FDA CDER Quality Management Maturity White Paper

FDA’s Office of Pharmaceutical Quality (OPQ) in the Center for Drug Evaluation and Research (CDER) recently published a white paper proposal on the development of a rating system to measure a firm’s quality management maturity (QMM) as a way to mitigate drugs shortages and enhance the quality of finished drug products. These ratings would be publicly available. This is very aligned in thought to the recent NAS study recommendations in a paper commissioned by Congress.

This fits nicely within the recent draft guidance on metrics, and the two are definitely meant to fit together.

I am a big advocate of this work. I definitely want to see the particulars, but this is a long time coming and greatly needed. Frankly, the best way to make them happen is to require the QMM to be a factor in purchasing decisions for Medicaid/Medicare and the Veterans Hospitals (and more if possible).

The agency will be holding two workshops on quality management maturity, on May 24 and May 25. The first workshop will address CDER’s QMM program and the second will discuss quality ratings.

FDA Prescription Drug User Fee Renewals

Senators grill industry groups over FDA user fee agreements to fund the agency through 2027

I am not a huge fan of PDUFA. It puts the wrong cast on things. Fees are something I pay for a service, and it should put me in the driver’s seat (well except for airlines and everyone hates that). We tax for government services. Making the FDA dependent on pharma creates an imbalance in power that quite frankly shouldn’t exist.

The extent of statutorily required industry input in the drug regulation and reauthorization processes has increased as a result of the PDUFA reauthorization. The centrality of user fees to the modern FDA has led some observers to express concern that they have contributed to “corrosive capture” of the agency (i.e., a weakening of regulatory independence and of the ability of the agency to uphold traditional efficacy and safety standards) by shaping discourse about how drugs should be regulated or by enabling an unhealthy culture of closeness between the FDA and industry. Each successive PDUFA has required the FDA to be increasingly responsive to industry concerns.

The FDA plays a crucial role in protecting the health of the public while approving new treatments in a timely fashion. Thirty years of experience with user fees has shown that, in the face of inadequate public funding of the personnel budget of the FDA, increased funding by its egulated industries can indeed improve regulatory timelines. This increased speed has also raised questions related to the decisions being made and the growing reliance of the agency on financial support from the companies it regulates, as the user-fee model has fundamentally changed the way that the FDA interacts with industry. In a different political climate, adequate public funding in place of user fees would allow the FDA to continue its current performance levels while adding further confidence that the public remains the primary client of the FDA.

Descriptive versus Prescriptive Regulatory Guidance and Quality

There are two different ways that language is discussed and taught: descriptive grammar vs. prescriptive grammar.

Prescriptive grammar describes when people focus on talking about how a language should or ought to be used. Prescriptive grammar tells you how you should speak, and what type of language to avoid. This is commonly found in English classes where the aim is to teach people how to use language in a very particular (typically described as ‘proper’ or ‘correct’) way.

Descriptive grammar, on the other hand, focuses on describing the language as it is used, not saying how it should be used. For example, think about a prescriptive rule like Don’t split infinitives. A descriptive grammarian would see a sentence like “To boldly go where no man has gone before” and would try to describe how the mental grammar can cause that ordering of words, rather than saying that the surface form is faulty due to prescriptive rules (which would require the sentence “To go boldly where no man has gone before”). Linguistics takes this approach to language.

We have a similar thing in pharmaceutical regulations, often seen by how the FDA looks at certain issues and how the EMA and PIC/S looks at them.

For example, the FDA is proceeding with draft guidance on setting up inspection testing programs for detecting visible particles in injectable drugs is meant to address this issue from a good manufacturing practices (GMP) standpoint. This is mostly a descriptive approach, as it sets a lot of desirable outcomes but you few strong requirements for how to get there.

The EMA has a draft Annex 1 which lays out a pretty strong set of requirements for exactly how to perform contamination control, telling you exactly what to have and what it should look like.

The difference can be pretty evident when you hear the different regulators discuss their approaches. I’ve certainly heard more than one present or former FDA regulator say that adopting Annex 1 isn’t necessary because the GMPs already have the requirements built in.

You see a similar approach when it comes to QPs or the GCPs.

The prescriptive versus descriptive difference even comes up during inspections. Most people will talk about how the FDA focuses on artifacts and the EMA goes deep on the process.

A similar divide can happen in your quality system where you see different approaches (often a hodge-podge) between controlling the bad and promoting the good.

Being a pragmatist I often see benefits in both approaches (the same way I find value navigating between FDA and EMA approaches). The key thing is being deliberate about it.

Increasing Transparency in Drug/Medical Device Manufacturers

The National Academies of Science, Engineering and Medicine (NASEM) has published a report on resiliency in the medical supply chain that calls for the US Food and Drug Administration (FDA) to publicly disclose the location of all manufacturing facilities that supply ingredients and parts for pharmaceuticals and medical devices approved in the US.

The report recommends FDA publicly disclose information on drug sourcing, manufacturing quality and volume, and capacity for medical products approved for sale in the US.

“The manufacturer for a pharmaceutical drug should be required to publicly disclose the manufacturing location, in particular the FDA Establishment Identifier (FEI), the city, and the country for the finished dosage form (FDF), active pharmaceutical ingredient (API, major excipients, and major packaging and delivery devices for all pharmaceutical drugs sold in the United States,” said a report summary.

The same recommendation also applies to devices; device manufacturers should publicly disclose the manufacturing location in the FEI, the city, and the country involved in the device’s manufacturing and final assembly.

The report also recommends FDA make its risk-based site selection model scores publicly available. Wow, not only would that be good for consumers, I’d love to know where my sites fall in on that scoring.

Hurry up and put this recommendation in place!

Transparency is a good thing and it is shown to increase consumer safety. It is a problem that even a fairly knowledgeable industry professional like myself cannot figure out where generics are manufactured without making a few phone calls and shaking down my friend network. And even then, I’m never positive that I understand where my family’s medicine is coming from and the status of the sites involved in manufacturing and distributing the product.