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Testing, Commissioning, Validation, Qualification, or Verification? A Brief History – Part 2

We left off in Part One, with spiraling costs for commissioning and qualification activities. Some companies, under regulatory pressure, would perform a full IQ/OQ for commissioning, then a “dry-run” IQ/OQ, and then the “real” IQ/OQ. That is three full qualification efforts! Even with all this expensive paperwork, the startup experience was rarely improved. Generating, approving, and executing all of these documents was so difficult and time consuming, that memos and exceptions were heavily employed to release systems to the process validation group on time. Instead of just letting the experts run the equipment, and then make the necessary adjustments and repairs, there was an army of protocol writers, often with little true start up experience, running around routing documents. The hoped for solution to this state of affairs was to be found in the Risk-Based Approach.

In the life sciences industry, the term “risk based” came into existence when the FDA released its Pharmaceutical cGMPs for the 21st Century – A Risk-Based Approach in the Fall of 2004. The only use of that term was in reference to how the FDA was going to prioritize its own inspections. There is no mention of using a risk based approach for equipment qualification. I have no idea who was first to use the term “risk based” in conjunction with equipment C&Q, but it took off like wild fire.  Industry saw the risk based approach as an opportunity to reign in the high cost of C&Q. To everyone’s surprise, cost went even higher.

Costs rose because in the conservative pharmaceutical industry, no one wants to go out on a limb and declare something is “low risk”, therefore not requiring documentation. What happened was that in addition to all the standard testing documentation, a risk assessment and pFMEA were now added to the list of required documents. To compound matters even more, quality assurance was borrowing heavily from GAMP with regards to equipment, utilities, and facilities. In 2005, for a simple tank, one might have been required to generate the following documents:

  • Project Validation Master Plan
  • Risk Assessment
  • FMEA Assessment
  • User Requirements Specification
  • Functional Specification
  • Design Specification
  • Factory Acceptance Test
  • Site Acceptance Test
  • Installation Qualification
  • Operational Qualification
  • Trace Matrix
  • Summary Report

That is 12 documents for one tank! A medium sized capital expansion project could easily require 400-500 documents. All individually authored in MS Word, with little or no engineering information on-hand (to get a jump on the schedule). It’s a recipe for disaster.

ASTM Committee E55 was formed in 2003 to help bring a more rational approach to Qualification of

Biopharmaceutical and Pharmaceutical Manufacturing Systems. By 2006 a draft document was released to industry. It was fairly radical. A final, much watered down version was officially released in August of 2007. As of late the 2013 the ASTM approach is still struggling to gain acceptance within the industry.

In Part 3 of this series, I’ll describe the intent and reality of ASTM E2500 along with some practical advice   implementing an ASTM 2500 risked based approach to qualification of Biopharmaceutical and Pharmaceutical Manufacturing Systems.


Nels Hackl

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