BP702T - INDUSTRIAL PHARMACY-II (Theory)

UNIT-I 

Pilot plant scale up techniques: Pilot plant and scale-up techniques are both integral and critical to drug discovery and development process for new medicinal products. 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.

 

1. Reporting responsibilities

In order to facilitate smooth transfer of products from a laboratory scale to a commercial scale, there is a need for be adequate records and reporting arrangement. How effective a pilot plant is may be determined by the ease with which new products or processes are

 

2. Personnel Requirement

Those employed during the scale up process should be individuals with required qualifications for position in a pilot plant organization. It should be included good theoretical knowledge of pharmacy and some practical experience in the pharmaceutical industry. Practical experience in pilot plant operations is also invaluable. 

 

3. Space Requirements

The space requirements of a pilot plant are of four types:

a. Administrative and information processing

There should be sufficient office and desk space for both the scientists and technicians to facilitate proper documentation of their activities and observations.

 

b. Physical Testing Area

There should be sufficient working area where the analysis and physical testing of samples can be performed (in-process quality control analysis) which helps in early identification of production error. This area should provide permanent bench top space for routinely used physical testing equipment like balances, pH meters, viscometers etc.

c. Standard pilot plant equipment floor space

This has to do with where all the relevant equipment used in the pilot plant scale up techniques is kept. The equipment should be available in a variety of sizes known to the representative of all production capability.

d. Storage Area

Separate provision should be made for the storage of active ingredients and excipients. Different areas should be provided for the storage of the in-process materials, finished bulk products from the pilot plant and materials from the experimental scale-up batches made in the production. Storage area for packaging materials should also be made available.

 

4. Raw Materials

The raw materials used during small scale formulation trials may not meet the requirements of large volume shipments of materials used in full manufacturing scale. Also, active ingredients used in a laboratory scale need to meet up with the rising needs of the product when subjected to scale up.

There may be variations in particle size, shape, or morphology resulting in different handling properties or differences in density, static charges, rate of solubility, flow properties etc., of active/inert ingredients as the batch size increases.

 

5 Process Evaluation

This step critically evaluates the process and optimizes its performance based on that evaluation. Processes that should be examined include the following:

1. Order of addition of components, including adjustments of their amounts.

2. Mixing speed and mixing time.

3. Rate of addition of granulating agents, solvents, solutions of drugs, slurries etc.

4. Heating and cooling rates.

5. Filter sizes for liquids preparations

6. screen sizes for solid preparations

7. Drying temperatures and drying times.

Knowledge of the effect of these important process parameters on in-process and finished product quality is the basis for process optimization and validation. This is accomplished by monitoring the within batch variation of measurable parameters (content uniformity, moisture content and compressibility). This provides data that helps in accessing and identifying where the process is performing as intended and where problem areas may be found.

 

6. Preparation of Master Manufacturing Procedure

This is concerned with the manner of presentation of the manufacturing procedures to facilitate easy compliance and understanding by the processing technicians. The procedures include; manufacturing directives, chemicals weigh sheet, sampling directions, in-process, and finished product specifications.

The weight sheet, for instance, should clearly identify the chemicals required in the batch, their quantities and order in which they will be used. To also prevent confusion and possible errors, both names and identifying numbers for the ingredient should be used on batch records and these should correspond with those on the bulk material containers. The process directions should be precise and explicit.

The batch records’ directions should include specifications for addition rates, mixing times, mixing speeds, heating and cooling rates, and temperatures. The actual times, temperature, and speeds used should be documented. The time and manner in which in-process and finished samples are to be taken from a batch and the way in which they are handled and stored should be clearly specified with the batch record.

 

7. Good Manufacturing Practice (GMP) Considerations

A list of GMP items that should be part of scale-up of a new product or process introduction may include the following;

  1. Equipment qualification

  2. Process validation

  3. Regularly scheduled preventative maintenance

  4. Regular process review and revalidation

  5. Relevant written standard operating procedures

  6. The use of competent, technically qualified personnel

  7. Adequate provision for training of personnel

  8. A well-defined technology transfer system

  9. Validated cleaning procedures

 

8. Transfer of Analytical Methods to Quality Assurance

All analytical test methods developed in research during scale up of a new product, must be transferred to the quality assurance department. The quality assurance staff should review the process to make sure that the proper analytical instrumentation is available and that personnel are trained to perform the tasks.

Research personal should review the assay procedure and the data obtained during the validation studies to verify that the analytical methods have not been altered in a way that might affect the reliability, precision or accuracy of the tests.

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