delayed coming into force:

Regulatory development

Consultation

Previous consultations

The guidelines and policies that formed the basis for the Regulations were consulted on prior to their implementation. For example, Health Canada’s policy approach to RMPs was established based on the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (PDF) E2E guidelines, which were developed from input from the international pharmaceutical industry. Prior to implementing Health Canada’s final RMP guidance, which was well received by industry, significant consultation was done to more closely align with international guidelines implemented in other jurisdictions.

In addition, Health Canada also heard from stakeholders on the need for regulatory agility during the 2018 Health and Biosciences: Targeted Regulatory Review – Regulatory Roadmap process.

Consultations were also held before bringing forward several of the interim orders and regulations addressing COVID-19. The outcomes of the drug-related consultations are summarized in a What Was Heard Report, as well as in the regulatory impact analysis statement that accompanied the regulations that transitioned the drug interim order into the FDR. The outcomes of the medical devices-related consultations are summarized in the three medical devices interim order explanatory notes (No.1, No. 2, and No.3) and the regulatory impact analysis statement that accompanied the regulations that transitioned the medical devices interim order No. 3 into the MDR.

Furthermore, for more than 10 years the Department has engaged industry stakeholders in a policy and scientific technical analysis of Part C, Division 4 of the FDR, including in December 2022 with the publication of a notice to stakeholders on Biologic drugs (Schedule D drugs) – Division 4 proposed regulatory amendments. Throughout this engagement, stakeholders shared their support for these modernization efforts.

Stakeholder feedback on some of the components of the Regulations was requested following publication of a 90-day Notice of Intent in Canada Gazette, Part I. The consultation ran from July 31, 2021 to October 28, 2021. During this time, industry stakeholders were also asked to complete a cost-benefit survey. Meetings were also held with health technology assessment (HTA) organizations and health system partners such as the provinces and territories. These meetings were used to provide an overview of the Notice of Intent and answer any questions stakeholders had about the proposed changes to the FDR and MDR.

In response to the Notice of Intent, Health Canada received comments from pharmaceutical and medical device companies, industry associations, HTA organizations, provinces and territories, associations representing health care professionals, and individuals. In addition, completed cost-benefit surveys were also received from industry stakeholders.

Stakeholders were generally supportive of the proposal; however, they did request that additional details respecting implementation be provided. The feedback received was used to refine the Regulations prior to publication in Canada Gazette, Part I.

Pre-publication in Canada Gazette, Part I

Stakeholder feedback was requested following pre-publication of the Agile Licensing Regulatory Impact Analysis Statement and the Regulations in Canada Gazette, Part I. The 130-day consultation ran from December 17, 2022 to April 26, 2023. Meetings were also held upon request with HTA organizations, health system partners, industry associations, pharmaceutical and medical device companies and patient advocacy organizations. These meetings were used to provide an overview of the proposal and answer any questions stakeholders had about the proposed changes to the FDR and MDR.

Response

The Department received approximately 2,800 comments, roughly 60 of which were from pharmaceutical and medical device companies, industry associations, HTA organizations, associations representing health care professionals, and academics. The majority of the remaining comments were from individuals. Of these, a significant number were part of a letter-writing campaign based on standardized language that did not reference any of the individual components of the proposal. All feedback received was considered and, where appropriate, refinements were made to the amendments to the FDR and MDR.

Stakeholders who made specific comments on the substance of the proposal and its components were generally supportive of the Regulations. They expressed particular support for Health Canada’s efforts to increase regulatory agility and international alignment, reduce known irritants, improve access to drugs and medical devices, and enhance post-market oversight throughout the lifecycle of a drug or device.

Unless otherwise indicated, the analysis below is based on the feedback provided by stakeholders who made specific comments on the individual substantive components of the Regulations.

Terms and Conditions – Drugs and Medical Devices (amendments to the FDR and MDR)

Comment: Stakeholders were generally supportive of the amendments related to T&Cs. With respect to the changes proposed, industry stakeholders recommended that T&Cs for drugs and medical devices should only be used when necessary. Response: The amendments to the FDR and MDR outline considerations that the Minister would have to take into account before imposing a T&C, for example, whether existing requirements under the Act or its regulations are sufficient to meet the proposed objectives rather than using T&Cs.

Comment: Several stakeholders requested clarification on the relationship between the decision to authorize a drug and any T&Cs, including whether T&Cs would be considered when making a decision to authorize a drug that meets Health Canada’s NOC/c policy. Response: The NOC/c policy will be removed upon implementation of the T&Cs authorities. To reflect the long-standing practice under the NOC/c policy and provide clarity to stakeholders regarding the relationship between T&Cs and the drug authorization, the amendments make clear that the Minister may consider T&Cs prior to making a decision on the issuance of the notice of compliance for drugs that meet the specified criteria, i.e. drugs for serious or life-threatening diseases where there are significant uncertainties with respect to the effectiveness of the drug. Although the NOC/c policy only applies to drugs for human use, the Department has previously indicated to stakeholders its intent to expand this policy to drugs for use in animals. Therefore, amendments have been made to the Regulations to reflect the current practice under the NOC/c policy such that the Minister may take into account T&Cs prior to making a decision to authorize both human and animal drugs that meet the criteria. For drugs that do not meet the criteria, the Minister’s decision to issue a notice of compliance would not take into account any T&Cs to be imposed.

The amendments related to T&Cs do not lessen pre-market requirements for drug and medical device submissions or adjust the issuing threshold for authorization. Rather, the Department continues to require the same high evidentiary standards for these products prior to authorization for sale. Furthermore, the consideration of T&Cs by the Minister prior to authorization of certain drugs does not in any way change the requirements for issuance of a notice of compliance. For example, in the case of an eligible drug, the decision to authorize it for sale may be based on promising evidence of clinical effectiveness such as a surrogate marker.

Risk Management Plans (amendments to the FDR)

Comment: Overall, there was support for the amendments related to RMPs. However, stakeholders did raise concerns with the proposed provisions to allow a stop-sale where a manufacturer fails to provide an RMP in the time requested. Response: Health Canada is in agreement and has removed RMP-specific stop-sale provisions, as it may result in critical drugs no longer being available for sale which may result in serious or life-threatening situations for people in Canada. Furthermore, the Minister can rely on other existing authorities in the FDR to manage risks arising from continued sale when the manufacturer fails to provide an RMP requested by the Minister.

Comment: Feedback was also received on the proposed requirement for bilingual RMP summaries. For example, industry stakeholders wanted greater flexibility as to when the RMP summary could be submitted, including its translation. Response: Although the regulatory requirement to provide the RMP summary in both official languages prior to authorization of the drug has been retained, flexibility will be given with respect to when the translation can be provided during the examination of the submission. This will reduce the number of translation iterations as the RMP is revised during review. This will reduce burden on industry and Health Canada and will prevent unnecessary filing delays while also supporting timely publication of the summary in both official languages following NOC issuance.

Comment: Stakeholders also indicated that Health Canada’s review of the RMP should not delay authorization of their drug. Response: For RMPs required as part of a drug submission, once the final RMP is received, the Department plans to complete the review and approval within established performance standards to ensure there is no delay in market access. Furthermore, the time required to review and approve a new or updated RMP received in the case of a post-market request will not impact the manufacturer’s ability to continue to sell their drug.

Public Health Emergency Drugs (amendments to the FDR)

Comment: Overall, feedback received was supportive of the proposed amendments related to public health emergency drugs. Although some requested that Health Canada consider expanding the scope of eligible drugs, overall, stakeholders acknowledged that the amendments would improve the Department’s regulatory framework by allowing certain flexibilities to support timely authorization of critical drugs during a public health emergency situation.

In addition, for public health emergency drugs subject to a rolling review, stakeholders requested that more information be allowed to be provided later on during the review of the submission. Response: The minimum information requirements for the initial transaction serve to optimize the review of the submission and facilitate timely access to critical drugs. The amendments therefore reflect the amount of information needed to begin the review.

Comment: Stakeholders requested confirmation that the amendments for public health emergency drugs would also apply to supplements to new drug submissions. Response: Since the Department would like to allow the flexibilities related to new drug submissions for public health emergency drugs to also apply to supplements to new drug submissions for public health emergency drugs, the Regulations have been updated to reflect this.

Comment: Some stakeholders indicated that they would be supportive of the amendments related to public health emergency drugs as long as Health Canada continues to require the same rigorous amount of scientific and clinical evidence as for all other submissions. Response: While the option of a rolling review for a public health emergency drug allows Health Canada to begin the review of the drug submission sooner, the submission will continue to be required to include all of the necessary information to assess the safety, effectiveness and quality of the drug and satisfy all requirements of the FDR. The decision to authorize these drugs can only be made when all the required information, including any missing information, has been provided, reviewed, and found to be acceptable.

