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FDA Approval Process for New Drugs

By Shelley Jain

Occasionally studies that you read on MD Lingo concern drugs in various phases of FDA approval. Below, we have provided you with a short outline of the FDA approval process for new drugs.

As technology and medical science advances, patients and doctors alike look towards biotechnology for new drugs to treat and cure disease. However, in order for companies to market their medications, they must first go through a long and rigorous approval process by the Federal Drug Administration (FDA). This includes a Preclinical Testing Phase, Phase 1 Testing, Phase 2 Testing, Phase 3 Testing, the New Drug Application, and then Post-Marketing Follow Up.

Preclinical Testing Phase:
New drugs are developed through the support of sponsors that include pharmaceutical companies, research institutions, and not-for-profit fundraising organizations. The drugs are first tested in laboratory animals and live human tissues. When a group feels their compound has potential as a therapeutic agent, an Investigational New Drug Application (IND) is submitted to the FDA. Sponsors must show the FDA the results of their preclinical trials and what they propose for human testing trials. Based on the results of the preclinical trials, the FDA decides whether the company should move to the next phase of testing their drug in humans. The three phases of human clinical trials that follow preclinical testing are the most tedious components of the drug approval process – taking years and hundreds of millions of dollars to complete. The costliness (time and money) of the process has an unfortunate downside. For a company to embark on a search to find a drug for a particular ailment, they must see the potential for financial gain. Since drug approval is so expensive, rare diseases and those with competing drugs on the market are often less desirable for companies, due to the limited profit margin available. It is this paradigm that makes the efforts of research institutions and non-profits vital in the drug discovery world. Getting back to the process, Phase 1 follows preclinical testing.

Phase 1:
Review of the IND is followed (hopefully) by approval of the clinical trials protocol by an institutional review board. This board is composed of experts who ensure the safety of the patients and the ethical soundness of the research. Between 20 and 80 human volunteers are enrolled in this phase of the study. Sometimes, these volunteers are healthy and function as a way for the researchers to measure how the drug acts biochemically within the human body. In other situations – take chemotherapy drugs as an example – participants have many different types of cancers and researchers are trying to determine in which types the drug has an effect. A promising result in this phase of study allows the compound to be pushed forward into Phase 2 trials.

Phase 2:
Phase 2 hones in on specific disorders, the goal being to determine the maximum safe dose of the drug and to compare the response achieved to that of the current standard treatment. The number of subjects that the drug is tested on in this phase ranges from a few dozen to about 300. Successful Phase 2 drugs are those that can be given safely (with minimal or acceptable side effects) while demonstrating beneficial effects on the symptoms, staging, or diagnosis of the chosen disease.

Phase 3:
Phase 3 studies are the holy grail of drug development. Many drugs that have looked exceedingly promising throughout the prior stages will crash and burn in this stage. The method of study in this stage is called a Randomized Controlled Trial (RCT), in which numbers of patients reaching the thousands are randomly assigned to either drug receiving or placebo (fake drug)-receiving groups. Both the patients and the researchers are unaware of the group of which a particular patient is a member, and results are blindly recording throughout the duration of the study. Results from this study are stratified into different patient populations, different drug dosages, and in combination with other drugs to determine the drug and patient combinations that are most likely to ensure benefit. A drug that summits the Phase 3 mountain is a drug that will, with near certainty, be hitting the pharmacy shelves within a year. Much of what remains is paperwork and bureaucracy.

The new drug studies published on MD Lingo generally concern this phase of the FDA approval process.

New Drug Application:
Companies complete this final application, the New Drug Application (NDA), for formal approval by the FDA to consider approving a new drug for marketing. This application contains data from preclinical trials in animals, all phases of human trials (Phases 1-3), and analyses of the data. It also contains information about how the drug behaves in the body and how the companies manufacture it. The FDA has 60 days to decide whether they want to file the NDA for review. After the NDA is approved for review, the FDA is expected to review and act no later than 10 months after it is received (6 months for priority drugs).

Post-Marketing Follow-Up:
After the drug has been approved for marketing by the FDA, companies are required to continue following up on the drug’s safety, effectiveness, and impact to patients. They are expected to continue gathering additional information on the drug, ensuring patient safety and the investigation of adverse reactions and outcomes. The drug approval process is long and rigorous, but for good reason – to guarantee the safety of patients, effectiveness of the drug, and optimization of the treatment.

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