According to ICH Q6, specifications are “a list of tests, references to analytical procedures, and appropriate acceptance criteria which are numerical limits, ranges, or other criteria for the tests described.”
The primary goal of a specification is to ensure patients receive a safe and effective product.
As such, specifications represent a crucial element of each MarketingAuthorizationApplication.
Dialogue between Regulatory Agencies and Industry on the principles for setting specifications has been ongoing for several years, with recent emphasis on accelerated access scenarios and patient-centric (or clinically relevant).
The COVID19 pandemic has further highlighted the necessity to consolidate strategies for setting specifications, without compromising product quality, safety, or efficacy, when development timelines are extremely short.
Collectively, these discussions underline the need for an update of the ICH Q6A and Q6B Guidelines, which were first issued in 1999.
Concurrently, ICH Quality Discussion Group (QDG) proposed in 2021 that revision of the ICH Q6A and Q6B Guidelines is of the highest priority for ICH 8, and EWG activities are expected to start soon.
The core principles of patientcentric specifications, include new product modalities, foster harmonization across different regions, align the expectations for specification setting to more recent ICH Guidelines, clarify guidance on use of pharmacopoeias, integrate contemporary science/ risk- based approaches, and enable accelerated development and lifecycle management.
In this context, EFPIA has identified the following issues with guidance in the current versions of ICHQ6A and B.
- Attributes required in specifications may go beyond those which are critical to safety and efficacy e.g., the ICHQ8 Critical Quality Attributes (CQAs).
- Limits are primarily defined based on statistical assessment of available manufacturing batch data.
- There is no clear mention of the use of ICHQ8-11 (QbD) principles to develop the specification as part of a holistic control strategy.
- Q8-11 tools such as priorknowledge from similar products and processes and Quality Risk Management are not mentioned in the guidance.
References:
- ICH Q6A Guideline: Specifications: Test Procedures and acceptance criteria for new Drug Substances and New Drug Products: chemical substances
- ICH Q6B Guideline: Specifications: Test procedures and acceptance criteria for biotechnological/ biological products
- ICH E6 (R3) Guidelines on Good Clinical Practices
- Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle
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