This week, the Pharmaceutical Inspection Co-operation Scheme (PIC/S) finally announced that its new guidance on good practices for data management and integrity for pharmaceutical manufacturers and distributors has come into effect.
This final version is of a draft document originally introduced in 2016 and re-issued as a draft in 2018. It’s been a long road to get final version. Final version here.
PIC/S recently updated an Aide Mémoire on inspections of biotech manufacturers in January. The aim of this AiM is to harmonize GMP inspections in biotechnological and biological facilities and to ensure their quality. There wasn’t much new in this version, the revision history says “Minor edits to update cross-references to PIC/S GMP Guide (PE 009-14),” but this is a good time to review the document.
Changes meet their intended objectives and pre-defined effectiveness criteria. Any deviations from those criteria are adequately assessed, accepted and managed/justified. Whenever possible, quantitative data are leveraged to objectively determine change effectiveness (e.g. statistical confidence and coverage).
Sufficient data points, as described in the implementation plan, gathered to a described timeline, before an assessment of the change is made.
The success criteria should be achieved. If not, reasons why they have not been achieved should be assessed along with the mitigation steps to address the reasons why, including reverting to the previous operating state where appropriate. This may require the proposal of a subsequent change or amendment of the implementation plan to ensure success.
Data and knowledge gathered from implementation of the change should be shared with the development function and other locations, as appropriate, to ensure that learning can be applied in products under development or to similar products manufactured at the same or other locations
As part of the quality risk management activities, residual risks are assessed and managed to acceptable levels, and appropriate adaptations of procedures and controls are implemented.
These are action items in the change control.
As part of the closure activities, revise the risk assessment, clearly delineating risk assessment in two phases.
Any unintended consequences or risks introduced as a result of changes are evaluated, documented, accepted and handled adequately, and are subject to a pre-defined monitoring timeframe.
Leverage the deviation system.
Prior to or after change closure
Any post-implementation actions needed (including those for deviations from pre-defined acceptance criteria and/or CAPAs) are identified and adequately completed.
If you waterfall into a CAPA system, it is important to include effectiveness reviews that are to the change, and not just to the root cause.
Relevant risk assessments are updated post-effectiveness assessments. New product/process knowledge resulting from those risk assessments are captured in the appropriate Quality and Operations documents (e.g. SOPs, Reports, Product Control Strategy documents, etc.)
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.
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.
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.
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.
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.
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.
The Pharmaceutical Inspection Convention Cooperation Scheme (PIC/S) on 01-Jan-2019 released a long-awaited guidance to help regulators harmonize the classification and reporting of good manufacturing practice (GMP) deficiency outcomes from inspections. The guidance is designed as a “tool to support the risk-based classification of GMP deficiencies from inspections and to establish consistency amongst inspectorates.”