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20 BioPharm International ® Quality and Regulatory Sourcebook March eBook 2023 www.biopharminternational.com Validation noninferiority of variabilities) that can be used to sup- port risk assessment and evaluation of performance equivalence for procedure transfer and analytical con- ditions changes supporting change management and procedure qualification. These statistical approaches for procedures comparability are also cited in the cur- rent version of the FDA guidance on procedure valida- tion, chapter VIII.B (35). The USP chapters mentioned previously do not consider currently the connectiv- ity between the different APLC stages and may be reviewed in the near future. Although USP <1220> provides a holistic approach to manage the APLC, it does not provide clear guidance for multivariate procedures development and connectivity with the multivariate model life cycle, which is described at a high-level in USP <1039>. Building the interconnec- tions between both of these chapters would facilitate the development of enhanced control strategies using online/at-line/in-line PATs to support the implemen- tation of innovative manufacturing approaches such as continuous manufacturing and real time release testing (RTRT). Currently, USP <1039> has a greater focus on spectroscopic applications and may also be revised to allow the expansion of its scope to other techniques and applications. In the ICH Q guideline series, Q14 is the first to ad- dress approaches for procedure design and is similar to stage 1 and 3 according to USP <1220>. Q2(R2) can be seen, at least in part, as similar to stage 2 described in USP <1220>. In contrast to the framework described in USP <1220>, ICH Q14/Q2(R2) EWG split both top- ics, attempting to keep the status quo and avoid a drastic change to the structure of Q2(R1). Although Q14 a nd Q2(R2) represent g reat prog ress towa rd implementation of sound science and QRM, their publication as separate documents still leaves some gaps because a comprehensive and continuum APLC is not presented. These draft guidelines also discuss l it t le or not h i ng about essent ia l A PLC elements (e.g., Q2(R2) does not include ATP and Q14 does not emphasize ongoing performance verification). Sim- ilarities and differences bet ween USP <1220> and Q14/Q2(R2) and their implications are discussed in Part II of this article. In summary, the APLC framework is considered as an enhanced approach and represents the evolution of AP validation concepts that may likely replace tra- ditional/minimal approaches in the future since it offers several advantages. These advantages include development of more robust and optimized proce- dures, increased reliabilit y of deciding whether a product is conforming or out-of-specification and reg ulator y f lex ibi lit y for post-approva l changes. Furthermore, APLC and AQbD could drive innovation and the continuous improvement of quality based on risk/knowledge management. References 1. ICH. ICH Draft Guideline Q14 Analytical Procedure Development (ICH, 2022). 2. ICH. ICH Draft Guideline Q2(R2) Validation of Analyt- ical Procedures (ICH 2022). 3. Weitzel, J. et al., AAPS J. 2021 23:112. https://doi. org/10.1208/s12248-021-00634-5. 4. FDA. Guideline on General P r inciples of P rocess Validation. 1987. 5. Castillo,F.C.; Cooney, B. and Levine, H.L. Pharmaceu- tical Engineering 2016. 6. Juran, J.M. Juran on Quality by Design: The New Steps for Planning Quality into Goods and Services (The Free Press, New York, 1992). 7. Borman P, Chatfield M, P. Borman, et al. PharmTech. 2007 31 (10) 142–152. 8. FDA, Pharmaceutical cGMPs for the 21st Century- A Risk Based Approach, 2004. 9. P. Nethercote, and J. Ermer. Chapter 1. Analytical Validation within the Pharmaceutical Lifecycle, in Method Validation in Pharmaceutical Analysis: A Guide to Best Practice (Wiley, 2014). 10. ICH. Q8(R2) Pharmaceutical Development (ICH, 2009). 11. ICH. Q9 Quality Risk Management (ICH, 2009). 12. FDA. Guidance for Industry, Process Validation: General Principles and Practices (2011). 13. EMA. Guideline on Process Validation (2012). 14. Wechsler, J. FDA's CMC Pilot Program Moves For- ward. PharmTech.com, Sept. 12, 2006. 15. EMA and FDA, EMA-FDA Pilot Program for Parallel Assessment of Quality by Design Applications, 2011. (accessed June 29, 2022). 16. EMA and FDA. Report from the EMA-FDA QbD Pilot Program, 2017. (accessed June 29, 2022). 17. ICH. Q12 Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management. (ICH, 2019). 18. ICH. Q13 Draft Guideline Continuous Manufacturing of Drug Substance and Drug Products (ICH 2021). 19. FDA. Report on the State of Pharmaceutical Quality, FDA.gov, 2021. 20. FDA. Quality Management Maturity: Essential for Stable U.S. Supply Chains of Quality Pharmaceuti- cals (2022) (accessed July 12, 2022). 21. G.P. Martin, et al. Lifecycle Management of Ana- lytical Procedures: Method Development, Proce- dure Performance Qualification, and Procedure Performance Verification, USP Stimuli Article. Pharmacopeial Forum 2013 39(5). 22. Burgess, C. et al. Fitness for Use: Decision Rules and Target Measurement Uncertainty, USP Stimuli Article. Pharmacopeial Forum 2016 42(2). 23. Barnett,K.L. et al. Analytical Target Profile: Struc- ture and Application Throughout the Analyti- cal Lifecycle, USP Stimuli Article. Pharmacopeial Forum 2016 42(5).