Managing Raw Materials in the QbD Paradigm, Part 1: Understanding Risks - An initial assessment of materials must extend beyond the material specification to include the supplier's manufacturing proce


Managing Raw Materials in the QbD Paradigm, Part 1: Understanding Risks
An initial assessment of materials must extend beyond the material specification to include the supplier's manufacturing process, quality systems, and sourcing strategy.

BioPharm International
Volume 23, Issue 11, pp. 34-40


1. International Conference on Harmonization. Q7, GMP guide for active pharmaceutical ingredients. Geneva, Switzerland; 2000 Nov.

2. ICH. Q8(R1), Pharmaceutical development, Geneva, Switzerland; 2008, Nov.

3. ICH. Q9, Quality risk management, Geneva, Switzerland; 2005 Nov.

4. US Food and Drug Administration. Guidance for industry: BACPACI: intermediates in drug substance synthesis: bulk actives postapproval changes: chemistry, manufacturing, and controls documentation. Rockville, MD; 2001 Feb. Withdrawn Fed. Regist. Notice 2006 June 1.

5. European Commission (Enterprise Directorate General). EMA Guidelines to Good Manufacturing Practice, Medicinal Products for Human and Veterinary Use, Part II, Basic Requirements for Active Substances used as Starting Materials. Brussels, Belgium: 2005 Oct.

6. Ministry of Health, Labor, and Welfare. Pharmaceutical and Food Safety Bureau. Guidelines on Mentions in Manufacturing/Marketing Approval Application Dossiers for Pharmaceuticals and Others Based on Revised Pharmaceutical Affairs Law, PFSB/ELD 020001. Tokyo, Japan: 2005 Feb 10.

7. Shadle PJ. Qualification of raw materials for biopharmaceutical use. BioPharm Int. 2004;17(2).

8. Heidemann R, Zhang C, Qi H, Rule JL, Rozales C, Park S, Chuppa S, Ray M, Michaels J, Konstantinov K, Naveh D. The use of peptones as medium additives for the production of a recombinant therapeutic protein in high-density perfusion cultures of mammalian cells. Cytotechnol. 2000;32:157–67.

9. Zheng X, Baker H, Hancock WS, Fawaz F, McCaman M, Pungor E. Proteomic analysis for the assessment of different lots of fetal bovine serum as a raw material for cell culture, Part IV. Application of proteomics to the manufacture of biological drugs. Biotechnol Prog. 2006;22:1294–1300.

10. Rodionova OY, Sokovikov YV, Pomerantsev AL. Quality control of packed raw materials in pharmaceutical industry. Analytic Chimica Acta. 2009;642:222–7.

11. Kirdar AO, Chen G, Rathore AS. Combining near-infrared (NIR) spectroscopy and multivariate data analysis (MVDA) for screening of raw materials used in the cell culture medium for the production of a recombinant therapeutic protein. Biotechnol Prog. 2010;26:527–531.

12. Lanan M. QbD for raw materials. In: Rathore AS, Mhatre R, editors. Quality by Design for biopharmaceuticals: perspectives and case studies. Hoboken, NJ: Wiley Interscience; 2009. 193–210.

13. Rathore AS, Winkle H. Quality by Design for pharmaceuticals: regulatory perspective and approach. Nat Biotechnol. 2009;27:26–34.

14. Rathore AS. A roadmap for implementation of Quality by Design (QbD) for biotechnology products. Trends Biotechnol. 2009;27:546–53.

15. Jain S, Schilling BM, Shukla AA. Determining the effect of raw materials on manufacturing-scale cell-culture performance. Bioprocess Int. 2008 Jun; 36–40.

16. Peysson LF. Tracing and control of raw materials sourcing for vaccine manufacturers. Biologicals. 2010; doi:10.1016/j.biologicals.2010.01.011.

17. Illing GT, Timko RJ, Billett L. Drug substance starting material selection. Pharm Technol. 2008 Dec; 52–7.

18. USP General Chapter <467> Residual Solvents.

19. European Commission (Enterprise Directorate General). EMA Guideline on the specification limits for residues of metal catalysts or metal reagents. Brussels, Belgium; 2008.

20. ICH. Q5A (R1), Viral safety evaluation of biotechnology products derived from cell lines of human or animal origin, Geneva, Switzerland; 1999.

21. FDA Guidance for Industry. Pharmaceutical components at risk for melamine contamination. Rockville, MD; 2009.

22. 21 CFR 211.72 Filters. 2009.

23. ICH. Q10, Pharmaceutical quality system, Geneva, Switzerland; 2008.

24. A Guide to Supply Chain Risk management. Pharmaceutical Quality Group. 2010. Available from:

25. ASTM Standard E-2500, 2007, "Standard guide for the Specification, Design and Verification of Pharmaceutical and Biopharmaceutical Manufacturing Systems and Equipment" ASTM International, West Conshohocken, PA, 2007.

26. Low D, Phillips J. Evolution and integration of Quality by Design and Process Analytical Technology. In Rathore AS, Mhatre R, editors. Quality by Design for biopharmaceuticals. Hoboken, NJ: Wiley Interscience; 2009. 255–86.

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