FDA Process Validation

Purpose

1. The purpose of the Federal Drug Administration's process validation procedures, according to the FDA, is to establish "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." The guidelines issued by the FDA pertain to pharmaceuticals and medical devices.

Quality Assurance

2. To ensure quality, FDA guidelines state that "quality, safety and effectiveness must be designed and built into the product, quality cannot be inspected or tested into the finished product and each step of the manufacturing process must be controlled to maximize the probability that the finished product meets all quality and design specifications." The goal of quality assurance is to produce goods that work as they are intended to.

Process Validation

3. Process validation is key to meeting standards that will lead to FDA approval of a product. Carefully designing both the process and the process controls can reduce dependence on finished product testing, though end-product testing is important and required. To this end, the manufacturer must produce a written validation protocol that identifies the procedures and tests that will be performed, the data that will be collected, the purpose of collecting the data, the number of replicate process runs to be performed that will demonstrate reproducibility, and a way to measure variability in successive runs. The variability measurement must take into account "processing limits and circumstances" that would result in the greatest chance of process or product failures, such as machines going down, changes in environmentals or other scenarios that can affect the manufacture of the product outside of optimal conditions.

Pharmaceuticals

4. For pharmaceuticals, "there shall be written procedures for production and process control designed to assure that the drug products have the identity, strength, quality and purity they purport or are represented to possess." There must also be control procedures that monitor the output and validate the processes that cause variability in the drug product. There must also be written procedures designed to prevent microbiological contamination of the product.

Medical Devices

5. For medical devices, it is required that "written manufacturing specifications and processing procedures shall be established, implemented and controlled to assure that the device conforms to its original design or any approved changes in that design." The goal is to ensure that the manufacturing process has sufficient control measures to consistently produce a product that is in keeping with the approved design product characteristics.

Elements of Process Validation

6. The FDA lists the following as the required elements for proper process validation. Prospective validation must take into account changes in manufacturing processes that can affect product characteristics and includes the equipment used in the manufacture, the testing used to determine that the product consistently performs as designed, and product testing to ensure that the process used to produce the product does not adversely affect the finished product. A formal technical review should also be conducted to compare the approved product specifications with the actual product, validate the testing procedures and determine if the change-control program is adequate. It is imperative that the validation program is sufficiently documented and maintained.