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The immediate and future market demands of a product should be considered when determining production rates and the type/sizes of production equipment to be used in the production process. The size of the equipment and its utilization should be proportional to each other.
The choice of equipment and process to be used is dependent on product loss in equipment during manufacturing process, time required to clean up equipment between batches and the number of batches needed for testing.
This step critically evaluates the process and optimizes its performance based on that evaluation. Processes that should be examined include the following:
1. Order of addition of components, including adjustments of their amounts.
2. Mixing speed and mixing time.
3. Rate of addition of granulating agents, solvents, solutions of drugs, slurries etc.
4. Heating and cooling rates.
5. Filter sizes for liquids preparations
6. screen sizes for solid preparations
7. Drying temperatures and drying times.
Knowledge of the effect of these important process parameters on in-process and finished product quality is the basis for process optimization and validation. This is accomplished by monitoring the within batch variation of measurable parameters (content uniformity, moisture content and compressibility). This provides data that helps in accessing and identifying where the process is performing as intended and where problem areas may be found.
This is concerned with the manner of presentation of the manufacturing procedures to facilitate easy compliance and understanding by the processing technicians. The procedures include; manufacturing directives, chemicals weigh sheet, sampling directions, in-process, and finished product specifications.
The weight sheet, for instance, should clearly identify the chemicals required in the batch, their quantities and order in which they will be used. To also prevent confusion and possible errors, both names and identifying numbers for the ingredient should be used on batch records and these should correspond with those on the bulk material containers. The process directions should be precise and explicit.
The batch records’ directions should include specifications for addition rates, mixing times, mixing speeds, heating and cooling rates, and temperatures. The actual times, temperature, and speeds used should be documented. The time and manner in which in-process and finished samples are to be taken from a batch and the way in which they are handled and stored should be clearly specified with the batch record.
A list of GMP items that should be part of scale-up of a new product or process introduction may include the following;
1. Equipment qualification
2. Process validation
3. Regularly scheduled preventative maintenance
4. Regular process review and revalidation
5. Relevant written standard operating procedures
6. The use of competent, technically qualified personnel
7. Adequate provision for training of personnel
8. A well-defined technology transfer system
9. Validated cleaning procedures
10. An orderly arrangement of equipment for easy material flow and prevention of cross-contamination.
All analytical test methods developed in research during scale up of a new product, must be transferred to the quality assurance department. The quality assurance staff should review the process to make sure that the proper analytical instrumentation is available and that personnel are trained to perform the tasks.
Research personal should review the assay procedure and the data obtained during the validation studies to verify that the analytical methods have not been altered in a way that might affect the reliability, precision or accuracy of the tests..
References
The title of this article is General Considerations During Pilot Plant Scale-up