Rolling Reviews (amendments to FDR)

Comment: Stakeholders were generally supportive of rolling reviews in principle but emphasized the need for greater flexibility and the need to further incentivize their use. For example, some stakeholders requested an expansion of the scope of eligible drugs, that more information be allowed to roll, that the Department commit to more aggressive review timelines once all the missing information is provided, and that stakeholders be permitted to provide the missing information without a time limit in as many transactions as needed.

Concerns and questions were also raised respecting the implementation of a rolling review as it relates to intellectual property rights set out under the Patent Act and its associated regulations and the data protection provisions of the FDR. For example, the ability to file a submission earlier would either increase the volume of submissions that would meet the timely filing requirement for a certificate of supplementary protection and lead to increased barriers to access for subsequent entry drugs, or allow manufacturers of subsequent entry drugs to potentially circumvent intellectual property obligations.

Response: Given the concerns noted above and operational issues identified during the consultation period, it became apparent that significant, additional policy development and stakeholder engagement would be required to overcome these issues. As a result, rolling reviews have been limited to those for public health emergency drugs. Health Canada will continue to explore accelerated review mechanisms outside of the context of these amendments to the FDR. Experience gained from expanding rolling reviews to public health emergency drugs could help inform future policy for rolling reviews more broadly or other regulatory pathway efficiencies.

Assuring Drug Quality During Manufacturing (amendments to the FDR)

Comment: Stakeholders were supportive of the amendments related to good manufacturing practices that would require that every lot is fabricated, packaged/labelled, tested and stored, including during transportation, in a manner that assures the quality of the drug.

Modernizing Requirements for Biologics (amendments to the FDR)

Comment: In general, stakeholders were supportive of the modernization of the requirements for biologics. Some stakeholders requested additional clarity in the Regulations as to whom the exemption to indicate the expiry date on the label for stockpiled drugs applies. Response: The Regulations now clarify that this exemption applies to different levels of Canadian government.

Comment: Stakeholders also encouraged Health Canada to simplify lot release requirements by making them more risk-based. Further, they asked that consideration be given when the lot of a drug has already been tested by the EMA or USFDA when assessing whether the lot is suitable for sale. Response: The Department’s Guidance for Sponsors: Lot Release Program for Schedule D Biologic Drugs will reflect this feedback. Health Canada will continue to conduct its own lot release testing to make a determination about suitability for sale.

Comment: With respect to labelling flexibilities, stakeholders indicated that based on experience from the COVID-19 pandemic, Health Canada should, in certain situations such as for small volume products, accept universal labels or digital labels such as QR or 2D barcodes. More specifically, some stakeholders requested that Health Canada allow internationally recognized statements, notations, or symbols (e.g. ISO symbols) to indicate sterility on the label for biologics instead of the explicit requirement to indicate sterile in both English and French. In addition, stakeholders indicated that the requirement to put the biological source material on the label will be quite challenging since these products may have multiple biologic source materials used in the fabrication of the drug. Response: While the Regulations do not prohibit the use of additional digital labeling, such labeling cannot be used as a substitute for the information that is required to appear on the drug label. However, in response to these comments, the Regulations have been amended to allow flexibility as to how sterility is indicated on the label for biologics, as appropriate. The Regulations also now clarify that the label must include an indication of whether any of the drug’s medicinal ingredients are sourced or derived from human or animal biological source material. This requirement does not capture those ingredients that are consumed in the fabrication of the drug or those that are non-medicinal.

Comment: Stakeholders also requested that Health Canada eliminate the Canadian-specific discretionary practice for yearly biologic product reports (YBPRs) and instead rely on internationally accepted Annual Product Quality Reports during inspections. More specifically, stakeholders indicated that the YBPRs are in a Canadian-specific format and create significant burden on the manufacturer and also delay Health Canada’s receipt of the most up-to-date information. Response: Health Canada will maintain the current practice of accepting information presented in Annual Product Quality Report format with additional information. The use of the template specified in the guidance on lot release is recommended. If alternate formats are used, Health Canada recommends including Canadian-specific information not already included in the alternate format.

Information Considered to Support the Examination of Drug Submissions (amendments to the FDR)

Comment: Stakeholders were generally supportive of the amendments that clarify the Minister’s ability to consider information obtained outside of a drug submission during its examination. Some stakeholders indicated that the information must be from a reputable source, such as a trusted foreign regulator or from an inspection conducted by Health Canada. Response: Per the Department’s current practice, the validity of information received from other sources will continue to be scrutinized and confirmed before it is considered to support the examination of the submission. Furthermore, information or material is examined on a risk-based, case-by-case basis.

Disaggregated Clinical Trial Data for New Drug Submissions and Supplements to New Drug Submissions (amendments to the FDR)

Comment: Stakeholders were generally supportive of providing disaggregated clinical trial data for new drug submissions and supplements to new drug submissions as submitted to the USFDA and the EMA. However, some stakeholders cautioned against future amendments that would result in Canadian-specific requirements for disaggregated data. Response: Health Canada would consult with stakeholders on any disaggregated clinical trial data-related amendments proposed in the future. Some drug manufacturers have generally shown keen interest in receiving direction/guidance on conducting inclusive clinical trials reflective of the diverse Canadian population.

Standards (amendments to the FDR)

Comment: Stakeholders were generally supportive of the removal of the Canadian-specific requirements for indicating the standard on a drug label, although a small number did express a general overall concern with this change. Stakeholders representing pharmacy professionals indicated that they do not often refer to the drug standard used as there is an expectation that the quality of the product has already been assured through Health Canada’s authorization process. They also stated that as long as Health Canada fulfills its oversight obligations in ensuring the quality of drug products in Canada, an indication of the standard used does not need to appear on the drug label.

Comment: Stakeholders were also generally supportive of the removal of the Canadian-specific requirements related to manufacturer’s standards. Some stakeholders requested that the exemption from the requirement to meet the most stringent limits for purity and potency in the pharmacopoeias listed under Schedule B of the Act be expanded to drugs regulated solely under Part C, Division 1 of the FDR. Response: Due to the application requirements for drugs regulated only under Part C, Division 1 of the FDR, sufficient information is not available for Health Canada to assess a manufacturer’s standard that does not meet the most stringent limits for purity and potency set out in the listed pharmacopoeias.

Comment: Some feedback was also received that opposed the changes related to manufacturer’s standards, in order to preserve strong quality requirements. Response: Regardless of whether a manufacturer’s standard is used, all of the information that is normally required to establish the safety, effectiveness, and quality of a drug must be provided and found to be acceptable (e.g. including limits that may differ from those in the pharmacopoeias) before the drug can be authorized for sale.

Implementation

Comment: In addition to the feedback on the Regulations outlined above, Health Canada received a significant number of substantive comments on implementation of the Regulations. Response: These comments were considered as part of the Department’s efforts to implement and operationalize the Regulations and will be addressed through mechanisms such as policy and guidance.

Cost-benefit analysis

Comment: Stakeholders noted that the cost-benefit analysis (CBA) did not account for significant additional capacity that was perceived to be needed within Health Canada due to the number of T&Cs stacked year over year. Response: As per Canada’s Cost-Benefit Analysis Guide for Regulatory Proposals, the CBA accounts for the incremental impacts that result from the Regulations, and Health Canada has carefully considered the level of effort needed to support the yearly additional volume.

Comment: Stakeholders also provided comments related to the CBA associated with rolling reviews, citing:

Response: As indicated previously, rolling reviews have been limited to those for public health emergency drugs. As a result, the CBA has been adjusted to reflect that change.

As part of its role as the federal regulator, Health Canada assesses and approves drugs. The CBA examines the direct costs and benefits of any regulatory amendments related to that process. Organizations and agencies such as the Patented Medicine Prices Review Board and HTAs, play a role in the decision making that determines drug costs in Canada and influences drug reimbursement policy in Canada, such as which drugs get listed on provincial formularies and at what price. This assessment process ultimately determines which drugs will be covered by both public and private drug payers. It is outside the scope of the CBA to account for the costs and benefits associated with the policies of other organizations.

General Comments

Comment: Some stakeholders indicated that there was a lack of detail about how well some features of the current regulatory system are functioning and that not enough information was provided about how Health Canada will evaluate the successes or failures of the Regulations. Response: The evaluation of Departmental activities, including the regulation of drugs and medical devices, are conducted via Health Canada’s Office of Audit and Evaluation, which regularly audits and publishes its findings (e.g. Evaluation of the Pharmaceutical Drugs Program).

