The Generic Drug Approval Process
Talking to Ted Sherwood, Director, Office of Regulatory Operations, Office of Generic Drugs, Center for Drug Evaluation and Research
Generic drugs are copies of innovator or brand-name prescription drugs and make up about 88 percent of prescriptions filled in the United States. Brand-name drugs must demonstrate their safety and effectiveness through expensive and time-consuming research and development programs, including clinical studies. In contrast, generic drug developers can use data from their brand-name counterparts, resulting in much less expensive development programs and affordable access to treatments for many patients and consumers.
FDA requires a generic drug company produce enough data to demonstrate it can make a drug that can be appropriately substituted for its brand-name counterpart. The challenge to the generic drug maker is to prove to FDA that the generic version is substitutable with a brand-name drug that has been shown to be safe and effective. FDA’s challenge is to carefully review that data to ensure it proves the same thing. Let’s look at how both do their job.
What kind of data do generic drug companies submit to FDA?
There are several types of data generic companies must submit to us for review and evaluation. For one, it is critical that the data show the manufacturing process – how the generic drug will be made by combining the active ingredient, which really provides the treatment, and the inactive ingredients. These data let us know if the manufacturer can reliably make a high-quality product.
It is also critical that the company show its product will behave the same way in patients as its brand-name counterpart. To prove this, the company is often required to conduct trials with human volunteers who take both the brand and generic drug products. We compare the data from these trials to validate that the generic drug is safe, effective and can be substituted for the brand product. Patients should be able to take the brand drug product on one day and the generic drug on another day and still receive the same treatment effect.
So basically manufacturers have to prove the active ingredient is the same as the brand drug that is being copied. They also must show that the right amount of the active ingredient goes to the place in the body where it has an effect, and any inactive ingredients used are safe. Companies also need to show that the drug will not deteriorate over time, that the manufacturer can produce the same drug every time, and that the labeling is the same as the brand name drug.
What is FDA’s role once the generic drug data is submitted for review?
Health care professionals and scientists with a wide range of expertise work together to make sure that every generic drug is safe, effective, high quality and substitutable to the brand name drug. We also conduct a thorough examination of the data submitted by the generic drug company and the evaluation of information obtained by our investigators while inspecting the related testing and manufacturing facilities. With these reviews, patients can be confident in the generic drug they are taking.
Once a generic drug is approved, manufacturers must report any problems and serious adverse health effects to us for evaluation. We will periodically inspect manufacturing plants and continue to monitor drug quality. And we evaluate any proposed changes to the generic drug product after it is approved. Significant changes require review and approval by FDA before the changed generic drug is released to patients.
Why can’t sponsors bring a generic version of a drug to market immediately after the brand drug is approved?
When approved, the brand drug is often awarded patent and other protections. The patent protection period provides the brand drug company time to recover the cost of discovering and developing the drug.
Would approving generic drugs faster reduce the overall cost of prescription drugs?
For the majority of generic drugs, we are able to complete our review and the generic drug is approved as soon as patent and exclusivity protections for the brand drug have expired. Of course, this only applies to situations where we’ve received a complete application in a reasonable time period, ahead of the first allowable approval date.
Usually, as more generic drugs are approved the cost of the generic versions drop, so faster approval times helps facilitate approval of the second, third and beyond generic versions. So yes, the overall cost of prescription drugs is reduced by faster generic approval times.
What’s the average time between generic drug application submission and approval?
It depends on the complexity of the drug product and the completeness of the application. Some generic versions of priority drugs – drugs that CDER has determined to potentially provide a significant advance in medical care -- have been approved in six months or less. Other times it may take years before FDA’s scientific and medical team is 100 percent confident in an approval decision.
It often takes several rounds of communication between FDA and the generic drug company before the product is shown to be safe, effective, high quality, and substitutable for the brand name counterpart. Some generic drugs are never approved, because the company is unable to meet FDA’s rigorous standards for approval.
What can sponsors do to reduce generic approval times?
Submit a complete application. One that contains all of the information needed to show the generic drug is safe, effective, high quality, and substitutable to the brand name counterpart. In addition, they can make sure their facilities and contractors are in good standing with the FDA.
How are reviews prioritized?
We prioritize reviews of potential first generics by monitoring the legal issues affecting generic competition, determining the earliest date a first generic could be eligible for approval, and helping ensure approvals are as timely as possible.
How has the Generic Drug User Fee Amendments of 2012 (GDUFA) had an impact on approval times?
It provides us with additional resources that help reduce the time to review generic drug products. We are already seeing the results with a record number of approvals.
How is FDA working to reduce generic approval times?
We are providing additional guidance to companies earlier in the research and development period. This helps them understand what is required for approval, especially for newer or more complex products. If companies follow the steps to approval outlined by FDA, then review and approval times will be reduced, and more generic drug products will be available for patients. We are taking steps during the review phase to reduce approval times, while working to provide the public with generic drugs that are safe, effective, substitutable alternatives.
- What is the Generic Drugs Program at FDA?
- Fact Sheet: What's Involved in Reviewing and Approving Generic Drug Applications?