Guidance document on submission information for biologic drugs (Division 4, Schedule D): Requirements – Other

On this page

• C.02.012.1 – Storage
• C.08.003.1 – Information or material obtained from sites for the review of drug submissions
• Expiry date
• Corresponding regulations
• Consequential amendments

C.02.012.1 – Storage

Regulation

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.^{Footnote 1Footnote 2}

C.02.012.1:

• replaces the former C.04.050 to C.04.683 because they are overly prescriptive, product-specific or outdated
• maintains the original intent behind approximately 17 regulations about storage from the former C.04.050 to C.04.683

Explanation in comparison to current practice

There is no change to current practice or expectations.

The regulation makes explicit the understanding that drugs should be prepared, stored and transported in a manner that preserves their quality. Storage includes transportation. The inclusion of “including during transportation” is for greater clarity and certainty.

As part of the renewal of Division 4, the regulation about storage is included in Division 2 as it relates to good manufacturing practices.

For further guidance on assuring the quality of drugs during storage, including during transportation, consult the Guidelines for Environmental Control of Drugs During Storage and Transportation (GUI-0069) (refer to References).

C.08.003.1 – Information or material obtained from sites for the review of drug submissions

Regulation

• 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
  • (a) information or material provided by any person under the Act;
  • (b) information or material obtained from sites at which the new drug or any active ingredient, as defined in subsection C.01A.001(1), of the new drug is or is proposed to be fabricated or packaged/labelled within the meaning of those terms in that subsection, or tested; and
  • (c) information or material obtained directly or indirectly from a foreign regulatory authority, as defined in subsection C.10.001(1).^{Footnote 1Footnote 2}

Explanation in comparison to current practice

There is no change to current practice or expectations.

In general:

• C.08.003.1 is revised to reflect activities under current practice.
• In line with current practice, C.08.003.1 clarifies 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 assessment of a drug submission. The authority is to flexibly use discretionary activities as optional tools to help ensure product quality and thus product safety.
• C.08.003.1 provides greater transparency for the current practices of potentially considering information or material obtained from sites, information filed under the FDA (for example, Divisions 1, 5 and 8) and information from foreign regulatory partners for assessing drug submissions.
• Health Canada currently applies a risk-based approach when deciding if additional information on the implementation of the manufacturing process in proposed sites is required. This information supports decision-making related to a submission or its supplement for a biologic drug. The regulation provides transparency on the consideration of information obtained directly at, or indirectly from, manufacturing sites in the decision-making process for the market authorization of biologic drugs. This approach allows for the use of flexible, discretionary, risk-based, case-by-case activities that support changes in current practice in the review of drug submissions, now and in the future, as needed.
• An on-site evaluation (OSE) is one tool used to obtain additional information from a manufacturing site. It is a product-specific evaluation that the Biologic and Radiopharmaceutical Drugs Directorate (BRDD) conducts at the site of manufacture of a Schedule D drug (intermediate or finished product). The evaluation assesses how the drug is manufactured, the process, conditions and control of manufacture, and conformity with the information submitted.
• Most of the content in Division 4 relates to requirements that extend throughout the life cycle of biologic drugs. However, OSEs are a point-in-time activity directly related to pre-market review. As a result, the regulation supporting OSEs is included in Division 8 because OSEs are used to assess the following:
  • a new drug submission (NDS)
  • an extraordinary use new drug submission (EUNDS)
  • an abbreviated new drug submission (ANDS)
  • an abbreviated extraordinary use new drug submission (AEUNDS) or
  • a supplement to any of those submissions

This point-in-time information is for consideration in the context of drug submission review and is distinct from GMP inspections.

• Stakeholders may additionally discuss with BRDD the OSE for their particular product.

Expiry date

Regulation

No regulation is added to Division 4.

