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PILOT PLANTSCALE- UP TECHNIQUE
Dr. Basavaraj K. NanjwadeM. Pharm., Ph. D
Associate Professor
Department of Pharmaceutics
KLE University, JN Medical College
BELGAUM - 590010
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Contents
Definition
Objectives
Steps in scale-up General considerations
GMP considerations
Advantages and Disadvantages References
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Plant:- It is a place were the 5 Ms likemoney, material, man, method andmachine are brought together for themanufacturing of the products.
Pilot Plant:- It is the part of thepharmaceutical industry where a lab scaleformula is transformed into a viableproduct by development of liable and
practical procedure of manufacture. Scale-up:- The art for designing ofprototype using the data obtained from thepilot plant model.
Definitions
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Objective
To try the process on a model of proposedplant before committing large sum ofmoney on a production unit.
Examination of the formula to determine itsability to withstand Batch-scale andprocess modification.
Evaluation and Validation for process andequipments
To identify the critical features of theprocess.
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Guidelines for production and processcontrols.
To provide master manufacturing formulawith instructions for manufacturing
procedure.
To avoid the scale-up problems.
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STEPS IN SCALE UP
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Define product economics based on projected market size andcompetitive 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
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Design and construct a pilot plant including provisions for process and
environmental controls, cleaning and sanitizing systems, packaging andwaste 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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Why conduct Pilot PlantStudies?
A pilot plant allows investigation of a product andprocess on an intermediate scale before largeamounts of money are committed to full-scale
production It is usually not possible to predict the effects of
a many-fold increase in scale
It is not possible to design a large scaleprocessing plant from laboratory data alone withany degree of success
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A pilot plant can be used for
Evaluating the results of laboratory studies andmaking product and process corrections andimprovements
Producing small quantities of product for sensory,
chemical, microbiological evaluations, limitedmarket testing or furnishing samples to potentialcustomers, shelf-life and storage stability studies
Providing data that can be used in making adecision on whether or not to proceed to a full-scaleproduction process; and in the case of a positivedecision, designing and constructing a full-size
plant or modifying an existing plant
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General considerations
1. Reporting Responsibility
R & Dgroup withseparate
staffing
The formulator whodeveloped the product cantake into the production
and can provide supporteven after transition intoproduction has been
completed
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Scientists with experience inpilot plant operations as well
as in actual production areaare the most preferable
As they have to understandthe intent of the formulatoras well as understand the
perspective of theproduction personnel.The group should have some
personnel with engineeringknowledge as well as scale
up also involves engineeringprinciples
2.Personnel Requirement:-
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3. Space Requirements
Administrationand informationprocessing
Physicaltestingarea
Standardequipmentfloor space
Storagearea
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Administration and information process:
Adequate office and desk space should be
providedfor both scientist and technicians.The space should be adjacent to the workingarea.
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Physical testing area:-
This area should provide permanentbench top space for routinely usedphysical- testing equipment.
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Standard pilot-plant equipment floor space:-
Discreet pilot plant space, where the equipment
needed for manufacturing all types of dosage form
is located.
Intermediate sized and full scale production
equipment is essential in evaluating the effects ofscale-up of research formulations and processes
Equipments used should be made portable whereever possible. So that after use it can be stored inthe small store room.
Space for cleaning of the equipment should be alsoprovided.
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It should have two areas dividedas approved and unapprovedarea for active ingredient aswell as excipient.
Different areas should providedfor the storage of the in-
process materials, finished bulkproducts from the pilot-plant &materials from the experimentalscale-up batches made in the
production.Storage area for the packingmaterial should also beprovided.
Storage Area:-
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4. Review of the formula:A thorough review of the each aspect offormulation is important.
The purpose of each ingredient and its
contribution to the final product manufactured onthe small-scale laboratory equipment should beunderstood.
Then the effect of scale-up using equipment that
may subject the product to stresses of differenttypes and degrees can more readily bepredicted, or recognized.
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5. Raw materials:-
One purpose/responsibility of the pilot-plant is the approval & validation of theactive ingredient & excipients raw
materials.
Raw materials used in the small scaleproduction cannot necessarily be therepresentative for the large scaleproduction
Why?
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6. Equipment:-
The most economical and the simplest & efficient
equipment which are capable of producingproduct within the proposed specifications areused.
The size of the equipment should be such that
the experimental trials run should be relevant tothe production sized batches.
If the equipment is too small the process
developed will not scale up,Whereas if equipment is too big then thewastage of the expensive active ingredients.
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7. Production Rates:-
The immediate as well as the future
market trends/requirements areconsidered while determining theproduction rates.
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8. Process Evaluation:-
PARAMETERS
Order of mixing ofcomponents Mixing
speed
Mixingtime
Rate of addition ofgranulating agents,
solvents,
solutions of drug etc.
Heating and cooling
Rates
Filters size(liquids)
Screen size
(solids)
Drying temp.And drying time
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Why to carry out process evaluation????
The knowledge of the effects ofvarious process parameters as fewmentioned above form the basis forprocess optimization and validation.
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9. Master Manufacturing Procedures:-
The three important aspects
Weight sheet Processingdirections Manufacturingprocedure
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The weight sheet should clearly identify thechemicals required In a batch. To preventconfusion the names and identifying nos. for theingredients should be used on batch records.
The process directions should be precise andexplicit.
A manufacturing procedure should be writtenby the actual operator.
Various specifications like addition rates, mixing
time, mixing speed, heating, and cooling rates,temperature, storing of the finished productsamples should be mentioned in the batchrecord directions.
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10. Product stability and uniformity:-
The primary objective of the pilot plant isthe physical as well as chemical stability of
the products.Hence each pilot batch representing thefinal formulation and manufacturing
procedure should be studied for stability.Stability studies should be carried out infinished packages as well.
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GMP CONSIDERATION
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
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Advantages
Members of the production and quality controldivisions can readily observe scale up runs.
Supplies of excipients & drugs, cleared by the
quality control division, can be drawn from themore spacious areas provided to the productiondivision.
Access to engineering department personnel isprovided for equipment installation, maintenanceand repair.
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Disadvantages
The frequency of direct interaction of theformulator with the production personnel in themanufacturing area will be reduced.
Any problem in manufacturing will be directedtowards its own pilot-plant personnel's.
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Important Questions
What is the significance of pilot plant scaleup with routine production procedure ?
What do you mean by pilot plant scale upand give examples ?
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Reference
The theory & practice of industrialpharmacy by Leon Lachman, Herbert A.Lieberman, Joseph L. kenig, 3rd edition,
published by Varghese Publishing house.
www.google.com
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E-mail:bknanjwade@yahoo.co.in
C ll N 09742431000
mailto:bknanjwade@yahoo.co.inmailto:bknanjwade@yahoo.co.in