Summary

42 Industrial Pharmacy II

3. Engineering

4. Maintenance

5. Calibration

6. Material control

7. Inventory

8. Orders

9. Labelling

10. Process and manufacturing activities

11. QA and QC activities

SCALE-UP

It is defined as art for designing of a prototype using the data obtained from the pilotplant process/model. The size of the set-up is bigger than the pilot-plant but smaller

than commercial manufacturing.

Steps in Scale-up

1. Define product economics.

2. Conduct of laboratory studies and scale-up techniques.

3. Identification of key-controlling steps.

4. Conduct large-scale studies.

5. Design, construction and evaluation of pilot-plant results

Objectives of Scale-up

i. To produce physically and chemically stable quality therapeutic and diagnostic

drugs

ii. To review the processing equipment used in the manufacturing of a product

iii. To check compliance with guidelines for production and process control

iv. To conduct evaluation and validation of process

v. To identify the critical characteristics of the process

vi. To provide master manufacturing formula

GENERAL CONSIDERATIONS

General consideration includes the following points to be kept in mind while planning

for scale-up:

1. Reporting responsibilities: There should be adequate records and reporting

arrangements to make the transfer of products from laboratory-scale to a commercialscale smooth.

2. Personnel requirement: It is very important for the smooth transfer of products

from laboratory-scale to pilot-plant and then to commercial-scale to have wellqualified staff.

3. Space requirements: There are four types of space requirements of a pilot plant:

i. Administrative and information processing

ii. Physical testing area

iii. Standard pilot plant equipment floor space

iv. Storage area

Summary 43

4. Review of the formula: A thorough and critical review of each prospect of a

formulation is important.

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.

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.

7. Production rate

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 specific equipment and process

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

vi. The number of batches required for testing

8. Process evaluation: The knowledge of the effect of 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 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.