Before commencing a validation 4u task; an experimental runs must be planned.
These runs must establish the exact parameters that your validation run is going to use and or attain in the final qualification runs of the system under qualification.
Most validation efforts require some degree of prospective experimentation to generate and establish validation support data. This particular type of process validation 4u is normally carried out in connection with the introduction of a new drug or medical device and or their manufacturing processes.
The formalized process validation program should
never be under taken unless and until the following operations and procedures have been completed satisfactorily:
- The facilities and equipment in which the process validation is to be conducted meet CGMP requirements (completion of DQ, IQ, OQ and PQ).
- The operators and supervising personnel who will be “running” the validation batch (es) have a comprehensive understanding of the process and its requirements.
- The design, selection, and optimization of the formula have been completed.
- The validation 4u trials using an agreed size of pilot-laboratory batches have been completed, in which the critical processing steps and process variables have been identified, and the provisional operational control limits for each critical test parameter have been provided
- Detailed technical information on the product and the manufacturing process have been provided, including documented evidence of product stability.
- Finally, at least one validation4u trial of a significantly larger production batch has been made and shows up; on scale-up, that there were no significant deviations from the expected performance of the process.
The retrospective validation 4u option is chosen for established products whose manufacturing processes are considered stable and when on the basis of economic
considerations alone and resource limitations, prospective validation programs cannot be justified.
Prior to undertaking retrospective validation 4u, wherein the numerical in-process and/or end-product test data of historic production batches are subjected to statistical analysis, the equipment, facilities and subsystems used in connection with the manufacturing process must be qualified in conformance with CGMP requirements.
The concept is also recognized in the FDA’s Guidelines on General Principles of Process Validation 4u Using either data-based computer systems [28,29] or
manual methods, retrospective validation 4u may be conducted in the following manner:
- Gather the numerical data from the completed batch record and include assay values, end-product test results, and in-process data.
- Organize these data in a chronological sequence according to batch manufacturing data, using a spreadsheet format.
- Include data from at least the last 20–30 manufactured batches for analysis. If the number of batches is less than 20, then include all manufactured batches and commit to obtain the required number for analysis.
- Trim the data by eliminating test results from noncritical processing steps and delete all gratuitous numerical information.
- Subject the resultant data to statistical analysis and evaluation.
- Draw conclusions as to the state of control of the manufacturing pro- cess based on the analysis of retrospective validation 4u data.
- Issue a report of your findings (documented evidence).
VALIDATION 4U PROCESS.