Updates on the Bioequivalence Studies for Drugs Submitted to Under an ANDA

From time to time, the Food and Drug Administration (FDA) offers a lot of updates to its materials and practices, and any person involved with the industry needs to stay alert for new releases, educational events, and training. This can focus on highly specific topics that are especially important for investigators, clinical personnel, sponsors, and individuals that are otherwise engaged in the pharmaceutical industry. One aspect of this is the need to keep up with updates and changes that the FDA makes to ensure better results, high-quality data, and a smooth approval process for all kinds of drugs. FDA has focused especially on changing and improving the process associated with generic drugs that are highly important for public health.

In 2021, FDA revised the draft guidance for Bioequivalence (BE) Studies with Pharmacokinetic Endpoints for Drugs Submitted Under an ANDA; providing an update to the current recommendations, assistance to ANDA applicants and supplements, and, overall, to support the patients’ access to lower cost and high-quality medications and drugs. (1)

What is ANDA? ANDA stands for Abbreviated New Drug Application, and it involves submission to FDA for a new drug. Last month, (February 24, 2022), the FDA hosted a webinar titled Bioequivalence Studies with Pharmacokinetic Endpoints for Drugs Submitted Under an ANDA to discuss agency thinking on some other points and answered questions related to this updated and the revised guidance.

It is worth noting the previous guidelines came out in 2013, which signifies a big shift in the process. The webinar is a must for people involved in the generic drug industry, current applicants and potential applicants, regulatory reviewers, and policymakers. The webinar is a more specialized topic with a wide reach thanks to the focus on generic drugs, as bioequivalence studies most commonly are associated with the possibility of releasing more generics. (1)

In order to understand what this centers on, it is important to understand what bioequivalence is. Bioequivalence study with pharmacokinetic endpoints of a drug product is essential for ANDA and the improvement of pharmaceutical readiness in the pharmaceutical business. (2) It is usually used to establish similarity between a generic drug and a reference drug, which leads to establishing if there are no significant differences in the availability of the active ingredient at the site of action of the drug. (3) Furthermore, bioequivalence studies are very important to expand the use of nonspecific medications, reduce the costs for the patients and users, which has a big impact on public health but also on the pharmaceutical industry gain access to FDA support and fast approval and market release.  (4)

So, what are some of the major changes associated with the 2021 revision of the guidelines? Firstly, it updates and clarifies content on Reference Listed Drug (RLD) and Reference Standard (RS) in the Orange Book, clarifying the difference between the two and their application. The second major change involves an expansion in regards to sex (male/female), age (pediatric and elderly)， and other sociodemographic characteristics. For instance, studies should justify the use of a single-sex study sample or include comparable samples of men and women. This was introduced due to studies that did research on single-sex samples for products meant to be used with men and women both. The guidelines also suggest using more participants over 60 for drugs meant to be used by the elderly and justify pediatric use if the study was carried out with adults only. Another change involves demonstrating additional strengths for modified-release drug products based on the mechanism of release and dissolution profile similarity. The guidelines add new sections on other dosage forms, such as sublingual or transdermal, and adds a section on alternative forms of administration, such as a nasogastric tube. There are new sections on handling outliers and a section in the appendixes for highly variable drugs and their scaled average BE analyses. It also removes the section of Orally Administered Drugs Intended for Local Action from the previous draft guidance. (5)

What are the implications of these? The meeting offers guidance for anyone looking to introduce or research generic drugs. While the changes require a better grasp on the guidelines, they outline the importance of having high-quality research that is up to date with the current FDA regulations in order to receive the proper support, recognition, and permits as well. If you want to know more about generic drugs and different types of bioproducts, Pharmasources would be a great choice.

This webinar will be especially useful for potential and current applicants who might be affected by the changes and who need to have a strong grasp of current guidelines and regulations. The webinar offers a simple introduction to the topic and the changes, as well as the more intricate details and the resources to discover more information. You can find all the related information and the current guidelines that were introduced in 2021 and are being adjusted and shared widely by FDA. It is possible to seek assistance from FDA directly for support with the application process and all the related submissions and paperwork.  

The meeting might sound highly specialized, but it has many benefits for the general public as well. Today, most people can benefit from lower-cost medication, such as generic drugs, that can be used for a variety of conditions. Generics are very significant for public health because they provide more affordable options for drugs across the board, and FDA has been working to encourage more investigators to study these drugs and to release more generic options.

The content of the meeting is also freely available on YouTube and via the website of FDA. It is meant for more professional audiences and makes heavy use of professional terms, however, it also provides an introduction to the topic of bioequivalence and the existing guidelines, the changes and the rationale behind them, as well as a panel of FDA experts who address the central questions behind the changes and associated with the topic. 

References

1.  FDA. (2022). Bioequivalence Studies with Pharmacokinetic Endpoints for Drugs Submitted Under an ANDA. https://www.fda.gov/drugs/news-events-human-drugs/bioequivalence-studies-pharmacokinetic-endpoints-drugs-submitted-under-anda-02242022?utm_medium=email&utm_source=govdelivery

2.  https://www.fda.gov/regulatory-information/search-fda-guidance-documents/bioequivalence-studies-pharmacokinetic-endpoints-drugs-submitted-under-abbreviated-new-drug

3.  Reddy, S.P., Ni, C.S., & Wu, J.J. (2016). Chapter 14 – Biosimilars. https://www.sciencedirect.com/science/article/pii/B9780323447973000141).

4.  Rita, B., & Akhilesh, T. (2015). Journal of Pharmaceutics and Nanotechnology, 3, 89-96.

5.  FDA. (2022). Bioequivalence Studies with Pharmacokinetic Endpoints for Drugs Submitted Under an ANDA. https://youtu.be/jGffUS-8JVA

About the Author:

Lin Zhang, M.D., senior director of a health care industry company in the United States. With the experience in clinical medicine, biotechnology, health industry and other fields, he is responsible for the research and development of plant medicine, functional food and health products. He was a clinician and worked for the National Cancer Institute, FDA and the National Cancer Center of Japan for many years.