Prospective Validation

1.0 Introduction

Validation is the evaluation of action for proving effectiveness and is an integral part of quality assurance.

Significance:

Validation plays a significant role in attaining quality and reduces cost, capital expenditure, quality cost and increases output. It eases the maintenance of equipments and instruments.

1.1 General Aspects

Prospective validation provides documented evidence that a system performs in accordance with the specifications on the pre-planned protocol.

This validation is done before a new product is distributed or product is made under revised manufacturing process.

It is performed on three consecutive batches

Here before the process is employed for commercial use, validation protocol is executed

In the product development phase production process is divided into individual steps

Every step is evaluated based on experience or theoretical data to elucidate the parameters which impact quality of final product

To determine the criticality of the factors in prospective validation series of experiments are designed.

The experiments designed should be planned and documented in the protocol.

Validation of equipments, analytical testing methods, environment in the production area is done.

Master batch documents are prepared after identifying the critical process parameters and machine settings, environmental conditions and component specifications.

Theoretically the number of process runs and observations made should allow establishment of extent of variation & trends to ease the evaluation of data. A proper validation process is attained by when three consecutive batches are run with the desired parameters and final product is attained.

Practically it may time consuming to gather data.

1.2 Considerations in selecting validation strategy

• Producing batches in different shifts
• Using raw materials & excipients from different lots
• Using different equipment & facilities for commercial production
• Analysis of process data
• Operating range of critical processes
• Revalidation

When processing the validation batches, sampling & testing on product is done in various stages and documented.

Testing should be detailed on package of final product

When review is completed recommendations on in process controls and extent of monitoring of production is given.

These recommendations should be implemented in batch manufacturing, packaging record and SOPs.

Any frequencies and corrective actions should be specified if they have exceeded values

1.3 Contents

Prospective validation should include the following

• Brief description of process
• Summary of critical processing steps which need to be investigated
• List of facilities and equipments to be used with their calibration status
• Specifications for the finished product release
• Analytical methods list
• In process controls with acceptance criteria
• Sampling plan
• Testing with analytical validation and acceptance criteria
• Methods for recording results and evaluating them
• Proposed time table
• Responsibilities and functions
• Batches which are made for process validation should be of the same size as industrial scale batches
• When selling or supplying validation batches good manufacturing & market authorization practices should be followed

1.4 Personnel

Team for validation should comprise personnel from various departments. They should be trained and well qualified in relevant discipline

Prospective validation, revalidation, analytical testing methods, quality assurance