is a systematic approach to gathering and analyzing sufficient data
which will give reasonable assurance (documented evidence), based upon
scientific judgment, that a process, when operating within specified
parameters, will consistently produce results within predetermined
validation is establishing documented evidence which provides a high
degree of assurance that a specific process (such as the manufacture of
pharmaceutical dosage forms) will consistently produce a product meeting
its predetermined specifications and quality characteristics.”
- “Process validation is defined as the collection and evaluation of data, from the process design stage through commercial
production, which establishes scientific evidence that a process is
capable of consistently delivering quality product.”
is the act of demonstrating and documenting that a procedure operates
effectively. Process validation is the means of ensuring and providing
documentary evidence that processes (within their specified design
parameters) are capable of consistently producing a finished product of
the required quality.”
Importance of Validation
- Increased throughput
- Reduction in rejections and reworking
- Reduction in utility costs
- Avoidance of capital expenditures
- Fewer complaints about process-related failures
- Reduced testing in-process and in finished goods
- More rapid and reliable start-up of new equipment
- Easier scale-up from development work
- Easier maintenance of equipment
- Improved employee awareness of processes
- More rapid automation
Stages/Phases of Validation
Stage 1: Process Design (Pre-Validation Phase)
This is the step where building and capturing of the process knowledge and understanding took place. Early design of processes and experiments should be performed during this stage. It covers all activities relating to product research and development, formulation, pilot batch studies, scale-up studies, transfer of technology to commercial scale batches, establishing stability conditions, storage and handling of in-process and finished dosage forms, equipment qualification, installation qualification, master production documents, operational qualification, process capability. Also this is the stage in which the establishment of a strategy for process control is taking place using accumulation knowledge and understanding of the process.
Stage 2: Process Qualification (Process Validation Phase)
This stage is confirmation that the process design is capable of reproducing the manufacturing process. It confirms that all established limits of the Critical Process Parameters are valid and that satisfactory products can be produced even under “worst case” conditions. GMP compliant procedures must be followed in this stage and successful completion of this stage is necessary before commercial distribution of a product.
Stage 3: Continued Process Verification (Validation Maintenance Phase)
The Validation Maintenance Stage requires frequent review of all process related documents, including validation audit reports to assure that there have been no changes, deviations, failures, modifications to the production process, and that all SOPs have been followed, including change control procedures. Before any batch is distributed for marketing, the manufacturer must have full assurance of its performance. A successful validation program depends on the knowledge and understanding and the approach to control manufacturing processes. These include the source of variation, the limitation of the detection of the variation, and the attributes susceptible of the variation. It is the responsibility of the manufacturer to judge and provide evidence of a high degree of assurance in its manufacturing processes. They are also responsible for maintaining the degree of assurance accomplished, even if some minor changes occurred due to personnel, material and process changes.
Type of Validation
- Prospective Validation
- Concurrent Validation
Concurrent validation is of great use when the test employed is not destructive and can determine the product meet predetermined standards and quality. Concurrent validation is also carried out on product or process which is previously validated process to ascertain that the product or the process meets required standards and is validated.
- Retrospective Validation
- Re validation
Re-validation may be divided into two broad categories:
• Re-validation after any change having a bearing on product quality.
• Periodic re-validation carried out at scheduled intervals.