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A Patient-Centric Review of ICH Q6A and Q6B (Part II)


A patient centric specification (PCS) is a set of CQAs and acceptance ranges to which product quality attributes should conform for the product to be safe and effective when used as labeled. 

Justifications for acceptance ranges focus on risk/knowledge-based assessment of the impact to patient and improve access to medicines through reliable, robust supply chains.

Patient-centric specifications may also be referred to as clinically relevantspecifications (CRS) and Patient Centric Quality Standards (PCQS) in the literature.

In 2012, FDA suggested “CRS are those specifications that take into consideration the clinical impact of variations in the critical quality attributes (CQA) and process parameters assuring a consistent safety and efficacy profile” .

Within a patient centric paradigm, the role of the specification is assuring patient safety and product efficacy. Consistency is assured through direct process controls (input material controls, process parameter controls, in-process controls, etc.) and ongoing process verification within an appropriate quality management system to meet cGMP requirements.

Revision of ICHQ6 to incorporate patient- centric principles, based on control of CQAs, is consistent with strategies currently outlined in ICHQ8 (R2), stating that “Adoption of the principles in the guideline can support the justification of alternative approaches to the setting of specification attributes and acceptance criteria as described in Q6A and Q6B.”

ICH Q8 (R2) goes further to indicate that, if appropriately supported by enhanced process and/or product knowledge,product specifications can be based on desired product performance rather than batch data. 

Revision of ICH Q6 would align concepts for creation of a control strategy with those for establishment of specifications, particularly the concept of Drug Product and Drug Substance CQAs,as well as how these are linked to input materials attributes, process parameters etc, as the basis for the specification, in the context of control strategy.

The establishment of a holistic control strategy, is key to build confidence on the ability to consistently manufacture commercial products, and to ensure appropriate selection of CQAs to be included in specifications.

The focus of a patient-centric revision to ICH Q6 will further strengthening the statements around risk/knowledge-based approaches (aligning to ICH Q8-10) and re-focus on the primacy of drug substance/product safety and efficacy considerations. 

In addition, the revision could clarify and expand how different pharmaceutical development approaches (e.g., minimal vs. enhanced/QbD) impact the ability to develop an integrated control strategy and the inclusion of prior/platform knowledge into the considerations of establishing specifications.

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Resource person: BARBARA PIROLA
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