Summary of changes: Draft guidance on Lot Release Program for Schedule D (biologic) drugs

Background

Health Canada has revised the Guidance document on the Lot Release Program for Schedule D (biologic) drugs to capture proposed administrative, terminology and operational changes or updates. Clarifying edits and more details about Health Canada's regulatory authority are also included.

Stakeholder comments on this revised guidance document will be considered. We will also consider comments previously received concerning lot release during the consultation on proposed amendments to Division 4 of Part C of the Food and Drug Regulations (regulations).

Administrative edits

Administrative edits include updates to the names of 2 organizations:

Biologics and Genetic Therapies Directorate (BGTD) to Biologic and Radiopharmaceutical Drugs Directorate (BRDD)
Regulatory Affairs Division (RAD) to Office of Regulatory Affairs (ORA)

We have added a new document name:

DIN-B: Drug Identification Number-Biologics (DIN-B drugs)

The fax-back process is now a notification process by email. The Group 1A Lot Notification Form and Group 4 Lot Notification Form replace the fax-back forms. We will update the generic email address brdd_faxback_dmbr@hc-sc.gc.ca.

Terminology edits

The following terms have been edited or added:

a definition for sponsor is added
biochemical replaces chemical
notifications replaces fax-back
documentation review replaces protocol review
Schedule D is mentioned once, then the document refers to biologic drugs
pre-market testing replaces consistency testing and a definition is provided
lot documentation replaces protocol of tests and protocol
- lot documentation is a more general term that can include the protocol, certificate of analysis or any other supporting documentation (for example, in-process test results, gel images or chromatograms) that we might ask for to support the release of a given batch
special replaces exceptional in regard to expedited release in special cases for Group 2 (also, for prophylactic vaccines, in special circumstances, BRDD will contact a sponsor if we require more information and/or samples for testing)
documented product shortage in Canada replaces product shortage
Yearly Biologic Product Report (YBPR) is replaced by periodic quality reporting

Clarifying edits

Edits have been made to:

give a targeted timeframe for a BRDD release decision
add guidance about foreign marketed products used in clinical trials
clarify when a sponsor does not need to submit a Group 1A lot notification form
provide more guidance for prophylactic vaccines and the certificate of analysis (CoA)
describe production history factors when assigning a drug product to an evaluation group
describe a scenario where a subset of lots manufactured in a new facility may be in 1 evaluation group while another subset of lots of the same product may be in another group

Regulatory authority

The guidance provides more details about Health Canada's regulatory authority to:

request information about specific lots of a biologic drug
make appeal decisions

Operational updates

The guidance clarifies operational updates:

BRDD reviews lot release activities on an ongoing basis. As the level of product oversight may change based on benefit and risk considerations, a product may be moved to a different evaluation group over its lifecycle.
After receiving the notice of compliance (NOC) or decision letter (DIN-B), the sponsor should follow the process for the post-approval evaluation group assigned to the product.
For prophylactic vaccines: Where BRDD has requested the submission of lot documentation, a written approval in the form of a release letter is required

Proposed updates

BRDD is looking to harmonize the process for movement between evaluation groups. Products are continuously being assessed with respect to their evaluation group.

Factors when assigning products to evaluation groups is updated. In addition, BRDD may reassign a product to a different evaluation group at any time.

Pre-market testing replaces consistency testing and is defined. Group 1B guidance text is updated and includes the following statement: "Sponsors must follow the requirements for the assigned evaluation group post-authorization."

An update to targeted testing (formerly Appendix II) to indicate that not all tests are applied to all lots. Added product stability profile and shelf life as a consideration in the targeted testing regime.

If BRDD has requested lot samples for periodic testing (formerly Appendix III), the targeted timeframe for release is 6 weeks from the date that all required information and samples are received.

BRDD has included the drug identification number-biologics (DIN-B) within the lot release process.

The following proposed changes include reducing the scope for notifications:

Change in scope for other biologics: "Other biologics" are clinical trial materials associated with authorized clinical trial applications (CTAs). Sponsors must complete and file a Group 1A lot notification form for lots derived from human plasma or containing human-derived excipients, such as albumin.
Group 1A notification process is required for products derived from human plasma or those containing human-derived excipients
- Group 1A Lot Notification Form with updated fields replaces the CTA Fax-back Form Clinical Trial Materials.
- The sponsor must send in the Group 1A notification before using the lot in the related clinical trial. The sponsor does not need to wait for a signed response from BRDD before using the lot in a clinical trial.
- The Group 1A Lot Notification Form no longer has check boxes for testing specifications, as out of specification for Group 1A can no longer be sent as a fax-back notification. Clinical trial lots that are out of specification are addressed through Division 5 of the regulations.
Group 4 notification process is required for products derived from human plasma or those containing human-derived excipients
- Group 4 Lot Notification Form with updated fields replaces the Fax-back Form Group 4 Products and Group 4 Products containing human excipients
The Yearly Biologic Product Report (YBPR) is replaced by periodic quality reporting
- Submitting the periodic quality report section is updated to reflect the proposed new scope and application.
- Periodic quality reporting is risk-based. For example, BRDD may issue a product specific communication to the market authorization holder for a product or group of products. In some cases, the communication may be for more than 1 product under the same DIN owner.
- As an alternative, you may submit a report prepared for another competent regulatory authority that has similar information as the periodic quality report. If you do, ensure it is updated with Canadian-specific information.
- The periodic quality reporting frequency and requirements may vary depending on the product. BRDD will communicate this to the sponsor.
- BRDD will notify the sponsor if there is a change resulting from our review of the periodic quality report, such as:
  - an approved CPID
  - feedback to provide to the sponsor and/or
  - a change to the lot release evaluation group for the product

Replacement of documents

Relevant text from the "Frequently asked questions – Guidance for sponsors: Lot Release Program for Schedule D (biologic) drugs" and "Yearly biologic product reports: Questions and answers" is edited and merged into the revised guidance document.

This draft guidance, once finalized, will replace the following documents:

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Date modified:: 2024-03-18

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