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.

John Oliver on Medical Devices

I firmly believe that quality and ethics go hand-in-hand, and frankly it shakes some of my confidence on my profession when I read of organizations that supposedly subscribe to quality principles and standards (such as the ISOs) still not meeting the grade.

There are four widely accepted principles in biomedicine, which applies equally to medical devices and pharmaceuticals:

  • Principle of respect for autonomy
  • Principle of nonmaleficence
  • Principle of beneficence
  • Principle of justice

It seems a failure of ISO 13458 that adherence to this quality standard does not lead to results aligned to these four principles. It should surprise no one who knows me that this is one of the reasons I support strong regulations in this space.


  • Beauchamp T, Childress J. Principles of Biomedical Ethics, 7th  Edition. New York: Oxford University Press, 2013

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

FDA launching pilot program on established conditions

The FDA has announced a pilot program to “propose explicit established conditions (ECs) as part of an original new drug application (NDA),
abbreviated new drug application (ANDA), biologics license application
(BLA), or as a prior approval supplement (PAS) to any of these.”

As the FDA mentioned, this is a followup of two draft guidances: The 2015 FDA ‘‘Established Conditions: Reportable CMC Changes for Approved Drug and Biologic Products’’and the draft Q12.

It is exciting to see Q12 move forward. We can argue about its imperfections, but at the end of the day this is a big step for the industry.

Avalanche or Roadblock: FDA Publishes Flurries of Biologic and Biosimilar Materials

The proposed technical correction regulation, the other two guidance documents, and the list deal with the transition of certain biological products from NDAs to BLAs.  Starting with the simplest, the proposed (so-called) technical correction would amend the definition of “biological product” in 21 C.F.R. § 600.3(h) to conform to the definition implemented in the BPCIA and provide an interpretation of the statutory terms “protein” and “chemically synthesized polypeptide.”  FDA calls it a “technical correction” in the proposed rule, but this isn’t really technical, nor is it a correction.  Indeed, it reflects a significant change to the definition of biological product because the rule would replace the phrase  “means any” with the phrase “means a” and would add the phrase “protein (except any chemically synthesized polypeptide)” to the definition of “biological product.”  Consistent with the April 2015 Questions & Answers guidance, the proposed rule would amend 21 C.F.R. § 600.3(h) to further define protein as any alpha amino acid polymer with a specific defined sequence that is greater than 40 amino acids in size, and the term chemically synthesized polypeptide as any alpha amino acid polymer that: (1) is made entirely by chemical synthesis and (2) is greater than 40 amino acids but less than 100 amino acids in size.  Given that that FDA has been using this definition since the publication of the April 2015 final version of this Question and Answer guidance,  this proposed regulation is unlikely to catch industry by surprise.  But this is just one of multiple steps FDA is taking to prepare industry for the March 2020 transition of certain biological products approved under NDAs to BLAs.
— Read on www.fdalawblog.net/2019/01/avalanche-or-roadblock-fda-publishes-flurries-of-biologic-and-biosimilar-materials/