The document discusses pilot plant scale up for sterile veterinary parenteral solutions (SVPS). It defines key terms like plant, pilot plant, and scale up. The objectives and steps of scale up are outlined. The document describes the typical layout and working areas of a parenteral pilot plant, including warehousing, compounding, aseptic, and HEPA filter areas. It discusses evaluating laboratory studies and producing samples at the pilot plant scale. The document also covers different types of parenteral dosage forms that may be tested at a pilot plant, such as solutions, suspensions, emulsions, and dry powders.

1. PILOT PLANT SCALE UP FOR SVPS
Dr. Prashant L. Pingale
Associate Professor,
GES’s Sir Dr. M. S. Gosavi College of Pharm. Edu. and Research, Nashik-422005

2. Plant, pilot plant and scale up
• Plant: It is a place were 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 development of liable and
practical procedure of manufacture.
• Scale-up: The art for designing of prototype using the data obtained from the
pilot plant model.
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3. What is pilot plant scale up?
• In the pilot plant, a formulae is transformed into a viable product by the
development of a reliable and practical method of manufacturing.
• Pilot plant is the intermediate plant between the laboratory scale and the
production plant.
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4. Objectives of scale-up
• To try the process on a model of proposed plant before committing large sum of money on a
production unit.
• Examination of the formula to determine it’s ability to withstand Batch-scale and process
modification.
• Evaluation and Validation for process and equipments.
• To identify the critical features of the process.
• Guidelines for production and process controls.
• To provide master manufacturing formula with instructions for manufacturing procedure.
• To avoid the scale-up problems.
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5. Steps in scale-up
✓ 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 rate-controlling step to aid
in plant design
✓ 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 a
decision on whether or not to proceed with a full scale plant development
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6. Purpose of conducting Pilot Plant Studies
✓To evaluate the effect on the process of a large scale of operation and to collect
other data so that a good design of a larger unit may be made with a high
probability of commercial success.
✓To find and examine all products or waste which may not be seen in
laboratory scale.
✓By the use of pilot plant, it is possible to minimize the wastes, hence better
yield of prescribed dosage form.
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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 or furnishing samples to potential
customers, 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.
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8. Pilot plant scale-up: Injectables
• The majority of the parenteral solutions requiring a variety of equipments for
liquid mixing, filtration, transfer and related activities.
• Most of the equipments are composed of stainless steel, with glass lined
vessels employed for preparation of formulations sensitive to iron and other
metal ions.
• The vessels can be equipped with external jackets for heating and/or cooling
and various types of agitators, depending upon the mixing requirements.
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9. Typical Layout of Parenteral Pilot-plant
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10. Working area of a parenteral pilot plant
• Incoming goods are stored in special areas for Quarantine, Released and
Rejected status.
• A cold room is available for storage of temperature-sensitive products.
• Entrance into the warehouse and production areas is restricted to personnel.
• The route for final products is separated from the incoming goods.
• Storage of final products is done in designated areas in the warehouse.
• Sampling and weighing of the raw material is performed in a dedicated
sampling area and a central weighing suite, respectively.
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11. Warehousing
• All samples should be aseptically taken, which mandates unidirectional airflow and
full operator gowning.
• These measures reduces the potential for contamination ingress into materials that
are yet to receive any processing at any site.
• First the materials are passed through class 100,000 i.e. grade D environment for
presterilization.
• Transfer of materials are carried out in air-locks to avoid cross contamination.
• The preparation areas are supplied with HEPA filters.
• There should be more than 20 air changes per hour.
• The preparation place is Class 100 area.
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12. Compounding area
• In this area formulation is compounded.
• Cabinets and counters are made up of stainless steel.
• They should fit tightly to walls so that there are no void spaces where dirt
can accumulate.
• The ceiling walls and floor should be constructed of impervious materials
so that moisture will run off.
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13. Aseptic area
• The ceiling walls, floor must be sealed so that they can be washed and
sanitized with disinfectant.
• The filling of the formulations is performed in a class 100 environment.
• Air locks serve as a transition points between one environment and another.
• They are fitted with the UV lights, spray systems or other devices that may be
effectively utilized to prevent contamination of the materials.
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14. HEPA filters
• HEPA filters, by definition, remove at least 99.97% of Airborne particles
0.3 micrometers (µm) in diameter.
• HEPA filters are composed of a mat of randomly arranged fibers.
• These fibers are typically composed of fiberglass and possess diameters
between 0.5 and 2.0 micron.
• The air space between HEPA filter fibers is much greater than 0.3 μm.
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15. Types of parenteral dosage form: Solutions
• Solutions of drug are suitable for parenteral administration are referred as
injections.
• They are manufactured by dissolving the drug and suitable excipients, adjusting the
pH, filtration through 0.22µm membrane and autoclaving the final product.
• These are of two types:
• Large Volume Parenterals (LVP)
• Small Volume Parenterals (SVP)
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16. Types of parenteral dosage form: Suspensions
• Suspensions is one of the most difficult parenteral dosage form.
• It can be injected through a 18 to 21 gauge needle.
• Formulation consists of active ingredients suspended in aqueous solution.
• Two methods are used to prepare parenteral suspension:
• Sterile vehicle & powders are combined aseptically.
• Sterile solutions are combined and the crystals formed in-situ.
• Penicillin G procaine injectable suspension USP
• Sterile Testosterone injectable suspension USP
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17. Problems associated with suspensions
• Syringeability: It refers to the handling characteristics of a suspension
while drawing and manipulating it in a syringe.
• Injectability: It refers to the properties of the suspension during
injection.
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18. Types of parenteral dosage form: Emulsions
• Emulsions is a dispersion of two or more immiscible liquids.
• It includes following types:
• Water-in-oil emulsions of allergenic extracts (subcutaneously)
• Oil-in-water sustained-release depot preparations (intramuscularly)
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19. Types of parenteral dosage form: Dry Powder
• Many drugs are physically or chemically unstable and hence formulated as
dry powders, which can be reconstituted in solution by addition of water.
• Sometimes it may be an aqueous suspension such as ampicillin trihydrate and
spectinomycin hydrochloride.
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