The FDA Approval Process

5/26/2020

We are all hearing about a number of potential drugs in the development stage for the possible vaccine to combat COVID-19. In the forefront, leading the way, are the Moderna and Pfizer studies, finding our miracle cures that will end our fears of the pandemic. Nevertheless, no matter how promising or effective a new drug/treatment may be, the approval process, established by the Food and Drug Administration (FDA), is a long journey. And regardless of how desperate or dire a situation may be, by ignoring or skipping steps in this established course of action, the results could be disasterous.

According to the Tufts Center for the Study of Drug Development (https://csdd.tufts.edu/), it takes over $2.6 billion for a manufacturer to get a new drug from the laboratory onto the pharmacy shelf. The full research, development and approval process can last from 12 to 15 years.  However, the FDA has four distinct processes for which the approval process can be hastened:

• Priority Review
• Breakthrough Therapy
• Accelerated Approval
• Fast Track

The specific reasons for a quick approval process are based on necessity. Such is the case when a promising drug comes along that is designed fight such ailments as cancer, AIDS and Alzheimer’s Disease (one case that was not life threatening but placed on the Fast Track was Viagra®).   The specific time it takes for a drug to be approved through any of the above acceptance criteria, is not specified, as each drug will follow its own unique process as dictated by the FDA.  Recently the FDA announced that if all testing goes according to plan, Moderna’s COVID-19 Vaccine might receive approval in 18 months.

Most drugs that undergo preclinical (animal) testing never even make it to human testing (followed by the FDA review process). The drugs that do, must undergo a rigorous evaluation process, which scrutinizes everything about the drug; from the design of clinical trials to the severity of side effects to the conditions under which the drug is manufactured.  Below is a list of the various steps necessary for a drug to be approved for human consumption.

1. Preclinical (animal) testing.
2. An investigational new drug application (IND) outlines what the sponsor of a new drug    proposes for human testing in clinical trials.
3. Phase 1 studies (typically involve 20 to 80 people).
4. Phase 2 studies (typically involve a few dozen to about 300 people).
5. Phase 3 studies (typically involve several hundred to about 3,000 people).
6. The pre-NDA period, just before a new drug application (NDA) is submitted. A common time for the FDA and drug sponsors to meet.
7. Submission of an NDA is the formal step asking the FDA to consider a drug for marketing approval.
8. After an NDA is received, the FDA has 60 days to decide whether to file it so it can be reviewed.
9. If the FDA files the NDA, an FDA review team is assigned to evaluate the sponsor’s research on the drug’s safety and effectiveness.
10. The FDA reviews information that goes on a drug’s professional labeling (information on how to use the drug).
11. The FDA inspects the facilities where the drug will be manufactured as part of the approval process.
12. FDA reviewers will approve the application or issue a complete response letter.

The FDA has legal authority to regulate both medical devices and electronic radiation-emitting products through the Federal Food Drug & Cosmetic Act (FD&C Act) and has its regulations under Title 21 of the Code of federal Regulations (21 CFR – “Food and Drugs”) and cover various aspects of design, clinical evaluation, manufacturing, packaging, labeling and post market surveillance of medical devices.

• 21 CFR searchable database
• Parts 1 – 99 (product jurisdictions, protection of human subjects, institutional review boards, etc.)
• Parts 100 – 799 (food, human and animal drugs, biologics, cosmetics)
• Parts 800 – 1299 (medical devices and radiation emitting products)
• Parts 1300 – 1499 (controlled substances)

The FDA got its start with the passage of the country’s first major food and drug safety bill: The 1906 Pure Food and Drug Act. That law’s origins stem from a decades-long fight for the government to regulate food. The final push came from the 1906 publication of Upton Sinclair’s The Jungle. This powerful exposé, which set out to document the inhumane labor conditions in America’s factories, also ended up drawing attention to the horrifically unsanitary production of many processed foods. As Upton Sinclair wrote: “I aimed at the nation’s heart and by accident hit its the stomach.”

Around the same time, the investigative journalist (known by the term, muckraker), Samuel Hopkins Adams, published a 12-part expose on the fraudulence and dangers of the patent-medicine industry in the widely read Collier’s magazine. Soon after the book and series’ publication, an outraged President Theodore Roosevelt signed the bill into law on June 30, 1906.

If you could kick the person in the pants responsible for most of your trouble, you wouldn’t sit for a month

Theodore Roosevelt