FDA Q&A: Addressing Biosimilar Safety, AI in Drug Development, and Supply Chain Challenges

As the US unravels the results from the presidential election, a Q&A with an anonymous FDA spokesperson discusses efforts to reduce misinformation about biosimilars, emphasizing education and experience to build confidence in their safety. The FDA is also collaborating with international regulators to streamline biosimilar development and reduce costs, aiming to enhance global competition and accessibility. To build public trust, the FDA continues to educate the public on the rigorous approval process for biosimilars, ensuring they meet high safety standards.

Regarding drug shortages, the FDA works with manufacturers to address supply disruptions, particularly for glucagon-like peptide-1 (GLP-1) inhibitors. Lastly, artificial intelligence (AI) is increasingly used in drug development, with the FDA exploring its potential in enhancing process control and optimizing the pharmaceutical supply chain.

The Q&A provides insights into the FDA’s approach to managing biosimilar development, public education, and its collaboration with global regulators. | Image credit: Postmodern Studio - stock.adobe.com

This transcript has been edited for clarity and length.

The American Journal of Managed Care® (AJMC®): The FDA has made a number of efforts to clarify what interchangeability means and how to obtain it for biosimilars, including issuing new draft guidance to remove switching study requirements and a legislative proposal to deem all biosimilars as interchangeable, but confusion still remains. What more needs to be done to address misinformation about this designation and concerns about biosimilar safety?

FDA: Education is one of the main tactics for reducing misinformation; however, it is not a universal solution. Experience prescribing and using biosimilars combined with education seems to be most impactful and helps increase confidence in the fact that biosimilars and interchangeable biosimilars are both as safe and effective as their respective reference product. We are continuing to develop materials and conducting outreach to educate health care providers, patients, and payors about biosimilars.

AJMC: How is the FDA collaborating with international regulatory bodies to harmonize biosimilar approval standards, and what role does this play in improving accessibility and competitiveness for US patients?

FDA: The FDA has been working with global regulators through the International Pharmaceutical Regulators Programme Biosimilar Working Group (BWG) to discuss efforts to streamline biosimilar development, mainly focusing on the role of comparative efficacy studies (CES).

We led a workshop last September that included international regulators and industry. Participants in the public sessions discussed the utility and limitations of CES and biosimilar development challenges for international regulators and manufacturers developing biosimilars for global markets. The regulators-only sessions included discussions about jurisdictional requirements and current perspectives, risk-based considerations for when a CES is or is not useful, and then next steps for BWG. Harmonizing these approaches is important for helping support global development and reducing costs and increasing efficiency of biosimilar development, which ultimately should lead to greater competition and accessibility.

However, this is easier said than done, as there are varying opinions about the need for these types of studies. In addition, there are different regulatory requirements each regulatory authority must follow. The next steps are to refine and align on the details of a risk-based framework and publish a white paper for comment.

For more information about these efforts and the workshop summary report, visit: https://www.fda.gov/drugs/news-events-human-drugs/increasing-efficiency-biosimilar-development-programs-reevaluating-need-comparative-clinical.

AJMC: Public confidence in the FDA’s approval process is critical for the adoption of biosimilars and generics, especially in light of public skepticism during the pandemic. What steps is the FDA taking to enhance public trust in the safety and efficacy of these products and its approval processes?

FDA: As stated in our response to question 1 above, education is one of the main tools for reducing misinformation, and we continue our work of educating the public that FDA-approved biosimilars are safe and effective and that they undergo a rigorous approval process.

Ensuring public trust starts with the work manufacturers do to develop high-quality biosimilars and with the FDA’s work to review and assess the data and information submitted by the manufacturers. Accumulated evidence shows that there are no differences in efficacy, safety, or immunogenicity for patients starting on biosimilars or switching to biosimilars from a reference product. There is also an increasing amount of experiential data being published in the medical literature that supports the safety, efficacy, and quality of biosimilars.

All FDA-approved biosimilars undergo a rigorous evaluation so that health care providers and patients can be confident of the safety, effectiveness, and quality of these products. Having safe, effective, high-quality products helps to ensure public trust.

AJMC: As the FDA considers the potential for GLP-1 inhibitors to be extended to patients with kidney disease, how does the agency evaluate the demand for these medications in light of current shortages? What strategies are being implemented to balance the needs of patients with diabetes, obesity, and those with cardiovascular or kidney conditions?

FDA: The FDA recognizes the potential impact that lack of availability of certain products may have on health care providers and patients. Although the agency does not manufacturer drugs and cannot require a pharmaceutical company to make a drug, make more of a drug, or change the distribution of a drug, the FDA works closely with manufacturers and others in the supply chain to understand, mitigate, and prevent or reduce the impact of intermittent or reduced availability of certain products.

Importantly, regarding potential supply disruptions due to increased demand— while there is no requirement for companies to notify the agency of increased demand, the FDA continues to encourage companies to notify the agency when there is a spike in demand so that the FDA can work with companies early on to mitigate or prevent any impacts on availability.

AJMC: Could you elaborate on how AI is currently being implemented in drug application reviews, and what specific improvements in speed and accuracy the FDA has observed so far?

FDA: The FDA's Center for Drug Evaluation and Research (CDER) has seen an increase in the number of drug and biological product applications using AI components for drug development, with over 500 submissions with AI components since 2016. Common uses of AI applications in these submissions include clinical outcome prediction, covariate selection/confounding adjustment, pharmacometric modeling, anomaly detection, dose selection and optimization, and real-world-data (RWD) phenotyping and natural language processing, among others. 

CDER, in collaboration with the Center for Biologics Evaluation and Research (CBER) and the Center for Devices and Radiological Health (CDRH), published a May 2023 discussion paper, “Using Artificial Intelligence & Machine Learning in the Development of Drug & Biological Products,” to facilitate engagement, mutual learning, and discussion with interested parties on using AI in drug development. The FDA received over 800 comments from 65 entities on this discussion paper.

In March 2024, the FDA published a paper that describes 4 areas of focus for CBER, CDER, CDRH, and the Office of Combination Products (OCP) regarding the development and use of AI across the medical product life cycle, titled "Artificial Intelligence & Medical Products: How CBER, CDER, CDRH, and OCP are Working Together." CDER is now working with other centers on publishing a guidance document that focuses on considerations for using AI to support regulatory decision-making for drug and biological products.

There are many engagement options for interested parties to engage with the FDA for the use of AI. For example, manufacturers interested in employing AI for pharmaceutical manufacturing are encouraged to engage with CDER’s Emerging Technology Program. The FDA issued a discussion paper for public comment through November 2023 and held a workshop with the Product Quality Research Institute in September 2023 to engage interested parties on AI in drug manufacturing. At this workshop, 56 sponsors reported plans to engage with the FDA and submit a marketing application in the next 3 years for a product manufactured using AI.

Advanced analytics leveraging AI in the pharmaceutical manufacturing industry offers many possibilities for a variety of medicines, including, but not limited to, enhancing process control, increasing equipment reliability and throughput, monitoring early warnings or signals that the manufacturing process is not in a state of control, detecting recurring problem clusters, and preventing batch losses. The use of AI to support pharmaceutical manufacturing can be deployed together with other advanced manufacturing technologies (eg, process analytical technology, continuous manufacturing) to achieve desired benefits. AI could also be used to improve the reliability of the manufacturing supply chain through forecasting product demand, analyzing production schedules, estimating, and mitigating the impact of potential disruptions, and optimizing inventory.

As the FDA and other interested parties continue to gain experience across the drug development life cycle, we will better understand which applications are gaining prominence and the impact of such applications.