Comment: Many of the comments received as part of the letter-writing campaign were not directly related to the Regulations but rather provided feedback on Health Canada’s overall approach to COVID-19 drug authorization, and the Advanced Therapeutic Products pathway which was introduced in the 2019 Budget Implementation Act. These comments are out of scope of this regulatory proposal.

Comments received that could relate to the Regulations generally expressed opposition to the proposal based on concerns that certain amendments would:

Response: The Department’s modernization efforts, including those in the Regulations, are to provide people in Canada with access to much-needed treatments as quickly as possible, without lowering authorization requirements for safety, effectiveness and quality. Through the introduction of amendments related to T&Cs and RMPs, the Regulations increase post-market oversight without compromising pre-market rigour.

The Regulations also build upon some of the flexibilities that were introduced into our regulations to address the COVID-19 pandemic. This includes modified requirements, such as pre-positioning and the option of a rolling review, for drugs that may be needed to address future public health emergencies.

All drug submissions, including rolling reviews for public health emergency drugs, and medical device licence applications will continue to be required to include all of the necessary information and data to assess the safety, effectiveness and quality of the drug or medical device, and satisfy all requirements under the FDR and MDR prior to authorization and once on the market.

Comment: Health Canada also received a number of additional comments from other individuals and organizations that were outside the scope of the regulatory proposal, including that:

Response: These comments have been shared with the appropriate groups within Health Canada for their consideration.

Modern treaty obligations and Indigenous engagement and consultation

​As required by the Cabinet Directive on the Federal Approach to Modern Treaty Implementation, a detailed assessment of modern treaty implications was conducted on the proposal. The assessment did not identify any modern treaty implications or obligations.

Instrument choice

Health Canada considered the following regulatory and non-regulatory options:

Option 1: To not introduce regulatory amendments and maintain status quo

Without the amendments to the FDR and MDR, the Department would not meet its commitments under the Health and Biosciences: Targeted Regulatory Review – Regulatory Roadmap and Agri-food and aquaculture sector: Targeted regulatory review. These commitments include development of regulatory flexibilities, keeping pace with innovation and facilitating access to advanced treatments and promising therapies, while continuing to ensure authorized drugs and licensed medical devices are safe, effective, and subject to appropriate oversight. The absence of amendments to codify these flexibilities would result in a lack of certainty for manufacturers that the agilities would be consistently available and applied.

Furthermore, without the amendments, legally binding commitments for the management of risks and uncertainties by way of T&Cs would continue to apply to opioids and designated COVID-19 drugs only. Under Part 1 of the MDR, T&C powers would be limited to tests for Class II, III and IV medical devices, while broad T&Cs would only apply to medical devices for which there is an urgent public health need in Canada that are authorized under Part 1.1 of the MDR.

The option to retain the status quo would not ensure that there are legal foundations in place to implement a drug framework which effectively oversees regulated drugs throughout their lifecycle. It also would not enhance the existing legal foundation or framework to oversee medical devices throughout their lifecycle.

Option 2: Propose regulatory amendments to introduce modernization elements to the regulatory framework for drugs and medical devices

This is the preferred option as the Regulations ensure that the Minister has the appropriate tools for oversight of the safety and effectiveness of drugs and medical devices such as through enforceable T&Cs. The Regulations establish a legal framework to proactively mitigate risks through regulatory requirements such as those for T&Cs and RMPs. It also supports timely access for people in Canada to critical drugs, through amendments such as the option of a rolling review for public health emergency drugs.

This option allows the Department to begin to address the commitments made within the Health and Biosciences: Targeted Regulatory Review – Regulatory Roadmap and the Agri-food and aquaculture sector: Targeted regulatory review, to reduce burden on industry and to bring its regulations up to date with current practice so they are clear to stakeholders.

Regulatory analysis

Benefits and costs

The CBA aims to quantify the benefits and costs of the Regulations and is a combined result of literature reviews, input from stakeholders, subject matter expertise at Health Canada, and internal database analyses.

The CBA has been modified to reflect updated data, and as such, changes have been made to key assumptions and variables. The significant changes from Canada Gazette, Part I are predominantly due to the revised delayed coming into force for some of the regulatory amendments that require additional time to operationalize, the adjustment in the estimated number and distribution of T&Cs for drugs and medical devices in the pre- and post- market, and the limitation of rolling reviews to those for public health emergency drugs. Additionally, information technology (IT) costs to government have been reassessed to reflect these changes, and new costs to government have been identified for the screening, review and tracking of RMPs. Values previously presented in Canada Gazette, Part I have also been inflated to 2024 dollars.

The full CBA report is available upon request by email at lrm.consultations-mlr@hc-sc.gc.ca.

Cost-benefit statement

The incremental costs to industry are estimated at $183 million (present value [PV]) over a 10-year period. It is expected that the cost to government over the same period will be $7 million (PV) and includes reviewing T&Cs and managing T&Cs and RMP summaries. As a result, the total anticipated costs of the Regulations are $190 million (PV) over a 10-year period, discounted at 7%, or an annualized average of $27 million.

The quantified benefits derived from the elimination of regulatory requirements around standards would benefit industry by a cost saving of $62 million (PV) over a 10-year period, discounted at 7%, or an annualized average of $9 million.

Monetized benefits
Impacted stakeholder Description of benefit Year 1 Year 2 Year 3 Year 4 Final year Total (PV) Annualized value
Industry Standards (labelling, monitoring and retesting) $0 $9,534,409 $9,534,409 $9,534,409 $9,534,409 $62,118,887 $8,444,332
All stakeholders Total benefits $0 $9,534,409 $9,534,409 $9,534,409 $9,534,409 $62,118,887 $8,844,332
Monetized costs Numbers may not add up due to rounding.
Impacted stakeholder Description of cost Year 1 Year 2 Year 3 Year 4 Final year Total (PV) Annualized value
Government T&Cs – Drugs (transition) $0 $642,865 $0 $0 $0 $600,808 $85,542
T&Cs – Drugs (operation) $0 $0 $0 $133,020 $177,360 $798,678 $113,714
Compliance and enforcement $0 $0 $0 $10,126 $18,986 $79,240 $11,282
IT Solution – T&Cs $0 $67,500 $100,000 $10,000 $10,000 $197,500 $28,120
T&Cs – Medical Devices (transition) $0 $75,000 $0 $0 $0 $70,093 $9,980
T&Cs – Medical Devices (operation) $0 $0 $312,662 $312,662 $312,662 $1,744,858 $248,428
RMPs $0 $0 $0 $512,650 $683,533 $3,078,044 $438,244
IT Solution - RMPs $0 110,000 $332,500 $40,000 $40,000 $581,511 $82,794
Industry T&Cs – Drugs $0 $0 $0 $10,098,078 $40,078,423 $154,032,859 $21,930,814
T&Cs – Medical Devices $0 $0 $1,360,190 $2,720,380 $4,080,570 $19,285,839 $2,745,870
RMPs $0 $0 $0 $1,796,706 $2,395,608 $9,484,707 $1,350,409
All stakeholders Total costs $0 $895,365 $2,105,352 $15,633,622 $47,797,143 $189,954,138 $27,045,196
Summary of monetized costs and benefits
Impacts Year 1 Year 2 Year 3 Year 4 Final year Total (PV) Annualized value
Total benefits $0 $9,534,409 $9,534,409 $9,534,409 $9,534,409 $62,118,887 $8,844,332
Total costs $0 $895,365 $2,105,352 $15,633,622 $47,797,143 $189,954,138 $27,045,196
NET IMPACT $0 $8,639,044 $7,429,057 ($6,099,213) ($38,262,734) ($127,835,250) ($18,200,864)
Qualitative impacts

In terms of the qualitative benefits:

The qualitative costs would be:

Baseline scenario

The baseline reflects current business and review processes and is used as the basis for the calculation of any incremental costs.

Prior to enacting Vanessa’s Law (2014), the MDR allowed the Minister to impose T&Cs with respect to tests on a medical device licence. Health Canada only had limited tools to keep a product on the market while dealing with a safety concern, such as issuing a safety warning and possibly negotiating a label change with the manufacturer. In some cases, the product would have been removed from the market, potentially depriving people in Canada of life-saving therapies. The lifecycle powers introduced by Vanessa’s Law at the level of the Act improved the regulatory options to keep products on the market while improving the ability of Health Canada to address safety issues.

These authorities have helped move Health Canada towards a lifecycle approach of product regulation; however, a number of Health Canada policies were exercised through guidance.

