The document discusses pilot plant scale up for pharmaceutical manufacturing. It defines key terms like pilot plant and scale-up. The objectives of the pilot plant include standardizing the formula, evaluating equipment, and identifying critical process parameters. The significance is that the pilot plant optimizes production rates and provides information for full-scale manufacturing. Steps in scale-up involve laboratory and pilot studies, process and equipment design, evaluation of results, and determining if full-scale production is viable. The pilot plant must be properly operated, validated, staff trained, and engineering supported to ensure quality and compliance.

1. PILOT PLANT SCALE UP
PREPARED BY: JATIN PATEL
GUIDED BY: Dr. MANSI DHOLAKIYA
FACULTY OF PHARMACY
DHARMSINH DESAI UNIVERSITY, NADIAD
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2.  DEFINITIONS
• 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. Pilot Scale and Scale-Up
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Pilot Scale
Scale-Up
R & D
Large Scale
Production

4.  OBJECTIVES OF PILOT PLANT
 Avoidance of the problems associated with the scale-up.
 Production and process controls guidelines preparation.
 To identify the critical features of the process
 Preparation and providing of Master Manufacturing Formula for
manufacturing.
 Evaluation and Validation for process and equipment.
 Examination of the formula to assess the batch stability.
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5.  SIGNIFICANCE OF PILOT PLANT
 Standardization of formula.
 Review of range of relevant processing equipment.
 Optimization and control of production rate.
 Information on infrastructure of equipment during the scale up batches.
 Information of batches physical space required for equipment.
 Identification of critical features to maintain quality of a product.
 Appropriate records and reports to support GMP.
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6. PILOT PLANT
DESING
Formulation and
process
development
Clinical supply
manufacture
Technology
evaluation, Scale-
Up and Transfer
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7.  STEPS IN SCALE UP
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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

8. 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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9. PILOT PLANT OPERATION
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10. Operational
Aspects
Validation
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Training
Engineering support
Maintenance and
Calibration
Inventory, Orders,
Labeling
Material control
Process &
Manufacturing
Activities
QA & QC

11. Design
specifications
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Installation
Qualification
Operational
Qualification
Performance
Qualification
Compliance with
cGMPand
FDA standards
V
A
L
I
D
A
T
I
O
N

12. Compliance with
GMP
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Safety and
environmental
responsibilities
Compliance with
SOPs
Technical skills
and knowledge TRAINING

13. ENGINEERING SUPPORT
Design of facility
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Construction
of facility
Co-ordination, scheduling,
direction of ongoing operations
Validation
of facility

14. To ensure data integrity
and equipment
reliability
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To meet cGMP
norms
Maintenance & Calibration

15. Computerizedsystem
Material
control
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Inventory
Orders
(FIFO)
Labeling
(GMP-GLP)

16. PROCES
AND
MANUFACTURING
ACTIVITIES
Formulation & Process
Development studies
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Technology evaluation,
ScaleUp, & Transfer
Clinical supply
manufacture

17.  QUALITYASSURANCE
• Auditing pilot plant
• Auditing and approval of component suppliers
• Reviewing, approval and maintaining batch records for clinical supplies
• Sampling and release of raw materials and components required for
clinical supplies
• Release of clinical supplies
• Maintaining and distributing facility and operating procedures (SOPs)
• Review and approval of validation and engineering documentation
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18.  QUALITY CONTROL
• Release Testing of finished product
• Physical, Chemical and Microbiological testing of finished clinical
products, components required for clinical supplies
• Testing for validation and revalidation programs
• QC in-process testing during development, Scale Up and Technology
transfer activities
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19. Parenteral:
 The majority of parenteral solution requiring a variety of tankage,
Piping and ancillary equipment for liquid mixing, filtration, transfer
And related activities.
 The majority of equipment are made up of Stainless steel With glass
lined vessel employed For preparation of formulation sensitive to iron
or metals.
 The vessels are equipped With external heating jacket And/or cooling
and various types of agitator depending upon mixing requirement of
individual Formulation.
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20. 20

21. Working area for parenteral
 The incoming goods are stored in special area for quarantine, released and rejected
purpose.
 The cold room is available for temperature sensitive sample
 Entrance to the warehouse and production area is restricted to authorized personnel.
 Sampling and weighing of raw material is performed in dedicated sampling area.
 Storage of final product is done in designated areas in warehouse while they are awaiting
for shipment.
 Several clothing and cleaning procedure in controlled transport zone and production area
ensure the full quality compliance.
 Technical area is located in between production zone and area for research and
formulation.
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22. 22

23. Facility design
 To provide the control of microbial, pyrogen and particles control over
production area is essential.
Warehousing
 All samples should be aseptically taken which mandates unidirectional
airflow and fall operator gowning.
 These measures reduce the potential for contamination ingress isto
material that are yet to receive any processing at any site
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24. 24

