"Points to Consider" documents.
Q–IWG therefore developed several "Points-to-Consider" to further clarify concepts and practices. The single document, covering
additional Q8, Q9, and Q10 implementation issues, is meant to supplement the existing Q&A document and the workshop materials
(2, 3). The industry and regulators are encouraged, however, to use all of these documents together.
The Points-to-Consider document covers the following key areas.
Criticality of quality attributes and process parameters. The information developed to determine critical quality attributes (CQAs) and critical process parameters (CPPs) will help
to develop the control strategy, ensure the quality of the product throughout the product lifecycle, and increase product
and process knowledge as well as the transparency and understanding for regulators and industry evaluating any changes.
The following points could be taken into consideration for establishing CQAs and CPPs: the relationship between risk and criticality,
various considerations for identifying and documenting CQAs, possible evolution of the CQAs and CPPs throughout the product
lifecycle, and the relationship of criticality to control strategy. The critical aspect is the high risk of significant impact
to product quality, safety, or efficacy, which requires a degree of control.
Control strategy. The main elements needed to develop and maintain the control strategy over the product lifecycle include continual improvement
and change management. Different control strategies can be applied for the same product. As stated in ICH Q10, knowledge management
is a key enabler. Further details are provided in the Point-to-Consider document on the suitability of control strategy at
different scales, specifications and Certificate of Analysis for RTRT, and on the process for a deciding when to release a
Level of documentation in enhanced regulatory submissions. It is helpful for regulators to have a statement describing the proposed regulatory outcome and expectations of a QbD or
enhanced approach, as described in the submission. It is important to note that every study performed and/or data generated
during product development does not need to be submitted to the appropriate regulatory authority. The document provides details
on which studies and data to consider with regard to risk-management methodologies, design of experiments, and the manufacturing
process description (4).
Design space. The Q–IWG training workshops demonstrated that clarification on how to develop a design space was also desired by the industry
and regulators. The Points-to-Consider document therefore addresses the verification and scale-up of a design space, documentation
of the space, and its life-cycle management (4).
Role of modeling in QbD. The categorization of models is a key part. After developing and implementing models, considerations on model validation
and model verification during the lifecycle conclude with the documentation of model-related information in a regulatory submission.
Process validation/process verification. This section of the Points-to-Consider document provides general considerations on the continuous process verification (4).
Please note that the the term continued process verification is used in the FDA process validation guidance to describe stage 3 of the life-cycle approach to process validation (5).
Since the approval of its Quality vision in 2003, ICH has made available appropriate guidance and training material for the
industry and regulators to use in the implementation of science- and risk-based approaches to drug development and manufacturing
at the global level. It is important to read, understand, and think about the concepts presented in the Quality guidelines
before implementing them. ICH's goal is therefore to provide the key information and considerations needed to achieve a harmonized
approach. The ultimate benefit is for patients in that quality is built into their products, thereby reducing the number of
complaints, deviations, issues, recalls, and inspection observations.