Terms and Conditions

Formerly under the MDR, the Minister was granted the authority to impose T&Cs related to testing on Class II, III, and IV medical device licences and to amend them to take into account any new development with respect to the device. With respect to drugs, the FDR gave the Minister a broad power to impose or amend T&Cs on opioids and designated COVID-19 drugs. Under Health Canada’s NOC/c policy, manufacturers accept to adhere to conditions intended to confirm the effectiveness of new human drugs with promising clinical evidence of effectiveness to treat serious or life-threatening conditions. The conditions under the NOC/c policy are similar to T&Cs in other jurisdictions; however, they rely on voluntary compliance and are not enforceable. The NOC/c policy has not been applied to veterinary drugs nor have T&Cs been imposed on drug identification numbers for veterinary drugs.

Risk Management Plans

Previously, manufacturers voluntarily complied with guidance on the submission of RMPs. Typically, RMPs were submitted in the same format as required by the EMA. Health Canada assumed some costs from negotiation during the submission review process to bring RMP content in line with recommendations in guidance for Canadian-specific content. As RMPs were not a requirement in regulation, the Minister had limited authority to compel a manufacturer to submit a complete RMP in a timely manner, which led to additional time being spent negotiating with the manufacturer. Information about the content of RMPs is important to health care providers who use these drugs and manufacturers of generic and biosimilar drugs who refer to innovator drugs with RMPs. There are costs to Health Canada associated with sharing information about RMPs with stakeholders.

Regulatory scenario

The regulatory amendments are described under each distinct component below.

Costs to Industry

Terms and Conditions for Drugs

Under the Regulations, T&Cs could be imposed at any time, but it is intended that they would not be imposed on every authorized drug. They will be used to manage the uncertainties relating to benefits or risks (e.g. to request confirmatory clinical studies, quality or effectiveness studies, and/or measures to address risks or uncertainties).

As per criteria under the NOC/c policy, conditions are currently applied to new human drugs with promising clinical evidence to treat serious or life-threatening conditions. The incremental costs and benefits are measured against the current practice of the NOC/c policy.

The NOC/c policy has never applied to veterinary drugs; therefore, there had not been any NOC/c nor T&Cs applied to veterinary drugs. However, the regulatory amendments for T&Cs for all drugs will mean that manufacturers of veterinary drugs could be subjected to this authority.

On an annual average, Health Canada issues seven market authorizations under the NOC/c policy for human drugs. Based on internal analysis and the expected increase in the application of more complex drugs such as drugs to treat Alzheimer’s disease or cancers, it is anticipated that there may be an increase of 14 T&Cs issued at the time of authorization and 11 in the post-market annually; these anticipated T&Cs would include both human and veterinary drugs. Through a costing survey sent to industry (Agile CBA Survey), stakeholders indicated a wide range of costs of T&Cs, both based on their experience with NOC/c and T&Cs in other jurisdictions, and anticipated costs. The reported costs range from $4,000 to $6.2 million. These costs include providing clinical study reports for ongoing studies, monitoring and providing any updates on disease changes, providing additional information, and conducting a clinical study.

T&Cs imposed at the time of market authorization will likely be for studies to confirm benefits of a drug or to continue providing evidence of effectiveness of the new drug. Based on the Agile CBA Survey, the average cost to fulfill these types of T&Cs is about $2 million. For the T&Cs imposed post-market, the types of T&Cs imposed would likely be for additional data to determine risk factors, additional or a follow-up analysis, or reporting on the effectiveness or milestones of the RMPs. The average cost to comply with a post-market T&C is about $2.2 million.

It is assumed that a T&C is to be fulfilled within three years, as indicated by some stakeholders, and that its cost will be distributed equally over this period. The coming-into-force date is April 1, 2027.

The estimated cost of T&Cs to the industry in the first year of implementation (fourth year of the Regulations) is $10,098,078, the second year is $26,771,264 and every year after is $40,078,423. The estimated PV is approximately $154,032,859 over a 10-year period, discounted at 7%.

Terms and Conditions for Medical Devices

The Regulations expand the scope of T&Cs beyond testing requirements to allow the Minister to impose or amend T&Cs at the time a Class II, III, or IV medical device licence is issued or any time after, and are expected to pertain mainly to maintaining the safety and effectiveness of a medical device.

It is expected that T&Cs could be used to assess the long-term safety or effectiveness of a medical device in response to evidence, including real-world evidence, that is not available at the time of licence issuance. They could also be used to require the medical device licence holder to make changes to the medical device to continue to maintain safety and effectiveness.

On average, annually, there are approximately 1,785 medical device licences authorized and 116 T&Cs letters issued. Under the Regulations, it is anticipated that there would be an increase of 5% - 10% of T&Cs imposed. To be conservative, it is assumed T&Cs would increase by 10% or 12 additional T&Cs would be imposed per year with 9 at the time of authorization and 3 in the post-market. Moreover, historical data has shown that a T&C is typically resolved within three years. As such, the cost of complying with T&Cs for medical devices is distributed over the three-year period.

Based on the responses to the Agile CBA Survey, the costs of fulfilling T&Cs range from $4,000 to $1M. This is based on stakeholders’ experience with T&Cs both at the time of market authorization and in the post-market. It includes a range of activities from submitting final study results, additional non-clinical data, or study results of an ongoing study, to the conduct of a new clinical study to confirm effectiveness. The average costs reported of fulfilling T&Cs imposed at the time of authorization and in the post-market are $452,000 and $4,100, respectively.

The coming-into-force date is January 1, 2026.

The expected cost of T&Cs for medical devices in the first year of implementation (third year of the Regulations) is $1,360,190, the second year is $2,720,380 and every year after is $4,080,570. This translates to an estimated PV of $19,285,839 over a 10-year period, discounted at 7%.

Risk Management Plans

The Regulations formalize the practice of obtaining and reviewing RMPs from manufacturers of human drugs. As per previous practice, RMPs include Canadian-specific information as applicable to the Canadian context and marketplace when relevant. The Minister could also request an updated RMP if there are reasonable grounds to believe that an updated RMP is needed to respond to significant differences in the risks and uncertainties associated with the drug, or in the measures warranted to manage a serious risk of injury to human health. The amendments create a new obligation for manufacturers to submit a summary of new and updated RMPs in both official languages. The coming into force will be April 1, 2027.

Through voluntary compliance with Health Canada’s policy on RMPs as set out in the RMP Guidance, the Department receives an average of 103 new RMPs annually. Of the 103 RMPs, most also already have summaries provided but only in English. This is used as a proxy to estimate the number of new RMP summaries to be translated as a result of the Regulations. In addition, Health Canada receives an annual average of 321 updated RMPs. Under the Regulations, all 321 updated RMPs will require a summary in both official languages.

In response to the Agile CBA Survey, stakeholders provided a wide range of costs from developing a core RMP, to creating a summary, to translating. It should be noted that most of the costs provided were based on actual experience of developing RMPs either in Canada or in other jurisdictions. It was recognized that translating an updated summary would require significantly less time and effort than preparing the initial summary, as most changes to a summary involve adding or removing a safety concern or a risk minimization measure; therefore, the cost of translating an updated summary should also be less. However, due to lack of data and also to be conservative, Health Canada used the cost to translate a new summary as a proxy for the cost to translate an updated summary.

It is anticipated that a total of 424 (103 + 321) summaries will be translated per year at a cost of $5,650 per summary. The expected cost in the first year of implementation is $1,796,706, and the following subsequent years is $2,395,608 annually, non-discounted. The estimated PV is $9,484,707 over a 10-year period, discounted at 7%.

Public Health Emergency Drugs

It is not anticipated that there will be any impacts to industry as the amendments are limited to public health emergency drugs like those that treat COVID-19. The decision to consider pre-positioning of a public health emergency drug would continue to be driven by the Chief Public Health Officer of Canada for conditions set out on the List of Conditions that Threaten Public Health.

Assuring Drug Quality During Manufacturing

The amendments to Part C, Division 2 of the FDR, are not anticipated to introduce any additional cost or burden on industry. They support the policy set out in the Guidelines for environmental control of drugs during storage and transportation (GUI-0069), work with other requirements of Division 2 and do not change the established expectations for all drugs.

Modernizing Requirements for Biologics

It is not anticipated that there will be any incremental costs to industry as the amendments repeal outdated product-specific provisions spanning between C.04.050 and C.04.683, and reflect current practice.

Information Considered to Support the Examination of Drug Submissions

It is not anticipated that there will be any incremental costs to industry as the amendments are in line with current practice.

Disaggregated Clinical Trial Data for New Drug Submissions and Supplements to New Drug Submissions

It is not anticipated that there will be any incremental costs to industry as manufacturers are already requested to submit clinical trial data that support the safety and effectiveness of a drug, broken down into population subgroups for both new drug submissions and supplements to new drug submissions, where the disaggregated data has already been submitted to the USFDA or the EMA.

