Q&As from the Live Online Training "Introduction to the AQCG's new AIQSV Guide" - Part 1

The ECA Analytical Quality Control Group (AQCG) has developed a new Guide for an Integrated Lifecycle Approach to Analytical Instrument Qualification and System Validation. Version 1 of the new document was adopted at the ACQC Board Meeting in November 2023 in Düsseldorf/Neuss. The document was written by Dr Christopher Burgess (Chairman of the AQCG Board) and Dr Bob McDowall (Members of the AQCG Board and of the ECA IT Compliance Interest Group).

The Group organized a Live Online Training Introduction to the AQCG’s new ECA Guide for an Integrated Lifecycle Approach to Analytical Instrument Qualification and System Validation on 29 April 2024. During the training, Dr Christopher Burgess and Dr Bob McDowall provided an insight into the new Guide and the rationale for the lifecycle approach. The training included a USP speaker update on the Analytical Procedure Lifecycle by Dr Amanda Guiraldelli-Mahr (Scientific Affairs Manager at USP).

In the Q&A session after the presentations, many interesting aspects were discussed. Selected questions raised during the meeting are listed below with the teaching team's answers underneath. Part 2 will be published in a few weeks.

Part 1 of the Questions and Answers

1. You have mentioned that the PQ as testing SST is wrong. What then would be the correct PQ in your opinion? Should we have an initial PQ (done directly after OQ and before the release of the system) and the continued PQ (e.g. SST, control checks, periodic maintenance)? Or continued PQ is sufficient? If initial PQ is required, what would be the tests to be performed? SST? or tests with product?

Answer: It depends! The PQ in AIQ relates to ongoing proper instrument functionality. SSTs generated as part of routine analytical procedures are not appropriate for this assurance. SSTs for proper instrument function can be, for example, instrument diagnostics in firmware which give metrological performance data. However a holistic approach may be applied for HPLC where a simple standard test mixture and a standard column with a simple isocratic mobile phase are used which are designed to be robust under controlled conditions. This should be established as part of the OQ for instrument/system release and could then used as part of ongoing performance verification.

2. Question to URS update for the selected system. I would like to understand better this part. The extreme example. We wanted an audit trail and included it in URS, but the only system available on a market doesn't have audit trail, should we then update URS and remove the audit trail? Or we didn't want a cleaning function in initial URS, but selected instrument allows cleaning function, and we decided to use it, then we need to update the URS?

Answer: The URS is a living document and needs to reflect the intended use of the system / instrument. If you have specified a function and it is not in the system: update the URS. Conversely if you have a new function that you want to use, update the URS to accommodate it.

3. How should companies "deal" with procurement buying a different instrument than the one you select / want.

Answer: As mentioned in the CDS presentation, you need to work with Purchasing to understand that their function is not to change the instrument / system selected but to negotiate a better price for the item and any professional services offered. If the selection were down to two suppliers, Purchasing could discuss the two offers to obtain a better price.

4. In some companies the lab has to specify their user requirements at the instrument specification - or procurement will buy a cheaper instrument.

Answer: Again, you need to work with the Purchasing. I was involved in training the whole site for data integrity and I included a session for HR, Purchasing and IT. There was a section on the role of purchasing and how not to screw up the integrity of data but selecting a poor system based solely on price.

5. What "prevents" pharmacopeia harmonization at the general chapter level?

Answer: Pharmacopeial harmonization is the scope of discussions of few groups like IMWP and Pharmacopeial Discussion Group (PDG). PDG focuses on selected official, broad-impact General Chapters and excipient monographs to support the elimination/minimization of the need to perform multiple tests and procedures and to comply with multiple acceptance criteria for the same article.

Although these groups deal with Ph. harmonization there are several challenges, such as:

• diverse regulatory frameworks: different regions and countries have their own regulatory requirements and frameworks for pharmaceuticals, which makes challenging the harmonization

• cultural differences which can influence the interpretation and implementation,

• historical contexts, each Ph has its own history, process and stakeholders

• technical variations: variations in analytical techniques, methodologies, and scientific understanding can pose challenges to harmonization efforts. Differences in technology, equipment availability, and scientific expertise may lead to disparities in standards and methods across pharmacopeias

• resource constraints, and regulatory hierarchy

These factors make it challenging to align standards and practices across pharmacopeias, despite ongoing efforts to promote collaboration and mutual recognition agreements.

6. Is the presence of PC being the only decisive criteria between group B and group C? In same cases the application software on a PC can be less complex than firmware (from the run time configuration point of view), but it is till group C and firmware is still group B even if it is complex.

Answer: Yes.

7. User management in modern group B instruments. Are we obliged to use user management provided by the instrument? Or if we didn't include the user management in URS for our group B instrument, we are not obliged to use those functions?

Answer: It is imperative that you attribute work to a named individual, so yes, you need to use the user management functions in the instrument. Simply writing initials on the printout is not acceptable.