Suggestions for improvements in philosophy
- The QA (QU) should be involved from the onset and participate in the review and acceptance of not only the use of vendor documentation
but commissioning and verification-related testing. This does not necessarily mean QA will approve the all of the testing,
but certain key documents will require their approval.
- If the SME concept is adopted, and they are to be independent, then these SMEs should reside in QA. QA should be populated
with appropriately trained technically competent personnel and engineers.
- QA needs to review all documents and appropriately approve at critical junctions. QA need not approve every test document
but should be aware and allowed to review them as well and at will.
- QA needs to qualify vendor and supplier GMP-compliance issues and documentation for all commissioning and qualification.
- The IQ and OQ should remain as the staple practices for qualification documentation with the verification steps included.
The expectation of IQ and OQ should be defined and standardized to eliminate the issues of bottlenecking as well the repeat
of installation and operational-related testing. If the words IQ and OQ are to be discontinued, then some sort of qualification
inclusive of verification needs to be instituted to be in compliance with FDA expectations. With this QA needs to play an
- Commissioning or commissioning-like activities should remain as a practice and especially for those systems designated as
noncritical and supportive in nature. FDA has to formally accept this practice and not just give it honorable mention.
- Commissioning and verification testing for each and every system where it is applied should be completed with a QA-reviewed
and approved closeout report or summary. This document would legitimize the information being leveraged.
- All systems and equipment will have an aspect of commissioning or commissioning-like verification, and for those critical
systems the information gathered should be leveraged for use in qualification activities.
- All equipment and system testing need not reside in commissioning or installation-verification testing. Many tests can only
properly be done with documented qualification. The boundaries of commissioning and installation verification testing need
to be defined and standardized.
- Critical systems, once deemed so, should be qualified as a whole if possible, and not be broken down into critical and noncritical
aspects. If a system or equipment is deemed critical it should remain as such.
- Process validation and performance qualification are necessary to satisfy current regulations, and the practice should be
- The role of the VMP needs to remain in place and associated with other overall facility and corporate plans for validation
- Change control and change management need to be maintained for all approved documents and activity prior to actual production
activity. This change can be performed by QA engineering, which should be an arm of QA. Once production takes place, change
control now becomes more product specific and needs to be done in collaboration with the overall CAPA system.
- Above all, and in compliance with process improvement and the principles of quality, requalification and revalidation should
take place as needed and when necessary. This needs to be driven by product and process change control, process review over
time, and process improvements.
Louis A. Angelucci is the director of corporate validation at MedImmune, One MedImmune Way, Gaithersburg, MD 20878, tel. 301.398.2949, email@example.com
References and additional reading
1. FDA, Guideline on General Principles of Process Validation, (Rockville, MD, May 1987.)
2. ASTM, E 2500–07, Standard Guide for Specification, Design, and Verification of Pharmaceutical and Biopharmaceutical Manufacturing
Systems and Equipment (Aug. 2007).
3. FDA, Draft Guidance for Industry, Process Validation: General Principles and Practice (Rockville, MD, Nov. 2008).
4. ICH, Q9 Guidance for Industry Q9 Quality Risk Management, June 2006.
5. FDA, Pharmaceutical CGMPs for the 21st Century: A Risk-Based Approach, (Feb. 2003).
6. ICH, Q8 (Q8R) ICH Harmonized Tripartite Guideline, Pharmaceutical Development, Q8(R1) Step 4 version, Nov. 13, 2008.
7. ICH, Guidance for Industry, Q7A Good Manufacturing Practices for Active Pharmaceutical Ingredients, (Aug 2001).
ASTM, E–2537–08 Standard Guide for Application of Continuous Quality Verification to Pharmaceutical and Biopharmaceutical Manufacturing (Feb. 2003).