Standards

It is not expected that this amendment will impose any incremental costs to industry, but rather it will reduce unnecessary regulatory burden.

Where a manufacturer uses a manufacturer’s standard for new drugs (i.e. drugs regulated under Part C, Division 8 of the FDR), other than those regulated under Schedule C, the Regulations exempt them from having to meet the most stringent limits for purity and potency of all the Schedule B pharmacopoeias in which the active ingredient or drug appears. For all drugs, other than those regulated under Part C, Divisions 3 and 4 (i.e. radiopharmaceutical and biologics) of the FDR, the Regulations remove the requirement for the standard used for the drug to be indicated on the package label. Biologics, which were already exempt from having to indicate the standard used on the package label, will continue to be exempt, while radiopharmaceuticals will continue to be required to indicate the standard used on the package label. Removing this labelling requirement for certain drugs provides manufacturers with additional space to include information that is more relevant to health care providers and patients.

Costs to Government

Terms and Conditions for Drugs

Uncertainty exists over the frequency and type of T&Cs that Health Canada may impose in the future. There are two factors which could create an increase in the number of T&Cs imposed. The first is an increase in receipt of drug submissions and applications based on promising evidence for drugs to combat diseases such as cancer, Alzheimer’s disease or autoimmune diseases (where the likelihood of imposing T&Cs is relatively high).footnote 6 The second is a general increase in use should new information about a drug post-authorization lead to risks or uncertainties that may not have been identified at the time of authorization. The CBA recognizes an initial incremental increase in the number of T&Cs imposed due to the Regulations; however, it is expected there would be no additional growth over the 10-year analysis period because many factors, such as feasibility, less burdensome means, or application of other requirements, would be taken into account before imposing T&Cs.

Although implementation of the T&C authorities for all drugs will begin when the amendments come into force on April 1, 2027, the Department must develop new standard operating procedures (SOP), templates and proper training in order to assist market authorization holders efficiently. The cost to develop these tools and training is estimated at $642,865 and will be recognized in the second year of the Regulations. The total PV cost for the transition cost is expected to be $600,808 discounted at 7%, or an annualized average of $85,542.

It is anticipated that the annual average cost for the Department to manage T&Cs for drugs is approximately $7,100 per T&C. This includes activities such as issuing an anticipatory T&C letter, evaluating new evidence, amending T&Cs, and overall tracking and monitoring of T&Cs. The estimated cost to manage T&Cs for drugs in the first year of implementation is $133,020 and every year after is $177,360, non-discounted. The total estimated PV cost is $798,678 discounted at 7%, or an annualized average of $113,714.

In addition, it is expected that compliance and enforcement activities may increase with the introduction of T&Cs related to a DIN. T&Cs are imposed to manage risks or to address significant uncertainties relating to a drug. This may result in more complex inspections and compliance verifications, increased preparation time, and more complex documentation. The increased workload is anticipated to cost Health Canada an annualized average of approximately $11,282 per year which represents an estimated $79,240 (PV) over a 10-year period using a 7% discount rate.

To assist with the management of T&Cs for drugs, Health Canada will be updating an IT system to enhance operational efficiencies and facilitate seamless information exchange between the Department and manufacturers. The expected costs for development of this IT system during the first two years of implementation are $167,500 and ongoing maintenance for every year after is $10,000. This translates to an estimated PV of $197,500 over a 10-year period, discounted at 7%.

Terms and Conditions for Medical Devices

There are approximately 116 medical device letters issued with T&Cs annually under the MDR and it is estimated that this will increase by 5-10% due to the expanded scope of T&Cs under the Regulations. If the upper bound is used, there will be approximately 12 new T&Cs issued annually at an average cost of $26,000 per T&C. Similar to T&Cs for drugs, Health Canada needs to develop internal processes and training to manage T&Cs for medical devices. This is a one-time cost of $75,000 incurred in the second year of the Regulations. The expected total PV is $70,093 over a 10-year period using a 7% discount rate.

The annual cost of imposing and managing T&Cs for medical devices once they are implemented is $312,662. This translates to an estimated total PV of $1,744,858 over a 10-year period, discounted at 7%.

Risk Management Plans

Health Canada has been receiving RMPs voluntarily; however, the Department has often negotiated with applicants to bring the RMP contents in line with what is described in guidance, particularly for inclusion of an addendum covering Canadian-specific information. Prior to the Regulations, comments and recommendations that were provided by Health Canada were addressed approximately 90% of the time, with 70% of these submissions having been “accepted with minor changes.” Almost all manufacturers included a summary with their RMP submission and approximately 40% included an addendum of Canadian-specific information.

Even though receiving RMPs is a long standing practice set out in the RMP Guidance, the Regulations set out that, when required, an RMP is part of the decision making when the Minister assigns a DIN, in the case of a DIN application under Part C, Division 1 of the FDR, or when the Minister issues a notice of compliance, in the case of a submission under Part C, Division 8 of the FDR, so there is a level of effort in screening and commitment tracking as a result. Furthermore, the Department expects to review 424 translated RMP summaries annually. With the coming into force of April 1, 2027 for the amendments related to RMPs, the anticipated cost to government in the first year of implementation is $512,650 and every year after is $683,533. This results in an estimated total PV of $3,078,044 over a 10-year period.

Incremental costs for government may arise from compliance and enforcement activities that would be necessary to address a failure by an organization to submit an updated plan in accordance with the Regulations; however, these cases are expected to be rare.

To assist with the management of RMPs, Health Canada will be implementing an IT system to enhance the intake process by enabling applicants to submit RMP summaries in a standard correspondence template and provide immediate notification updates to Health Canada upon the receipt of an RMP. The expected costs for development of this IT system during the first two years of the Regulations are $442,500 and ongoing maintenance for every year after is $40,000. This translates to an expected PV of $581,510 over a 10-year period.

Public Health Emergency Drugs

The amendments allow any public health emergency drug to be pre-positioned if the importer is the holder of a drug establishment licence that authorizes the import of the class of drug to which the public health emergency drug belongs. This is critical for future public health emergencies that relate to conditions on the list. The amendments are not anticipated to result in any new or additional information to be submitted or reviewed and would not impact current government operations. Anticipated costs are expected to be negligible.

Assuring Drug Quality During Manufacturing

No changes are anticipated to Health Canada’s oversight of drugs or current operational practice with respect to GMP inspections as a result of the amendments. No additional costs to government are anticipated.

Modernizing Requirements for Biologics

The amendments are intended to bring current operational and industry practice into regulations. Given that the baseline of the cost analysis is current practice, no additional costs to government are anticipated as a result of these amendments.

Information Considered to Support the Examination of Drug Submissions

No costs to government have been identified.

Disaggregated Clinical Trial Data for New Drug Submissions and Supplements to New Drug Submissions

It is not anticipated that there will be an impact on the number of submissions as a result of the amendments related to disaggregated data. Reviewers already analyze any disaggregated data voluntarily provided. This requirement may increase the quality of the submitted data, which reviewers will continue to analyze as is currently done. The Department is considering adding an additional screening step, but the additional work is not expected to be significant and would be managed by existing staff. Reviewer training will be required as well as the development of SOPs, but resources required are part of the implementation of the Department’s Sex- and Gender-based Analysis Plus Action Plan.

Standards

No costs to government have been identified.

Benefits

Measures introduced as part of Heath Canada’s ongoing modernization efforts, including amendments to the MDR and FDR, support a drug and medical device framework that more effectively oversees regulated products over the entirety of their lifecycle. These amendments provide clarity to both industry and the regulator while allowing greater flexibility for dealing with future innovations.

While it is acknowledged that many of the provisions in these amendments simply codify existing practice, the clarity provided is expected to promote greater innovation and earlier access to products in Canada and provide some efficiencies to industry, payers, and medical professionals while improving safety and effectiveness, and resolving uncertainty.

Combined, the Regulations would contribute to the lifecycle approach to the regulation of drugs and medical devices necessary to help Health Canada deal with the balance between protecting Canadians from harm from the therapeutic products they use and providing them with therapeutic benefits.

Benefits to Industry

Terms and Conditions for Drugs

The cost of developing a drug for market has been estimated to be between $800 million and $2.5 billion when all research and development costs, including drug failures, are included. The process takes between 9 and 15 years from discovery to approval.footnote 7 During the drug development process, approximately 60% of all drugs fail due to the lack of evidence of safety and effectiveness. Once a drug is on market, its performance in real-world conditions can be different from that in a clinical trial setting. A major failure in safety not only puts the health and safety of patients at risk, but the subsequent removal of a drug can cost industry millions of dollars. In some cases, the drug may have been very beneficial to a segment of the population while only posing a risk to another segment. The Regulations are meant to reflect current practice, facilitate market access, and help manage uncertainties and risks to reduce the probability of product failure.

