Medical device manufacturers are expected to mind their IQ's, OQ's and PQ's.

In fact, both the U.S. Quality System Regulation 21 CFR Part 820 and ISO 13485:2003 have explicit elements requiring the manufacturer to perform tasks associated with IQ's, OQ's and PQ's, but these terms are not defined and the actual abbreviations don't even appear – so what exactly do these terms mean and what are the expectations for medical device manufacturers?

Last week, we introduced the Global Harmonization Task Force (GHTF) as a source for internationally harmonized publications of great potential value to medical device manufacturers in understanding and implementing regulatory and quality systems requirements. One particular publication will help us with our IQ's, OQ's and PQ's. GHTF publication GHTF/SG3/N99-10:2004 Edition 2, (PDF) "Quality Management Systems – Process Validation Guidance" is one of the most useful GHTF guidances available. This guidance is intended to assist manufacturers in understanding quality management system requirements concerning process validation – that is, how manufacturers should validate the manufacturing processes associated with their products.

Both 21 CFR Part 820 and ISO 13485 require manufacturers to validate production processes where the results of the process cannot be fully verified with subsequent inspection, monitoring and test. See 21 CFR Part 820.75 "Process Validation" and ISO 13485:2003 7.5.2 "Validation of processes for production and service provision". Based on these requirements, it is an expectation that manufacturers will validate many of their production processes. For IVD manufacturers, production processes typically requiring validation include sterilization, cleaning, mixing, storage and labeling.

Here are some useful definitions from the GHTF Process Validation Guidance:

Installation qualification (IQ): establishing by objective evidence that all key aspects of the process equipment and ancillary system installation adhere to the manufacturer's approved specification and that the recommendations of the supplier of the equipment are suitably considered. (In other words, has your manufacturing equipment been installed correctly, according to supplier’s recommendations?)

Operational qualification (OQ): establishing by objective evidence process control limits and action levels which result in product that meets all predetermined requirements. (In other words, have you completed the engineering analyses required to establish the operational limits of the manufacturing process?)

Performance qualification (PQ): establishing by objective evidence that the process, under anticipated conditions, consistently produces a product which meets all predetermined requirements. (In other words, have you achieved production quality with multiple production runs using final process specs, documentation and operators?)

So now we have some standardized terminology for our tasks at hand. In order to validate production processes, medical device manufacturers are expected to implement Installation Qualifications (IQ's), Operational Qualifications (OQ's) and Performance Qualifications (PQ's). Note that these explicit terms are not found in either 21 CFR Part 820 or ISO 13485:2003, but the requirements are clearly stated, and the GHTF guidance is an internationally harmonized document recognized by both the US FDA and ISO.

To best understand how to mind your IQ's, OQ's and PQ's, be sure to review GHTF's Process Validation Guidance. This is a very useful guidance document that provides real "hands-on" material on how to plan and implement medical device production process validations – you'll even find example protocol templates and a tutorial on statistical methods and tools.

Tags: EU, Ex-US, FDA, Quality Systems, Software Validation, V & V