Thank you, CAPT. Stodart. I am pleased to once again be a part of this important workshop, organized by the Office of Generic Drugs and Office of Pharmaceutical Quality, in collaboration with the office of Small Business and Industry Assistance. 

In my mind, there are few things as important to our work in health care as stimulating and support innovation in generic drug development.  To this end, I also want to thank the many developers and other stakeholders who have joined today’s discussion, as well as the support provided by industry to the generic drug development program to help make this program possible. 

The word “innovation” is an important one, and while there is sometimes a tendency to overuse it, when it comes to generic products I think that is an extremely appropriate description and aspect of our work in supporting advances in this industry.  

Certainly, the impact and benefits of generic products and the competition they produce to help lower costs and increase accessibility for patients cannot be overstated.  According to the Association for Accessible Medicines, in 2021 the health care system saved $366 Billion thanks to generic prescription medicines.  

Americans clearly appreciate and take advantage of these savings.  Generics today represent 91% of prescriptions filled, accounting for 18% of all prescription drug spending.  The value that patients place on generic is why providing access to affordable, safe, effective, and high-quality generic medicines  is a public health priority for the FDA.  

There are taken numerous actions we are taking to support this.  For example, OGD has continued its implementation of the FDA’s Drug Competition Action Plan (DCAP). Last October, we published draft guidances and product-specific guidances that provided recommendations for physicochemical and structural characterization tests, in vitro release test (IVRT) studies, and in vitro permeation test (IVPT) studies for topical generic drug products.  These guidances will be discussed in today’s workshop.

One of the key aspects of our work to promote innovation in the generic drug space is our engagement with developers. Early communications can help reduce a generic drug product’s time in the pipeline from concept to development, to market input, by strengthening development programs, improving FDA assessment efficiency, and enabling better ANDA submissions. 

In FY 2023 the FDA held numerous addition scientific meetings with industry as part of the first year of the second reauthorization of the Generic Drug User Fee Amendments, (or GDUFA III).  Many of these meeting were related to complex products, which are harder to develop and so those communications can reduce time and increase efficiency in the development process.  Those meeting occurred before ANDA submission, during ANDA review, as well as after a Complete Response action.  

GDUFA III also included new goal dates added for publishing product-specific guidances (or PSGs) for newly approved complex products.  Industry can also request to meet with FDA if they have started in vivo bioequivalence studies that are different from FDA’s recently published new or revised PSGs

Since I mentioned GDUFA, let me focus on one of the most important components of GDUFA since it began more than 10 years ago.  That is its emphasis on science and research, which is in line with the FDA’s focus on, and application of the best available science to help ensure the most definitive finding, results, and decisions.  

The GDUFA Science and Research Program is designed to help enable the FDA to address particularly challenging scientific issues for product-specific guidance development and to communicate with applicants through pre-ANDA meetings to help clarify regulatory expectations for prospective applicants early in the generic product development cycle.  

Let me briefly highlight one recently approved generic product that I think exemplifies the meaning of FDA-supported scientific innovation and what can come out of years of GDFUA supported research.

In July 2023, the FDA approved the first generic to Vivitrol. Vivitrol is a one-month extended-release injectable naltrexone that is used to help people maintain abstinence while recovering from opioid or alcohol dependence. These and other naltrexone drug products are an important tool in treating substance abuse. 

This is also the first generic that utilizes biodegradable PLGA [poly(lactide-co-glycolide)] polymer microsphere technology.  The PLGA microsphere formulation gives rise to the month-long extended release of naltrexone. Although a more complex product to develop than a once daily tablet, the once-a-month extended-release injection reduces the dosage regimen frequency and therefore may be advantageous in helping ensure patient compliance, which is critical to reducing potential relapse.

The complexity of developing and manufacturing products that utilize controlled release PLGA technology is exemplified by the limited number of products that have been approved even though PLGA is a well-known and highly tunable material to create extended-release formulations. Since the first FDA approved PLGA product more than 30 years ago, there have been approximately 12 other approved products, and this is the first generic product that has PLGA. 

