Introduction
Businesses that manufacture pharmaceuticals are regulated by the FDA and operate within a code of federal regulations (CFR) and specifically title 21. You will often see the abbreviation 21 CFR, for example 21CFR11 refers to CFR Title 21, part 11, which refers to electronic signatures. There are many parts to these regulations and some are specifically relevant for certain manufacturing areas. The other area that pharmaceutical manufacturers are obliged to abide by is the Current Good Manufacturing Practices (cGMP). These are enforced by the FDA, under Section 501(B) of the 1938 Food, Drug, and Cosmetic Act. The practices ensure that manufacturing is controlled and compliant with specifications. Validation is the documentation of the processes used in manufacturing that demonstrate consistency. Validation is required on process systems, equipment and computer systems, such as ERP implementations.
Background
The process of validation was proposed by the FDA over thirty years ago to improve the manufacturing quality of pharmaceuticals. The validation process initially started as a response to issue with sterile products, but soon spread to other manufacturing areas. Companies would have to validate that equipment was manufactured, tested, delivered and accepted according to a specific contract. The validation of a process demonstrated that there was consistency and the same results would be achieved each time the process was performed. The validation of computer systems was developed in the early 1980’s and pharmaceutical companies are required to validate the computer systems they use in manufacturingThe Validation Process
There are four stages to the validation process; Design Qualification (DQ), Installation Qualification (IQ), Operational Qualification (OQ), and Performance Qualification (PQ).
When a company is preparing to validate a computer system it should begin with a detailed validation plan. The plan will specify all of the validation processes that will take place; the scope of the validation, the responsibilities of those involved in the validation, and the timing of the stages to be completed.
Design Qualification (DQ): This stage of the validation is where the design of the system will be reviewed. This stage of the validation process will look to see that the design of the system will fulfill the initial user requirement specification (USR). It will also look at the training requirements of the system, the maintenance of the system, and the support documentation.
Installation Qualification (IQ): This stage verifies that the system, and its ancillary equipment has been installed in accordance with the necessary specifications. At this time a list of all the cGMP requirements will be produced that are applicable to this specific installation qualification.
Operational Qualification (OQ): The OQ looks at the Standard Operating Procedures (SOP) that are developed for the system. There should be an SOP developed covering every aspect of system usage. The SOP is vital in establishing and maintaining ongoing compliance with cGMP and FDA regulations. In the OQ phase, test scripts are developed for the SOP so that the processes are tested and compared against the expected results. The tests should be documented and available for review during any FDA inspection.
Performance Qualification (PQ): The PQ is to verify that the system performance satisfies all performance requirements including those specified in the user requirement specifications (USR). The performance tests will be made under actual production conditions, and verification data will be collected and attached to this PQ report. PQ is the final step to formally test and document proper performance of the system prior to normal operation. When the final PQ report is approved, the system is ready for normal production operation.
Summary
The FDA require the computer systems are validated and documentation supporting the validation is available during an inspection. The validation process is performed through the four defined stages and will demonstrate through documentation the consistency of the system.
