Pilot plant scale-up techniques involve reproducible manufacture of an experimental formulation on high-speed production equipment, in a cost effective manner. It is a part of the pharmaceutical industry where the same processes used during Research and Development (R&D) of dosage forms are applied to different output volumes; usually greater than that obtained during R&D.
In every emerging pharmaceutical industry or an already existing one, there is always a need to have an intermediate batch scale representing procedures and simulating that used for commercial manufacturing. This is achieved by determining the ability of formula to withstand batch-scale and process modification. There is equally a need for equipment evaluation and validation to ensure that the aim of your company which is the mass production of the drug in question is not defeated. For a pilot scale up to be successful a product must be capable of being processed in a large scale often with equipment that only remotely resembles that used in the development laboratory. The idea is that you
- Understand what makes these processes similar, identify and eliminate many scale-up problems before investing large sum of money on a production unit
- Maintain the chemical attributes of the product, its quality and efficacy even though the production processes are modified as a result of sample size increase and equipment changes.
Pilot plant scale-up must include:
- A close examination of the formula to determine its ability to withstand large scale and process modification.
- A review of a range of relevant processing equipment to determine which would be most compatible with the formulation as well as the most economical, simple and reliable in producing the product.
What happens during pilot plant scale-up
- Determination of the availability of raw materials that consistently meet the specifications required to produce the product.
- Determination of the physical space required and the layout of related functions to provide short term and long term efficiency.
- Evaluation, validation and finalizing of production and process controls.
- Issuing of adequate records and reports to support Good Manufacturing Practices (GMPs) and provide the historical development of the production formulation process, equipment train and specifications
- Development and validation of meaningful product reprocessing procedures.
- Identification of all critical, features of a scale up process, so that it can be adequately monitored to provide assurance that the process is under control and that the process at each level of the scale up maintains the specified attributes originally intended.
- Production rate and future market requirements.
Pilot plant scale-up is of practical interest to formulation scientist/ production managers and should be considered from the inception of a development project. This is because a process using the same type of equipment can perform quite differently when the size of the equipment and the amount of material involved is significantly increased. The chemical attributes of the product, its quality and efficacy should be maintained even though the production processes is modified as a result of sample size increase and equipment changes. You should also bear in mind that pilot plant scale up, in itself, does not guarantee a smooth transition. A well-defined process may fail quality assurance tests in full manufacturing scale even after generating a perfect product in both the laboratory and the pilot plant.
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- Levin M. (2001). Pharmaceutical Process Scale-Up. New York: Marcel Dekker, Inc.
- Tiwari S., Saxena S. and Kumar R. (2011). Process Scale Up of Ibrufen Tablet. Journal of Pharmaceutical Sciences and Research, .3(10), 1525-1529.
The title of this article is Pilot Plant Scale-up Techniques