Regulatory Decision Summary for Pfizer-BioNTech COVID-19 Vaccine

The purpose of this application was to obtain the market authorization, under the Interim Order respecting the Importation, Sale and Advertising of Drugs for Use in Relation to COVID-19, for the Pfizer-BioNTech COVID-19 Vaccine. To support the authorization of the Pfizer-BioNTech COVID-19 vaccine, efficacy, immunogenicity and safety data from two ongoing clinical trials were provided. Study BNT162-01, a first-in-human Phase 1/ 2 study (FIH) and, Study C4591001, a Phase 1/ 2/ 3 pivotal clinical trial.

Health Canada decision issued:

Pfizer-BioNTech COVID-19 Vaccine was authorized for use in relation to the COVID-19 pandemic, in accordance with section 5 of the Interim Order Respecting the Importation, Sale and Advertising of Drugs for Use in Relation to COVID-19.

Date of decision:

2020-12-09

Indication (use):

Pfizer-BioNTech COVID-19 Vaccine (COVID-19 mRNA Vaccine) is indicated for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) in individuals 16 years of age and older.

Health Canada analysis of known and potential benefits and known and potential risks:

The ongoing COVID-19 pandemic has a significant impact on public health. There is no vaccine authorized for the prevention of COVID-19 in Canada. The availability of a safe and effective vaccine will reduce the spread and severity of COVID-19 disease and reduce its social and economic consequences.

The vaccine efficacy of Pfizer-BioNTech COVID-19 Vaccine was demonstrated in a still ongoing Phase 3 randomized, placebo controlled study (Study C4591001). The study is conducted in the United States, Turkey, Germany, South Africa, Brazil and Argentina. A total of 43,651 participants (21,823 in the Pfizer-BioNTech COVID-19 Vaccine group and 21,828 in the placebo group) were randomised equally to receive 2 doses of Pfizer-BioNTech COVID-19 Vaccine or placebo separated by 21 days. Randomization was stratified by age: 16 through 55 years of age or 56 years of age and older, with a minimum of 40% of participants in the ≥ 56-year stratum. Note that subjects 12 through 15 years of age were not included in the analysis of efficacy.

Compared to placebo, vaccine efficacy was evaluated to be 95% (with 95% confidence interval (CI) of 90.3% to 97.6%) in subjects without prior evidence of SARS-CoV-2 infection 7 days after the second administration of the vaccine.

In subjects 65 years of age and older without evidence of prior infections with SARS-CoV-2, the efficacy of Pfizer-BioNTech COVID-19 Vaccine was 94.7%. Vaccine efficacy was consistent across age, gender, race and ethnicity demographics. Observed vaccine efficacy was >93% across subgroups identified by age, sex, race/ethnicity and country. A total of 10 severe cases of COVID-19 observed in the study, with 9 of the cases occurring in the placebo group and 1 in Pfizer-BioNTech COVID-19 Vaccine group. The confinement of the majority of severe cases to the placebo groups suggests no evidence for vaccine-associated enhanced respiratory disease (VAERD).

A total of 9531 and 9536 subjects (16 years old and older) in the vaccine and placebo group respectively, were followed for at least 2 months after the second administration. The most frequent adverse reactions in a random subset (N=8183) of study participants 18 years of age and older, who received the vaccine and were monitored for reactogenicity were: injection site pain (84.1%), fatigue (62.9%), headache (55.1%), muscle pain (38.3%), chills (31.9%), joint pain (23.6%) and fever (14.2%) and were usually mild or moderate in intensity and resolved within a few days after vaccine administration. The unsolicited AEs reported in the study was lymphadenopathy (0.3%) with no medical sequela reported and lasted for on approximately 10 days. There were no safety signals identified and no life-threatening AEs and death related to the vaccine. The adverse events (AEs) observed showed that the vaccine at 30 µg was safe and well-tolerated in participants and within demographic subgroups based on age, sex, race/ethnicity, country and baseline SARSCoV-2 status.

A Risk Management Plan (RMP) was included in the submission for Pfizer-BioNTech COVID-19 Vaccine. The RMP is designed to describe known and potential safety issues, to present the monitoring plan and when needed, to describe measures that will be put in place to minimize risks associated with the product. Upon review, the RMP was considered to be acceptable and identified appropriate monitoring (pharmacovigilance) activities and risk minimization measures based on the safety profile of the product. This included providing information in the product monograph and identifying populations where more data is needed. In addition to regulatory requirements for post-market monitoring and prioritized reporting of adverse events following immunization, monthly safety summary reports on the vaccine will be provided to Health Canada. Results related to safety and effectiveness from ongoing and planned studies will be submitted as they become available.

One limitation of the data at this time is the lack of information on the long-term safety and efficacy of the vaccine. The identified limitations are managed through labelling and the Risk Management Plan. The Phase 3 Study is ongoing and will continue to collect information on the long-term safety and efficacy of the vaccine. There are post-authorization commitment for monitoring the long-term safety and efficacy of Pfizer-BioNTech COVID-19 Vaccine.

In conclusion, the data provided supports favorably the efficacy of Pfizer-BioNTech COVID-19 Vaccine as well as its safety. The efficacy of the vaccine was established to be approximately 95%, the vaccine was well tolerated by participants and has no important safety concerns. The benefit to risk assessment for Pfizer-BioNTech COVID-19 Vaccine is considered favorable.

Pfizer-BioNTech COVID-19 Vaccine is therefore recommended for authorization for use under the Interim order respecting the importation, sale and advertising of drugs for use in relation to COVID-19, for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 16 years of age and older.

Quality (Chemistry and manufacturing)

Manufacturing of the Pfizer COVID-19 Vaccine (BNT162b2) consists in the production of the mRNA encoding the Spike protein for the SARS-CoV-2 virus followed by the encapsulation of mRNA into Lipid Nano-Particles. Evidence was provided to demonstrate that the vaccine is manufactured under Good Manufacturing Practices (GMP) at all manufacturing sites providing supply to Canada and that in-process controls, process parameters and quality control release tests have been established to monitor product quality throughout the process. The specifications used to evaluate key quality attributes and consistency of production were found acceptable. This information together with the terms and conditions support authorization under the Interim Order.

Directions for use:

Pfizer-BioNTech COVID-19 Vaccine is administered intramuscularly after dilution as a series of two doses (0.3 mL each) 21 days apart.

Pfizer-BioNTech COVID-19 Vaccine is a suspension for intramuscular injection which must be diluted prior to administration. After preparation, each vial contains 5 single doses of 0.3 mL.

For more information, refer to the Product Monograph for Pfizer-BioNTech COVID-19 Vaccine.

Terms and Conditions:

Terms and conditions were imposed upon the authorization with respect to quality, clinical, labelling, and Risk Management Plan requirements.

For more information, refer to the Authorization Terms and Conditions for Pfizer-BioNTech COVID-19 Vaccine.