The approach is to rely on 5 current regulations (C.01.001(1), C.02.027, C.02.028, C.08.002(2)(f) and C.08.002(2)(g)) to:

• replace the former C.04.050 to C.04.683 because they are overly prescriptive, product-specific or outdated
• maintain the original intent behind approximately 23 regulations about expiry date from the former C.04.050 to C.04.683
• support that the drug shall have an expiry date and that the drug shall be labelled with the expiry date, as is done for pharmaceutical drugs

Explanation in comparison to current practice

The 5 current regulations are:

• C.01.001(1): defines "expiration date"
• C.02.027: requires the DIN holder to establish the period that each packaged drug in dosage form and active ingredient will comply with the drug's specifications, which is interpreted to include data in support of the expiry date
• C.02.028: requires the DIN holder to monitor the stability of the packaged drug in dosage form and its active ingredient, which is interpreted to include data in support of the expiry date
• C.08.002(2)(f): requires the manufacturer to submit details of tests that control the potency, purity, stability and safety of the drug, which is interpreted to include data in support of the expiry date
• C.08.002(2)(g): requires the manufacturer to submit information to establish the safety of the new drug, which is interpreted to include information to support shelf-life, which is part of the "conditions of use recommended"

Corresponding regulations

Regulations and explanation

The repeal of the product-specific regulations from the former C.04.050 to C.04.683 is not expected to affect currently marketed biologic drugs. Two other regulations are also repealed in that context, the former C.04.002 and C.04.003.

• The former C.04.002 set out that the former Division 4 does not apply to a drug in oral dosage form that contains microorganisms if the drug is recommended solely for restoring, normalizing or stabilizing intestinal flora.
  • This regulation is no longer needed because such products are covered by the Natural Health Products Regulations (NHPR), which did not exist when the former C.04.002 was included in the former Division 4.
• The former C.04.003 is no longer needed because the corresponding product-specific regulations in the former Division 4 that rely on "date of issue" are replaced.
  • The requirements on "date of issue" are outdated because the temperature ranges are incorrect.

Consequential amendments

Explanation

The consequential amendments update regulations that refer to the amended regulations, such as updates to the references to Division 4 numbering.

Regulations

Part A:

• A.01.015(2) is about bilingual labelling for directions for use for drugs available for sale without prescription in an open self-selection area.
  • The regulation is updated with new Division 4 numbering, C.04.009(2)(f). This is in case there will be this type of non-prescription biologic drug in the future. The same labelling rule for directions for use applies to non-biologic drugs (Division 1 through C.01.004(1)(c)(iii)) and biologic drugs (Division 4 through C.04009(2)(f)).
• A.01.048(d) is about the exports and transshipments of drugs.
  • The regulation is updated with new Division 4 numbering, C.04.001 to C.04.006.

Part C:

• Division 1 - C.01.004(5) is about labelling.
  • The regulation excludes Schedule D drugs from some Division 1 labelling.
  • The exclusion, which was in Division 4 (the former C.04.019), is moved to Division 1 (C.01.004(5)(c)).
  • For the explanation that ties C.01.004(5)(b) and C.04.010(2)(b), refer to Labelling of prescription drugs.
• Division 2
  • The heading "Quality Control Department" before C.02.013(1) is replaced with the heading "Quality Control".
  • C.02.019(4.1) is about finished product testing. The regulation is updated with new Division 4 numbering, C.04.007(2).
• Division 3 - C.03.206 is about labelling with respect to the exclusion of Schedule C drugs from Division 4 labelling.
  • The regulation is updated with new Division 4 numbering, C.01.005 and C.04.009.
• Division 8
  • C.08.009.04 is about COVID-19 drugs. The regulation is updated with new Division 2 numbering, C.02.012.1.
  • C.08.011.2(2) is about Special Access Program (SAP) release drugs. The regulation is updated with new Division 2 numbering, C.02.012.1.
• Division 10
  • C.10.001(5) is about drugs for an urgent public health need. The regulation is updated with new Division 2 numbering, C.02.012.1.
  • C.10.002(2) is about drugs for an urgent public health need. The regulation is updated with new Division 2 numbering, C.02.012.1.

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

• 20(e) is about COVID-19 drugs. The regulation is updated with new Division 4 numbering, C.04.004, C.04.005, C.04.007, C.04.009, and C.04.010.

References