PROCESS LIFECYCLE VALIDATION - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 216

minor equipment where the visual limit is at or below the residue accept-
ability limit) may provide adequate data to support the conclusion that
dirty equipment hold times for product residues are not critical. For
example, rinse checks after cleaning are required for changeover cleaning
of major equipment that cannot be visually inspected in API manufac-
turing.
• Laboratory recovery study data for the product residues may have been
generated when residues are dried on representative sample surfaces
(coupons). These data may also support noncleaned equipment hold time
rationales or data demonstrating that DEHT is not critical. This may be
more applicable for chemical APIs, where only a single component is
typically removed during cleaning (versus active and excipient mixtures
in drug product).
8. Firm's Standards: Company requirements were reviewed to ensure compli-
ance.
9. Regulations: Local GMP regulations and inspectors' expectations.
Product groups and equipment groups can also be used in the analysis. In the
risk evaluation, products should be evaluated for each of these risk factors for
their potential failure mode. If necessary, additional mitigation can be achieved
by initiating cleaning immediately after equipment use to reduce or eliminate
the significance of dirty hold times with respect to product residue. This can
include post-campaign/batch flushing of the equipment. The type, complexity,
and amount of disassembly of equipment (valves, lines, and hoses) may influence
the amount of sampling needed to extend the hold time. Table 8.12 shows a
simplified example of FMEA.
8.11 SUMMARY
QRM is currently recognized by the industry and regulatory authorities as a valu-
able tool to define the type and extent of PV or performance qualification required
for product licensure. Performing new RAs involves upfront costs with potential
pay-off later both in terms of product quality and cost saving. To minimize any
subjectivity of the outcome, QRM application including tool selection should be
appropriate and robust, facilitated by trained QRM personnel, and the outcomes
and decisions documented and communicated.
QRM is not only a good business practice but it also meets regulatory expec-
tations. With early investment made in the validation lifecycle, the risk-based
approach focuses on performing appropriate studies, scientific data, and rationale,
and avoids non-value-added activities. It can be used to make decisions, prioritize
activities, investigate deviation, and achieve a level of confidence in the process.