U.S. Pharmacopeia (USP) brought together preeminent thought leaders from industry, global health organizations, regulatory agencies, standards setting organizations and other stakeholders at its virtual Global Biologics Summit on June 11, 2020. Discussions centered around challenges in developing and manufacturing quality biologics in an increasingly global pharmaceutical landscape.
Biologics was already a rapidly growing segment of drug development, and now with the onset of COVID-19, development in this area has become only more urgent. But compared to well-established therapeutics that are based on small molecule active pharmaceutical ingredients (APIs), biologic drugs remain a relatively new endeavor. The development, manufacturing and regulatory environments for biologics are complex and dynamic. Questions around quality, consistency, safety and effectiveness remain unanswered. The purpose of the summit was to begin a dialog to prioritize these and other issues, which can be solved through global collaboration.
Summit participants agreed that expectations for quality are high among healthcare providers and patients. The realities of biologic drug manufacturing, however, require acceptance of some variability, within acceptable limits. The complexity of both the biologic therapeutic substances and their manufacturing processes make it challenging to define those acceptable limits. This is especially true for biosimilars, where the analytical methods used to demonstrate a high degree of similarity to the originator is one of the most critical elements for successful development. But even before acceptable variability limits can be defined, the type and number of critical quality attributes (CQAs) required to ensure a product’s quality need to be established.
The panelists agreed that it is essential to understand which CQAs are important and the need for these to be correlated to patient outcomes. In vitro and in vivo assays to assess CQAs earlier in development could help manage the dependence on clinical trials for performing risk assessments. There was consensus that the right type of tools (e.g., standards) will be needed to link these non-clinical methods to patient outcomes. Publicly vetted, well characterized standards could be used to calibrate in-process analytical methods and potency assays, which could be a critical intermediate for correlating methods to clinical outcomes. Developing the right standards will require a common understanding of the CQAs that must be measured and acceptable variability ranges.
Because there are common challenges across the biopharmaceutical industry, panelists recommended greater collaboration through partnerships and consortia to identify CQAs, establish acceptable ranges of variability, and identify how these link to clinical outcomes. Other forward-looking solutions that were proposed included, training and education programs to promote standards and methods to align manufacturers around shared quality management systems, methodological guidance combined with physical standards, and creating a culture of quality fostered by roundtables and other opportunities that bring stakeholders together.
As a convener, USP brings stakeholders together for interactive discussions designed to identify areas of need and opportunity where standards that support quality initiatives will be most beneficial. An independent, nonprofit, scientific organization committed to global public health, USP works collectively with stakeholders to develop standards that help address industry challenges and support quality medicines. Gaps in communication between industry and the healthcare community impede trust, and as a result, uptake of innovative and potentially lifesaving treatments. Standards could be part of the underpinnings that bridge the gap. The standards used to measure CQAs coupled with an understanding of how they correlate to clinical outcomes will help demonstrate to the healthcare community and to patients the quality, safety and effectiveness of originator biologics and biosimilars. The experiences of some summit panelists confirm that adoption rates increase once trust is established between industry and healthcare providers.
For the past 200 years, USP has engaged with scientists and thought leaders from industry, regulatory agencies and other stakeholder groups to identify and develop standards that support therapeutic innovation. We invite summit participants and other members of the biopharmaceutical, regulatory and healthcare communities to collaborate with USP to develop standards that will be beneficial to the industry, foster innovation and enhance access to biologic drugs worldwide.