PILOT PLANT

SCALE- UP TECHNIQUE
 CONTENTS
 Definition
 Objectives

 Steps in scale-up

 General considerations

 GMP considerations

 Advantages and Disadvantages

 References

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 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 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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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 5
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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WHY CONDUCT PILOT PLANT
STUDIES?
A pilot plant allows investigation of a product
and process on an intermediate scale before large
amounts 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 scale
processing plant from laboratory data alone with
any degree of success
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 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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GENERAL CONSIDERATIONS
1. Reporting Responsibility

R&D The formulator who

group with developed the product can
separate take into the production
staffing and can provide support
even after transition into
production has been 9
completed
2. Personnel Requirement:-
Scientists with experience in
pilot plant operations as well
as in actual production area are
the most preferable
As they have to understand the
intent of the formulator as well
as understand the perspective
of the production personnel.
The group should have some
personnel with engineering
knowledge as well as scale up
also involves engineering
principles

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 3. Space Requirements

Administration Physical Standard Storage

and information testing equipment area
processing area floor space

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 Administration and information process:
Adequate office and desk space should be provided for
both scientist and technicians.
The space should be adjacent to the working area.

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 Physical testing area:-
This area should provide permanent bench top space for
routinely used physical- 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 of scale-up of
research formulations and processes
Equipments used should be made portable where ever
possible. So that after use it can be stored in the small
store room.
Space for cleaning of the equipment should be also
provided.

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  Storage Area:-
It should have two areas divided as
approved and unapproved area for
active ingredient as well as
excipient.
Different areas should provided for
the storage of the in-process
materials, finished bulk products
from the pilot-plant & materials
from the experimental scale-up
batches made in the production.
Storage area for the packing
material should also be provided.

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4. Review of the formula:
A thorough review of the each aspect of formulation is
important.
The purpose of each ingredient and it’s contribution to
the final product manufactured on the small-scale
laboratory equipment should be understood.
Then the effect of scale-up using equipment that may
subject the product to stresses of different types and
degrees can more readily be predicted, or recognized.

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5. Raw materials:-
One purpose/responsibility of the pilot-plant is the approval &
validation of the active ingredient & excipients raw materials.

Raw materials used in the small scale production cannot necessarily

Why?
be the representative for the large scale production

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6. Equipment:-
The most economical and the simplest & efficient
equipment which are capable of producing product
within the proposed specifications are used.
The size of the equipment should be such that the
experimental trials run should be relevant to the
production sized batches.
If the equipment is too small the process developed
will not scale up,
Whereas if equipment is too big then the wastage of
the expensive active ingredients.

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7. Production Rates:-

The immediate as well as the future market trends/requirements

are considered while determining the production rates.

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 8. Process Evaluation:-

Order of mixing of
Drying temp. components Mixing
And drying time speed

Screen size Mixing

(solids) PARAMETERS
time

Filters size Rate of addition of

(liquids) granulating agents,
Heating and cooling solvents,
Rates solutions of drug etc.

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 Why to carry out process evaluation????

 The knowledge of the effects of

various process parameters as few mentioned above form the
basis for process optimization and validation.

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9. Master Manufacturing Procedures:-
The three important aspects

Weight sheet Processing Manufacturing

directions procedure

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 The weight sheet should clearly identify the
chemicals required In a batch. To prevent confusion
the names and identifying nos. for the ingredients
should be used on batch records.
 The process directions should be precise and
explicit.
 A manufacturing procedure should be written by
the actual operator.
 Various specifications like addition rates, mixing time,
mixing speed, heating, and cooling rates, temperature,
storing of the finished product samples should be
mentioned in the batch record directions.

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10. Product stability and uniformity:-

The primary objective of the pilot plant is the physical as well

as chemical stability of the products.
Hence each pilot batch representing the final formulation and
manufacturing procedure should be studied for stability.
Stability studies should be carried out in finished 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 control
divisions can readily observe scale up runs.
 Supplies of excipients & drugs, cleared by the
quality control division, can be drawn from the
more spacious areas provided to the production
division.
 Access to engineering department personnel is
provided for equipment installation, maintenance
and repair.
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DISADVANTAGES
 The frequency of direct interaction of the
formulator with the production personnel in the
manufacturing area will be reduced.

 Anyproblem in manufacturing will be directed

towards it’s own pilot-plant personnel's.

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