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Quality by Design (QbD): Seeing the Glass as Half Full

Wednesday Aug 10, 2016

by: Brendan Cooney

As the biopharmaceutical manufacturing industry grows and becomes global, companies face demands to improve quality, while reducing costs and increasing output. The road to achieving these goals is through the adoption of QbD. A paradigm shift, when adopted by the FDA in 2004, QbD is modernizing the approach to pharmaceutical development by providing the industry with regulatory flexibility, increased development and manufacturing efficiency, and providing opportunities for innovation.


A recent article authored by BPTC consultant Brendan Cooney entitled; “Quality by Design for Monoclonal Antibodies, Part 1: Establishing the Foundations for Process Development”, describes the current best practices concerning the implementation of QbD in the manufacture of monoclonal antibodies. QbD is a systematic developmental approach that starts with a clear goal in mind and emphasizes understanding of how variability in both process and materials impacts the final product. Historically, product quality has been assured by either end product testing (drugs) or by strict and narrow control of the manufacturing process without a comprehensive understanding of the link between process parameters and product quality attributes (biologics). When QbD is properly implemented, quality is built into the process rather than being tested into the product, allowing for incremental process changes to be made within defined ranges without needing prior regulatory approval.


BPTC’s 2nd edition of “The Development of Therapeutic Monoclonal Antibody Products”, due to publish in September 2016, provides extensive coverage of QbD as applied through the CMC development cycle. This report provides a roadmap covering strategy, technical and regulatory requirements for the development of a monoclonal antibody product from initial discovery through the filing for first in human clinical trials.


FDA Doubles Down on QbD

Wednesday Jul 13, 2016

by: Brendan Cooney

After a 13 year gap the US FDA has updated its guidance on Comparability Protocols bringing it in line with contemporary thinking on modern pharmaceutical development practices. So what are the implications?

The key changes in this version of the guidance document involve updates to put the guidance in line with QbD, PAT, and Process Validation principles. FDA has long voiced its support for QbD to industry, but industry itself has not fully come around. For FDA to clearly state that things like continuous improvement, understanding the process, and risk management over the course of a product’s lifecycle are significant represents a shift from merely holding QbD up as an idealized model to actually spelling it out in what will eventually be a binding document. The potential for flexibility in product development offered by QbD is closer to being in reach with this guidance. FDA has made a clear statement that they are all-in for QbD with this document.

Comparability Protocols for Human Drugs and Biologics: Chemistry, Manufacturing, and Controls Information has, significantly, been brought into alignment with the principles of Quality by Design (QbD) outlined in ICH guidelines Q8(R2) Pharmaceutical Development, Q9 Quality Risk Management, Q10 Pharmaceutical Quality System, and Q11 Development and Manufacture of Drug Substance. The updated guidance has received a significant facelift, but, like renovators of a cherished historical home, the FDA has taken care to ensure that the foundations and original character of the document remain.

In Comparability Protocols for Human Drugs and Biologics: Chemistry, Manufacturing, and Controls Information the FDA shows the level to which it has embraced QbD and clearly wants people to take notice. The updated guidance contains notable references to the QbD guidelines listed above, as well as FDA’s Guidance for Industry: PAT and the 2011 Guidance for Industry: Process Validation. In some cases, the QbD guidelines are referenced directly, while in others the texts have a similar feel.

The Federal regulations that govern comparability, 21 CFR 314.70 and 21 CFR 601.12, have been updated four and six times respectively since 2003, when the comparability guidance was last updated. In addition to the QbD and federal regulation updates, new to Comparability Protocols is the inclusion of language that mandates the adherence to cGMP protocols when making any post-approval changes. This guidance is now relevant to anyone filing an NDA or BLA.

The greater embrace of QbD, PAT, and Process Validation may be easily absorbed for larger companies, but may place a significant burden on smaller firms with limited resources. It is, however, important to note that QbD principles should not be abandoned due to cost. Hiring a consulting firm to handle multiple aspects of the CMC operations or filing can be advisable and definitely affordable in the long run. As Ben Franklin quipped, “remember time is money”.


Opportunities for Continuous Manufacturing in Biopharmaceutical Production

Monday Jun 27, 2016

Thomas C. Ransohoff, M.S., Vice President and Principal Consultant at BPTC, gave a presentation entitled “Opportunities for Continuous Manufacturing in Biopharmaceutical Production” at the World BioPharm Forum 2016: Progress in Continuous Biomanufacturing, on June 28, 2016 held at Robinson College, Cambridge, UK. Tom’s presentation focused the potential benefits of continuous manufacturing in the production of bio/pharmaceuticals as well as the challenges in implementing these and other new technologies in the production of biopharmaceuticals. His presentation presented current trends in supply and demand for biopharmaceutical manufacturing capacity based on information from BPTC’s bioTRAK® database. Using this information, an analysis the application areas that represent the most attractive near-term opportunities for implementing continuous manufacturing in our industry were presented. Challenges specific to these application areas were also reviewed. Follow the link above for a pdf of Tom’s presentation.


CMC Strategy Forum

Monday Jun 20, 2016

Title: CMC Strategy Forum
Location: Gaithersburg, MD
Link out: Click here
Description: Joseph Siemiatkoski, Consultant at BPTC will be attending the CMC Strategy Forums “Emerging Strategies in Drug Product Comparability and Process Validation” and “Change Happens: Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management” during the CaSSS CMC Strategy Forum -Summer 2016 Symposium to be held at the Gaithersburg Marriott Washingtonian Center from July 18-21, 2016.
Start Date: 2016-07-18
End Date: 2016-07-21


Emerging Bio-Therapies and Their Manufacturing Challenges – BIO 2016

Friday May 20, 2016

Patricia Seymour, Senior Consultant, BioProcess Technology Consultants, Inc. will lead a panel discussion entitled, Emerging Bio-Therapies and Their Manufacturing Challenges at the BioProcess Intl, BioProcess Theater at BIO 2016 June 6-9 in San Francisco, CA. Panel experts will focus on the emerging therapies using cell and gene therapy, drug conjugates, bispecific antibodies and others, and the unique manufacturing challenges these therapies present. The panel will cover:

  • Process development and manufacturability of these therapies
  • Access to manufacturing facilities for these therapies – outsource or build
  • 20/20 – how prevalent will these therapies be by 2020 and beyond, and will industry be able to meet the demand

Please stop at the BPTC booth #6267 while at BIO 2016.