Pilot Scale Up Technique

8/3/2019 Pilot Scale Up Technique

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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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08 June 2009 SRTM University, Nanded 2

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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08 June 2009 SRTM University Nanded 33

E-mail:[email protected]

C ll N 09742431000
mailto:[email protected]:[email protected]

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Pilot Scale Up Technique

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