Define Scale up process, need of Scale up technique, Stages of scale up process Bench\lab scale, pilot plant, large scale up technique, validation of large scale up process

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Department of Pharmaceutical Sciences
Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur 440033
Presented by:
Dhanashree N. Sarwan
M. Pharm. First Year (Pharmaceutical chemistry)
STAGES OF SCALE UP PROCESS

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 Definition- Act of using results obtained from laboratory studies for designing a prototype and a pilot plant
process; construction a pilot plant and using pilot plant data for designing and constructing a full scale plant or
modifying an existing plant
 The goal of scale-up is to identify & develop a process that will successfully produce a desired product when
manufactured at a commercial scale.
Scale up is basically needed for:
1. Market growth.
2. Introduction of new processes.
3. Reduction in making expensive errors in design and operation.
4. Concentrate on addressing areas of doubts and uncertainty
5. Economic feasibility.
SCALE UP PROCESS

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1. Lab-Lab scale is to prove that a material or a product can be made from raw materials or precursors. It is a
proof of concept study.
2. Bench –Bench scale is to make enough amounts of material or product to test its properties, learn about
fundamentals of processing.
3. Pilot- Pilot scale is to try small scale production before bigger investment at high risk. There are more
requirements such as space and design requirements. Is a small industrial machine or setup that requires to be
operated, possibly has its own building, tens of kilograms of nanomaterials can be produced.
4. Industrial- Scale Industrial scale is the large scale production which is the final stage of the process.
STAGES OF SCALE UP PROCESS

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 These are produced at the research lab and early development laboratory stage.
 They may be of very small size (e.g., 100–1000 times less than production scale).
 Laboratory-scale batches or Bench scale up may be used to support formulation and packaging
development, early clinical and/or preclinical stages.
 It can also be analyzed to assist in the evaluation and definition of critical quality attributes (CQAs). A
CQA is a physical, chemical, biological, or microbiological property or characteristic that should be within
an appropriate limit, range, or distribution to ensure the desired product quality. CQAs are generally
associated with the drug substance, excipients, intermediates, and drug product.

Bench Scale up Process

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 These may be used in the process-development or optimization stage.
 They may be used to support preclinical and mid- to later-stage clinical evaluation and also to support formal stability
studies.
 If supporting formal registration, a pilot-batch size should correspond to at least 10% of the production-scale batch. For oral
solid-dosage forms, this size should generally be 10% of production scale or 100,000 units, whichever is greater.
 The choice of pilot scale is often difficult for the project team as members must balance parameters such as anticipated
product volumes, anticipated site of production, equipment constraints at that site, and regulatory expectations. With the
increasing trend toward developing orphan drugs, the authors believe that the regulatory expectation of pilot-scale batches
of 100,000 units is not always valid and should be discussed with the relevant regulatory authority.
Pilot-scale Process

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 Industry scale is defined as a machinery that may occupy factory size.
 These batches are of the size that will be produced during the routine manufacturing and
marketing of the product.
 Data on production-scale batches may not always be available prior to granting
marketing authorization.
Production or Large scale batches

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 The collection and evaluation of data, from the process design stage through commercial production,
which establishes scientific evidence that a process is capable of consistently delivering quality
products.(FDA)
 Documented evidence which provides a high degree assurance that a specific process will consistently
result in a product that meets predetermined specifications and quality characteristics. (WHO)
 The documented evidence that the process, operated within established parameters, can perform
effectively and reproducibly to produce a medicinal product meeting its predetermined specifications
and quality attributes.
VALIDATION OF LARGE SCALE PROCESS

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 Design Qualification(DQ) - Verification process to meet particular requirement relating to the quality of
Pharmaceutical and manufacturing process. DQ plan covers user requirement user specification, Technical
specification and DQ report.
 Operational Qualification (OQ)- Process of testing to ensure individual and combined systems function to
meet agreed performance criteria and to check how the result of testing is recorded. The purpose is to ensure that
all the dynamic attributes comply with the original design.
 Performance qualification (PQ)(Process qualification)- process of testing to ensure that the individual and
combined systems function to meet agreed performance criteria on a consistent basis and to check how the result
of testing is recorded.
 The purpose is to ensure that the criteria specified can be achieved on a reliable basis over a period of time.
 Process Validation- Owners are responsible for Validating Their Processes (personnel, equipment, methods,
SOPs) to ensure compliance to cGMP/GLP regulations.
Process validation- Role of assessment

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Thank You