As with all companies developing a PLGA product, this generic had to address several complex challenges in developing, manufacturing, and demonstrating that their naltrexone microsphere product is therapeutically equivalent to Vivitrol. 

OGD initiated its first research activities on PLGA based long-acting products in 2013. The two main focuses of these research activities were to develop 1) analytical methods that can facilitate the reverse engineering, characterization, and selection of PLGA, which is a critical first step for generic development; 2) in vitro drug release testing methods that improve understanding on how the drug is released from the formulation and how different polymer and manufacturing induced characteristics affect drug release behavior.  These methods have been included in FDA’s product-specific guidance and have been adopted by generic industry for supporting their generic development. In addition, the research on polymer and formulation characterization also enabled FDA to develop assessment criteria to make the generic pathway feasible for PLGA-based products.

The approval of the first generic Vivitrol provides a good model for future generic development of PLGA-based products. GDUFA research will continue to explore how modern analytical methods and modeling tools can be helpful for guiding product development and bioequivalence study design. The improved understanding of the design space for this group products will provide a good scientific foundation to explore novel approaches for product development and bioequivalence testing.  
In today’s workshop, you will have the opportunity to take a deep dive into some of the many ways that we work to modernize generic drug product development and enhance our science, policy and business processes in support of this goal.  

In addition to strengthening our process to increase interactions with industry to make submissions more complete and reviews more efficient, these modernization efforts include developing efficient bioequivalence approaches for products that eliminate unnecessary human studies and provide scientific approaches for generics for complex products and helping industry maximize the use of the 505(j) pathway and gain clarity around how to develop generic versions of complex products such as generic drug-device combination products.   

Before I close, I want to mention one other important facet of Generic Drug Development, which is its global significance and impact.   As we all know, the development of drugs today, including generic drugs, is part of a global enterprise, and the product of a global supply chain produced with the intent to market in multiple countries around the world.

I’m pleased to see that one of today’s session will focus on the topic of “Global Collaboration to Support Efficient Generic Product Development & Regulatory Assessment.” Though it is not the primary focus of the discussion, I think it’s important to mention one aspect of this dynamic, which is the challenge of drug shortages, which can be very frustrating and undermine the underlying goal of increased accessibility of these often life-saving products. 

As you know, the FDA doesn’t make drugs, and we can’t tell manufacturers which or how much of a drug to produce. But we do try to anticipate shortages and take action to prevent them, including working with drug makers that submit applications for new manufacturing capacity to increase supply of existing drugs or to facilitate market entry for new drugs. In addition, we have encouraged the adoption of advanced manufacturing technologies and mature quality management practices to help avoid or mitigate drug shortages. We also partner across government, academia, health systems, and industry to strengthen and diversify the supply chain and identify and address supply chain vulnerabilities and accelerate domestic manufacturing. 

There are many reasons for drug shortages, but one I want to mention involves manufacturers of older generic drugs, who sometimes face intense price competition, uncertain revenue streams, and investment requirements to maintain quality conditions.  U.S. patients benefit from access to less expensive generic drugs. But if the basic economics of the generic drug market are not fixed, more patients will be impacted by these shortages.  

This is just one of the many topics you will be addressing in your discussions today.  The diversity of generic products is enormous, as the meeting agenda makes abundantly clear. You’ll have discussions related to complex APIs, complex injectable products, topical drug products, ophthalmic emulsion products, orally inhaled drug products, noteworthy guidance development and updates, new processes, research and assessment tools, common issues related to the ANDA process, and more.

In short, you’ve got a full plate today, and we are here to support both these discussions and the developments that we hope flow from them.  By working in mutually supportive ways, we can translate science to approval and continue to deliver timely, high quality, safe, affordable, and effective generic products to the public. 

Thank you again for your participation and I hope you have a engaging and productive day.