Implications of Q14 and Q2(R2) draft guidelines
USP <1220>, Q14 and Q2(R2)
- No additional expectations or mandated requirements are expected in Q14, Q2(R2) and USP <1220>. The minimal approach can still be used.
- Q14 and Q2(R2) are consistent with the principles described in USP <1220>, but not in full agreement.
- Although Q14/Q2(R2) represent great progress towards implementation of sound science and QRM, their publication as separate documents still leaves some gaps since a comprehensive and continuous APLC is not presented.
- Presents strategies that allow for a more comprehensive AP change management and risk assessment (e.g., MODR, ATP, and ACS can be the basis for PACMPs and can be included in the regulatory dossiers).
- Provides flexibility for post-approval changes and potential reduction of burden in the industry.
- Presents the enhanced approach with a focus on fitness for use
- More connectivity with other stages of the APLC.
- Use of prior knowledge to design a more suitable validation protocol and implementation of risk-based approaches.
- Provides support for validation of multivariate procedures such as PATs using other techniques rather than just chromatographic procedures or offline procedures.
- No changes are required in terms of assessing specificity/selectivity, working range, accuracy and precision.
- An alternative approach for combined accuracy and precision may be used and may help to ensure fitness for use.
- <1225>, <1226>, and <1224> may be revised since they lack the connectivity to other APLC stages.
- <1039> may be revised to provide guidance on the development of multivariate procedures and complement the principles described in USP <1225> providing support for development of RTRT and PATs.
- <1220> and <1225> may be revised to be harmonized with Q14/Q2(R2).
- AQbD elements may be incorporated into compendial monographs. The enhanced approach may change how compendial monographs are written in the future, providing a certain degree of flexibility.