28.05.2019 | LOGFILE Feature 20/2019

A Report on the 2019 ISPE Europe Annual Conference

ICH Q12 - Set menu or buffet?

ICH Q12 - Set menu or buffet?

6 min. reading time | by Sabine Paris


The European Annual Conference of the International Society of Pharmaceutical Engineering (ISPE) attracted over 700 participants to Dublin from 1st to 3rd April 2019. The main topic was “Drive and Leverage Innovation for Pharma”.

One of the hot topics was ICH Q12 Product Life Cycle Management. It was excellently discussed in the Executive Forum and also in Track 3: Quality Risk Management, Process Validation, Continuous Process Verification & GAMP®.

In today’s leading article I have summed up two top-class lectures on the challenges and advantages of ICH Q12. I have also published this text (and much more) in my live coverage of the conference at Linkedin (#gmppublishing).

“ICH Q12 - Set menu or buffet?”, this question asked Graham Cook, Pfizer Pharmaceuticals and EFPIA Q12 Topic Lead, in his excellent presentation “ICH Q12: Making Change Easier“.

The ICH Q12 Guideline Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management reached Step 3 of the ICH process. In November 2017, it was published for consultation. More than 900 comments were received.

Product lifecycle management is a global challenge. Post-approval changes (PAC) take too long to implement. Around the world, the PAC system is totally heterogeneous. The system is globally insufficient.

Graham presented observations about the regulatory frameworks for PAC:

  • Regulatory frameworks may have detailed descriptions for changes and reporting categories or looser frameworks with examples
  • Regulatory frameworks may not have tiered, risk-based reporting categories
  • Some agreement across frameworks on higher risk changes and lower risk changes, but considerable heterogeneity in change classifications, especially for moderate risk changes
  • Regulatory review/approval of a change in a single country/region (e.g. Europe) is often relatively efficient

Challenges for industry are the diversity, the time needed and the approval times. Graham saw several opportunities for harmonization:

  • Clearly defined regulatory commitments / approved matters / established conditions
  • Harmonized PAC Management Protocols
  • Tiered, risk-based regulatory framework for assessment of variations

Objectives and potential benefits of ICH Q12 inter alia include:

  • Harmonization of change management
  • Facilitation of risk-based regulatory oversight
  • Control strategy as a key component of the dossier
  • Reduction of unnecessary cost and time burdens on industry and regulators
  • Support of continual improvement
  • Facilitation of innovations in manufacturing

Coming back to the question right from the beginning - ICH Q12 - Set menu or buffet?, Graham explained that ICH Q12 is an optional document. It introduces tools and concepts you can adopt, but you don’t have to. You can pick up what fits your products and operations.

ICH Q12 introduces two main concepts/tools:

1. Established Conditions

Necessary elements that are important for quality (subject to variation) – they differ from supportive information that would not require a regulatory submission.

2. Post-Approval Change Management Protocol (PACMP)

Regulatory tool that provides predictability regarding the information required to support a CMC change. It speeds up process.

What should I tell my colleagues about ICH Q12?“

Q12 is already serving as an agent for change within agencies to simplify the management of PACs.

  • Read the guideline and annex examples
  • Use of ICH Q12 tools depends on various factors (e.g. type of change, type of product, affected markets)
  • Effective use of ICH Q12 will require knowledge and understanding of the correct use of the tools, skills developed using the tools

Graham recommended to raise awareness and facilitating change within agencies.

„ICH Q12 - One of my favorite topics!“

Ursula Busse, Novartis, outlined in her lecture that ICH Q12 has the potential to be a transformational guideline for the management of post-approval technical changes.

Why do we need ICH Q12?

  • Novel approaches to manufacturing due to new therapies
  • Global companies act in many different markets. All these markets have different requirements (difference in approval timelines, pre-approval inspections) – that leads to complexity

Novartis has to handle about 10,000 changes per year. This is costly inter alia due to fees and stability studies. And with the more and more complex products you have the double amount of regulatory relevant changes.

Ursula presented the comprehensive tool box of ICH Q12. Tools should reduce regulatory burden and facilitate assessment and inspections. Tools are inter alia: Established Conditions (ECs), Post-Approval Change Management Protocols (PACMPs), PQS and categories of post-approval CMC changes.

„ICH Q12 promotes building knowledge and it should really make a difference.“

Implementation challenges need to be understood and addressed:

  • Understanding of new concepts
  • Application of the concepts versus regional regulations
  • Implementation in non-ICH regions

For commenting the draft guideline, different industry associations got together and provided one set of comments.

Some of the industry comments referred to:

  • Established Conditions (EC)
    • Remove „implicit“ / „explicit“ ECs
    • Remove Key Process Parameters (KPPs)
  • PACMPs - Risk of diverging PACMPs across regions
  • Product Lifecycle Management (PLCM) document – heavily debated
    • It is optional and to be used as a communication tool
    • Simplification
    • Harmonize the location of this document in the dossier
  • Legacy products - not appropriate for every legacy product

One of the big concerns is different understanding by regulators of old and new concepts. There will be a lot of dialogue needed to overcome the risk of divergence.

In non-ICH regions there are at least WHO guidelines on changes to approved products. But the WHO guidelines are not necessarily implemented. Nevertheless, we But we should encourage implementation of WHO guidelines –  they are complementary to ICH Q12

„What is needed in addition to ongoing efforts?“

Ursula mentioned many different things like dialogue, courage, examples, trust, harmonization, convergence and clarity. She closed her stimulating and motivating presentation with the advice:

„Implementation will be a journey. Strive for progress, not perfection!“


2019 ISPE Europe Annual Conference:

Graham Cook, Sr Director Process Knowledge/Quality by Design, Pfizer: ICH Q12: Making Change Easier

Ursula Busse, Head Quality Intelligence, External Engagement, Novartis: ICH Q12: Challenges to Global Implementation – An Industry Perspective

Sabine Paris


Sabine Paris, PhD
Senior GMP Expert / Chief Editor of the GMP Compliance Adviser
E-Mail: sabine.paris@gmp-publishing.com



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