Basic Concept Of Validation

1. Definition of Validation

•   Action of proving, in accordance with the principles of good manufacturing practice, that any procedure, process, equipment, material, activity, or system actually leads to the expected result
• Documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes and characteristics
• Obtaining and documenting evidence to demonstrate that a method can be relied upon to produce the intended result within defined limits
• Action to verify that any process, procedure, activity, material, system, or equipment used in manufacture or control can, will, and does achieve the desired and intended results.

1.1 Justification of Validation
Validation is basically good business practice. The objective is to achieve success
in the first production of a new product.

• Government regulations: Current good manufacturing practices (GMPs) have been established all over the world. The GMPs basically serve as guidelines but do not provide step-by-step directions on how to achieve them. However, the validation master plan and associated SOPs exactly define responsibilities: who, when, where, and how much is sufficient to demonstrate.
• Assurance of quality: Validation provides confidence in the quality of products manufactured as the over quality of a particular process cannot be established due to the limited sample size. Validation leads to less troubleshooting within routine production. As a result, it reduces the number of customer complaints and drug recalls.
• Cost reduction: Processes running at marginal levels often cause costs because of necessary re-inspection, retesting, rework, and rejection. Validation leads to the optimization of processes and results in minimization of those expenses. 

2. Type of Validation

• Retrospective Validation

• Prospective Validation

• Concurrent Validation

• Revalidation

2.1 Retrospective Validation

Validation of a process for a product already in distribution, based on accumulated production, testing, and control dates. Summary of existing historical data.Retrospective validation is used for facilities, processes, and process controls in operation use that have not undergone a formally documented validation process. Validation of these facilities, processes, and process controls is possible using historical data to provide the necessary documentary evidence that the process is doing what it is believed to do. Therefore, this type of validation is only acceptable for well-established processes and will be inappropriate where there have been recent changes in the composition of product, operating processes, or equipment.
This approach is rarely been used today because it’s very unlikely that any existing product hasn’t been subjected to the Prospective validation process. It is used only for the audit of a validated process.

2.2 Prospective Validation

Validation conducted prior to distribution either of a new product, or a product made under a revised manufacturing process. Validation is completed and the results are approved prior to any product release.This approach to validation is normally undertaken whenever the process for a new formula (or within a new facility) must be validated before routine pharmaceutical production commences. In fact, validation of a process by this approach often leads to transfer of the manufacturing process from the development function to production.

2.3 Concurrent Validation

A combination of retrospective and prospective validation. Performed against an approved protocol but product is released on a lot-by-lot basis. Usually used on an existing product not previously validated or insufficiently validated.This approach involves monitoring of critical processing steps and end product testing of current production, to show that the manufacturing process is in a state of control.

2.4 Revalidation

To validate change in equipment, packaging, formulation operating procedure, or process that could impact  product safety, efficacy, or potency. It is important to establish a revalidation program for critical equipment to maintain validity. Possible reasons for starting the revalidation process include:

• The transfer of a product from one plant to another.
• Changes to the product, the plant, the manufacturing process, the cleaning process, or other changes that could affect product quality.
• The necessity of periodic checking of the validation results.
• Significant (usually order of magnitude) increase or decrease in batch size.
• Sequential batches that fail to meet product and process specifications.
• The scope of revalidation procedures depends on the extent of the changes and the effect upon the product.

3. Importance of Validation

• Increased throughput
• Reduction in rejections and reworking
• Reduction in utility costs
• Avoidance of capital expenditures
• Fewer complaints about process-related failures
• Reduced testing in-process and in finished goods
• More rapid and reliable start-up of new equipment
• Easier scale-up from development work
• Easier maintenance of equipment
• Improved employee awareness of processes
• More rapid automation

For more information see also:
1) Component Of Master Validation Plan
2) Cleaning Validation And Its Importance In Pharmaceutical Industry