Pharmaceutical Technology - October 2020

PharmTech - Regulatory Sourcebook - October

Issue link: https://www.e-digitaleditions.com/i/1302985

Contents of this Issue

Navigation

Page 14 of 75

Pharmaceutical Technology Regulatory Sourcebook October 2020 15 Periodic meetings between the quality unit and production staff could help to meet intra- or in- ter-batch variations, sharing statistical data, and coordinating corrective or preventive actions. After this stage, ways to improve or optimize the process could be suggested by altering some aspects of the process or product, such as the operating condi- tions (ranges and set-points), process controls, compo- nents, or in-process material characteristics. In case of failure in accomplishing acceptance crite- ria, appropriate investigations must be started taking into account the failed statistical tool and concentrat- ing efforts on single batches/small groups of batches (trends, shift, and single values out of warning limits, outliers in histograms) or on entire population (capa- bility, not normal or not centered histograms, anoma- lies in descriptive statistic, warning limits out of speci- fication limits). Finally, Table VIII is a non-exhaustive list of CPPs that should/could be taken into account when assessing a statistical anomaly of several CQAs for a freeze-dried product. Before/when assessing any correlation of the CQA failure with the CPP, the analytical method and its validation data should also be evaluated to confirm that any anomaly is not generated at laboratory level (e.g., non-robust method, lack of repeatability). More- over, the possible influence of the variability of incom- ing materials and of relevant CMAs must be always taken into account for any CQA failure. It is worth not- ing that the sterilizing filtration step has been excluded from this table, although the type of membrane filter could in theory influence the assay due to adsorption of the active ingredient, because it is assumed that the selection of the membrane filter has been made dur- ing development studies. Filling volume and capacity of the vial, which could influence the appearance and cycle duration have not been included either, for the same reason, because it is assumed that these aspects have been optimized during the development studies. Conclusion This work has illustrated the approaches and the tools available to implement the modern vision of PV for pharmaceutical finished products as described by the main regulatory authorities. Specific examples have been given for sterile liquid and freeze-dried products. Following the same approach, solid oral dosage forms will be covered in "Enhancing Process Vali- dation for Solid Oral Dosage Forms: Part 2" in this eBook on pages 16–25 and general comments on the topic will be made. Disclaimer This article reflects the views of the authors and should not be construed to represent any pharmaceutical company's or regulatory agency's views or policies. References 1. L.X. Yu, Pharm. Res., 25 (4) 781–791 (2008). 2. ICH, Q8(R2) Pharmaceutical Development, step 4 version (2009). 3. FDA, Process Validation: General Principles and Practices Process (Rockville, MD, Jan. 2011). 4. ICH, Q9 Quality Risk Management, step 4 version (2005). 5. FDA, Quality by Design (QbD): An Example Pharmaceutical Devel- opment Report for an Immediate Release (IR) Dosage Form (Rock- ville, MD, 2012) 6. European Commission, EudraLex Volume 4, Annex 15: Qualifica- tion and Validation (Brussels, March 2015). 7. EMA, Guideline on Process Validation for Finished Products—Infor- mation and Data to be Provided in Regulatory Submissions (London, UK, Nov. 2016). 8. J.S. Oakland, Statistical Process Control (Elsevier Butterworth- Heinemann, Oxford, UK, 6th ed., 2008). 9. ISO 7870-1, Control Charts—Part 1: General Guidelines (2014). PT … ways to improve or optimize the process could be suggested by altering some aspects of the process or product … Contin. from page 12

Articles in this issue

Archives of this issue

view archives of Pharmaceutical Technology - October 2020 - PharmTech - Regulatory Sourcebook - October