The Challenges of Evolving Pharma from a Compliance to a Risk-Based Control Strategy Mindset Are Drawing Conference Spotlight


The challenges of and drivers for evolving the pharmaceutical industry from a compliance-oriented mindset to one based on a control strategy embodying the risk management principles of ICH Q9(R1) are at the forefront of the industry/regulator dialogue at public forums, as the complexities of processes, products, and big data handling continue to expand.

The Q9 revision, released in 2023, provides a clearer roadmap on embedding quality risk management (QRM) into a quality system and control strategy.

Also helping inform the current dialogue is the comprehensive revision of Annex 1 of the EU and Pharmaceutical Inspection Cooperation Scheme (PIC/S) GMP guidelines on the manufacturing of sterile medicinal products, which focuses on the “innovative tools” in ICH’s QRM and quality system guideline toolbox.

Annex 1 has increased the attention on how this evolution from a compliance to a risk-based quality paradigm needs to take place in the contamination control strategy (CCS) arena in particular, where these process, product and big data complexities are especially challenging and the regulatory guidelines and rules are not specific enough, in any case, to dictate the decision-making process.   

The word “risk” appears well over a hundred times in the annex. Emphasized is the need for “applying the principles” of QRM for the prevention of microbial, particulate, and endotoxin/pyrogen contamination.

In addition to the revised Annex 1, PIC/S has released other risk-oriented guidance for inspectors, including its “Good practices for data management and integrity in regulated GMP/GDP environments” and its “Aide Memoire” on the assessment of QRM.

This multipart story provides insights from leading experts in the CMC/GMP regulatory arena on what pharma’s evolution from a compliance to a risk-based mindset needs to encompass and how to further its progress.

The insights are drawn from presentations and discussions at the October 2023 PDA Pharmaceutical Microbiology Conference held in Washington DC, and the Ex-Pharmaceutical Inspectors Consortium (EPiC) GMDP Compliance & Inspection Symposium held online in December.

●  Part I: Critical Thinking in Risk Management and Data Governance

The first part of the story focuses on a provocative discussion at the PDA micro conference by an experienced former FDA international investigator, Peter Baker, on how pivotal critical thinking is on this compliance to risk-based thinking journey. He explained how the complexities of the new technologies and the vast amount of data involved – particularly in the aseptic processing arena – requires critical thinking and a “governance” mentality that the compliance approach of the past doesn’t accommodate.

He pointed to the lurking threats of subjective bias and “perfection paralysis,” and how investigators, with patient safety in mind, will want to see the new QRM tools and related ICH and PIC/S guidance put in practice to counter them.

●  Part II: Quality Culture/Oversight in Aseptic Operations

The second part of the story reviews the thoughts shared at the PDA micro conference by another former FDA regulator, Stephen Langille, on the current regulatory and enforcement trends in aseptic processing. After outlining the top 483 observations in the aseptic arena, he focused in on the inspection concerns related to environmental monitoring, contamination of critical surfaces, and aseptic quality oversight.

In the Q&A that followed, Langille explored further what stronger quality culture/oversight looks like and how to achieve it. Industry consultant Mitch Garber, who spoke earlier in the session, provided supportive comments during the discussion.

● Part III: Takeda’s Annex 1-Based Global CCS Program

Part III explores how the quality risk management (QRM) expectations in the revision of Annex 1 have helped guide Takeda in developing a more harmonized contamination control strategy (CCS) across its global manufacturing operations. At the October 2023 PDA Microbiology Conference, Takeda’s Hilary Chan explained how this CCS program unfolded, supported by templates and guidance developed in consultation with the various sites to make sure that the harmonized CCS QRM tools are viable for the different types of operations involved.

In the Q&A that followed at the session, Chan had the opportunity to further comment on the benefits of the risk-oriented approach taken by Takeda and how it reflected the perspectives offered in other sessions of the conference, as highlighted in Parts I and II of this story.

● Part IV: QRM Tools in Root Cause Analysis

The fourth part of the story moves forward to the December Ex-Pharmaceutical Inspectors Consortium (EPiC) GMDP Symposium, where industry consultant Lewis Corbett reviewed how quality risk management (QRM) and critical thinking needs to be deployed in making sure that the increasingly large pool of relevant data actually drives more effective root cause analysis (RCA) and continuous improvement.

The former MHRA inspector began by reviewing the use of data in risk-based inspections. He then focused in on deploying three key RCA tools – the “five whys,” the Ishikawa fishbone diagram, and Failure Modes, Effects and Criticality Analysis (FMECA) – along with critical thinking in implementing risk-appropriate corrective and preventive actions (CAPA). Corbett concluded with how the learnings in addressing the issues need to be conveyed in enhancing training, continuous improvement, quality culture and inspection readiness.

● Part V: Annex 1 Revisions and the CCS Implications

Also appearing at the December 2023 EPiC Symposium were two consultants and former MHRA GMP inspectors Darren Jones and Phil Rose, who gave a joint presentation on the Annex 1 revision and its contamination control strategy implications.

Jones highlighted the key changes in the Annex 1 revision and how developing and implementing a viable CCS is key to sustainable compliance with the current sterile product GMP expectations it provides. Rose then took a deeper dive into the development, formatting and implementation of a CCS and how to increase its effectiveness in different process and product contexts.

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