Regulatory Focus on Change Management

November was an exciting month for change management!

ICH Q12 “Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management” was adopted by the ICH in Singapore, which means Q12 is now in Stage 5, Implementation. Implementation should be interesting as concepts like “established conditions” and “product lifecycle management” which sit at the core of Q12 are still open for interpretation as Q12 is implemented in specific regulatory markets.

And then, to end the month, PIC/S published draft 1 of PI 054-1 “Recommendation on How to Evaluate / Demonstrate the Effectiveness of a Pharmaceutical Quality System in relation to Risk-based Change Management.”

This draft guidance is now in a review period by regulatory agencies. Which means no public comments, but it will be applied on a 6-month trial basis by PIC/S participating authorities, which include the US Food and Drug Administration and other regulators across Europe, Australia, Canada, South Africa, Turkey, Iran, Argentina and more.

This document is aligned to ICH Q10, and there should be few surprised in this. Given PIC/S concern that “ongoing continual improvement has probably not been realised to a meaningful extent. The PIC/S QRM Expert Circle, being well-placed to focus on the QRM concepts of the GMPs and of ICH Q10, is seeking to train GMP inspectors on what a good risk-based change management system can look like within the PQS, and how to assess the level of effectiveness of the PQS in this area” it is a good idea to start aligning to be ahead of the curve.

“Changes typically have an impact assessment performed within the change control system. However, an impact assessment is often not as comprehensive as a risk assessment for the proposed change.”

This is a critical thing that agencies have been discussing for years. There are a few key takeaways.

  1. The difference between impact and risk is critical. Impact is best thought of as “What do I need to do to make the change.” Risk is “What could go wrong in making this change?” Impact focuses on assessing the impact of the proposed change on various things such as on current documentation, equipment cleaning processes, equipment qualification, process validation, training, etc. While these things are very important to assess, asking the question about what might go wrong is also important as it is an opportunity for companies to try to prevent problems that might be associated with the proposed change after its implementation.
  2. This 8 page document is really focusing on the absence of clear links between risk assessments, proposed control strategies and the design of validation protocols.
  3. The guidance is very concerned about appropriately classifying changes and using product data to drive decisions. While not specifying it in so many words, one of the first things that popped to my mind was around how we designate changes as like-for-like in the absence of supporting data. Changes that are assigned a like-for-like classification are often not risk-assessed, and are awarded limited oversight from a GMP perspective. These can sometimes result in major problems for companies, and one that I think people are way to quick to rush to.

Much of my thoughts on implementing this can be found in my presentation on change management and change control.

It is fascinating to look at appendix 1, which really lays out some critical goals of this draft guidance: better risk management, real time release, and innovative approaches to process validation. This is sort of the journey we are all on.

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.

Sources

  • 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