Biologics, too
As pharmaceutical companies are weighing revisions to Q6a, biotech
manufacturers are examining similar options for Q6b, the ICH guideline
on setting specifications for biotechnological products. The need to
develop a rational approach for establishing and using specifications
through the biotech product life cycle was examined this past October
at a workshop sponsored by FDA, industry, and the American Association
of Pharmaceutical Sciences. Some 200 attendees explored the purposes of
specifications and challenges in identifying clinically relevant
measures. The session clarified that specifications are important
parameters that a product must meet, although limits apply to less
critical measures that a product should meet.
Participants acknowledged that specifications may not be needed for
certain product attributes that demonstrate little batch-to-batch
variation or sensitivity to manufacturing change, explained Keith
Webber, director of CDER's Office of Biotechnology Products. He noted
that critical quality attributes could include identity, strength,
quality, purity, and potency. At registration, a manufacturer may
estimate assay variability and proposed shelf-life. Continuous product
improvement is the goal of postmarketing activities that provide
additional understanding of a product and process. Webber noted that
current standards encourage the use of batch data to calculate shelf
life and other specifications and that further discussion by FDA and
industry is needed to resolve key issues related to using
specifications to ensure quality throughout a product's lifetime.
Concerns
and confusion
The PQRI March workshop generated considerable discussion about these
issues but appeared to fall short of its original goals. Meeting
organizers had hoped to achieve a consensus about how manufacturers
could identify the most critical parameters for a safe and effective
drug product as well as less vital measures. The three-day discussion
exposed some 500 attendees to innovative concepts, but in the end, most
participants had difficulty moving away from more traditional
approaches to ensuring product quality.
Some manufacturers questioned whether it's worth the time and cost
to reach a still unclear "desired state" of pharmaceutical development
within a somewhat vague "design space." And, they expressed fear that
innovative approaches will draw more regulatory scrutiny. There appears
to be a strong reluctance to shift from specifications determined by
clinical batch data or to loosen up tight acceptance criteria that
ensure the process is under control. Some of these issues were
discussed at the May meeting of FDA's Advisory Committee for
Pharmaceutical Science and further deliberations are expected in coming
months. If anything, the PQRI workshop revealed how important
specifications are to drug development and quality control, which are
key issues in any effort to modernize prescription drug manufacturing
and production. PT
