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Dr. Williams: Welcome to another episode of our podcast series, “Q&A with FDA”, from the FDA’s Division of Drug Information, where we answer some of the most frequently asked questions that we’ve received.

My name is Dr. Celia Williams, and today we will present the first episode in a series about generic drugs. The Office of Generic Drugs, or OGD, is responsible for the assessment of Abbreviated New Drug Applications, otherwise known as generic drug applications. I’m here with Dr. Sarah Ibrahim, an expert on this topic. Dr. Ibrahim is the associate director for Stakeholder and Global Engagement in the Office of Generic Drugs, known by the acronym “OGD”, in the Center for Drug Evaluation and Research.

Hi Dr. Ibrahim, it is great to have you here. We appreciate your willingness to join us today to discuss generic drugs.

Dr. Ibrahim: Absolutely!

Dr. Williams: Dr. Ibrahim, Let’s start with perhaps one of the most fundamental facts that highlights the importance of generic drugs to public health - that FDA-approved generic drugs account for more than 90 percent of prescriptions filled in the United States.

Dr. Ibrahim: That’s correct. Americans rely on generic drugs and our mission in OGD is to ensure that generic drugs are safe, effective and of high-quality for the American public. We accomplish this mission through a rigorous scientific and regulatory review process along with post-marketing activities.

Dr. Williams: Can you expand upon the standard for FDA approval for a generic drug application?

Dr. Ibrahim: Sure. FDA-approved generic drugs are essentially copies of their innovator or brand-name counterparts. They must meet the same high standards as brand-name drugs to receive FDA approval. Generic drugs have the same active ingredients, dosage form, strength, route of administration, safety, effectiveness, stability, and quality - so the clinical risks and benefits are the same as their brand-name counterparts.

While brand-name drugs must demonstrate their safety and effectiveness through expensive and time-consuming research and development programs, including clinical studies, generic drug applicants do not have to repeat these studies because it would be duplicative. This is why a generic drug application is called an Abbreviated New Drug Application, otherwise known as an ANDA.

Dr. Williams: Let’s dive a little deeper into the data. Can you talk more about the information that generic applicants must submit to FDA as part of an abbreviated new drug application?

Dr. Ibrahim: Yes, FDA requires a generic drug company produce enough data to demonstrate that the drug can be safely and effectively substituted for the brand-name product. Generic drug companies must demonstrate pharmaceutical equivalence by showing that the generic drug contains the same active ingredient, strength, dosage form, and route of administration. The generic medicine must also demonstrate bioequivalence to the brand-name product. This is shown through data that proves that the generic drug performs the same way in the human body and provides the same clinical benefits as the brand-name equivalent. With certain exceptions, the label for both products has to be the same. The generic drug must also be manufactured under the same strict standards as all other FDA-approved drugs.

Dr. Williams: I know there will always be a slight, but not medically significant, level of expected variability—just as there is for one batch of brand-name medicine compared with the next batch of brand-name product. Can you expand on this?

Dr. Ibrahim: Of course. This variability can and does occur for both brand-name and generic medicines during manufacturing. When a medicine, generic or brand-name, is made on a large scale, very small variations in size, strength, and other parameters are permitted. FDA limits how much of this variability is acceptable.

Dr. Williams: We hear from consumers who are concerned that this abbreviated process means a generic drug is less trustworthy than a brand name product. Can you share how you respond to those concerns to help our listeners who are having these same conversations with their patients?

Dr. Ibrahim: Of course. I think an understanding of why this abbreviated process is appropriate is the best place to start. As we already discussed, generic drug companies are not required to replicate the extensive clinical trials that have already been used in the development of the original, brand-name drug. This is because the safety and efficacy of the brand-name product has already been well established in clinical testing and frequently further supported by many years of patient use.

Instead, generic companies must scientifically demonstrate that their product meets our strict standards for pharmaceutical equivalence and bioequivalence, and prove that it performs in the same way and provides the same clinical benefits as the brand-name drug. To achieve this, the company is typically required to conduct small studies with human volunteers who take both the brand and generic drug products. FDA then compares the data from these studies to validate that the generic drug is safe, effective, and substitutable for the brand-name product.

Dr. Williams: It’s also critical that the data submitted show the manufacturing process – or how the generic drug will be made. Tell us more about this.

Dr. Ibrahim: Certainly. These data let us know if the manufacturer can reliably make a high-quality product. And companies also need to show that the drug will not deteriorate over time. We need to know that the manufacturer can produce the same drug every time and that the labeling is the same as the brand-name drug.

We thoroughly examine the data the generic drug company submits, and we evaluate information that our investigators obtain while inspecting the related testing and manufacturing facilities. With these reviews, patients can be confident in the FDA-approved generic drug they are taking.

Dr. Williams: Now, let’s talk about post-approval. Tell us about how OGD monitors a generic drug once it is on the market.

Dr. Ibrahim: Once a generic drug is approved, manufacturers must report any problems and serious adverse health effects to FDA for evaluation. FDA then investigates these reports from the public of negative patient side effects or other reactions. The investigations may lead to changes in how a product (brand-name and generic) is used or manufactured, and FDA will make recommendations to health care professionals and the public if the need arises.

FDA also periodically inspects manufacturing plants and continues to monitor drug quality. And we 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.

Dr. Williams: To close out our time together today, in your own words, why do you think generic drugs are so important to public health in America?

Dr. Ibrahim: Access to affordable medicines remains a significant public health priority for FDA. Because generic drug developers go through a different, less expensive, application process, the result is more affordable access to treatments for Americans. Enabling more generic competition, where Congress intended, helps reduce prices, provide more access, and improve public health. As more generics are approved, the medicines become more affordable and help meet this public health priority.

FDA really does its part to ensure that generic medicines work the same as brand-name medicines, from the rigorous pre-approval assessment and inspections of manufacturing plants, to ensuring compliance with the agency’s regulations on current good manufacturing practices and monitoring the products after approval.

Dr. Williams: We couldn’t agree more. FDA’s health care professionals and scientists have a wide range of expertise and work together to make sure that FDA-approved drugs are safe, effective, and of high-quality.

Dr. Ibrahim, thank you so much for taking the time to speak to us today about generic drugs. We look forward to talking with the Office of Generic Drugs in more detail in future episodes.

Thanks for tuning in to “Q&A with FDA” podcast series. The full podcast and transcript of this recording is available at fda.gov/QAwithFDA. And if you have drug-related questions, reach out to us at [email protected].

Resources:

• Generic Drug Facts
• What Is the Approval Process for Generic Drugs?
• Generic Drugs: Questions & Answers
• From our perspective: The importance of the physical characteristics of generic drugs
• The Generic Drug Approval Process
• FDA Ensures Equivalence of Generic Drugs
• Securing the U.S. Drug Supply Chain: Oversight of FDA’s Foreign Inspection Program
• FDA's Strengthened Global Inspection Program Helps Ensure Generic Drug Safety