Introduction to Pilot-Plant and Scale-up 3

Starting up a new production unit is tricky but it would become risky if unforeseen

difficulties would not be identified. At the initial stage of development the product is

manufactured at laboratory-scale. It is many folds smaller than that of commercial

scale. So, this is not an intelligent idea to directly transfer product from laboratory

scale to commercial stage due to possibility of birth of many problems, e.g. corrosion,

high cost on material, low yield, less profit, etc. So, to detect and avoid the unforeseen

problems pilot-plant is used.

Pilot-plant can be defined as “the manufacture of either drug or drug product by a

procedure fully representative of and stimulating that used for full manufacturing

scale.” Pilot-plant is a 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.

1.2.1 Reasons for Conducting Pilot-Plant Studies

i. Evaluation of results: The pilot-plant helps in evaluating the results of laboratory

studies so that process and product corrections can be made accordingly.

ii. Determination of qualitative and quantitative details of product: In pilot-plant

small quantities can be produced which enables sensory microbiological

evaluations, limited marketing testing by providing small samples to

potential customers and determination of shelf life as well as storage stability

studies.

iii. Determination of waste products: By pilot-plant studies the possible salable byproducts can be determined. It also helps in determination of methods by which

waste management can be done in future.

iv. Decision making: By pilot-plant studies enough data can be collected which help

in making decision either to start a full-scale production or not. In case of positive

results the designing or modifying of plant can be done.

v. Need to make supplies: Pilot-plant provides supplies for several studies like bench

studies, animal studies and clinical studies. These studies are essential to

determine product characters, purity, toxicology, pharmacokinetics, ADME,

efficacy of product.

1.2.2 Objectives of Pilot-Plant

i. To attempt the procedure on a model of a proposed plant before spending

substantial whole of cash on a production unit.

ii. To examine of the procedure to decide its capacity to withstand batch scale and

process alteration.

iii. To validate and evaluate for process and supplies.

iv. To detect unforeseen problems during commercialised production.

v. To make master manufacturing formula

vi. To identify the critical control points of a process

vii. To avoid scale-up problems

A Pilot-plant design should support the three key objectives

a. Formulation and process development

b. Clinical supply manufacture

c. Technology evaluation, scale and transfer

4 Industrial Pharmacy II

These three objectives can be achieved by the following attributes

a. Compliance with CGMP.

b. A highly trained and flexible staff with experience of concerned field

c. Equipment that can support multiple dosage forms development.

d. Equipment at multiple scales based on similar operating principles to those

in production.