FDA Perspectives: Scientific Considerations of Forced Degradation Studies in ANDA Submissions - Pharmaceutical Technology

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FDA Perspectives: Scientific Considerations of Forced Degradation Studies in ANDA Submissions
The author outlines the scientific aspects of forced degradation studies that should be considered in relation to ANDA submissions.


Pharmaceutical Technology
Volume 36, Issue 5, pp. 73-80

Conclusion

An appropriately-designed stress study meshes well with the QbD approaches currently being promoted in the pharmaceutical industry. A well-designed stress study can provide insight in choosing the appropriate formulation for a proposed product prior to intensive formulation development studies. A thorough knowledge of degradation, including mechanistic understanding of potential degradation pathways, is the basis of a QbD approach for analytical method development and is crucial in setting acceptance criteria for shelf-life monitoring. Stress testing can provide useful insight into the selection of physical form, stereo-chemical stability of a drug substance, packaging, and storage conditions. It is important to perform stress testing for generic drugs due to allowable qualitative and quantitative differences in formulation with respect to the RLD, selection of manufacturing process, processing parameters, and packaging materials.

Acknowledgments

The author would like to thank Bob Iser, Naiqi Ya, Dave Skanchy, Bing Wu, and Ashley Jung for their scientific input and support.

Ragine Maheswaran, PhD, is a CMC reviewer at the Office of Generic Drugs within the Office of Pharmaceutical Science, under the US Food and Drug Administration's Center for Drug Evaluation and Research,
Disclaimer: The views and opinions in this article are only those of the author and do not necessarily reflect the views or policies of the US Food and Drug Administration.

References

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2. ICH, Q1B Stability Testing: Photostability Testing of New Drug Substances and Products (Geneva, Nov. 1996).

3. H. Brittain, Analytical Profiles of Drug Substances and Excipients (Academic Press, London, 2002).

4. A. Srinivasan and R. Iser, Pharm. Technol. 34 (1), 5059 (2010).

5. A. Srinivasan, R. Iser, and D. Gill, Pharm. Technol. 34(8), 4551 (2010).

6. A. Srinivasan, R. Iser, and D. Gill, Pharm. Technol. 35 (2), 5867 (2011).

7. S. Klick, et al., Pharm.Technol. 29 (2) 4866 (2005).

8. K. M. Alsante, L. Martin and S. W. Baertschi, Pharm.Technol. 27 (2) 60-72 (2003).

9. D. W. Reynolds, et al., Pharm.Technol. 26 (2), 4856 (2002).

10. K. M. Alsante et al., Advanced Drug Delivery Reviews 59, 2937 (2007).

11. FDA, Guidance for Industry on Analytical Procedures and methods Validation Chemistry, Manufacturing, and Controls Documentation (draft) (Rockville, MD, Aug. 2000).

12. ICH, Q6A: Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances (Geneva, Oct. 1999).

13. ICH, Q3A(R2) Impurities in New Drug Substances (Geneva, Oct. 2006).

14. ICH, Q3B(R2) Impurities in New Drug Products (Geneva, June 2006).

15. FDA, Guidance for Industry ANDAs: Impurities in Drug Substances (draft), (Rockville, MD, Aug. 2005).

16. FDA, Guidance for Industry ANDAs: Impurities in Drug Products (draft) (Rockville, MD, Nov. 2010).

17. EMA, Guideline on the Limits of Genotoxic Impurities, Committee for Medical Products for Human Use (CHMP) (Doc. Ref EMA/CHMP/QWP/251344/2006) (Jan. 1, 2007).

18. K. A. Conners et al., Chemical Stability of Pharmaceuticals, Wiley and Sons, New York, New York, 2nd Ed., p. 19 (1986).


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