Addressing FDA’s Biggest Challenges

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.

As the Inflation Reduction Act (IRA) did for other critical industries like semiconductor manufacturing, the U.S. should invest in reshoring 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. 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. Wosińska, 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.

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 CivicaRx 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.

SOURCES:

1. https://www.pharmamanufacturing.com/production/unit-operations/article/55042959/mining-the-reshoring-rush-targeting-government-spending
2. https://media.licdn.com/dms/document/media/D5610AQHJjtHaCNCd2Q/ads-document-pdf-analyzed/0/1727193868014?e=1727913600&v=beta&t=0UQWZY2Ns3lyDroM_BObxSFgDyazIRO9qn6SaAVxqBA
3. https://www.armiusa.org/wp-content/uploads/2022/07/ARMI_Essential-Medicines_Supply-Chain-Report_508.pdf
4. https://curiaglobal.com/insights/the-shift-toward-us-pharmaceutical-manufacturing/
5. https://energycommerce.house.gov/posts/e-and-c-republicans-press-fda-over-inadequate-inspection-of-drug-manufacturing-in-india-and-china
6. https://www.pharmaceutical-technology.com/analyst-comment/manufacturing-inspections-down-china/?cf-view