PROCESS LIFECYCLE VALIDATION - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 181

• The unit operation has been validated for other product(s) of the same type
(e.g., monoclonal antibodies, water-soluble mixing), and comparable results
are obtained.
• Process parameters of the new process fall within the limits of the previously
validated processes.
8.5 CHALLENGES IN USING RISK-BASED VALIDATION
Owing to the increasing regulatory expectations, companies appear reluctant to
implement new approaches that they are not fully familiar with and that may
delay product approval. Before the FDA's 2002 initiative on risk-based approach
“Pharmaceutical GMPs for the 21st Century,” most firms used the traditional
validation approach of selecting three batches, which has been generally accept-
able and incurred little inspectional scrutiny. Risk-based approaches are currently
well accepted by the regulatory agencies. The challenge is determining the appro-
priate amount of validation data to ensure product quality and patient safety as
well as to deliver confidence to the company and regulators. If sound science
and reasoning is used along with documented rationale, the confidence goal is
attainable. However, the risk-based approach/strategy should not be an excuse to
avoid or minimize validation; even if a risk is deemed acceptable with current
controls and no new controls are required, the validation requirements still need
to be assessed and focused.
One approach to achieve that goal is by using a team of SMEs and fully
documenting the RAs and the scientific rationale used. In addition, it is essential
for risks to be communicated to appropriate stakeholders and decision makers at
various stages of the risk management process.
The following issues should be addressed when conducting formal RAs for
PV in order to make them successful and acceptable to the regulatory authorities.
1. Minimizing subjectivity during risk ranking that can lead to uncertainty
and bias in the results obtained. An unbiased facilitator who is trained in
the application of the formal RA tool plays an important role in ensuring
the success of the RA. Note that regulators may challenge the risk scoring
and the outcomes of the RA if the risk scores are inadequately justified.
Hence, the main focus should be on documenting the risks, controls, and
any supporting rationale that are truly scientific, knowledge based, and/or
data based.
2. Clarity of business versus GMP risks and patient versus compliance risks
is essential.
3. Document GMP controls and the risk acceptance and risk control decisions
made from the risk management exercise.
4. Robustness, flexibility, and documentation of the individual risk evalua-
tions (assigning of numerical scales and values). Use of appropriate RA
tools and training is essential.