PIC/S: How Inspectorates Should Assess Pharma Quality Systems For Changes
Executive Summary
Draft recommendation offers path to ICH Q12 regulatory relief.
A group of pharmaceutical inspectorates has drafted a recommendation on how to assess the quality systems drug makers could use to manage minor manufacturing changes internally under the International Council for Harmonisation’s new Q12 post-approval changes guideline.
The recommendation from the Pharmaceutical Inspection Cooperation Scheme, a cooperative arrangement among drug good manufacturing practice inspectorates, addresses a key challenge regulators face as they prepare to implement the Q12 guideline, which the ICH assembly approved during a meeting in Singapore in November. (Also see "Will Change Ever Come Easy? Authorities Share Their Top ICH Q12 Challenges" - Pink Sheet, 4 Dec, 2019.)
The problem is how to be sure companies have pharmaceutical quality systems that are good enough to manage changes to "non-established conditions" of their manufacturing processes without regulatory oversight. Established conditions are factors such as critical quality attributes and critical process parameters that are directly relevant to the process control strategy. Non-established conditions are supporting information also included in the quality submission.
Anticipating this challenge, the Pharmaceutical Inspection Cooperation Scheme’s experts on quality risk management have been developing advice on how PIC/S member inspectorates should assess corporate pharmaceutical quality systems.
Six-Month Trial Begins
The draft PIC/S recommendation applies on a six-month trial basis to GMP inspections conducted by its 52 participating authorities. The organization will revise the guidance based on trial results, then proceed with formal adoption. PIC/S is not accepting industry comments on the draft.
Member authorities had to demonstrate comparability of their GMP inspection systems to join the group and are subject to periodic reassessments. When the latest recommendation is adopted, it will be added to PIC/S’ expectations for their GMP inspection systems.
An Opportunity For Regulatory Relief
More significantly, however, the recommendation “will likely become especially important when inspecting a company that is seeking regulatory relief for change management as envisaged by ICH Q10 and ICH Q12,” the PIC/S QRM Expert Circle’s coordinating committee explained in a 7 October “concept note” that PIC/S published 28 November along with the draft recommendation document.
Such regulatory relief could promote the type of lifecycle continual improvement that the US FDA began advocating with its 21st Century GMP initiative in 2002, the concept note says.
The note explains that the document “provides clear and practical guidance that meets current expectations, and which the industry could use within their companies to demonstrate an effective PQS in context of risk-based change management.”
The Recommendation’s Origins
The expert circle decided to develop the document when it met in Taipei, Taiwan, after running an advanced QRM training course for GMP inspectors there.
The experts had been including risk-based change management as a training topic for several years and viewed the PQS effectiveness topic as a natural progression, particularly given the pending Q12 guideline.
The concept note mentions that an industry expert on risk-based change management contributed to the discussion in Taipei but does not name the expert.
The expert circle’s coordinating committee drafted the document in April 2019 when it met in Dublin, Ireland.
The experts plan to use the document in developing related training materials. They note that PIC/S also could use the document when updating its QRM Aide Memoire with a risk-based approach to inspecting change management programs.
How Document Builds On PIC/S GMP Guide
The committee notes that the PIC/S GMP Guide laid the groundwork for the document with language in its first chapter calling for “a comprehensively designed and correctly implemented PQS incorporating GMP and QRM.” Annex 15 of the guidance discusses application of the PQS to change control.
The document provides practical guidance on how GMP inspectors should evaluate pharmaceutical quality systems for manufacturing changes, the note said.
It covers all steps of change management from proposal to assessment, planning and implementation, as well as review and effectiveness checks. For each step, it outlines what makes a quality system effective.
The document outlines:
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Key elements of risk-based change proposals;
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Expected depth and breadth of the risk-based assessments;
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Change categorization;
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How risk assessments should drive change planning and implementation; and
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How changes should be reviewed, assessed and monitored.