Process validation is defined as 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 product. Process validation involves a series of activities taking place over the lifecycle of the product and process. Process validation activities categorized in three stages, such as

The process is defined during this stage based on knowledge gained through development and scale-up activities such as lab scale / trial batches and optimization / pre – validation batches.

During this stage, the process design is evaluated to determine if the process is capable of reproducible commercial manufacturing with three consecutive validation batches.

Ongoing assurance is gained during routine production that the process remains in a state of control through product Quality review.

• Any changes during the project phase or during commercial production, the risk assessment shall be performed, as required.

• Quality Risk Assessment (QRM) shall be performed prior to execution of new product.

• Process knowledge from development studies should be available to the manufacturing site, unless otherwise justify, and be the basis for validation activities.

• Batches under Process validation shall be released for distribution after following

1. Drug Product should be fully complying with cGMP, with the validation acceptance criteria.

2. Any deviation observed during validation has been assessed to have no impact on product quality prior to release of batches.

3. Finished product samples of batches are tested as per ‘Release’ specifications and found to be satisfactory

4. The batches meet all other requirements as per Batch release procedure.

5. Raise deviation and perform investigation if any significant changes to the approved protocol during execution.

• The goal of this stage is to design a process suitable for routine commercial manufacturing that can consistently deliver a product that meets its quality attributes.

• A successful validation program depends upon information and knowledge from product and process development. This knowledge and understanding is the basis for establishing an approach to control that is appropriate for the manufacturing process.

• Formulation Research and Development shall develop the product based on their development studies. Formulation Research and Development shall provide key inputs to process design and quality attributes for manufacturing process.

• Formulation Research and Development or shall document this information and same information shall be considered for process qualification and continued process verification stage of process validation.

• Formulation Research and Development shall define process control for each process operation and overall process based on process knowledge & understanding gained during product development.

Trial batches, pre- validation/Optimization batches shall be a part of process design phase.

• During this stage, the process design is evaluated to determine if the process is capable of reproducible commercial manufacturing.

• Validation team shall ensure that equipments and utilities are qualified before manufacturing of commercial batches for process performance qualification.

• Process Performance Qualification has to perform to confirm that the process design is capable of commercial manufacturing as expected.

• This stage needs to be completed prior to commercial distribution.

• Following activities shall be completed before Process Performance Qualification as follows

1. Manufacturing facility has been qualified to meet cGMP requirements.

2. Equipment to be used in manufacturing has been qualified.

3. Utilities to be used in manufacture of the product (example- Purified Water, Compressed Air, HVAC Systems etc.) have been qualified.

4. Instruments used in processing have been calibrated (example- Temperature Sensors, weighing balances etc.)

5. Trained Personnel shall be involved in manufacturing, testing and in process control.

6. Process Performance Qualification & Exhibit Batch Protocol shall be prepared and approved

7. All the activities shall be performed as per Approved validation Protocol.

8. A product / process shall be considered as qualified when qualification batches meet the acceptance criteria established in the protocol.

9. In case a batch fails to meet acceptance criteria established for the particular product, complete investigation shall be carried out to find cause of failure.

10. Decision regarding repeat the batch manufacturing for qualification batch, to implement a process change or repeat the sample analysis shall be taken.

11. The decision will be based on findings of investigation and If required necessary inputs shall also be taken R & D (F) need based.

• Objective of this stage of process validation is continual assurance that the process remains in state of control and in validated state during commercial manufacturing.

• During this stage monitoring of critical process parameters and critical quality attributes at the level established during the process qualification stage shall be done.

• In case of new drug products, Critical Process Parameters (CPPs) and Critical Quality Attributes (CQAs) to be monitored as a part of continued process verification shall be as per (but not limited) Process performance qualification protocol.

• In case of existing drug products, Production and Technology Transfer department shall identify the Critical Process Parameters (CPPs) & Critical Quality Attributes (CQAs) to be monitored. Identified Critical Process Parameters (CPPs) & Critical Quality Attributes (CQAs)

• Quality Assurance shall ensure that CPPS and CQAs value are within control limits prior to release of batch. This shall be enclosed with Batch Manufacturing Record.

These are key variables affecting the production process. CPPs are attributes that are monitored to detect deviations in production operations and product output quality or changes in Critical Quality Attributes. These includes the Physical parameters like Impeller and chopper reading, Mixing time, Blender RPM, Compression and coating etc.

 A Physical, Chemical, Biological or Microbiological property or characteristic that should be within an appropriate limit and range to ensure the desired product quality. These includes the Analytical Parameters like Assay, Dissolution, Related Substances etc.

Re-validation to be carried out to evaluate a change in existing process/ equipment/ input materials etc. which will impact product quality.

Re validation may be restricted to a particular process step(s) that is/ are impacted by the change. (Ex: Change of compression machine, change in coating lot size).

Re validation shall be carried out under following criteria (but not limited to)

• Change in Batch size (Scale up or Scale down)

• Change in Manufacturing process

• Change in Source of API

• Change in Capacity of Equipment