This presentation include basic introduction to pilot plant and scale up technology. following points are definition, objective , process evaluation, SUPAC , advantages and dis advantages etc

1. Pilot Plant And Scale Up Technique
Introduction
Presented By –Vasanti G. Patil
M. Pharm First Yr.(QAT) 2019/020
Roll No. 26
Guided By – Dr. S.Daswadkar
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2. Content
• Definitions
• Introduction
• Discussion
• Objective
• Process evaluation
• SUPAC
• Advantages
• Disadvantages
• Layout pf pilot plant of Tablet
• Case study of production ( SUNPHARMA )
• Conclusion
• Growth chart of Indian pharma industry up to2019
• References
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3. 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.
Plant of Torrent pharmaceuticals
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4. 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.
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5. Scale-up :- The art for designing of prototype using the data
obtained from the pilot plant model
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6. Pilot scale and scale up process
R and D Pilot scale Scale up
Large
scale
Production
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7. Pilot Scale and Scale-Up Means
Pilot scale
Intermediate
Batch Scale
Manufactures Drug Product By
a Procedure Fully
Represrntative Of And
Simulatory To That Of
Manufacturing Scale
Scale -up
Next to Pilot
Scale
Process Of Increasing The Batch
Size (Mixing) /Procedure For
Applying The Same Process To
Different Output Volumes
(Tabletting)
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8. Objective
 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 provide master manufacturing formula with instructions for
manufacturing procedure.
 To avoid the scale-up problems.
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9. Why conduct Pilot Plant Studies?
• It is not possible to design a large scale processing plant from
laboratory data alone with any degree of success.
• It is usually not possible to predict the effects of a many-fold
increase in scale.
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10. Continue……
• It Gives rough idea about physical space required and of related
functions.
• Production rate adjustment after considering marketing
requirements.
• Appropriate records and reports are issued to support good
manufacturing practices.
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11. Development process for formulation Development
batches
1
• Development batch / laboratory scale batch
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• Pre-exhibit batch / process qualification batch
3
• pivotal batch /Production scale batch
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12. Laboratory scale batch
• Early development at laboratory stage.
• It is generally 100-1000 times less than production batch.
• It is 1X (3-10 kg or 3-10 liters or 3000-10000 unit) batch.
Uses
• To support formulation.
• For packaging development.
• For preclinical trial.
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13. Pre-exhibit batch
• It is 1st step in scale up.
• It generally 70 % of the size of the exhibit batch.
• It prepaid with the complete process documentation and fully
validated analytical methodology.
Uses
• To detect any problem arise in manufacture of exhibit batch .
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14. Exhibit batch
• It is demonstration batch.
• It contains the mfg. documentation, product specification,
accelerated stability data submitted to FDA.
• It generally 10 % of the production scale batch.
• It is 10X (30-100 kg or 30-100 liters or 30000-100000 unit) batch.
• It is manufactured under GMP.
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15. Exhibit batch also called as :-
• NDA or ANDA batch
• Regulatory reference batch
• Bioequivalence batch
• Fully GMP batch Stability tested batch
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16. Production batch
It is produced during the routine marketing of product.
It is 100X batch means :-
300-1000 kg or
300-1000 liters or
300000-1000000 unit
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17. What is Scientific scale up
Should done in incremental manner.
Process being validated for each new scale.
The equipment should possess following similarity
1) Geometric similarity
2) Kinematic similarity
3) Dynamic similarity
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18. Reporting
Responsibility
R & D group with
separate staffing
The formulator who developed the product
can take into the production and can provide
support even after transition into production
has been completed.
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General considerations

19. 2. Personnel Requirement:-
Scientists with experience in pilot plant operations.
As they have to understand the intent of the formulator as well as
perspective of the production personnel.
personnel with engineering knowledge
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3.Space Requirement
Administration
And
Information
processing
Physical
Testing
Area
Standard
Equipment Floor
Space
Storage
Area

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3. 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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4.Physical testing area:-
This area should provide permanent bench top space for
routinely used physical- testing equipment

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5 .Standard pilot-plant equipment floor space:-
• Discreet pilot plant space, where the equipment needed for
manufacturing all types of dosage form is located.
• Intermediate – Equipments used should be made portable where
ever possible.
• Space for cleaning of the equipment should be also provided.
floor space
Epoxy
coating
PVC coating

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5.Storage Area:-
• It should have two areas divided as approved and unapproved
area for active ingredient as well as excipient.
• Different areas 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.

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Review of the formula
• The purpose of each ingredient and it’s contribution to the final
product 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 checking
Raw materials used in the small scale production cannot necessarily
be the representative for the large scale production

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6. Equipment:-
• economical , simplest & efficient equipment
• The size of the equipment should be relevant.
• 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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Order of mixing
Mixing speed
Mixing speed Mixing time Rate of
addition of granulating agents,
solvents, solutions of drug etc.
cooling
Rates
Filters size (liquids)
drying
time
Drying
temp.
Process Evaluation Parameter

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Master Manufacturing Procedures:-
The three important aspects
• Weight sheet
• Processing directions
• Manufacturing procedure

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Scale-up and post approval changes (SUPAC)
FDA and American Association of Pharmaceutical Scientists (AAPS)
provided the scientific foundation for the scale up and post approval
changes required for immediate release product Called as SUPAC.
It provide guideline for post approval changes in the following
• Component Composition
• Site of mfg.
• Process and equipment

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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 will be reduced.
• Any problem in manufacturing will be directed towards it’s
own pilot-plant personnel's.

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LAYOUT OF TABLET PILOT
PLANT

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•
• Case Study
• The case study critically examines the supply chain strategy
of ‘SUN pharma’ company and its acquisition strategy of
Ranbaxy.
• The case illustrates the story of the mergers and acquisition
from a supply chain theory point of view and thereby states
how SUN has moved forward from its regional presence to
global expansion.

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Sun Pharma's annual sales revenue before and after the acquisition of Ranbaxy

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• Before merge, Ranbaxy used Aqua Logistics services to track
and trace the shipments in order to avoid distribution centres at
various overseas and domestic locations by keeping track of the
current position of the shipment dispatched by it.
• To enhance global supply chain capability Sun Pharma, used
Radio Frequency Identification (RFID) technology replacing
their bar coding system in order to track the stocks
automatically.

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INDIAN Pharma Industry Growth Chart

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Conclusion:-
A pilot plant is a small industrial system which is operated to
generate information about the behaviour of the system for use in
design of larger facilities.
Pilot plants are used to reduce the risk associated with construction
of large process plants
To avoid the scale-up problems.

39. References :-
• The theory & practice of industrial pharmacy by Leon
Lachman, Herbert A. Lieberman, Joseph L. Kenig, 3rd edition,
published by Varghese Publishing house.
• “Pharmaceutical process scale –up” by Michael Levin marcel
dekker inc volume-157, 2003.
• “Pharmaceutical process validation” by Robert A. Nash and
Alfred H Wachter marcel dekker inc volume-129, 2003 . Page
no. 17-21. 5.
• “Text book of industrial pharmacy” by Shobha Rani R.
Hircmath, orient Longman pvt ltd Chennai .
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