1. A pilot plant allows for transforming a lab scale formula into a viable product by developing reliable manufacturing procedures at an intermediate scale. This helps identify any issues before committing to full-scale production. 2. Key objectives of a pilot plant include evaluating results from laboratory studies, producing small quantities of product for testing, and determining parameters for full-scale production. 3. Important considerations for pilot plant development include the type and size of equipment needed, proper location, staffing requirements, and ensuring compliance with Good Manufacturing Practices.

1. PILOT PLANT SCALE UP TECHNIQUES
R & D Production
Pilot plant Laxmidhar sahoo,
Assistant
professor,RIPS,
berhampur

2. Pilot plant: Defined as a part of the
pharmaceutical industry where a lab scale
formula is transformed into a viable product by
the development of liable practical procedure
for manufacture.
Scale-up is the process of increasing the batch
size or a procedure for applying the same
process to different output volumes.

3. A pilot plant is a pre-commercial production system
that employs new production technology and/or
produces small volumes of new technology-based
products, mainly for the purpose of learning about
the new technology.
The knowledge obtained is then used for design of
full-scale production systems and commercial
products, as well as for identification of further
research objectives and support of investment
decisions

4. 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
• Determining possible by-products or waste stream requiring
treatment before discharge
• 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

5. 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 complex
processing plant from laboratory data alone with any
degree of success

6. Considerations in pilot plant development
• Kind and size – depends on goals; evaluating
product and process; producing samples of
product for evaluation; market testing or
furnishing to potential customers
• Location: near R&D facility? At an existing plant?
Close liaison between R&D and pilot plant
staff is essential.
• Labor requirements and costs: engineering staff,
skilled operations and maintenance staff. The pilot
plant may be used for training personnel for a full-
scale plant

7. Pilot plant studies include the close examination of
the formula to determine :
Its ability to withstand batch scale .
Process modification .
Compatibility of the equipment with the
formulation
Cost factor .
Availability of raw materials meeting the
specifications required to produce the product .
Market requirement .
Physical space required and the layout of the
related functions

8. In short , all critical features of a process must
be identified so that as the process is scaled
up , it can be adequately monitored to provide
assurance that the process is under control
and that the product produced at each level of
the scale up maintains the specified attributes
originally intended.

9. Objective of scale up
“Find mistakes on small scale and
make profit on large scale ”

10. To produce physically and chemically stable therapeutic
dosage forms.
Review of the processing equipment.
Guidelines for productions and process control.
Evaluation and validation of process and equipment.
To identify the critical features of the process.
To provide master manufacturing formula

11. Significance of Pilot Plant:
Standardization of formulae.
 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.

12. PILOT PLANT DESIGN
A pilot plant design should support three key strategic
objectives :
Formulation and process development .
Clinical supply manufacture .
Technology evaluation , scale up and transfer .
Attributes playing a key role in achieving the above
objectives are :
cGMP Compliance .
A flexible highly trained staff .
Equipment to support multiple dosage form
development .
Equipment at multiple scales based on similar operating
principles to those in production .

13. General consideration:
Transition
Laboratory Routine processing
(full scale production facility)
Develop a reliable and practical method of
manufacture

14. 1. Reporting responsibilities
2. Personnel Requirement
3. Space Requirements
4. Raw Materials
5. Training
6. Review of formula
7. Processing equipment
8. Process Evaluation
9. Preparation of Master Manufacturing
Procedure
10. Good Manufacturing Practice (GMP)
Considerations
11. Transfer of Analytical Methods to Quality
Assurance

15. Reporting responsibilities
The objective of the reporting responsibility is to facilitate the
transfer of a product from the laboratory into production.
Transfer of products from a laboratory scale to a commercial scale,
there is need for be adequate records and reporting arrangement
To achieve this, there should be a good relationship and effective
communication between the pilot plant group and the other groups
(R&D, processing, packaging, engineering, QA/QC, regulating and
marketing) with which they interact during the process)
The formulator continues to provide the support to the other
departments even after the transition into the production has been
completed.

16. Personnel Requirement
individuals with qualifications required for
position in a pilot plant organization
It should be a blend of good theoretical
knowledge of pharmacy and some practical
experience in the pharmaceutical industry
Ability to develop good relationships with other
personnel.
 Good communication skill (Writing and
speaking).

17. Should be able to understand the intent of the
formulator and perspective of production
personnel.
Must have minimum knowledge on Engineering,
Electronic and Computer.
 Must have knowledge on Physical, Chemical,
and Medical attributes of dosage form.
Must be aware on the principle of GMP Practices

18. Space requirement
Administration
& information
processing
Physical testing
Area
Standard pilot
plant equipment
floor space
Storage Area

19. Administrative and information
processing
There should be adequate office and desk space
for both the scientists and technicians to facilitate
proper documentation of their activities and
observations.
This should be adjacent to the work area but
sufficiently isolated to permit people to work
without undue distraction.

