Validation (drug manufacture)
In the pharmaceutical industry, it is very important that in addition to final testing and compliance of products, it is also assured that the process will consistently produce the expected results.
Validation is a requirement of food, drug and pharmaceutical regulating agencies such as the US FDA and their good manufacturing practices guidelines.
The concept of validation was first developed for equipment and processes and derived from the engineering practices used in delivery of large pieces of equipment that would be manufactured, tested, delivered and accepted according to a contract[2] The use of validation spread to other areas of industry after several large-scale problems highlighted the potential risks in the design of products.
In use, several interconnected problems led to several devices giving doses of radiation several thousands of times higher than intended, which resulted in the death of three patients and several more being permanently injured.
The FDA has also been very focused on this final area of distribution and the potential for a drug substances quality to be impacted by extreme temperature exposure.
Range: The range of an analytical procedure is the interval between the upper and lower concentration of analyte in the sample for which it has been demonstrated that the analytical procedure has a suitable level of precision, accuracy and linearity FDA, or any other food and drugs regulatory agency around the globe not only ask for a product that meets its specification but also require a process, procedures, intermediate stages of inspections, and testing adopted during manufacturing are designed such that when they are adopted they produce consistently similar, reproducible, desired results which meet the quality standard of product being manufactured and complies the Regulatory and Security Aspects.
Within the references given in the VP the protocol authors must ensure that all aspects of the process or equipment under qualification; that may affect the efficacy, quality and or records of the product are properly qualified.
This combined testing of OQ and PQ phases is sanctioned by the European Commission Enterprise Directorate-General within ‘Annex 15 to the EU Guide to Good Manufacturing Practice guide’ (2001, p. 6) which states that: "Although PQ is described as a separate activity, it may in some cases be appropriate to perform it in conjunction with OQ."
[5] Recently both the American FDA and the UK Medicines and Healthcare products Regulatory Agency have added sections to the regulations specifically for the use of computer systems.
Weichel (2004) recently found that over twenty warning letters issued by the FDA to pharmaceutical companies specifically cited problems in Computer System Validation between 1997 and 2001.
Annex 11 states "Risk management should be applied throughout the lifecycle of the computerised system taking into account patient safety, data integrity and product quality.
The documentation surrounding a spreadsheet containing a simple but "GxP" critical calculation should not match that of a Chromatography Data System with 20 Instruments) Determination of a "GxP critical" requirement for a computer system is subjective, and the definition needs to be tailored to the organisation involved.
Validation process efforts must account for the complete product life cycle, including developmental procedures adapted for qualification of a drug product commencing with its research and development phase, rationale for adapting a best fit formula which represents the relationship between required outputs and specified inputs, and procedure for manufacturing.
Each step is required to be justified and monitored in order to provide a good quality food and drug product.
The FDA emphasizes the product life cycle approach in its evaluation of manufacturer regulatory compliance as well.
