On March 17th 2020, Pfizer and BioNTech companies announced that the companies have agreed to a letter of intent regarding the co-development and distribution of a potential mRNA-based coronavirus vaccine aimed at preventing COVID-19 infection(*1). Today, on November 18th 2020, Pfizer and BioNTech concluded Phase 3 study of COVID-19 vaccine candidate with 95% efficacy (*2).
But, what does this mean? When can we expect to have a vaccine available for public use in the marketplace? What are the different phases in a drug discovery & development process?
In this two-part article on the drug development process, we will look at a typical lifecycle for developing a new drug and compare it with the fast-tracked process for releasing COVID-19 vaccine. Since Pfizer and BioNTech are following US FDA approval process, let us understand the typical drug development process in the US.
Note that every country has its own regulatory agency. The regulatory agency in USA is the US Food and Drug Administration, in India it is the Central Drug Standards Control Organization (CDSCO). You can find regulatory authorities of different nations here.
The Drug Development Process
Step 1: Discovery
Research for a new drug begins at this stage. Thousands of compounds may be identified as potential candidates for developing a treatment. Researchers identify a small number of compounds as promising and take them for further analysis on factors such as amount of dosage, side effects, best form of administering the drug, its effectiveness compared to alternatives and so on.
Step 2: Preclinical Research
This stage combined with Discovery (Step 1) could take anywhere between 6 to 7 years during which the manufacturer/researcher completes synthesis and purification of the drug. Prior to testing a new drug among humans, researchers must provide important information about the efficacy and safety of the drug. The two types of preclinical research are — In Vitro (in glass, as in a test tube in a laboratory) and In Vivo (in a living organism). Out of an average 5000 compounds tested, approximately 5 enter the next phase of filing an Investigational New Drug Application (IND). Only after the IND is approved by FDA, the manufacturer can move to the Clinical Trials phase.
Step 3: Clinical Trials
Clinical trials are conducted in three phases, each phase designed to answer specific questions related to investigating the efficacy and safety of the new drug.
- Phase 1 — Conducted on 20 to 100 healthy volunteers, this phase is carried out in about 1.5 years. Primary goal is to determine if the drug is safe for humans and identify information about dosage amount and dosage administration method.
- Phase 2 — Conducted on 100 to 500 volunteers diagnosed with the target condition, this phase spans about 2 years. Primary goal is to determine efficacy and occurrence of any side effects.
- Phase 3 — Conducted on 1000 to 5000 volunteers diagnosed with the target condition, this phase spans about 3.5 years. Primary goal is to confirm efficacy and identify any adverse effects from long-term use of the drug.
Step 4: FDA Drug Review
If the drug manufacturer has sufficient evidence in support of safety and efficacy for intended use of the new drug, the manufacturer submits a New Drug Application (NDA) to the FDA with enough information gathered during preclinical and clinical trials phases. Once the FDA receives an NDA, and the review team decides it is complete, the review process can take up 6 to 10 months before making a decision of approval or otherwise. Overall, out of the 5 compounds that enter the clinical trials, only 1 final compound is approved as the final drug.
Step 5: Post-Market Drug Safety Monitoring
In this phase, the drug is monitored after it has received approval and reached the marketplace for use by the general public. Although rigorous experiments have been conducted over the course of 12–14 years, there are limitations during clinical trials. The true picture of a new drug’s efficacy and safety evolves over the months and years of the product lifetime in the market. FDA reviews reports from market and can decide to add cautions or usage information and also update this information as necessary.
In part 2 of this article, we will discuss how this typical approach compares against the process followed for developing the COVID-19 vaccine.