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2.1.5 Raw Materials

One of the main responsibilities of the pilot-plant is to validate and approve the

excipients and active ingredients used in pharmaceutical product's formulation. The

raw materials used in laboratory-scale production may not fit for the large-scale

production batches. There may be several variations in size, shape, density, and

solubility, flow properties, etc. A single supplier may not be able to fulfil the need of

raw material for large-scale production and can leave the manufacturer defenceless.

So, several batches with different alternatives to raw materials (supplied by two or

more suppliers) need to be manufactured. All the data regarding the performance of

this different raw materials (stability, quality tests, etc.) should be well-documented

so that can be thoroughly analysed.

2.1.6 Equipment

On small and laboratory-scale basic equipment has been used during the development

of drug product. So during scale-up alternative manufacturing equipment should be

used. The equipment should be:

i. Economical

ii. Simplest processing

iii. Efficient

iv. Capable of consistently producing products within the set specifications

v. Of optimum size (in accordance with production batch size)

vi. Can be cleaned easily (in case of used for the multiple product manufacturing)

2.1.7 Production Rate

The production rate should be determined by keeping the following things into

consideration

i. Immediate and future market demands and trends

ii. Type and size of equipment that is to be used in production

iii. Proportionality of size of the equipment and its utilization

iv. Product loss data during using a specific equipment and process

v. Clean up time between batches or between multiple product manufacturing

vi. The number of batches required for testing

2.1.8 Process Evaluation

In this step the critical evaluation of process is done and based on the evaluation results,

the process is optimized. The processes that should be evaluated include:

i. Mixing speed and mixing time

ii. Filter size for liquids preparations

12 Industrial Pharmacy II

iii. Screen sizes for solid preparations

iv. Drying time and drying temperature

v. Rate of the addition of solvents, solution of drugs, granulating agents, etc

vi. Order of addition/mixing of components, and their respective adjustments

vii. Heating and cooling rates

The knowledge of the effect of these above mentioned important process parameters

on the finished product and in-process quality is the basis for process validation and

optimization. This is accomplished by monitoring the within the batch variation of

measurable parameters (content uniformity, moisture content and compressibility).

This provides data that helps in identifying and accessing where the process is

performing as intended and where problem areas may be found.

2.1.9 Preparation of Master Manufacturing Procedures

The manufacturing procedure includes manufacturing directives, sampling directions,

weight sheet, finished and in-process product specifications (Fig. 2.2). This section is

related with the manner of presentation of manufacturing procedures which helps in

facilitating easy compliance and understanding of processing technicians.

The weight sheet should clearly categorize the chemicals which are required in the

batch, their order and quantities in which they will be used. The names and identifying

numbers for the ingredient should be used on batch records. These names and

identifying number should be in correspondence with those on the bulk material

containers. The process directions should be explicit as well as precise.

Various specifications (like addition rates, mixing times, mixing speeds, heating

and cooling rates and temperatures, the actual times, temperature and speeds, the

time and the manner in which finished and in-process samples are to be taken, handled

and stored) should be mentioned in the batch record directions. The manufacturing

procedure should only be written by actual operator.

Fig. 2.2: Different aspects included in manufacturing procedure

General Considerations and Pilot-Plant Considerations for Different Dosage Forms 13

2.1.10 Product Stability and Uniformity

Each pilot-plant batch should be studied for stability. The physical as well as chemical

stability studies should be performed on pilot-plant batches. The stability studies of

finished packages should be carried out.

2.1.11 Good Manufacturing Practices (GMP) Considerations