Biomedical Engineering Reference
In-Depth Information
may be needed to support QbD applications for biotechnology products. As experience
with QbD increases, the data in submissions may decrease; however, the relevant data
should be available on inspections.
2.9 IMPLEMENTATION PLANS
It is clear that both agency and industry need experience to move forward with QbD
for biotechnology products. The small-molecule world has made notable progress in
implementing QbD through a variety of conferences, Cooperative Research and
Development Agreements (CRADAs), and workshops [49] using mock products
[50]. However, one of the most beneficial programs for moving forward has been
the QbD pilot program by the Office of New Drug Quality Assessment (ONDQA) at
CDER [8]. By encouraging industry to provide real examples, important issues were
clarified. The use of risk assessments and DOE were important topics in QbD pilot
submissions [51].
Although information from the ONDQA QbD pilot and other small-molecule
experience is very relevant for biotechnology products, there are special considerations
for complex products and processes. To deal with these considerations, a pilot for
biotechnology products has been suggested and discussed at a number of venues [52, 53].
This pilot should focus on unique issues for biotechnology products and also provide
information on applying QbD to both unit operations and entire applications. Since there
are fewer biotechnology product applications than small-molecule applications, it would
be useful to include supplements for already approved products in the pilot. Full QbD
applications should ideally involve multiple unit operations that are linked, and such
applications could benefit from earlier sponsor-agency interactions. In addition to the
pilot, workshops discussing mock biotechnology QbD applications would also be of
value.
One important issue that was highlighted by the small-molecule pilot was the need
for an approach to regulatory opportunities. Industry is very interested in regulatory
approaches to managing postapproval changes under QbD. One approach to this would
take advantage of current regulations for protocols [54, 55]. Comparability protocols are
a type of protocol used for manufacturing changes. Comparability protocols provide
upfront information and criteria for a type of change and if approved, allow for a reduced
reporting category for that change. Although comparability protocols have been used for
multiple changes, they have often been used for a single change. By providing the
enhanced product and process knowledge associated with QbD, a protocol could cover a
broader range of changes. Such a protocol could be called an expanded change protocol
and would be a useful tool in a biotechnology QbD pilot. The use of specific protocols by
sponsor's quality systems in dealing with design space uncertaintywas suggested earlier.
Expanded change protocols could provide information on developing quality systems
protocols for industry managed changes. The pilot could also provide information on
approaches to site changes and inspectional issues for QbD submissions. For QbD
submissions using an expanded change protocol, the protocol may be another possible
location for the QbD narrative.
