Guidance for market authorization requirements for COVID-19 vaccines: Quality, manufacturing and lot release requirements

Establishment licensing

To bring a COVID-19 vaccine to market in Canada, a company must have an establishment licence to manufacture, package/label, test, import, distribute or wholesale a health product. An establishment licence is issued under the Food and Drug Regulations.

A company without such a licence must apply for one.

During the Drug Establishment Licence (DEL) application review process, a company must demonstrate compliance with good manufacturing practices (GMP). Depending on several criteria, including where the building is located, a company can demonstrate GMP compliance through:

a Health Canada on-site inspection
a certificate of GMP compliance issued by a partner with whom Health Canada has a mutual recognition agreement
an inspection report from a regulatory authority, qualified authority, the WHO or, in some cases, a corporate/consultant auditor

The pandemic has created pressures on the drug supply chain and there is an urgent need for COVID-19 vaccines. Under the IO, Health Canada is issuing establishment licences more quickly. Licensing decisions are based on the materials submitted in the application.

Product quality

COVID-19 vaccines authorized under the IO must be manufactured under GMP conditions. These conditions are in line with international requirements, which are outlined in the International Council for Harmonization Q7A guideline and applicable Health Canada guidance.

We require sufficient data to demonstrate that the manufacturing process is well controlled and consistent. This involves details on the manufacturing process for both the drug substance and drug product, including information on:

source materials
virus and cell banks
in-process control testing based on specifications developed to evaluate critical process parameters

Data should be collected in a sufficient number of batches to demonstrate process consistency. Critical assays such as potency and impurities should be validated.

Authorization will also require establishment of stability parameters and expiry date on the drug product in its final container and formulation. Stability and expiry parameters should:

indicate vaccine potency whenever possible and
be from enough lots to be broadly representative of the product as a whole

Lot release

Biologic drugs in Canada are subject to lot release program requirements as outlined in section C.04.015 of Canada's Food and Drug Regulations. Vaccines are considered biologic drugs and are generally subject to the highest level of regulatory oversight since they're administered to healthy children and adults.

Health Canada's lot release program allows the application of a flexible, risk-based approach. This approach considers the evidence on manufacturing quality and controls as a whole, as well as testing from other international regulatory authorities. For example, Health Canada is an associate member of the European Official Medicines Control Laboratory network, which supports the sharing of testing data among its members.

Health Canada's lot release program covers both the pre- and post-market stages for biologic drugs. Each lot of a biologic drug is subject to the lot release program before sale. We base the level of regulatory oversight (testing and/or protocol review) on the degree of risk linked to the product.

Health Canada has retained this requirement under section 13(1) of the IO. This section states that we have the authority to ask for information, material or samples to help us when deciding whether to grant, amend or suspend an authorization under the IO. The flexibilities offered in the IO make it possible for us to:

address the current public health emergency appropriately
take advantage of information gathered both pre- and post-authorization to develop a lot release strategy that adequately mitigates risks

Health Canada's COVID-19 vaccine lot release strategy

The IO gives Health Canada the ability to allow market access to vaccines that show promising clinical evidence of safety and efficacy and an adequate level of control over the manufacturing consistency and product stability.

Following authorization, clinical trials involving a sufficient number of participants will continue to be monitored. During this time, manufacturers will also continue to generate new information on the control and validation of their commercial manufacturing process, consistency of production and compliance with GMP. The lot release strategy for vaccines authorized under the IO must take into account these details in order to mitigate risks while allowing expedited access to address pandemic needs.

Health Canada's strategy includes the submission by the sponsor of a certificate of analysis for each lot before it's distributed on the Canadian market without the need to issue a lot release letter. This process will allow documentation of lots distributed in Canada and monitoring of product consistency. Following authorization, as part of our additional monitoring of product quality activities, we may ask for a summary of batch disposition information on a quarterly basis.

Normally, consistency testing would be conducted as part of the review process for full market authorization of a vaccine. To support expedited timelines under the IO process, Health Canada will use alternate approaches to ensure product quality. We will monitor product quality from time to time through key quality control tests. To further mitigate risks, Health Canada labs will also be reviewing the methodology used by the sponsor and the suitability of these tests for assessing product quality. During this period, we will begin the process for assay validation to support eventual lot release testing following transition of the vaccine to a full market authorization.

An important risk mitigation tool afforded to Health Canada through the IO will be the capacity to continue evaluating the quality of each vaccine throughout its lifecycle. Health Canada will be able to ask for additional information, such as an annual product report and/or product quality review. By using these tools, Health Canada can exercise more appropriate risk mitigation measures on a case-by-case basis at any time during the lifecycle of the vaccine. For example, Health Canada could implement more stringent lot release measures by placing a vaccine into Group 2 Lot Release in response to signals indicating increased risk.

Health Canada will communicate the requirements for lot release to each sponsor at the time of pre-submission discussions/meetings. We anticipate that considerations may need to be made on a case-by-case basis given the complexity of vaccine distribution (for example, prepositioning of lots before authorization). Decisions will be documented as part of the submission review process.

Vaccines authorized under the IO will transition to a market authorization through the new drug submission (NDS) process. At that time, the lot release requirements will be re-assessed. It is likely that methodologies and relevant quality management system processes will be in place at that time.

By implementing the flexible strategies outlined above, Health Canada can:

mitigate the risk of potentially having lots distributed that don't comply with the approved specifications
allow for expedited access to safe, effective and high-quality vaccines for Canadians

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Guidance for market authorization requirements for COVID-19 vaccines: Quality, manufacturing and lot release requirements

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Establishment licensing

Product quality

Lot release

Health Canada's COVID-19 vaccine lot release strategy

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