Driving for Mature Quality Organizations – FDA recent perspective

Theresa Mullin, FDA’s Associate Director for Strategic Initiatives for the Center for Drug Evaluation and Research recently gave a presentation “Update from FDA CDER” at GMP by the Sea (I need to go to that that some-year).

As in other FDA presentations this presentation summarized the Quality Metrics Research Final Report by the University of St. Gallen as the appropriate steps to ensure quality maturity:

  1. Optimized set-up and cleaning procedures are documented as best practice process and rolled out throughout the whole plant.
  2. A large percentage of equipment on the shop floor is currently under statistical process control.
  3. For root cause analysis, the firm has standardized tools to get a deeper understanding of the influencing factors for problems.
  4. Goals and objectives of the manufacturing unit are closely linked and consistent with corporate objectives and the site has a clear focus.
  5. Manufacturers have joint improvement programs with suppliers to increase performance.
  6. All potential bottleneck machines are identified and supplied with additional spare parts.
  7. For product and process transfers between different units or sites,standardized procedures exist that ensure a fast, stable and compliant knowledge transfer.
  8. Charts showing the current performance status such as current scrap rates and current up times are posted on the shop floor and visible for everyone.
  9. The firm regularly surveys customers’ requirements.
  10. The firm ranks its suppliers and conducts supplier qualifications and audits.

This are some pretty low hanging fruit. They are also the pretty necessary in any organization, not just pharmaceuticals.

There was also a little discussion on the use of Q10 that really makes me wish I had been there to hear exactly what was said. I hope it was “Just freaking implement it already.”

In general, useful slides, I recommend going and checking them out.

Quality Challenges of Accelerating Investigational Products

Last November, officials from the European Medicines Agency (EMA) and US Food and Drug Administration (FDA) met with industry representatives in London to discuss the various quality challenges that arise when the development of investigational products is accelerated .

The report was recently published, and can be found here.

The workshop discussed process validation, control strategies, good manufacturing practice (GMP) compliance, comparability, stability and regulatory tools of early access approaches. Throughout they discussed two elements:

  • Scientific which includes technologies and scientific concepts or principles for development, manufacture and quality risk management, which may or not be present or implied in existing guidelines. Examples include concurrent validation, new modelling methodologies, new analytical techniques, etc.
  • Regulatory/procedural tools are described in the legal, regulatory framework and can be specific to PRIME (or Breakthrough Therapies) (e.g. kick-off meetings) or generally applicable [e.g. Post-approval change management protocols (PACMPs), recommendations, scientific advice (SA)].

I strongly recommend reading the report in it’s entirety.

FDA enforcement actions decline

Investigative report on FDA enforcement under Trump from Science’s news department shows a steep decline in enforcement actions.

I’ve noticed this, but it is good to see actual data behind it.

I’ll be frank, it would take a lot of data that does not exist to make me feel the companies under the FDA’s oversight have gotten better as a whole. Anecdotally, well there are a lot of less than sterling players out there.

I have mostly questions:

  1. Have we seen this trend in previous Republican administrations, and is it more pronounced here?
  2. Is there any evidence that the increase under Obama was a reaction to the previous Republican administration? Are we in a cycle of lax and then tougher enforcement that maybe evens out? That sort of variance is not healthy.
  3. What, if any data, will we be able to see about impact? There are certainly concerns that the FDA has not done enough. Will this be exacerbated?
  4. What will it take for this to start affecting the mutual recognition agreements with the EU and other major bodies?

The FDA and Prescription Drugs: Current Controversies in Context

Harvard is offering a free course though edX on how the FDA regulates pharmaceuticals and explore debates on prescription drug costs, marketing, and testing.
— Check out  www.edx.org/course/the-fda-and-prescription-drugs-current-controversies-in-context

According to the syllabus, the course will be set up with six modules:

Module 1: Overview and history of the FDA
Module 2: Drug development and approval
Module 3: Drug pricing in the United States
Module 4: Marketing strategies
Module 5: Post-approval evaluation
Module 6Emerging medical technologies

An Analysis Of FDA FY2018 Drug GMP Warning Letters

BioProcess Online has a nice summary of the drug GMP warning letters issued in FY2018, as well as a comparison of trends since fiscal year 2013.
— Read on www.bioprocessonline.com/doc/an-analysis-of-fda-fy-drug-gmp-warning-letters-0003

Data Integrity definitely continues to be a theme, and I agree that we are seeing a growing trend around process validation. I also think root cause investigations was a theme of 2018 that we are going to be seeing a lot more of.