April 30, 2021,
NATIONAL AGENCY FOR FOOD AND DRUG ADMINISTRATION AND
NAFDAC VACCINE COMMITTEE
NAFDAC RECOMMENDED PFIZER-BIONTECH COVID 19 VACCINE FOR EMERGENCY USE AUTHORIZATION
APRIL 30, 2021
National Agency for Food and Drug Administration and Control (NAFDAC) received the permission from World Health Organisation to access the dossier on March 11, 2021.
Pfizer-BioNTech COVID-19 Vaccine is a white to off-white, sterile, preservative-free, frozen suspension for intramuscular injection. The vaccine contains a nucleoside-modified messenger RNA (modRNA) encoding the viral spike glycoprotein (S) of SARS-CoV-2. The Pfizer-
BioNTech Covid-19 Vaccine is supplied as a preservative-free, multi-dose concentrate to be diluted for intramuscular injection, intended for 6 doses.
Each vial, containing 0.45 mL of the Drug Product at pH 7.4 is designed to deliver a total of 6 doses after dilution by addition of 1.8 mL of sterile 0.9% sodium chloride solution, with each dose containing 30 µg of RNA in 0.3 mL.
The product is available in a 2 mL clear vial (type I glass) with a stopper (synthetic bromobutyl rubber) and a flip-off plastic cap with aluminium seal. Pack size: 195 vials. The multidose (5 dose) vial is stored frozen and must be thawed prior to dilution. After thawing, the vaccine should be diluted and used immediately.
After dilution with 1.8 mL sodium chloride (0.9%) solution (not supplied), one dose (0.3 mL) contains 30 micrograms of COVID-19 mRNA Vaccine (embedded in lipid nanoparticles).
The section on formulation development describes and justifies the chosen formulation and is sufficiently comprehensive.
The formulation development studies of the RNA containing lipid nanoparticles have been thoroughly described. The LNPs consists of four lipids, each has a functional or structural purpose. The formed RNA-containing LNPs are solid particles. Furthermore, the accumulated batch-data to date show consistent manufacture of lipid nanoparticles both with respect to size and polydispersity.
The finished product is batch released by Pfizer Manufacturing Belgium NV, Puurs, Belgium or BioNTech Manufacturing GmbH, Mainz, Germany. The GMP status of the manufacturing and testing sites of the finished product have been confirmed.
The product has the following shelf life depending on the storage condition:
Up to six (6) months when stored in ultra-low-temperature freezers at -80°C to -60°C,
Up to thirty (30) days when stored in Pfizer thermal shippers in which doses will arrive (-800C to -600C), which can be used as temporary storage units by refilling with dry ice every five days.
Five (5) days at refrigerated 2-8°C conditions.
SAFETY AND EFFICACY
- A clinical trial was conducted with a total of 44,000 participants in a randomized controlled trial, this enables them to establish efficacy of the vaccine. The primary efficacy endpoint being incidence of Covid 19 among participants without evidence of SARS-CoV-2 infection before or dose 2 vaccination regimen. The efficacy analysis of the participants without evidence of SARS- CoV-2 infection prior 7 days after completing the vaccination regimen was reported at 95% with 8 cases of COVID 19 in the vaccine groups and 162 cases in the placebo group. The subgroup analysis also showed similar efficacy endpoint estimates.
- The phase 2/3 study participants were stratified by age and it included younger participants ages 12 through 15 years, 16 through 54 years and 55 years and older. The study also included participants at high risk of the disease e.g. healthcare workers, individuals with auto immune disorders, chronic but stable heath conditions such as asthma, diabetes.
- A continuation of the trial is expected even after EUA is issued and the follow up is expected to remain blinded with the aim of getting a long-term assessment of the safety and efficacy of the vaccine. The EUA requirement should include the strategies that will be implemented to ensure the long-term safety and efficacy data is gathered that will be sufficient to support the eventual vaccine licensure.
SUMMARY OF THE CLINICAL TRIAL
The non-clinical toxicological study did not raise any specific safety concerns, the study conducted in the animal challenge models supported the vaccines immunogenicity and reduction of the SARS-CoV-2 pulmonary load.
The phase 2/3 study participants were stratified by age and it included younger participants ages 12 through 15 years, 16 through 54 years and 55 years and older. The study also included participants at high risk of the disease e.g. healthcare workers, individuals with auto immune disorders, chronic but stable heath conditions such as asthma, diabetes.
The efficacy analysis of the participants without evidence of SARS- CoV-2 infection prior 7 days after completing the vaccination regimen was reported at 95% with 8 cases of COVID 19 in the vaccine groups and 162 cases in the placebo group. The benefits far outweighed the benefits.
Pharmacovigilance of Covid-19 Vaccines
Safety of the vaccine is premium to NAFDAC and a lot of efforts are being put into this regulatory function. The Agency initiated multi-stakeholder collaboration with National Primary Health Care Development Agency (NPHCDA), Nigeria Center for Disease Control (NCDC), UNICEF, GAVI, WHO and Ministry of Health. The focus is to use a holistic approach for the effective immunization or delivery of the vaccines and monitor any Adverse Events Following Immunisation (AEFI). The multi-stakeholder technical working groups have been meeting to address different issues, from access to distribution to traceability (track and trace) of the vaccines, to monitoring of adverse events following immunization.
The Agency will be using its recently launched Med Safety App for Active Pharmacovigilance of the vaccines in collaboration with the sister agencies. The App is free, and millions of healthcare workers can download it free for Adverse Drug Reaction (ADR) reporting. In-country training on the use of the App has begun for the healthcare givers.
NAFDAC plans to also use the Traceability with GS1 technology to monitor the vaccine distribution using Global Trade Item Number (GTIN). This is to prevent fake vaccines from infiltrating the supply chain and to ensure there is no diversion. This effort will create a reliable and predictable supply chain.
At the continental level, NAFDAC is on the Regulators Steering Committee of African Union -3S (Smart, Safety Surveillance) with Ghana, South Africa and Ethiopia. The committee was formed as a preparatory caucus for safety monitoring of medicines but using COVID-19 vaccine as a pilot.
Prof Mojisola Christianah Adeyeye, PhD, FAS