Contents of this chapter

• General considerations – including significance of personnel requirements, space requirements, raw materials

• Pilot plant scale up considerations for solids, liquid orals, semi solids and relevant documentation

• SUPAC guidelines

• Introduction to platform technology

Pilot Plant Scale Up

• In every emerging pharmaceutical industry or an already existing one, there is always a need to have an intermediate batch scale representing procedures and simulating that used for commercial manufacturing

• This is achieved by determining the ability of formula to withstand batch-scale and process modification


What is 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.”

Why conduct Pilot Plant Studies?

• A pilot plant investigates 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 food processing plant from laboratory data alone with any degree of success

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-live and storage stability studies

• Determining possible salable 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

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 customer

• 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

• Pilot plant costs may exceed those of usual plant production costs. The pilot plant may be used for training personnel for a full- scale plant

Scale-up: - The art for designing of prototype using the data obtained from the pilot plant model

• Pilot plant scale-up techniques involve reproducible manufacture of an experimental formulation on high-speed production equipment, in a cost effective manner

• It is a part of the pharmaceutical industry where the same processes used during Research and Development (R&D) of dosage forms are applied to different output volumes; usually greater than that obtained during R&D





Representative and simulates Manufacturing scale






Process of increasing the batch size/ procedure for applying the same process to different output volumes

Objective of scale up

 “Find mistakes on small scale and make profit on large scale.”

• To produce physically and chemically stable therapeutic dosage forms

• Review of the processing equipment

• Guidelines for productions and process control

• Evaluation and validation

• To identify the critical features of the process.

• To provide master manufacturing formula.

Pilot plant scale up must include:

• 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

Pilot Plant Design

A pilot plant design should support three key strategic


1.   Formulation and process development

2.   Clinical supply manufacture

3.   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

General considerations

1. Personnel Requirements: Personnel should have –-

• Scientists with experience in pilot plant operations as well as in actual production area (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

2. Space Requirements

Administrative and information processing

Physical testing area

Standard equipment floor space

Storage area

2a. Administrative and Information processing

• Adequate office and desk space should be provided for both scientist and technicians

• The space should be adjacent to the working area

2b. Physical testing area

• This area should provide permanent bench top space for routinely used physical- testing equipment

2c. Standard 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.

• Equipment’s 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

2d. Storage area

• Two separate areas for approved and unapproved active ingredient as well as excipients

• Separate 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, packing material

3. Review of the formula

• A thorough review of the each aspect of formulation

• The purpose of each ingredient and its contribution to the final product manufactured on the small-scale laboratory equipment

• 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.

4. 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 be the representative for the large scale production

5. Relevant Processing 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

6. Production Rates

• It can be determined by the immediate future market requirements

• Equipment and the process should be chosen on the basis of production of a batch at a frequency that takes into consideration:

1. Product loss in the equipment during manufacture

2. The time required to clean the equipment between batches

3. The number of batches that will need to be tested for release

7. Process Evaluation

• It is the basis of process validation

• Documentation of process is to be done

• Process is validated only if there are no changes in the formula, quality of the ingredients, or the equipment configuration

• Revalidation needs to be done to ensure that changes have not taken place

8. Preparation of Master Manufacturing Procedures

Manufacturing directions

Sampling directions

In process QC

Final product QC

Helps in better understanding by the technician and compliance

9. 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

10. GMP considerations

GMP items that should be a part of scale up are –

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

11. Transfer of Analytic methods to Quality Assurance

• During scale up the analytical test methods developed in research should be transferred to the QA dept.

• QA staff to review process to make sure proper analytic equipment’s are available and personnel are trained

• They should review the assay procedures and the that obtained during validation studies to verify that the there are no changes in the analytical procedure

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