Recently life sciences professionals from around the world gathered in Boulder, Colo., to participate in Aegis Analytical’s annual software user conference, DISCOVER 2011. Among the highlights of the conference were an opening keynote delivered by Ajaz Hussain, Ph.D., former FDA Deputy Director of the Office of Pharmaceutical Science (OPS), and a closing presentation by Blair Okita, Ph.D., president of BioPCS Consulting and former senior vice president of quality and technical operations at Genzyme Corp. Both are industry movers and shakers who propagate the notion that quality is not an option but rather a necessity. With drug shortages making headlines on a weekly basis, companies need to leverage data for efficient tech transfer, process understanding and continuous improvement to help ensure adequate supply, lower production costs and greater profitability.
Hussain provided an historical overview of the events and thinking that led to new approaches to continuous improvement and the challenges that have kept life sciences manufacturers lagging behind. In his conference-opening keynote address titled “Pharmaceutical Quality in the 21st Century: Personal Reflections,” Hussain walked through the state of the FDA and the industry as a whole that led to the creation of new FDA initiatives around quality. Prior to 2002 the number of annual product recalls were sharply increasing, quality issues led to drug shortages, and the FDA, not the industry, increasingly was doing defect discovery. Investments and technology were applied to R&D while manufacturing remained low tech. Opportunities for improvements seemed limitless, yet internal and external debate surrounded the “FDA Initiative on Pharmaceutical Quality for the 21st Century.”
The quality problems, which other industries solved 20 years ago, resulted from human behavior, and were not technical in nature, according to Hussain. “We were all mired by turf battles not collaboration…debates were ongoing over the difference between process validation—is it not just a well-rehearsed demonstration?—and process control and understanding.”
One primary requirement was that the FDA and industry needed better tools and information to make science and risk-based decisions, along with more collaborative language and a team approach between Chemistry, Manufacturing and Control (CMC) reviewers and the cGMP team at the FDA. Hussain discussed the development of the FDA’s Process Analytical Technology (PAT) Initiative in 2002 which led to subsequent “desired state” initiatives including several International Conference on Harmonisation (ICH) guidances and eventually to the evolution of the Quality by Design (QbD) initiative and where it stands today in the life sciences industry:
“People appear to be forgetting that QbD is not an option, Design Space is,” said Hussain. “PAT innovation was an option, but quality has to be built into products by design.”
He referred to a July 2011 McKinsey presentation “State of QbD Implementation: Adoption, Success and Challenges”1 which notes that companies are in various stages of QbD implementation—from experimenting, increased acceptance and understanding to full implementation where it is systematic and comprehensive from development through production. While many life sciences companies, and particularly newer organizations, see the value and business benefits of QbD, many companies remain challenged in several areas. Some of those challenges include the required cultural changes, inadequate collaboration internally and with third parties, inadequate tools for data collection and technology tools to execute efforts, and industry support challenges with the FDA and other international regulatory bodies.
Hussain remains hopeful the FDA and life sciences industry will continue to evolve, in part, by confronting current challenges such as figuring out how to effectively manufacture biosimilars–an area in which the EMA is ahead of the U.S. He suggested that established biologics “lend themselves to a high level of mechanistic understandings” and time to market is critical so uncertainty needs to be minimized. “Biosimilars exemplify an opportunity for using a mechanistic understanding for regulatory approval and decisions when to require clinical trials,” he said.
Okita concluded the DISCOVER 2011 conference with some similar observations in his presentation “Sustainable Pharmaceutical Manufacturing: Fiction, Assumptions or Facts.” He shared insights related to 21st century QbD – with a central theme of data transformed into knowledge that can be used to achieve sustainability.
Okita defined sustainability as the capability to supply pharmaceutical products to each patient, now and in the future. “It is the ability to adapt and thrive in an evolving environment and is one of the most important attributes to have in pharmaceutical manufacturing,” he said. He stressed the importance of working as a product team, process understanding and rigorous change control, and how all of these “efforts need comprehensive, integrated tools for data capture and analysis.”
He shared a case study from his time at Genzyme about “Manufacturing in a crisis – leveraging knowledge management in a viral contamination investigation” and the key takeaways from that crisis which included:
- The importance of the systematic gathering and analysis of data, which is a good business practice as well as a regulatory expectation.
- The associated, sophisticated support tools to analyze and visualize what is going on with complexity of processes and supply chains.
- The integration of information across the manufacturing process and product life cycle should be minimal expectations.
He concluded that “the transformation of information into product and process knowledge is the new norm” leading to quality and sustainability.