Pilot plant scale-up techniques General Considerations
“Defined as a part of the pharmaceutical industry where a lab-scale formula is transformed into a viable product by the development of a liable practical procedure for manufacture.”
• A pilot plant allows investigation of a product and process on an intermediate scale before large amounts of money are committed to full-scale production
• It is usually not possible to predict the effects of a many-fold increase in scale
• It is not possible to design a large complex food processing plant from laboratory data alone with any degree of success
• Evaluating the results of laboratory studies and making product and process corrections and improvements
• Producing small quantities of product for sensory, chemical, microbiological evaluations, limited market testing or furnishing samples to potential customers, shelf-live and storage stability studies
• Determining possible salable by-products or waste streams requiring treatment before discharge
• Providing data that can be used in making a decision on whether or not to proceed to a full-scale production process; and in the case of a positive decision, designing and constructing a full-size plant or modifying an existing plant
• Kind and size – depends on goals; evaluating product and process; producing samples of product for evaluation; market testing or furnishing to potential customers
• Location: near R&D facility? At an existing plant? Close liaison between R&D and pilot plant staff is essential
• Labor requirements and costs: engineering staff, skilled operations and maintenance staff- pilot plant costs may exceed those of usual plant production costs. The pilot plant may be used for training personnel for a full-scale plant
To produce physically and chemically stable therapeutic dosage forms.
Review of the processing equipment.
Guidelines for productions and process control.
Evaluation and validation.
To identify the critical features of the process.
To provide a master manufacturing formula.
Personnel requirements
Scientists with experience in pilot plant operations as well as in actual production areas are the most preferable
As they have to understand the intent of the formulator as well as understand the perspective of the production personnel.
The group should have some personnel with engineering knowledge as well as scale-up also involves engineering principles
Space Requirements
Space Requirements
Separate provisions for API and excipients are further segregated into approved and unapproved areas according to GMP.
Storage area for in-process materials, finished bulk products, retained samples, experimental production batches, and packaging materials (segregated into approved and unapproved areas).
Controlled environment space allocated for storage of stability samples
Review the Formula
A thorough review of each aspect of the formulation is important.
The purpose of each ingredient and its contribution to the final product manufactured on the small-scale laboratory equipment should be understood.
Then the effect of scale-up using equipment that may subject the product to stresses of different types and degrees can more readily be predicted or recognized.
Processing equipment
The most economical and the simplest & efficient equipment which are capable of producing product within the proposed specifications are used.
The size of the equipment should be such that the experimental trials run should be relevant to the production-sized batches.
If the equipment is too small the process developed will not scale up,
Whereas if the equipment is too big then the wastage of the expensive active ingredients.
Process evaluation
It is the basis of process validation Documentation of the process is to be done. The process is validated only if there are no changes in the formula, quality of the ingredients, or equipment configuration.
Revalidation needs to be done to ensure that changes have not taken place.
Master Manufacturing Procedure
The chemical weighs sheet. It should clearly identify the chemicals required in a batch and present the quantities and the order in which they will be used.
The sampling directions
In-process and finished product specifications
Manufacturing directions should be in a language understandable by the operator termed SOP.
Batch Record Directions should include specifications for additional rates, mixing times, mixing speeds, heating and cooling rates, and temperature.
Proper documentation should be carried out.
Product stability and uniformity
The primary objective of the pilot plant is the physical as well as chemical stability of the products.
Hence each pilot batch representing the final formulation and manufacturing procedure should be studied for stability.
Stability studies should be carried out in finished packages as well
GMP Considerations
Equipment qualification
Process validation
Regularly schedule preventative maintenance
Regularly process review & revalidation
Relevant written standard operating procedures
The use of competent technically qualified personnel
Adequate provision for training of personnel
A well-defined technology transfer system
Validated cleaning procedures.
An orderly arrangement of equipment so as to ease material flow & prevent cross-contamination
Analytical methods for Quality assurance
Analytical methods developed in research must be transferred to the QA department. The transfer process includes –-
- Review the process to make sure that the proper analytical instrument is available.
- Personnel should be trained to perform the test.
- The reliability of the test should be checked.
At the last assay, the procedure should be reviewed before transfer
Suggested readings
Recommended readings
- Pharmaceutical Regulatory Science
- BIOSTATISTICS AND RESEARCH METHODOLOGY Theory
- Social Pharmacy Practical D Pharm
- Pharmaceutical Biotechnology Theory
