PROCESS LIFECYCLE VALIDATION - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 178

• The use of detection in an overall risk score should increase as the project
moves from development into the validation or process performance qual-
ification (PPQ) stage. Detections are controls and the evaluation of the
effectiveness of these controls is an essential part of validating a system.
Thus, the value of using detection could be determined on a case-by-case
basis.
Appropriate statistical methods should be applied throughout the PV program
as a means of ensuring the robustness of the experimental design and result-
ing data, as well as supporting the application of QRM [12,13]. The statistical
approach and methods, including justification and rationale, should be docu-
mented. Potential application of statistical methods includes the following:
• setting of acceptance criteria;
• design of testing and sampling plans;
• data analysis and trending; and
• process robustness and capability analysis.
8.4 GENERAL CONSIDERATIONS OF QRM IN PROCESS
VALIDATION
A number of factors such as manufacturing equipment, raw materials, and pro-
cessing conditions are likely to impact product quality. Assurance of product
quality is derived from product and process design, adequate control of input
process parameters, and testing of in-process and finished product samples. Each
step of the manufacturing process must be controlled to maximize the probability
that the finished product meets all quality and process requirements. The valida-
tion project plan (VPP) or master plan should document a complete list of PV
studies required for product/process licensure. Note that any study that supports
process parameter ranges in the license application and/or master batch record is
identified as a PV study that includes development, characterization, and valida-
tion studies. The plan may incorporate a risk-based approach to rank activities
based on risk and/or criticality and frequency of the activity. In addition, this
will help identify an appropriate level of effort and timing of PV activities.
The following are some factors that may lead to unsuccessful PV; this is not
an all inclusive list.
1. Inadequate risk management, inappropriate RA tool selection, lack of
involvement of the SMEs, inadequate identification of hazards, inaccurate
evaluation of risks, or insufficient or lack of timely control of unacceptable
risks.
2. Poorly written protocol execution cannot be completed as written or
repeated by other operators.