Pilot Plant Scale-Up Technique PDF

Pilot Plant Scale-Up Technique  Definitions  Plant: It is a place where the 5 M factors (money, material, man, method, and machine) are brought together to manufacture products.  Pi l ot Plant:- ✓ It is a part of the pharmaceutical industry where a lab-scale...

Pilot Plant Scale-Up Technique  Definitions  Plant: It is a place where the 5 M factors (money, material, man, method, and machine) are brought together to manufacture products.  Pi l ot Plant:- ✓ It is a part of the pharmaceutical industry where a lab-scale formula is transformed into a viable product by producing small quantities of new technology-based products and developing reliable and practical manufacturing procedures. ✓ It is the pre-commercial production system.  Scale-up:- ✓ The art of designing a prototype using the data obtained from the pilot plant model. ✓ It is the process of increasing the batch size or a procedure for applying the same process to different output volumes. 2 Objectives of pilot plant To try the process on a model of the proposed plant before committing a large sum of money to a production unit. To examine the formula to determine its ability to withstand batch-scale and process modification. Avoidance of the problems associated with the scale-up. Guidelines for production and process controls. To identify the critical features of the process Preparation and providing of Master Manufacturing Formula Evaluation and validation of processes and equipment. 3 Scale Up Steps 4 Define product economics based on projected market size and competitive selling and provide guidance for allowable manufacturing costs Conduct laboratory studies and scale-up planning at the same time Define key rate-controlling steps in the proposed process Conduct preliminary larger-than-laboratory studies with equipment to be used in the rate-controlling step to aid in plant design 5 Design and construct a pilot plant, including provisions for process and environmental controls, cleaning and sanitizing systems, packaging and waste handling systems, and meeting regulatory agency requirements Evaluate pilot plant results (product and process) , including process Economics, to make any corrections and decide whether or not to proceed with a full-scale plant development. 6 Why conduct Pilot Plant Studies? A pilot plant allows the 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. Pilot plant studies can be beneficial to address this issue. It is not possible to design a large-scale production plant from laboratory data alone with any degree of success. Pilot plant studies can be beneficial to address this issue. 7 A pilot plant can be used for  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, shelf-life and storage stability studies.  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 8  General considerations 1. Reporting Responsibility The effectiveness of the Pilot plant requires a good relationship between the pilot plant group and other groups. R & D group Formulator 9 2. Personnel Requirement ❖ Scientists with experience in pilot plant operations as well as in actual production are the most preferable. They have to understand the formulator's intent as well as the perspective of the production personnel. ❖ The group should have some personnel with engineering knowledge (engineering principles). ❖ Knowledge of computers & electronics 10  3. Space Requirements The space required in the pilot plant is divided into 4 areas Administration Physical Standard Storage and information testing area equipment area processing floor space 11  Administration and information process: Adequate office and desk space should be provided for both scientists and technicians. The space should be adjacent to the working area. 12  Physical testing area:- This area should provide permanent bench top space for routinely used physical-testing equipment. 13  Standard pilot-plant equipment floor space:- ✓ Sufficient pilot plant space, where the equipment needed for manufacturing all types of dosage forms is located. ✓ Intermediate-sized and full-scale production equipment is essential in evaluating the scale-up effects of research formulations and processes. ✓ Equipment used should be made portable so that after use it can be stored in the small storeroom. ✓ Space for cleaning of the equipment should also be provided. 14   Storage Area It should 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 & materials from the experimental scale-up batches made in the production. Storage area for the packaging material should also be provided. 15 4. Review of 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 using small-scale laboratory equipment can be understood. Then, the effect of scaling up using equipment that may subject the product to different types and degrees of stresses can be more readily predicted or recognized. 16 5. Raw materials:- One of the main purposes/responsibilities of the pilot plant is the approval & validation of the raw materials (active ingredients & excipients). Why? Raw materials used in small-scale production cannot necessarily be representative of large-scale production. 17 6. Equipment:- The most economical, simple, and efficient equipment capable of producing a product within the proposed specifications is used. The size of the equipment used in the trial run should be relevant to the production size: ❑If the equipment is too small, the process developed will not be suitable to scale-up ❑Whereas if equipment is too big, expensive active ingredients are wasted. 18 7. Production Rates:- The immediate and future market trends/requirements are considered while determining the production rates. 19 8. Process Evaluation:- Order of mixing of Drying temp. components Mixing And drying time speed Screen size Mixing (solids) PARAMETERS time Filters size Rate of addition of (liquids) granulating agents, Heating and cooling solvents, Rates solutions of drug etc. 20 Why should we carry out process evaluation? Understanding the effects of various process parameters (such as a few previously mentioned examples) forms the basis for process optimization and validation. 21 ❖The process remains validated only if there are no changes in the formula, quality of the ingredients, and equipment configuration. ❖The manufacturing process and quality control information should be reviewed annually and re- validated to ensure no changes have occurred. 22 9. Master Manufacturing Procedures:- The three important aspects Weight Processing Manufacturing sheet directions procedure 23  The weight sheet should clearly identify the chemicals required in a batch. To prevent confusion, the names and identifying numbers for the ingredients should be used on batch records.  The process directions should be precise and explicit. Various specifications and parameters (such as addition rates, mixing time, mixing speed, heating, cooling rates, temperature, and storage conditions of the finished product samples) should be mentioned in the batch record directions.  A manufacturing procedure should be written by the actual operator. 24 10. 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 should be studied for stability. Stability studies should be carried out in finished packages as well. 25  Transfer ofAnalytical Method to Quality Assurance  During the scale-up of a new product, the analytic test methods developed in research must be transferred to the quality assurance department. The transfer process includes the following aspects: ❖ To review the process to make sure that the proper analytic instrumentation is available ❖ To make sure that personnel are trained to perform the tests. 26 26  GMP CONSIDERATION The checklist of the GMP items that should be a part of the scale-up or new product or process, includes the following;  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 27 28