25. 25

26. Compounding area:
 The manufacturing of parenteral is carried out in Grade-C controlled eminement in
which class 100 unidirectional flow hoods are utilized to provide greater enviamental
control during material addition.
 These area are designed to minimize microbial, pyrogen and particulate contamination
to the formulation prior to sterilization.
Aseptic filling room:
 The filling of formulation is performed in class 100 environment.
Capping and crimp sealing area:
 The air supply in capping area should be of class 100.
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27. Corridors:
 They serve to interconnect various rooms, such as filling room,
growning room, air-lock room are assessed from the corridor.
Air-lock and pass through:
 The air-lock serve as transition point between one environment and
other.
 They are fined with UV lights, spray system, or other device that
may be effectively utilized.
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28. Formulation Aspects:
Solvent:
 The mod widely used solvent for parenteral production is WFI (water for injection).
 The WFI is prepared by distillation or by reverse osmosis.
 Sterile water for injection is used as vehicle for reconstitution of sterile solid product before
administration and is terminally sterilized by autoclaving.
Solubilizer:
 They are used to enhance and maintain the aqueous solubility of poorly water.
Solubilizing agent used in sterile product include:
 The co-solvent: Glycerine, Ethanol, Sorbitol.
 Surfactant: Polysorbate 80, Polysorbate 20, Lecithin.
 Complexing agent : Cyclodexitrine, etc
They act by reducing dielectric constant property of solvent system thereby reducing electric
conductance of solvent and hence increases solubility.
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29. Buffers:
 They are used to maintain PH level of solution in range that provide either maximum stability
of drug against hydrolytic degradation or to obtain optimum stability and solubility of drug in
solution.
Antioxidant:
The antioxidant act by reacting prefentially with molecular oxygen and minimizing and/or
terminating the free radical auto-oxidation reaction. Example: Phenol, m- cresol, etc.
Sterilization and depyrogentation:
 Steam sterilization
 Dry-heat sterilization
 Gas and vapour sterilization
 Radiation sterilization
 Sterilization by filtration
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31. 31

32. 32

33. Quality assurance:
 The dissolution of drug in solution.
 Potency of drug in suspension.
 Temperature uniformity in suspension.
 Microbial control.
 Product uniformity
 Final volume.
 Stability
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34. SCALE UP FOR SEMISOLID PRODUCTS
 In general semisolid dosage form are complex formulation having complex
structure.
 Often they are composed of two phases (oil and water) one of which is continues
phase and other is dispersed phase.
 The active ingredient is dissolved in one phase although occasionally the drug is
not fully soluble in the system and is dispersed in one or both phases thus creating
the three-phases system.
 The physical properties of dosage form depend upon various factor including the
size of dispersed particle coefficient of active ingredient between phases and
product rheology.
 These factors combine to determine the release characteristic of drag as well as
other characteristic such as viscosity.
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35. SCALE UP FOR SEMISOLID PRODUCTS
 The following parameters are to be considered during the scale up of semisolid products :
 Mixing equipment (should effectively move semisolid mass from outside walls to the center
and from bottom to top of the kettle)
 Motors (used to drive mixing system and must be sized to handle the product at its most
viscous stage.)
 Mixing speed
 Component homogenization
 Heating and cooling process
 Addition of active ingredients
 Product transfer
 Working temperature range (critical to the quality of the final product)
 Shear during handling and transfer from manufacturing to holding tank to filling lines
 Transfer pumps (must be able to move viscous material without applying excessive shear and
without incorporating air)While choosing the size and type of pump ,
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36.  While choosing the size and type of pump ,
1. Product viscosity
2. Pumping rate
3. Product compactibility with the pump surface
4. Pumping pressure
required should be considered .
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37. Formulation of semi solid dosage form
 Ingredient used in preparation of semi-solid dosage form are:✓
 Active pharmaceutical ingredient
 Bases
 Preservative
 Humes tand
 Antioxidant
 Emulsifier
 Gelling agent
 Permeation enhancer
 Buffer
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38.  The Theory and Practice of Industrial Pharmacy : Leon Lachman , Herbert A
Lieberman , Joseph L Kanig : Section IV : Chapter 23 : Pilot Plant Scale-Up
Techniques : Page No . 681 – 710 .
 Encylopedia of Pharmaceutical Technology : James Swarbrick , James C
Boylan : Volume 12 : Pilot Plant Design : Page No . 171 – 186 .
 Drugs and The Pharmaceutical Sciences : Pharmaceutical Process Scale-Up :
Marcel Dekker series : Michael Levin : Volume 118
Parenteral Drug Scale-Up : Page No. 43 – 56 .
38 REFERENCES

39. THANK YOU
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