August 5, 2021: Pharmaceutical Interview Questions and Answers
#ProcessValidation #ContinuedProcessVerification #ProcessQualification #StagesOfProcessValidation
1. What are the Stages of Process Validation?
Stage 1 – Process Design
Stage 2 – Process Qualification
Stage 3 – Continued Process Verification
2. What is integrated team approach to process validation?
Integrated team approach to process validation that includes expertise from a variety of disciplines (e.g., process engineering, industrial pharmacy, analytical chemistry, microbiology, statistics, manufacturing, and quality assurance).
3. Explain “Process Design”, Stage 1 of process validation.
Objective: To design a process that can consistently deliver a commercial product meeting quality attributes.
a. Building and Capturing Process Knowledge and Understanding from
• Previous experience with similar processes
• Product and process understanding (from clinical and pre-clinical activities)
• Analytical characterization
• Published literature
• Engineering studies/ batches
• Clinical manufacturing
• Process development and characterization studies
• Product development activities
• Design of Experiment (DOE) studies to develop process knowledge and relationships between the variable inputs (e.g., component characteristics 13 or process parameters) and the resulting outputs (e.g., in-process material, intermediates, or the final product)
• Computer-based or virtual simulations of certain unit operations or dynamics can provide process understanding and help avoid problems at commercial scale
• Documentation of process understanding, activities and studies
b. Establishing a Strategy for Process Control
An appropriate control strategy is based on knowledge and experience gained in Stage 1 that will help to control manufacturing process.
Strategy for Process Control includes the following elements:
• Raw material controls
• In-process and release specifications
• In-process controls
• Performance parameters
• Process parameter set points and ranges
• Process monitoring (data review, sampling, testing)
• Processing and hold times
• Process Analytical Technology (PAT)
4. In which scenarios process control through operational limits and in-process monitoring is essential?
In case of following two possible scenarios, process to be controlled using operational limits and in-process monitoring:
a. When the product attribute is not readily measurable due to limitations of sampling or detectability (e.g., viral clearance or microbial contamination) or
b. When intermediates and products cannot be highly characterized and well-defined quality attributes cannot be identified.
5. Explain “Process Qualification”, Stage 2 of process validation.
Objective: In this stage, the process design is evaluated to determine if it is capable of reproducible commercial manufacture.
This stage has two elements:
i. Design of the facility and qualification of the equipment and utilities
ii. Process performance qualification (PPQ).
a. PPQ Protocol
b. PPQ Protocol Execution and Report
CGMP-compliant procedures must be followed. Successful completion of Stage 2 is necessary before commercial distribution. Products manufactured during this stage, if acceptable, can be released for distribution.
6. Explain “Continued Process Verification”, Stage 3 of process validation.
Objective: The goal of the third validation stage is continual assurance that the process remains in a state of control (the validated state) during commercial manufacture. A system or systems for detecting unplanned departures from the process as designed is essential to accomplish this goal.