PTE: In August 2011, FDA released a strategic plan, Advancing Regulatory Science at FDA. Priority 3 of that plan focuses on
product manufacturing and quality, including enabling the development and evaluation of novel and improved manufacturing methods
to improve product quality, namely through continuous manufacturing, novel manufacturing technologies, excipients and complex
dosage forms, and process analytical technology (PAT) and quality-by-design (QbD) approaches. What does FDA and the industry
hope to gain by focusing on these areas?
FDA: FDA is responsible for protecting the consumer through the availability of quality products. These approaches focus on good,
sound science in achieving a high quality product. By applying QbD and understanding the role of excipients and complex dosage
forms, a higher level of product and process understanding will be obtained. The other approaches, (PAT, continuous manufacturing
and novel manufacturing technologies) utilise that understanding to achieve a more robust and capable manufacturing processes,
resulting in higher product quality. With this higher level of product quality, the product failure rate is expected to drop,
which in turn, will increase product availability, and reduce product cost. Therefore, by focusing on these science-based
approaches, FDA is confident that the overall quality of pharmaceutical products [will] continue to increase.
Modernising manufacturing approaches for pharmaceuticals, such as through QbD, continuous manufacturing and/or PAT, has the
potential to benefit industry, regulators, and patients. Already, there have been multiple reports of quality and cost benefits
to manufacturers through the use of QbD and/or PAT approaches. For patients, these approaches can lead to increased assurance
of quality and product availability. For regulators, it potentially means less regulatory oversight postapproval due to regulatory
flexibility (e.g., design space) filed with the application. FDA is currently pursuing additional pathways to ease postapproval
changes for well-understood and controlled processes under a robust quality system.
Continuous manufacturing, although new to most pharmaceutical manufacturing, is a commonly used technology in food and chemical
processing. As more companies are gaining experience with continuous manufacturing, benefits are emerging, including cases
of reduced manufacturing scale-up issues, reduced material usage in development, and flexible manufacturing capacities. Because
of the changing dynamics of new drugs toward more specialised, lower-volume products, continuous manufacturing could become
more commonplace in the years ahead.
Finally, it is becoming increasingly important to understand the interactions between drug(s), excipients, and device components
as pharmaceutical dosage forms are becoming more complex, such as multiple active ingredients in a single drug product or
drug–device combinations. The higher level of understanding should allow for more robust products that deliver their intended
performance when either planned or unplanned changes are introduced.
PTE: Priority 3 in the strategic plan also calls for developing new analytical methods, including those to determine 'similarity'
between reference products and biosimilars as well as tools to detect physical properties of complex dosage forms. What gains
are hoped for amongst agency scientists in these analytical areas?
FDA: Advances in analytical methods to determine 'similarity' between reference products and biosimilars, as well as tools to
detect physical properties of complex dosage forms, will allow for greater confidence that there are no structural differences
between products or that any differences observed are minor. For biosimilars, this will reduce uncertainty and allow for a
targeted development program. This can also facilitate the development and approval of generics with complex dosage forms,
as well as inform control strategies for quality of complex originator products.