The Generic Drug Approval Process
Mar 17 2022
FDA requires a generic drug company to produce enough data to demonstrate the company can make a drug that can be appropriately substituted for the brand-name product. The generic drug maker’s challenge is to prove to FDA that its generic is substitutable with a brand-name drug that has been shown to be safe and effective.
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.
1. 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.
2. The company must also show its generic product will behave the same way in patients as the brand-name product.
To prove this, the company is often required to conduct studies with human volunteers who take both the brand and generic drug products. FDA compares the data from these trials to validate that the generic drug is safe, effective and can be substituted for the brand-name product. Patients should be able to take the brand-name drug on one day and the generic drug on another day and receive the same treatment effect.
3. So basically, manufacturers have to prove the active ingredient is the same as the brand- name drug that is being copied.
The manufacturers 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 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 for the brand-name drug.
What is FDA’s role once the generic drug data is submitted for review?
FDA’s 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.
FDA thoroughly examines the data the generic drug company submits, and the agency evaluates the information that their investigators obtain 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. FDA will periodically inspect manufacturing plants and continue to monitor drug quality. And They evaluate any proposed changes to the generic drug product after it is approved. Significant changes require FDA review and approval before the changed generic drug is released to patients.
Why can’t companies bring a generic of a brand-name drug to market immediately after the brand-name drug is approved?
When approved, the brand drug often receives patent and other protections. The patent protection period provides the brand drug company time to recover the cost of discovering and developing the drug.
When can a company start to market a generic drug once it receives approval?
After FDA approves a drug, the application holder makes the ultimate decision as to when to market the drug. Business and other considerations may impact how quickly a generic becomes available.
How do generic drugs reduce the overall cost of medication in the U.S.?
Usually, as FDA approves more generics of a brand-name drug, the cost drops. Generally, multiple generic drugs for the same product create marketplace competition. A single generic competitor can lead to price reductions of 30%, while five competing generics are associated with prices drops of nearly 85%.
What’s the average time between generic drug application submission and approval?
It depends on the complexity of the drug and the completeness of the application. Some generics of priority drugs – drugs that FDA’s CDER has determined are important to public health -- have been approved in six months or less. Other times, it may take several revisions to the application and several cycles of review before an application meets our rigorous approval standards.
Because of complexity, some generics are harder for applicants to develop and take longer for FDA to review. Examples include drugs that include a device, such as auto-injector pens; dermatological drugs that are administered on the skin; or drugs that are inhaled through the nose. Known as complex generics, these drugs require more complex research and data to ensure they are the same as the brand-name drug. Because of the difficulty involved in developing these complex products, FDA has several enhanced efforts in place to ensure applicants have the latest scientific and regulatory information they need to meet FDA’s standards for approval and ultimately improve patient access to these important treatments.
For example, FDA publishes product-specific guidances (PSGs) that describe the agency’s thinking on scientific expectations for specific generic drugs, including complex generics.
These PSGs aim to help industry streamline the development and assessment process so that more generics can ultimately reach the market. Through these guidances as well as scientific workshops, communications with generic drug developers, and other efforts, FDA is working to maximize use of its generic drug approval pathway for generic drugs.
Faster approval times also help many generic drugs gain approval as soon as patent and exclusivity protections expire.
All generics, including ones with faster approval times, must meet FDA’s rigorous standards for approval.
What can companies do to reduce generic approval times?
Companies can study the appropriate FDA guidances, including PSGs, before developing their product or submitting their application to us. Companies can also request meetings with FDA to ask questions early in the drug development process or during the application review process.
If there are still questions, companies can take advantage of the controlled correspondence process to confirm their path forward. Then, they should ensure they are submitting an application that contains all the information needed to show the generic drug is safe, effective, high-quality and substitutable to the brand-name counterpart. In addition, companies can make sure their facilities and contractors are in good standing with FDA.
If companies follow the steps to approval that FDA has outlined, they can reduce their generic drugs’ review and approval times. We are taking steps during the review phase, such as providing more communications to companies before and during the application review period, to reduce approval times, while working to provide the public with generic drugs that are safe, effective, substitutable alternatives.
How are reviews prioritized?
FDA prioritize reviews of certain products, such as products that are in shortage, potential first generics, and products related to public health emergencies, 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 have the Generic Drug User Fee Amendments (GDUFA) had an impact on approval times?
GDUFA provides us with additional resources that help us appropriately staff our program, which can reduce the time to review generic drug products. We have seen approval times drop since GDUFA started in 2012. That is great news for patients and companies.
Ted Sherwood, Director, Office of Regulatory Operations, Office of Generic Drugs, Center for Drug Evaluation and Research (CDER)
Note: This CDER Conversation with Ted Sherwood was updated in 2022 to reflect OGD’s progress and current activities.
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