How Inspectorates Will Judge Quality Systems' Ability To Manage Manufacturing Changes
Executive Summary
PIC/S document will help authorities see which manufacturing sites can manage less-significant changes effectively without oversight, as ICH Q12 allows.
A 15 July document that explains how the world’s top pharmaceutical inspectorates believe they should assess the ability of companies to manage changes could help pharmaceutical companies simplify their global manufacturing processes.
The Pharmaceutical Inspection Cooperation Scheme’s PI 054-1 recommendation document provides advice on how to evaluate the effectiveness of a company’s pharmaceutical quality system, at least for managing changes. By the same token, it can help pharmaceutical companies demonstrate PQS effectiveness.
PIC/S is a Swiss association of national pharmaceutical inspectorates, currently numbering 54, that have comparable enforcement systems.
Smoothing The Way For ICH Q12
The document applies to the PIC/S good manufacturing practice guide and dovetails with two quality guidelines from the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use – ICH Q10 and Q12. Q10 broadly defines pharmaceutical quality systems, while Q12 calls for companies to manage changes to what it calls mere “supportive information” within their quality systems. Changes to more important factors, which the guideline describes as “established conditions for manufacturing and control,” require varying degrees of regulatory oversight.
Regulatory authorities have acknowledged the difficulty of assessing pharmaceutical quality systems has made it difficult to keep their attention focused on established conditions instead of supporting information. (Also see "Will Change Ever Come Easy? Authorities Share Their Top ICH Q12 Challenges" - Pink Sheet, 4 Dec, 2019.)
Manufacturers can use the same approach everywhere for changes they manage within their quality systems. But they may have to use different approaches in each country for changes that regulatory authorities oversee, which can prevent global harmonization. (Also see "Why Industry Says Global Post-Approval Complexity Must Change" - Pink Sheet, 8 Aug, 2016.)
Defining Effective Quality Systems
Because the Q12 guideline now being implemented allows supporting information to be managed internally by an effective PQS, it raises the question for inspectorates of how to determine whether a company’s PQS is effective.
This is where the new PIC/S recommendation document comes into play by providing a checklist that auditors and auditees alike can use to assess PQS effectiveness in four key areas:
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Proposals to decide whether a change is needed;
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Change risk assessments;
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Change planning and implementation; and
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Change review and effectiveness.
If a pharmaceutical manufacturer follows the recommendations, this “should provide sufficient evidence of an effective science- and risk-based change management system,” the document concludes.
The PIC/S team that wrote the guideline, called an expert circle, considered input from industry representatives when developing the recommendations.
A Source Of Regulatory Relief
A 7 October 2019 concept note by the PIC/S quality risk management expert circle’s coordinating committee explained that the group agreed during a September 2018 meeting in Taipei, Taiwan, that, while the topic had not been addressed extensively in training materials, “it has become a topic of high relevance at this time, given the pending agreement of ICH Q12, for which PQS effectiveness in relation to risk-based change management is a core concept.”
The QRM expert circle will use the document as a guide in developing training materials. The recommendations also may be used in updating the PIC/S QRM aide memoire.
The concept paper alludes to the regulatory relief industry anticipated but never received by adopting the ICH Q8, Q9 and Q10 trio of guidelines and by demonstrating effective pharmaceutical quality systems, describing that relief as “opportunities for some form of risk-based regulatory oversight from regulators to promote lifecycle continual improvements.”
A Vision For Training
The paper noted that the concept reflected the 21st century vision articulated at the US Food and Drug Administration in 2002 of a “maximally efficient, agile, flexible pharmaceutical manufacturing sector that reliably produces high quality drugs without extensive regulatory oversight.”
The paper went on to acknowledge that “despite ICH Q10 being in place for over 10 years now, the above vision of ongoing continual improvement has probably not been realized to a meaningful extent.”
One reason, and the expert circle plans to help change the situation through training, is that GMP inspectors may need help assessing PQS effectiveness, at least for change management systems.