The application of T&Cs imposed on a DIN, either at the time of authorization or after authorization, alongside the use of RMPs may help identify safety and effectiveness issues sooner, allowing Health Canada to apply risk mitigation strategies to address real-world safety signals to reduce harm, while allowing a product to continue on market with appropriate safety oversights where deemed necessary. This will potentially allow industry to keep a product on market without disruptions.

Terms and Conditions for Medical Devices

The amendments enhance Health Canada’s capacity for continued oversight, assessment, and communication at both the time of authorization and once medical devices are on the market. For industry, this could mean the rapid identification and resolution/mitigation of risks that arise while still allowing medical devices to remain on the market without disruption.

Risk Management Plans

The Minister intends to make information from risk management plans publicly available through bilingual summaries, making it easier for generic and biosimilar companies to prepare submissions for market entry.

Assuring Drug Quality During Manufacturing

The expected benefit is clarity around the Regulations.

Modernizing Requirements for Biologics

Since the regulatory amendments serve to modernize the regulations and reflect current practice, the anticipated benefit is greater clarity to industry.

Information Considered to Support the Examination of Drug Submissions

The expected benefit is clarity around the regulatory intent.

Disaggregated Clinical Trial Data for New Drug Submissions and Supplements to New Drug Submissions

No benefits to industry have been identified.

Standards

Manufacturers of new drugs, with the exception of radiopharmaceuticals that use a manufacturer’s standard, will no longer need to meet the most stringent limits for purity and potency of all the Schedule B pharmacopoeias, provided the different limits for purity and potency are acceptable to the Minister. This will prevent certain manufacturers who use a manufacturer’s standard from having to monitor the pharmacopoeias and will reduce the cost of retesting their drugs in order to ensure they meet the most stringent limits for purity and potency.

With the exception of radiopharmaceuticals, the amendments also exempt manufacturers from having to indicate the standard on the label. This will open up some space, giving manufacturers flexibility to provide other valuable information to patients and health care practitioners. This exemption will also prevent manufacturers from having to change their labels in the case where they switch to a different standard, for example, from a manufacturer’s standard to a pharmacopoeial standard.

While the benefit is not limited to only manufacturers of generic drugs, they will be most likely to benefit from the regulatory change due to their volume on the Canadian market. Stakeholders indicated savings from labelling ranging from $125,000 to $418,000 annually; this includes disposal cost for labels. Furthermore, savings from manufacturer’s standards are reported to range from $47,000 to $680,000 a year, in respect of monitoring and retesting drugs. The administrative cost savings of monitoring Schedule B pharmacopoeias, assessing the impacts and reporting to Health Canada is estimated to be about 37.5 hours for each pharmacopoeia and assumes there are three publications per year. Taking an average approach, annual cost savings from labelling and manufacturer’s standards would be about $272,000 and $363,600, respectively. Given that there are at least 15 firms supplying subsequent entry drugs in Canada, it is estimated that the savings from the Regulations could be $9,534,400 per year.

15 firms x ($272,000 + $363,600) = $9,534,400

It is expected that the amendments will yield annual savings of $9,534,400 or $62,118,887 PV over a 10-year period. Furthermore, stakeholders also indicated that the previous regulations occasionally caused drug shortages as the new standards needed to be met. The Regulations are expected to reduce such disruptions in sales.

Benefits to Government

Terms and Conditions for Drugs

The amendments codify in law existing practices under the NOC/c policy and allow the imposition of T&Cs both at the time of market authorization and in the post-authorization period. They may reduce the time required to achieve a resolution in discussions with a manufacturer around the manner in which to deal with the potential safety and uncertainty issues of a product. The amendments are also expected to allow Health Canada to adapt to innovation and change.

Terms and Conditions for Medical Devices

The amendments codify in law some of the existing T&Cs practices at Health Canada and broaden the scope of T&Cs that can be imposed on a medical device licence. The amendments will provide the Minister with appropriate tools for the risk-based oversight of medical devices throughout their lifecycle while also better enabling adaptation to innovation and change.

Risk Management Plans

The amendments allow Health Canada to compel manufacturers to submit and amend RMPs to address any deficiencies in a timely manner where they may not do so voluntarily. Efforts to make RMPs transparent will be simplified through the availability of bilingual summaries provided by manufacturers.

Modernizing Requirements for Biologics

Clearly written, modern regulations may reduce the number of enquiries from industry regarding the provisions, saving some time and resources for Health Canada.

Information Considered to Support the Examination of Drug Submissions

These amendments provide clarity regarding the Minister’s authority to consider, as part of a submission, information obtained directly or indirectly from a building or other site where a biologic is fabricated, packaged/labelled or tested, when making a decision about whether to authorize the drug.

Disaggregated Clinical Trial Data for New Drug Submissions and Supplements to New Drug Submissions

The requirement to provide disaggregated data, if already submitted to the USFDA or EMA, is expected to increase the utility of the submitted data, making identification of any potential differences in safety or effectiveness between different population subgroups more apparent.

Standards

No benefits to government have been identified.

Benefits to Canadians

Combined Benefits

The use of T&Cs for drugs and medical devices and RMPs for drugs, as well as the receipt of disaggregated data, is intended to increase the safety of these products in Canada, and is expected to help reduce the incidence of adverse drug reactions (ADRs) and medical device incidents, and manage uncertainties around the safety and effectiveness of drugs and medical devices under real-world conditions. Better management of risks, benefits and uncertainties of both new and existing products will lead to better patient outcomes and quality of life.

Terms and Conditions for Drugs

The ability to impose T&Cs at the time of authorization has been limited to designated COVID-19 drugs and certain opioids. Under the Regulations, T&Cs could be used to manage risks or uncertainties, or to collect data to assess potential changes to safety and/or effectiveness, and therefore should improve product safety.

Despite rigorous evaluations, monitoring of real-world safety and effectiveness often identifies harms and uncertainties not demonstrated during pre-market clinical evaluations. In 2019, Health Canada received over 96,000 domestic ADR reportsfootnote 8 relating to drugs and it has been estimated that only 10% of all ADRs are reported.footnote 9 Estimates show that as many as 1 in 1,000 Canadians under the age of 65 will go to hospital as a result of an ADR in their lifetime. The number jumps to 1 in 200 for Canadians over the age of 65.footnote 10 Of over 96,000 ADRs reported to Health Canada, 18,852 reports mentioned hospitalization; ADRs may have contributed to as many as 6,119 deaths.footnote 8 Women are more likely to experience an ADR than men.footnote 11 Pediatric medicines rarely have the same information available as drugs for adults given the obvious ethical limitations to testing products on children. Other populations who are generally under-represented in the clinical trials conducted in preparation of a regulatory drug submission are similarly likely to see benefits.

The direct medical cost of ADRs has been calculated to be as high as $20 billion (in 2019 dollars) annually.footnote 12 Based on the data reported to Health Canada in 2019, 19.5% of ADRs were linked to hospitalization and 2.6% reported a potential life-threatening condition.footnote 13 While it is not possible to determine to what extent the Regulations will reduce the frequency of ADRs in Canada, the potential impact could be significant. For example, even a 0.1% decrease in ADRs would reduce the number of deaths by 6 (6,119 x 0.1%), which when applied to a $8.59 million value of a statistical life used in Canada,footnote 14 would represent a benefit of $50 million. Similarly, a 0.1% decrease in the estimated direct medical annual cost of $20 billion would represent a savings of $20 million per year. However, it is not possible to estimate the reduction in ADRs that might result from the Regulations.

In addition to the direct cost of an ADR to the health care system or an individual, family members and other caregivers must take time off to care for a senior, child, or other persons that have been hospitalized or otherwise incapacitated. A reduction in the number of ADRs as a result of improved lifecycle oversight would reduce the hardship of having to care for another. ADRs also cause absenteeism from work and presenteeism (working while sick with reduced productivity), affecting economic activity.

Terms and Conditions for Medical Devices

Expanding the scope of T&Cs beyond testing requirements and the ability to impose and amend T&Cs throughout the lifecycle of a device is intended to help improve oversight and product safety.

Expanded T&Cs can be used to help address uncertainties that become apparent at the time of licensing but also in the post-market, such as risks identified after the real-world use of a device. This may also be helpful in identifying patient populations that could benefit the most from the mitigation of serious health risks.

Despite rigorous pre-market evaluations, monitoring of real-world safety and effectiveness sometimes identifies harms and uncertainties not demonstrated during pre-market evaluations. Imposing T&Cs may reduce medical device incidents and prevent the withdrawal of a product from market that could be used safely with more appropriate risk mitigation strategies.

