PILOT PLANT SCALE UP TECHNIQUES

PILOT PLANT SCALE UP TECHNIQUES

PILOT PLANT SCALE UP TECHNIQUES

PILOT PLANT SCALE UP TECHNIQUES

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

R & D  à PILOT SCALE   à SCALE UP  à LARGE SCALE MANUFACTURE

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

PILOT SCALE

â

INTERMEDIATE BATCH SCALE

â

Representative and simulates Manufacturing scale

SCALE UP

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NEXT TO THE PILOT SCALE

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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

Objectives:

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.

Why?

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

Challenges in Scale-Up

Scaling up production comes with challenges:

Homogeneity: Achieving uniformity in larger batches can be challenging, particularly with chemical reactions.

Equipment Adaptation: Adapting laboratory or pilot-scale equipment to larger-scale operations may require significant modifications.

Quality Assurance: Maintaining stringent quality control throughout the scale-up process is essential.

FAQ

What is pilot plant scale-up in industrial processes?

Pilot plant scale-up refers to the process of transitioning from a small-scale operation, such as a laboratory or pilot plant, to a larger commercial-scale production facility while maintaining product quality and consistency.

Why is pilot plant scale-up important in various industries?

Pilot plant scale-up is essential because it allows industries to efficiently produce larger quantities of products, reduces costs, maintains quality, meets regulatory requirements, and ensures timely market availability.

What are the key techniques for successful pilot plant scale-up?

Key techniques include understanding the process, assessing scalability, process optimization, equipment selection, and continuous monitoring of critical parameters.

How can one assess the scalability of a process during scale-up?

Assessing scalability involves evaluating whether the process can be successfully replicated on a larger scale without compromising product quality, efficiency, or safety.

What challenges are commonly encountered during pilot plant scale-up?

Challenges may include achieving homogeneity in larger batches, adapting equipment to larger-scale operations, and maintaining stringent quality control throughout the scale-up process.

Why is continuous monitoring of critical parameters important during scale-up?

Continuous monitoring helps ensure that the process remains within specified parameters, which is crucial for maintaining product quality and consistency at a larger scale.

Can you provide examples of industries that frequently utilize pilot plant scale-up techniques?

Industries such as pharmaceuticals, chemicals, food processing, and manufacturing often employ pilot plant scale-up techniques to transition from small-scale to commercial production.

Are there specific case studies that illustrate successful pilot plant scale-up?

Yes, case studies provide real-world examples of successful scale-up projects, showcasing the strategies and techniques used to achieve a smooth transition to larger-scale production.

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