Validation, Disposition and Change Control

A colleague asks “How do you manage changes and disposition when doing lon-term validation or specification setting in multiple markets?”

Process map for change control, validation, regulatory and disposition

Perhaps it is a cleaning validation, or a major process change, or a new filter or raw material. You need to be able to disposition product against a change control to some markets but not all.

It is important to realize that changes become effective at multiple times. Looking back on the post “Changes become Effective” we are managing after change-in-use where the regulatory approval is not being simultaneously gated and product will be sent to market on a case-by-case basis.

The change control contains a corresponding regulatory assessment with required variations for all impacted markets, and a disposition strategy aligned with validation activities. With action items (e.g. work, tasks) in the change control for ongoing evaluation of lots impacted by study.

That disposition strategy might include evaluation of data vs acceptance criteria for each lot via checklist (or other tool) included in disposition packet; or an evaluation of data through change control task and disposition references change control. They are pretty similar in results and it more ends up being a record management preference.

High level match between regulatory and inventory

29 questions to ask about your change management/change control system

While these questions are very pharma/biotech specific in places, they should serve as thought process for your own system checkup.

  1. Is there a written SOP covering the change control program that has been approved by the Quality Unit?
  2. Do procedures in place describe the actions to be taken if a change is proposed to a starting material, product component, process equipment, process environment (or site), method of production or testing or any other change that may affect product quality or reproducibility/robustness of the process?
  3. Does the SOP ensure that all GMP changes are reviewed and approved by the Quality Unit?
  4. If changes are classified as “major” or “minor,” do procedures clearly define the differences?
  5. Does your change management system include criteria for determining if changes are justified?
  6. Are proposed changes evaluated by expert teams (e.g. HSE, Regulatory, Quality…)?
  7. Is there a process for cancelling a change request prior to implementation? And Is a rationale for cancellation included?”
  8. Does your Change control management site procedure describe clearly the process to close a change request (After all regulatory approvals…)?
  9. Are any delays explained and documented?
  10. Is there a written requirement that change controls implemented during normal or routine maintenance activities be documented in the formal change control program?
  11. Is your change management system linked to other quality systems such as CAPA, validation, training?
  12. Does your change management system include criteria for determining if changes will require qualification/requalification, validation/revalidation and stability studies?
  13. Are “like for like” changes (changes where there is a direct replacement of a component with another that is exactly the same) clearly defined in all aspects (including material of construction, dimensions, functionality,,,) ? Are they adequately documented and commissioned to provide traceability and history?”
  14. Is there an allowance for emergency and temporary changes under described conditions in the procedures?
  15. Are the proposed changes evaluated relative to the marketing authorization and/or current product and process understanding?
  16. Does your change management system include criteria to evaluate whether changes affect a regulatory filling?
  17. When appropriate are regulatory experts involved? Does the regulatory affairs function evaluate and approve all changes that impact regulatory files?
  18. Are changes submitted/implemented in accordance with the regulatory requirements?
  19. Is there a defined system for the formalization, roles and responsibilities for change control follow-up?
  20. Is the effective date of the change (completion date) recorded and when appropriate the first batch manufactured recorded?
  21. Is there a periodic check of implementation of Change controls?
  22. Following the implementation, is there an evaluation of the change undertaken to confirm the change objectives were achieved and that there was no adverse impact on product quality?
  23. Is all documentation that provides evidence of change, and documentation of requirements, controlled and retained according to procedure?
  24. When necessary, are personnel trained before the implementation of the change?
  25. Are change controls defined with adequate target dates?
  26. If the change control goes beyond the target date, is there a new date attributed, evaluated and documented by Quality Assurance?
  27. Are there routine evaluations of the Change controls and trends (number, Change controls closure, trends as defined)?
  28. Are changes closed on due date ?
  29. Are the Change controls and follow-up formalized in a report and/or periodic meetings?

These sort of questions form a nice way to periodically checking up on your system performance and ensuring you are moving in the right direction.

Value of the ASQ

If I were to ask a hundred of my peers “How did you get into quality,” I would probably hear 100 different stories (with of course some commonalities). And yet, quality is definitely a distinct set of expertise and practice.

When I try to describe my job, I often find myself breaking down what I do into categories (I’m a project manager, a trainer, a problem solver, risk manager, a facilitator, a puzzle solver, a detective, etc). some of these are professional paths on their own, others not so much.

It is for this reason that I am a huge fan of the ASQ’s Quality Body of Knowledge, as it does a good job of uniting what we do. Sure, it’s not perfect but it is an excellent framework to build an understanding of just what a quality professional can bring to the table, as well as great development path.

One of the many things I love about this is the ability to learn from folks no matter what their industry. This cross-pollination is vital to innovation. And having the QBOK there gives a framework for common discussions.

With the QBOK goes a technical knowledge bolt-on. For example, in my case pharmaceuticals (strong) and medical devices (average).

The ASQ certification board I believe gets it wrong by calling these specific technical certifications “Leadership.” There is nothing leadership centric by getting the CPGP, for example.

I think we’re better breaking these certifications into QBOK core (e.g. quality improvement associate, quality process analyst, manager of quality), specific skills (e.g. six sigma, haccp, quality auditor, reliability and calibration) and then industry specific (e.g. CPGP, biomedical auditor)

As the ASQ goes through its current transformation, I hope the leadership and members remember the strength of the QBOK, work to enshrine it in everything the organization does, and continues to refine it. This is the value of my ASQ membership.


ASQ – Pharmaceutical GMP Professional Certification

The ASQ’s CPGP certification is a very broad body of knowledge that covers regulatory agencies, to facilities and utilities, to testing, to release. In short, about every aspect of a GMP facility.

I am maybe the only person I know in the field who has this certification. I don’t know the details, but uptake does not seem as high as other certifications I am aware of. Yesterday at lunch I ended up discussing this with a few colleagues. We discussed a few options:

  1. The certification is not well known. Most of my colleagues were not aware of it.
  2. Many pharmaceutical GMP professionals are more directed at the PDA and ISPE. The ASQ is well known, but perhaps not as important when considering options.
  3. This certification is a generalist. There was a general opinion that many quality professionals tend to be specialized and might not feel comfortable stretching their wings.

Is there value in this BoK? Definitely. I found this certification much harder than the CMQ/OE, and as a result, I’m prouder of having it. The major question is how can we make this more valuable to the field. This is certainly a question I’ll be asking next week in Seattle.


The Journey Begins

Thanks for joining me!

Start with what is right rather than what is acceptable. — Franz Kafka

Let me introduce myself. I am a quality manager in the pharmaceutical industry who for the last year has been doing quality systems deployment, and previous to that spent 4 years running the change management/change control program at a site under a consent decree with the FDA. I’ve spent almost two decades developing, implementing, and maintaining quality systems in biopharma. I an a senior member of the American Society of Quality with my Certified Manager of Quality/Operational Excellence (CMQ/OE) and Pharmaceutical GMP Professional certifications. I’ve been known to haunt one or three other professional associations.

This blog is my attempt to explore what I’ve learned. It is a example of thinking out loud. Perhaps, in that, it will be valuable to others.

The views and opinions expressed in this blog are those of the individual blogger (Jeremiah Genest) and should not be attributed to any company with which the blogger is now or has been employed or affiliated.