Why do we conduct pilot plant studies?
A pilot plant permits the investigation of a product and process on an intermediate scale before large amounts of money are committed to full-scale production.
- It examines a product and processes on an intermediate scale before utilizing a large number of products and processes in full-scale production.
- It helps in predicting the effects of a many-fold increase in scale.
- It designs a large complex food processing plant from laboratory data alone.
A pilot plant can be used to evaluate the results of laboratory studies and make product and process corrections and improvements. It is also used for producing small quantities of products for sensory, chemical, and microbiological evaluations and stability studies
It can provide data that can be used to decide whether or not to proceed to a full-scale production process and, in the case of a positive decision, design and construct a full-size plant or modify an existing plant.
Definition of Pilot Plant
Plant: “It is a place where the 5 M’s like money, material, man, method, and machine are brought together for the manufacturing of the products.”
Pilot Plant: “It is the part of the pharmaceutical industry where a lab-scale formula is transformed into a viable product by the development of a liable and practical procedure of manufacture.”
Scale-up: The design of the prototype using the data obtained from the pilot plant model.
R and D → Pilot Plant → Production
Objectives Of Pilot Plant
“Find mistakes on a small scale and make a profit on a large scale.”
- To try the process on a model of the proposed plant before promising a large sum of money on a production unit.
- To yield physically and chemically stable therapeutic drug delivery forms.
- Examination of the formula to determine its ability to withstand batch-scale and process modification.
- Review process equipment.
- Evaluation and validation for processes and equipment.
- Guidelines for production and process control.
- To find the critical features of the process guidelines for production and process controls.
- To provide a master manufacturing formula with instructions for manufacturing procedures.
- To sidestep the scale-up problems.
Steps in Scale-Up
Scale-up is the process of designing a prototype using the data acquired from the pilot plant model.
Applications of Scale-up Process:
- Competitive selling i.e. to reduce the cost of the already existing marketed product and guide allowable manufacturing costs.
- Conduct laboratory studies and scale-up planning at the same time.
- Define key rate-determining steps in the proposed process.
- Study preliminary larger-than-laboratory studies with equipment.
- Is used in the rate-controlling step to aid in plant design.
- Design and construct a pilot plant including requirements for process and environmental controls, cleaning and sanitizing systems, packaging and Waste management systems, and meeting regulatory agency requirements.
- Economics to make (To design the product for low cost or economy way) any corrections and a decision on whether or not to continue with a full-scale plant development.
Uses of Pilot Plant
1. Evaluation of results from Laboratory studies.
2. Product and Process corrections.
3. Sensory, chemical, and microbiological evaluation.
4. Self-life and stability studies.
5. Data from pilot plant can be used in making a decision whether or not to proceed to a full-scale production process. In the case of a positive decision to proceed a full- scale production, designing and constructing a full-size plant or modifying an existing plant.
GENERAL CONSIDERATIONS
These are studied under these headings:
- Reporting Responsibility
- Personnel Requirement
- Space Requirements
- Review of the formula
- Raw materials
- Equipment
- Production rates
- Process evaluation
- Master manufacturing procedures
- Product stability and uniformity
These are Explained Below:
1. Reporting Responsibility: Separate Research and Development staff should be available. The developer of the product can start the production and can provide support even after production has been completed.
2. Personnel Requirement: Scientists with experience in pilot plant operations as well as in actual production area are the most preferable. The people who have theoretical knowledge and the practical knowledge are selected. They have to know the intent of the formulator as well as know the perspective of the production personnel. The group should have some personnel with engineering knowledge as well as scale-up and also involve engineering principles.
3. Space Requirements:
- Management and information processing
- Standard equipment floor space
- Physical testing area
- Storage area
Management and Information Processing: Adequate office and desk space should be provided for both scientist and technicians. The space should be adjacent to the working area.
Physical Testing Area: This area should make available permanent benchtop space for regularly used physical- testing equipment.
Standard Pilot-Plant Equipment Floor Space: Discreet pilot plant space, where the equipment chosen for manufacturing all types of dosage forms is located. Intermediate-sized and full-scale production equipment is important in evaluating the effects of scale-up of research formulations and processes. Pieces of equipment used should be made portable wherever possible, so that, after us,e it can be stored in the small storeroom. Space for cleaning of the equipment should be also provided.
Storage Area: It would have two areas divided as:
- Approved, and
- Unapproved area
For active ingredient as well as excipient, different areas should be provided for the storage of the in-process materials, finished bulk products from the pilot-plant and materials from the experimental scale-up batches made in the production. Storage area for the packing material should also be provided.
4. Review of the Formula: A full valuation of each aspect of 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 result of scale-up using equipment that may subject the product to stresses of different types and degrees can more readily be predicted, or recognized.
5. Raw Materials: One purpose/responsibility of the pilot-plant is the approval and validation of the active ingredient excipients raw materials. Raw materials used in the small- scale production cannot necessarily be the representative for the large-scale production.
6. Equipment: The most cost-effective and the simplest and effective 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 equipment is too big then there will be wastage of the expensive active ingredients. 7. Production Rates: The forthcoming market trends/ requirements are considered while determining the production rates.
8. Process Evaluation: Factors to be considered and optimum values are determined. The knowledge of the effects of various process parameters as few mentioned above, form the basis for process optimization and validation. The purpose of process validation is to confirm that the selected manufacturing procedure assure the quality of the product at various critical stages in the process and in finished form
- Order of mixing of components
- Mixing time
- Solvents
- Heating and cooling
- Filters size (liquids)
- Drying temperature
- Mixing speed
- Rate of addition of granulating agents
- Solutions of drug
- Rates
- Screen size (solids)
- Drying time
9. Master Manufacturing Procedures: The three important aspects are considered:
(1) Weight sheet
(2) Processing directions
(3) Manufacturing procedure
The weight sheet should clearly identify the chemicals required in a batch to prevent confusion in the names and identifying numbers for the ingredients used on batch record The process directions should be precise and explicit. A manufacturing procedure should be written by the actual operator. Various specifications like addition rates, mixing time, mixing speed, heating, and cooling rates, temperature, storing of the finished product samples should be mentioned in the batch record directions.
10. Product Stability and Uniformity: The aim of the pilot plant is the physical as well as chemical stability of the products. Henceforth 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.
