The US Food and Drug Administration (FDA) has issued the 'Points to Consider' document covering topics relevant to the implementation of ICH Q8(R2), Q9, and Q10, which supplement the existing guidance Q8, Q9, and Q10.
The ICH Quality Implementation Working Group (Q-IWG) has prepared ‘points to consider’ which are based on questions raised during the ICH Q-IWG training workshop sessions in the three regions. They are intended to provide clarity to both industry and regulators and to facilitate the preparation, assessment, and inspection related to applications filed for marketing authorizations.
The development approach should be adapted based on the complexity and specificity of product and process. Therefore, applicants are encouraged to contact regulatory authorities regarding questions related to specific information to be included in their application.
According to the regulator, using the Quality by Design (QbD) approach does not change regional regulatory requirements but can provide opportunities for more flexible approaches to meet them. In all cases, Good Manufacturing Practice (GMP) compliance is expected.
Further, the regulatory authority has now listed the points to consider for criticality of quality attributes and process parameters. It stated that scientific rationale and quality risk management (QRM) processes are used to reach a conclusion on what are critical quality attributes (CQAs) and critical process parameters (CPPs) for a given product and process.
The quality target product profile (QTPP) describes the design criteria for the product and should therefore form the basis for development of the CQAs, CPPs and control strategy. The information developed to determine CQAs and CPPs will help to develop control strategy, ensure quality of the product throughout the product lifecycle, process knowledge, transparency and understanding for regulators.
The introduction of ICH Q9 states that “the protection of the patient by managing the risk to quality should be considered of prime importance”. The QTPP provides an understanding of what would ensure the quality, safety and efficacy of a specific product for the patient and is a starting point to identify the CQAs.
As part of risk assessment, risk analysis, as defined by ICH Q9 is the qualitative or quantitative process of linking the likelihood of occurrence and severity of harm. In some risk management tools, the ability to detect the harm also factors in the estimation of risk. Under the relationship between risk and criticality, there is the probability of occurrence and therefore the level of risk can change as a result of risk management. The quality attribute criticality is primarily based upon severity of harm and does not change as a result of risk management. The process parameter criticality is linked to the parameter’s effect on any critical quality attribute. It is based on the probability of occurrence and therefore can change as a result of risk management, the regulator stated.
Under the considerations for identifying and documenting CQAs can include the severity of safety and efficacy before taking into account risk control and the rationale for distinguishing CQAs from other quality attributes.
Under the Pharmaceutical Quality System, the link between the product lifecycle stages, facilitate the process validation lifecycle approach. Data, information and knowledge from process performance and product quality monitoring, as indicated in ICH Q10, support the lifecycle validation approach and the continual improvement of the product and process, stated the regulator.