Addressing FDA’s Biggest Challenges
Redica Systems
Empowering the life sciences champions of safety and quality with actionable data intelligence.
Author: Scott Sherrill , VP of Data Operations, Redica Systems
EDITOR'S NOTE: This was originally published on November 15th, 2024. The U.S. presidential election had just occurred and the one thing that was clear was that FDA would face potentially aggressive shake-up in 2025. That seems to be playing out. Our ideas about how to fix some of the FDA's biggest challenges have not changed however. We've made a few small updates to the original piece since.
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Keeping medicines safe, effective, and available for all Americans is an important goal with broad bipartisan support.
However, the agency tasked with achieving that goal, the U.S. Food and Drug Administration (FDA), is facing increasing challenges. FDA leaders have recently been called before Congressional committees to testify on matters ranging from preventing drug shortages to preventing poor-quality products from getting imported into the United States. These are highly interrelated challenges.
Preventing drug shortages is largely outside of the purview of FDA. Ensuring supply can meet demand is left up to industry. FDA’s primary responsibility is to ensure a high level of safety, effectiveness, and quality in the drug products that make it to market. The issue is that in a consolidated, global supply chain, if FDA interrupts supply from a major player due to quality concerns, that can lead directly to a drug shortage.
The global pharmaceutical supply chain has become increasingly reliant on facilities based in India and China. The United States Department of Health and Human Services (HHS) reported that 73 percent of establishments manufacturing active ingredients and 52 percent of those manufacturing finished drugs for the U.S. were located overseas as of March 2021. Approximately 32 percent of generic drugs and 45 percent of active pharmaceutical ingredients are from India and China specifically. FDA isn’t resourced, or sometimes able at all, to adequately validate that “current good manufacturing practices” (CGMP) are being followed in manufacturing facilities in countries like China and India.
There’s a variety of reasons why FDA isn’t able to conduct as robust inspections in India and China as they are in the United States. One of the more dire recent examples is that China has raised the risk of conducting any local inspections with new draconian espionage laws. After a Japanese executive from Astellas Pharma was arrested on espionage charges in 2023 in China, there’s a legitimate concern that FDA investigators may end up arrested for doing their jobs.
By contrast, FDA inspections on U.S. facilities are far more reliable. Those inspections are unannounced, and the inspection records are made available to the public. FDA investigators are mostly free from intimidation or arrest during domestic inspections.
FDA should be given a lot of credit. They are the gold standard of health regulators around the world for good reason. Transparency and accessibility of data is one of the reasons that the FDA is properly seen as the leader for tough but fair inspections – everyone is held to the same standards, and those standards are applied in inspection records that are accessible to all who ask, via the Freedom of Information Act.
They have maintained a high level of oversight and protection despite repeated budget cuts and the necessary curtailment of in-person inspection during the COVID-19 pandemic.
Better equipping FDA to achieve their mission is not simply a matter of increasing their resources. A bigger budget would certainly help them conduct more inspections in the U.S. and countries like India, but it won’t solve the difficulty of conducting inspections in China.
To solve that problem, we need to have a strategic plan to reduce the amount of pharmaceutical ingredients and finished products that come from China. Less reliance on importing those goods from anywhere outside the U.S. border would be tremendously helpful.
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As the Inflation Reduction Act (IRA) did for other critical industries like semiconductor manufacturing, the U.S. should invest in re-shoring (or at least near-shoring) advanced CGMP-compliant pharmaceutical manufacturing capacity for both branded and generics. Generics are a critical element in reducing the cost of healthcare for Americans, but they are also currently plagued by quality problems more than branded versions.
In generics, price is key, which is why quality often suffers. The 纽约时报 recently ran a piece detailing the rare public dissent regarding China's domestically produced drugs program. In summary, a race to the bottom on price usually results in declines in product quality. There is concern amongst some that the U.S. IRA will have a similar impact on the U.S. supply of generics.
It is possible, however, to raise the quality of generics through reshoring without destroying price competitiveness. The answer lies in scale, operational streamlining, and advanced manufacturing techniques (AMT).
There are complications with re-shoring that need to be addressed. Marta E. Wosinska, Ph.D. , former director of economics staff at the U.S. Food and Drug Administration (FDA) Center for Drug Evaluation & Research, has raised several, such as the cost and complexity of the scope. The U.S. would have to re-shore all aspects of the finished dosage form (FDF), including active pharmaceutical ingredients (API), excipients, and so on, in order to be genuinely self-reliant. If we onshore APIs, but we don’t do the same for key excipients, we remain vulnerable.
In a conversation with Redica Systems, Dr. Wosinska said, "To be fully self-reliant, we need to onshore not just excipients but all the precursors to API. The scope of what we would want to onshore is massive, so we need to think about how to friendshore."
The U.S. government, to its credit, has been giving the issue of life sciences supply chain vulnerability its due attention. The Biden administration issued an executive order on supply chain resilience in February 2021, and since then, we’ve seen developments like the Mapping America’s Pharmaceutical Supply (MAPS) Act, and the Biosecure Act. The Biden administration is continuing the work of the 2021 executive order.
The government did recently provide a grant to a U.S. company called Civica Rx that “emphasizes U.S. sourcing whenever possible, with the European Union and Canada as second choice. Finished drugs or active pharmaceutical ingredients are not sourced from China unless there is no other option.”
It should be noted, however, that even the E.U. and Canada are less transparent about their quality monitoring results than FDA.
And while FDA leads the world in terms of transparency and usability of data, there is progress yet to be made. Improving the structure of their data and the accessibility of that data via modern methods like an application programming interface (API) would help make that data far easier to analyze.
These efforts would go a long way toward ensuring that U.S. citizens have affordable access to safe, effective medicines.
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Great article that already feels out-of-date as we struggle with the events of the last few days.