Computer system validation (CSV) is the work of proving, with documented tests, that a computer system used to make or test medicines does exactly what it is meant to do, every time. Drug plants must also validate their machines, their processes and the cleaning of their equipment. Validation software records all this work digitally, instead of in binders of paper. It is also called a validation lifecycle management system, or paperless validation.
Why must a plant validate? A drug regulator does not test every tablet. It trusts the plant's records instead. So the plant must first prove that the systems making those records are correct. Validation shows that a machine or a program was installed correctly, that it works across its whole range of settings, and that it gives the same correct result batch after batch. These three stages are usually called installation qualification (IQ), operational qualification (OQ) and performance qualification (PQ).
In India, CDSCO's rules on good manufacturing practice, called Schedule M, require this. Plants that export to America must also follow the US FDA's rules, including its rule on electronic records and electronic signatures, known as 21 CFR Part 11. The wider rules for keeping such records are explained in GxP compliance.
Take, for example, a tablet plant in Baddi, in Himachal Pradesh. It installs a new tablet press, a machine that presses powder into tablets. The press is controlled by its own software. The validation team writes the requirements in the validation software. The press must run at speeds from 20 to 60 rotations a minute. It must make tablets that weigh 500 mg, within 5%. It must stop and raise an alarm if a tablet is too light. Each requirement is linked to a test. An engineer runs each test on the factory floor with a tablet computer, enters the result and signs it electronically. In one test, the alarm does not sound. The software records this as a failed test and opens a deviation in the quality management system (QMS). The supplier fixes the software, and the test is run again. Finally, three full batches meet every requirement. The quality head approves the report, and the press is released for use.
With paper, the same work fills several binders. Each page must be signed by hand, copied and filed. Finding one test result during an inspection can take hours. In the software, every requirement, test, result and signature is linked, and can be found in seconds.
The same software validates the plant's other systems. These include the manufacturing execution system (MES) and the laboratory's chromatography and mass spectrometry systems. Testing methods are often checked against pharmaceutical reference standards, samples whose content is known exactly.
How is validation different from quality control? Quality control tests the medicine itself, batch by batch. Validation tests the machines and the software once, before they are used, and again after every major change.