QbD is Changing the CMC Regulatory Landscape in the US and EU

The May 2010 issue of International Pharmaceutical Quality (IPQ) provides an in-depth analysis of how quality by design and the new Q8-10 regulatory paradigm is transforming the CMC review process at the agency and international levels.

THE QUALITY REGULATORY INITIATIVES UNDERWAY AS THE NEW DECADE BEGINS show the strong imprint of ICH Q8-10 at both the agency and international levels. From CMC application review to GMP inspections, from development to post-market manufacturing, from the ingredient supply chain through product distribution, the quality-by-design, risk management and quality system principles built into the new ICH guidelines are being integrated into industry/regulator interactions and the guidance, policies and initiatives that define them.  As experience with ICH Q8-10 implementation grows, the knowledge gaps that need to be filled are coming into sharper relief,and industry, regulators and academia are in close dialogue on how to fill them.  Managing and regulating the flow of quality-by-design knowledge from development into manufacturing and through the production lifecycle are central challenges on the table.The value of the QbD building blocks is becoming better understood while questions are emerging on how that value can best be realized and with what regulatory implications. The lifecycle interdependence of the Q8-10/QbD components is leading regulators to rethink the way their review and inspection organizations have interacted.

EDITORS’ NOTE:This issue of IPQ analyzes the impact the new QbD paradigm is having on the initiatives and dialoguea round reshaping the CMC review process. In the next IPQ issue (June), the focus will shift onto how the inspection and GMP enforcement components of the regulatory picture are being impacted as the quality system foundation for continuous improvement strengthens.


• CDER’s Christine Moore on implementing QbD for drugs(Appendix I, pp. 42-45)
• CDER’s Steven Kozlowski on implementing QbD for biotech products(Appendix II, pp. 46-48)
• EMA’s Evdokia Korakianiti on the implementation of QbD in Europe (Appendix III, pp. 49-53)
• CDER’s Nakissa Sadriehon regulating nanotechnology in therapeutics (Appendix IV, pp. 54-61)
• Genentech’s Christa Hartmann on a new knowledge management paradigm (Appendix V, pp. 62-64)



ICH Focusing On Q8-10 Implementation  3
Drug Substances, Methods Also On ICH Screen  5
ICH Takes On Heavy Metals  5
Cultural Change Takes Time And Effort  6


CDER QbD Experience Expanding  9
The Gaps That Need Filling  12
Continuous Manufacturing Touted by FDA  13
Biotech QbD Pilot Focuses On Clinical Relevance  14
CDER MAPPs Out Biotech Reviewer/Inspector Roles  15
FDA Generic Drug Review – Through QbR to QbD  17
ICH Vision Taking Shape In EU With PAT Team Help  19
Workshops, New Guidelines Support EMA Efforts  21
Ireland Following Suit With Industry Collaboration  23
FDA, EMA Work On Clearing CMC Change Pathway  24


Risk Management – What’s The Score?  25
Design Space Still Contains Some Rough Edges  26
QbD Puts Spotlight On Knowledge Management  28
The Burden Of Knowledge  29
Models Help Development And Submissions  30
QbD For Analytical Methods Having Strong Impact  32
Application of QbD In Analytics Poses Some Issues  33


NIST Offers Help In Biotech Measurement Standards  34
USP, PQRI Exploring Their Roles  36
QbD Gaining Traction In Non-ICH Countries  40

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