Risk Management Plans

The Minister intends to make information from risk management plans publicly available through bilingual summaries, enabling health care providers and patients to make better-informed decisions.

Public Health Emergency Drugs

Canadians are expected to benefit from the amendments. In the case of a future public health emergency, pre-positioning is expected to provide more timely access to drugs specific to the emergency. By amending the FDR to require that a licensed importer be authorized to import the category of drug to which the public health emergency drug relates, health and safety risks will be mitigated through application of requirements that support the oversight of the activity of importation.

Modernizing Requirements for Biologics

No benefits to Canadians are expected as innovation will continue as currently takes place under guidance and current practice.

Information Considered to Support the Examination of Drug Submissions

No benefits to Canadians are expected as this amendment reflects current practice.

Disaggregated Clinical Trial Data for New Drug Submissions and Supplements to New Drug Submissions

While no direct benefits to Canadians are expected as a result of these amendments, the requirement to provide disaggregated data may provide additional information respecting specific population subgroups that could lead to increased drug safety.

Standards

Industry indicated that the previous requirement related to manufacturer’s standards occasionally led to drug shortages. Canadians will benefit from a more stable drug supply.

Small business lens

The small business lens will apply as all pharmaceutical, medical device and veterinary industry stakeholders will be impacted by the Regulations.

Using internal data, Health Canada estimated that approximately 26% of all impacted applicants or manufacturers will meet the definition of small businesses in Canada. The largest proportion of small businesses within their product category are medical device (36%) and veterinary drug (27%).

Although there are no specific exemptions or processes in the Regulations for small businesses, the needs of small business were taken into consideration in the creation of the Regulations. Small businesses may also benefit from the greater flexibilities and clarity provided by them. For example, through T&Cs, small pharmaceutical and medical device manufacturers may benefit from risk mitigation strategies that will potentially keep their products on the market without disruption, or may spend their resources more efficiently as the amendments provide more clarity. Further, Health Canada would take into consideration feasibility or less burdensome means in imposing T&Cs.

Compliance costs
Activity Annualized value Present value
T&Cs $6,323,751 $44,415,384
RMPs $107,664 $756,184
Total compliance cost $6,431,415 $45,171,568
Cost per impacted small business $28,584 $200,763

One-for-one rule

The one-for-one rule applies since there would be an incremental decrease in administrative burden on business, and the Regulations would be considered administrative burden out under the rule. The amendments related to standards will save drug manufacturers the time spent on monitoring Schedule B pharmacopoeias and assessing the impacts. The resources required by businesses to monitor, assess the impacts and notify Health Canada when the standards have changed would be considered administrative burden. These activities require manufacturers to spend an average of 37.5 hours for each Schedule B publication at a rate of $32.26 an hour,footnote 15 and it is assumed there are 3 publications per year. The annualized reduction in administrative burden to businesses is estimated at $24,728 ($2012) or $1,649 ($2012) per business.

The objective of imposing T&Cs would be to manage the uncertainties relating to the benefits and/or risks of a product at the time of authorization or to manage emerging risks or uncertainties post-authorization. This requirement would be directly related to ensuring the health and safety of Canadians. Therefore, the costs of fulfilling the T&Cs are not considered as administrative burden as defined by the Red Tape Reduction Act as their primary purpose is not for ensuring compliance.

Currently, manufacturers are voluntarily submitting RMPs upon request as well as RMP summaries if available. Thus, it is not expected there would be incremental administrative requirements from the Regulations with respect to RMPs.

Regulatory cooperation and alignment

While these regulatory amendments are not part of a formal regulatory cooperation plan with any foreign regulator, they do further align Health Canada’s requirements with those of other jurisdictions such as the United States, the European Union and Australia.

United States

The USFDA has the ability to compel, by law, an authorization holder to conduct tailored activities to manage risks and ensure the benefits of their drugs once on-market, similar to the amendments that allow the Minister to impose T&Cs on any drug.

The USFDA has the ability to impose conditions at the pre-market approval application stage for medical devices, such as restrictions imposed on the sale, distribution, or use of the device. The USFDA also has the ability to impose post-approval requirements on certain classes of medical devices. These conditions may be related to sale restrictions, periodic reporting, labelling requirements or testing, similar to the amendments regarding T&Cs for medical devices.

For certain drugs, the USFDA can compel, by law, the submission of a plan outlining the manufacturers’ Risk Evaluation and Mitigation Strategies (REMS). REMS are similar to RMPs and therefore the amendments to the FDR better align Canadian requirements for risk mitigation strategies with those of the USFDA.

The USFDA allows the use of rolling reviews for certain drugs provided they meet the criteria outlined under its Fast Track, Breakthrough Therapy, Accelerated Approval, Priority Review programs. Inclusion criteria include a drug that could be used to address a public health emergency. Similarly, the amendments to the FDR related to public health emergency drugs also allow the option of a rolling review.

Before the approval of a new drug application for some small-molecule pharmaceuticals and biologics, the USFDA evaluates establishments through the use of on-site pre-approval inspections or by establishment file reviews. These are conducted by inspectors, investigators and other product-specialists in a risk-based manner, accounting for facility risk, product risk and process risk. The inspection is performed to contribute to the USFDA’s assurance that a manufacturing establishment named in a drug application is ready and capable of manufacturing a drug. It also ensures that submitted data are complete, accurate and consistent with that at the site of manufacture. This is analogous to Health Canada’s practice of conducting on-site evaluations and the amendment which allows for the materials or information collected to support the examination of a new drug submission.

The USFDA requires manufacturers to submit safety and effectiveness data broken down by certain subgroups (e.g. age, sex, race/ethnicity) and, in the case of effectiveness data, manufacturers must identify any modifications of dose or dose interval needed for these specific subgroups. For certain new drug submissions, the amendments to the FDR related to disaggregated data require that manufacturers provide clinical trial data broken down by population subgroup if that data has already been submitted to the USFDA or the EMA.

The USFDA requires that a drug must meet the standard of the United States Pharmacopoeia/National Formulary (USP/NF) if the drug appears in that pharmacopoeia, unless certain conditions are met. They do not require that a list of pharmacopoeias be monitored. Through these amendments, manufacturers that use a manufacturer’s standard for their drug will also no longer need to monitor a list of pharmacopoeias, and update their product, if necessary. Furthermore, as is the case with the USFDA the manufacturer will no longer need to indicate the standard used on the drug label.

European Union

The European Union’s EMA has the ability to compel, by law, an authorization holder to conduct tailored activities to manage risks and ensure the benefits of their drug once on-market, similar to the amendments that allow the Minister to impose T&Cs on all drugs. The EMA may also set conditions on medical devices in exceptional cases relating to public health or patient safety.

As outlined in their guidance on RMPs, the EMA requires manufacturers to submit RMPs when applying for a market authorization that are proportionate to the identified risks and the potential risks of the medicinal product, and the need for post-authorisation safety data. The amendments to the FDR therefore better align Canadian requirements for RMPs with those of the EMA.

Like the amendments to the FDR related to public health emergency drugs, the EMA allows submissions to be filed for rolling review in emergency situations such as during the COVID-19 pandemic.

The EMA requires manufacturers to submit information on the population of study participants disaggregated by age and sex, and to provide a rationale when this data is not available. For certain new drug submissions, the amendments to the FDR related to disaggregated data require that manufacturers provide clinical trial data broken down by population subgroup if that data has already been submitted to the USFDA or the EMA.

The EMA requires that drugs meet the European Pharmacopoeia standards when one exists. They do not require that a list of pharmacopoeias be monitored. Through the Regulations, manufacturers that use a manufacturer’s standard for their drug will also no longer need to monitor a list of pharmacopoeias, and update their product, if necessary.

The EMA does not require that a manufacturer indicate the standard used on the drug label. The Regulations are in alignment with this practice.

United Kingdom

The United Kingdom’s Medicines and Health care products Regulatory Agency (MHRA) has the ability to compel, by law, an authorization holder to conduct tailored activities to manage risks and ensure the benefits of their drugs once on-market, similar to the amendments that allow the Minister to impose T&Cs on all drugs.

All medicines (i.e. drugs) seeking authorization nationally in the UK with the MHRA must have an RMP and RMP summary. Submission of a new RMP or an update to an existing RMP may be required at any time during the product’s lifecycle. The MHRA continues to accept the European Union’s model of an RMP, but may also require an annex including domestic content. The amendments to the FDR for RMPs therefore improve alignment with the requirements of the MHRA.

