text on process validation

Definitions

Installation qualification - Establishing confidence that process equipment and ancillary systems are capable of consistently operating within established limits and tolerances.

Process performance qualification - Establishing confidence that the process is effective and reproducible.

Product performance qualification - Establishing confidence through appropriate testing that the finished product produced by a specified process meets all release requirements for functionality and safety.

Prospective validation - Validation conducted prior to the distribution of either a new product, or product made under a revised manufacturing process, where the revisions may affect the product's characteristics.

Retrospective validation - Validation of a process for a product already in distribution based upon accumulated production, testing and control data.

Validation - Establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its pre-determined specifications and quality attributes.

Validation protocol - A written plan stating how validation will be conducted, including test parameters, product characteristics, production equipment, and decision points on what constitutes acceptable test results.

Worst case - A set of conditions encompassing upper and lower processing limits and circumstances, including those within standard operating procedures, which pose the greatest chance of process or product failure when compared to ideal conditions. Such conditions do not necessarily induce product or process failure.

IV. GENERAL CONCEPTS

Assurance of product quality is derived from careful attention to a number of factors including selection of quality parts and materials, adequate product and process design, control of the process, and in-process and end-product testing. Due to the complexity of today's medical products, routine end-product testing alone often is not sufficient to assure product quality for several reasons. Some end-product tests have limited sensitivity.(1) In some cases, destructive testing would be required to show that the manufacturing process was adequate, and in other situations end-product testing does not reveal all variations that may occur in the product that may impact on safety and effectiveness.(2)

The basic principles of quality assurance have as their goal the production of articles that are fit for their intended use. These principles may be stated as follows:

(1) quality, safety, and effectiveness must be designed and built into the product;

(2) quality cannot be inspected or tested into the finished product; and

(3) each step of the manufacturing process must be controlled to maximize the probability that the finished product meets all quality and design specifications.

Process validation is a key element in assuring that these quality assurance goals are met

It is through careful design and validation of both the process and process controls that a manufacturer can establish a high degree of confidence that all manufactured units from successive lots will be acceptable. Successfully validating a process may reduce the dependence upon intensive in-process and finished product testing. It should be noted that in most all cases, end-product testing plays a major role in assuring that quality assurance goals are met; i.e., validation and end-product testing are not mutually exclusive.

The FDA defines process validation as follows:

Process validation is establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its pre-determined specifications and quality characteristics.

It is important that the manufacturer prepare a written validation protocol which specifies the procedures (and tests) to be conducted and the data to be collected. The purpose for which data are collected must be clear, the data must reflect facts and be collected carefully and accurately. The protocol should specify a sufficient number of replicate process runs to demonstrate reproducibility and provide an accurate measure of variability among successive runs. The test conditions for these runs should encompass upper and lower processing limits and circumstances, including those within standard operating procedures, which pose the greatest chance of process or product failure compared to ideal conditions; such conditions have become widely known as "worst case" conditions. (They are sometimes called "most appropriate challenge" conditions.) Validation documentation should include evidence of the suitability of materials and the performance and reliability of equipment and systems.

Key process variables should be monitored and documented. Analysis of the data collected from monitoring will establish the variability of process parameters for individual runs and will establish whether or not the equipment and process controls are adequate to assure that product specifications are met.

Finished product and in-process test data can be of value in process validation, particularly in those situations where quality attributes and variabilities can be readily measured. Where finished (or in-process) testing cannot adequately measure certain attributes, process validation should be derived primarily from qualification of each system used in production and from consideration of the interaction of the various systems.