20. Physical Testing Area
There should be an adequate working area where
the analysis and physical testing of samples can be
performed
(in-process quality control analysis)
which helps in early identification of production
error
This area should provide permanent bench top
space for routinely used physical testing equipment
like balances, pH meters, viscometers etc.

21. Standard pilot plant equipment floor space
The sufficient specified space must be there for
 free installation
operation and
 easy maintenance of the equipment
This arrangement helps make sure of the quality
of the scale up data collected, as well as being
prudent with expensive materials

22. STORAGE AREA
Separate provisions for API and excipients further segregated
into approved and unapproved areas according to GMP
Storage area for in process materials , finished bulk products ,
retained samples , experimental production batches , packaging
materials (segregated into approved and unapproved areas)
Controlled environment space allocated for storage of
stability samples
 Storage area for packaging materials should also be made
available.

23. Raw Material
One purpose/responsibility of the pilot-plant is the
approval & validation of the active ingredient &
excipients raw materials.
Why ?
Raw materials used in the small scale production
cannot necessarily be the representative for the
large scale production

24. There may be variations in particle size, shape, or
morphology resulting in different handling
properties or
differences in density, static charges, rate of
solubility, flow properties etc., of active/inert
ingredients as the batch size increases.
There is need for alternate suppliers of raw materials
because a single supplier may sometimes leave the
company defenseless with respect to price and supply
quality.

25. This means that several batches of products need
to be manufactured with these alternate materials
and their performance in the formulation and
stability of the finished product, evaluated relative
to the standard product.

26. Training
The employee those need training are divided into
the following categories;
 New employees.
Those employees who are assigned with a new
job.
 Those employee whose performance a task falls
below required standard.

27. The employee get trained on following activities as
per the GMP and FDA guidelines that are;
Technical environment
 Dealing with potent or dangerous chemicals
Working with system of weights and measures
Checking of manufacturing steps, containers,
equipment and drying racks.
Identification of packaging.
Proper stock rotation system.
 Raw material inspection.

28. Review of the Formula:
The objective of each ingredient and its contribution
to the final product manufactured on small scale
equipment must be thoroughly understood.
Relevant Processing Equipment:
The selection criteria for one equipment to produce
effective product within the proposed specifications
are -
equipment must be
 Economic
Simple (In installation, handling, cleaning and
maintenance)
Efficient and most capable of consistently producing
a product.

29. Process Evaluation:
The objective of process validation to ensure the
selected process could be able to produce quality
products at various critical stages of production
This is possible by critically monitoring the within
the batch variation of measurable parameters like
content uniformity,
moisture content and
compressibility

30. The process remains validated only if there is no
change in the formula, quality of the ingredients
and equipment configuration
The manufacturing process and quality control
information should be reviewed on an annual basis
and should be followed by re-validation to ensure
that changes have not occurred

31. Things that should be critically examined during
the Process Evaluation are;
Order of addition of the components including
adjustment of their amount.
Mixing speed and time.
 Rate addition of granulating agent, solvents and
drug solutions.
 Heating and cooling rates.
 Filter size for liquids.
Screening size for solids.
Drying temperature and time.

32. Preparation of Master Manufacturing Procedure
The Process or Manufacturing Direction.
Process direction should be precise and clear.
Must be written in a simple manner which
should be easily understood by the operator.
The Chemical Weight Sheet.
 Identification of chemical required.
Quantities of chemical to be added.
Order of chemicals to be added.
The name and Identification number of the
ingredient must be mentioned.

33. The Sampling Direction.
 Time of sampling of finished product.
Manner of sampling of finished products.
The Batch record direction.
The batch record directions should include
specification for mixing times, mixing speeds,
heating and cooling rates and temperature.
The In-Process Specification.
Must mention a simple and easy access
specification for easy understanding of operators.

34. The Finished Product Specification.
The drug in the dose specified.
The self-life of the product.
 The capability of the process.
The reliability of the test methods.
Storage condition

35. Good Manufacturing Practice (GMP)
Considerations
1.Equipment qualification
2. Process validation
3. Regularly scheduled preventative maintenance
4. Regular process review and revalidation
5. Relevant written standard operating procedures

36. 6.The use of competent, technically qualified
personnel
7. Adequate provision for training of personnel
8. A well-defined technology transfer system
9. Validated cleaning procedures
10. An orderly arrangement of equipment for
easy material flow and prevention of cross-
contamination.

37. TRANSFER OF ANALYTICAL METHODS TO QUALITY
ASSURANCE
Analytical methods developed in research must
be transferred to QA department .
Transfer process includes –
-1. Review the process to make sure that proper
analytical instrument is available .
-2. Personnel should be trained to perform the
test .
-3. Reliability of the test should be checked .