The MHRA released its guidance on rolling review submissions in December 2020 as part of its BREXIT policy to streamline the development of novel medicines, including new active substances, as well as biosimilars. The amendments to the FDR related to public health emergency drugs also allow the option of a rolling review.

Australia

The Australian Therapeutic Goods Administration (TGA) has the ability to impose conditions at the time a conformity assessment certificate is issued for a medical device, or after the certificate has been issued, similar to the amendments that allow the Minister to impose T&Cs on medical device licences.

TGA requires RMPs, summaries and updates for specified (higher-risk) products. They continue to accept the European Union’s model of an RMP, but may also require an annex including domestic content. The amendments to the FDR therefore better align Canadian requirements for RMPs with those of the TGA.

The TGA requires that when a standard is included for a drug in one of the default pharmacopoeias outlined in their legislation, a drug should meet or exceed that standard. Exceptions are considered on a case-by-case basis. With the amendment to the FDR, manufacturers who use a manufacturer’s standard for certain drugs will no longer need to meet the most stringent limits for purity and potency set out in the pharmacopoeias listed under Schedule B. Upon request, the manufacturer must qualify these limits with scientific information acceptable to the Minister. Manufacturers of new drugs, however, should routinely provide the Minister with this information (e.g. in drug submissions).

Like the amendments to the FDR, the TGA does not require that a manufacturer include the standard used on the drug label.

Alignment with other international initiatives

The amendments to the MDR align Canadian requirements with guidelines outlined by the International Medical Devices Regulators Forum (IMDRF) through its continued focus on the device’s safety and effectiveness.

Health Canada is a member of the International Council for Harmonisation (ICH), an initiative that brings together regulatory authorities and industry to establish guidelines and technical requirements for the development, approval and safety monitoring of drugs. In 2009, Canada adopted ICH guidelines for pharmacovigilance planning (ICH E2E Pvp (PDF)) which describe the fundamental elements of RMPs. In 2015, Canada published the associated domestic guidance document. Prior to these amendments to the FDR, with the exception of opioids, the Canadian system relied on this guidance alone, while other major jurisdictions (e.g. Europe, Australia) have regulations in place.

Other countries such as Australia, Singapore, Switzerland and the United Kingdom allow submissions to be filed for rolling review during emergency situations. The amendments to the FDR related to public health emergency drugs also allow the option of a rolling review in certain emergency situations.

With respect to the approach for biologics, Canada was similar to other jurisdictions (the US, European Union) and the World Health Organization in that it had product-specific rules. Canada’s product-specific rules were however overly prescriptive and out-of-date. The amendments to the FDR provide flexibility to keep pace with evolving science and technology over time through outcome-based regulations. In addition to the Regulations, Health Canada will also continue to rely on international guidelines, such as those set out by the ICH. Over the years, Health Canada has adopted a number of ICH guidelines covering topics related to quality, safety, efficacy and various multidisciplinary topics.

Strategic environmental assessment

In accordance with the Cabinet Directive on Strategic Environmental and Economic Assessment, a preliminary scan concluded that there will be no expected important environmental effects, either positive or negative; therefore, a detailed strategic environmental assessment is not required.

Gender-based analysis plus

Health Canada expects that the Regulations will have a positive impact on all individuals living in Canada. Furthermore, underrepresentation in clinical trials and unavailability of post-market data can result in specific subgroups facing disproportionate risks when using certain drugs and medical devices. Depending on the products authorized and the manner in which the Regulations are implemented, there is potential for some individuals to receive greater benefit and for some barriers faced by equity-seeking and rights-holding populations (e.g. women and gender diverse individuals, racial and ethnic minorities, persons with disabilities, First Nations, Inuit and Métis, etc.) to be addressed.

Terms and Conditions for Medical Devices

The number of people with disabilities in Canada is dramatically increasing due to an aging population and an increase in chronic health conditions.footnote 16 footnote 17 Furthermore, recognizing intersectionality, disability may be more prevalent in certain subgroups, with a higher prevalence appearing in elderly people, in womenfootnote 18 and particularly in Indigenous women.footnote 19 footnote 20 that the use of medical devices among individuals experiencing disabilities is disproportionately high compared to the overall population,footnote 21 these individuals are expected to benefit more from the amendments to T&Cs for medical devices.

In addition, race, sex and age could in some cases influence the safety or effectiveness of a medical device. At times, certain subgroups are underrepresented in the design of a medical device and their associated clinical studies or investigational testing, which could present difficulties in identifying any differences in the safety or effectiveness of a device in those populations. For example, as noted on Health Canada webpages about pulse oximeters, recent reportsfootnote 22,footnote 23 have identified that pulse oximeter readings can be less accurate in people with dark skin.

The amendments to T&Cs for medical devices should lead to increased levels of confidence in the devices used by the diverse populations in Canada.

Disaggregated Data, T&Cs and RMPs for Drugs

Providing clinical trial data to regulators that has been disaggregated by subgroup is a necessary step in improving the identification of potential differences in the effectiveness and safety of a drug within diverse populations. There is growing evidence that the safety and effectiveness of certain health products is impacted by a number of variables, including, among other factors, sex, age, ethnicity and race. For example, certain drugs are metabolized at different rates by male and female populationsfootnote 24 and by different racial groups sharing specific genetic traits.footnote 25,footnote 26 This can result in increased risks for these specific groups, contributing to inequities in health care outcomes.

Furthermore, some population subgroups remain underrepresented in clinical trials, such as those who are pregnant, elderly people, and people living in rural communities, making it difficult to identify key differences in drug safety or effectiveness for them. The amendments respecting disaggregated data are therefore an important step in promoting increased consideration of diverse subgroups in clinical trials and for the collection of additional information once the drug is on the market.

Where available, receiving data that is broken down by different subgroups (e.g. age, sex, race, and ethnicity) may allow Health Canada to evaluate the safety and effectiveness of a new drug within underrepresented groups. The Regulations could also enable the Department to request that the manufacturer further analyze any risks and uncertainties across relevant groups through measures introduced in an RMP. Specific measures could include outlining how data would be collected on various patient populations. In addition, T&Cs could be used to impose preventative safety measures in these subgroups. These measures and the safety information received by the Department as a result could be taken into account by the Minister in their ongoing post-market oversight of the safety of the drug.

Rolling Reviews for Public Health Emergency Drugs

While everyone is susceptible to infectious disease, certain populations are at risk of more severe outcomes (e.g. older adults, people with one or more chronic medical conditions, and people of any age who are immunocompromised).footnote 27 As was the case with the rolling review option for designated COVID-19 drugs, the expansion of these provisions to public health emergency drugs is expected to contribute to earlier approval of drugs that address other emerging infectious diseases that present a significant risk to public health in Canada and where immediate action is required. While this would benefit all individuals in Canada, those population subgroups that are most at risk of severe outcomes and who are more likely to be exposed to infectious disease would experience an increased benefit.

Standards and Modernizing Requirements for Biologics

It is not anticipated that the amendments respecting standards will impact any subgroups differently. In addition, given that the amendments for biologics support current practices, they are not anticipated to impact the general population.

Implementation, compliance and enforcement, and service standards

Implementation

The following regulatory amendments, which prioritize burden reduction for industry and ensure that Health Canada is well positioned to address any future public health emergencies, come into force upon publication of the Regulations in Canada Gazette, Part II:

The following regulatory amendments, which require additional time to operationalize will have a delayed coming into force:

Final guidance documents will be published on the Government of Canada’s website prior to the coming into force of each component of the Regulations. Guidance provides manufacturers with details of how they can meet the requirements under the new provisions.

Compliance and enforcement

Compliance and enforcement of the Regulations is in accordance with a risk-based approach, aligned with existing Departmental policies, including compliance promotion and monitoring and enforcement activities in accordance with the Department’s Compliance and enforcement policy for health products (POL-0001).

Health Canada employs a wide range of compliance and enforcement actions and tools. The actions, tools and level of intervention used are dependent on the situation, context and risk to health. Some actions and tools are designed to help regulated parties understand their responsibilities under the law, while other actions and tools are designed to induce compliance with the law. When necessary, enforcement actions are used to address non-compliance with the law. For example, failure to comply with T&Cs would be a contravention to section 21.7 of the Act and could result in the Department taking compliance and enforcement action in accordance with POL-0001 or referring the matter to the Public Prosecution Service of Canada for a potential prosecution.

Contact

Bruno Rodrigue
Executive Director
Office of Legislative and Regulatory Modernization
Policy, Planning and International Affairs Directorate
Health Products and Food Branch
Health Canada
Holland Cross, Suite P2108
11 Holland Avenue
Ottawa, ON
K1A 0K9
Address locator: 3001A
Email: lrm.consultations-mlr@hc-sc.gc.ca