cGMP System Suitability

[Consumer Products Guy]

I've got some cGMP System Suitability questions, and my QA department is either ducking the questions, just doesn't know or care, or is out of town at a fancy resort using up the company's money.

OK, we inject the calibration standard five times to obtain system suitability documentation.
(1) We've been injecting these all before any samples are injected. Is this what others do?
(2) Assume that we have 18 samples; after each nine sample vials we re-inject the calibration standard two additional times. How do we include those two in the system suitability information? Do we average those two in with the origianl five injections? And what about the two calibration standard injections at the end? Or do we reprocess the calibration data (all injections separately, then use that to calculate levels in the products?

Hurry and respond before the pointy-haired QA Director returns...

[Dan]

I have worked in the cGMP labs at several places and I have noted that these things vary slightly from place to place. It mostly depends on the SOP, but QA and managers can add their own twists to the procedures.

At one place, the manager insisted that the system suitability be run AND checked before any samples are injected. This is not always practical and the SOP didn't require it. So, we usually just proceeded with the entire run and trust that we did everything we could to avoid problems.

I like to start with a test injection (using a standard). I usually have set up the instrument for the entire run; with that test injection first, followed by the system suitability injections and then the rest of the injections. I will check the test injection to see if everything is OK. If not, then I just abort, fix the problem and start over. If time permits, then I check the system suitability results. Otherwise, I will check the results for the run after it is completed, usually the next day as I don't put in 24-hour shifts.

The system suitability is usually based on those 5 (or 6) initial standard injections. With there being acceptance criteria for tailiing, RSD and resolution which are the minimum requirements (see USP and EP). there may be other system suitability criteria such as check standard recovery, detector sensitivity, plates, etc. We did mention some of this before:

http://www.sepsci.com/chromforum/viewtopic.php?t=7976

For issue #2, you can look to the USP where it states that system suitability needs to be checked thoughout the run. Again, I have relied on SOPs to interpert this as I have seen nothing from the USP, FDA, EP or EMEA for clarification. The procedure that I have used (at several different companies) is to check the RSD for the peak areas of the standards throughout the run and that includes the 5 (or 6) system suitability injections.

That's what the SOPs have stated where I have worked. Those SOPs were usually written by the scientists and approved by QA. I am not sure that I would want QA to write those SOPs.

Regards,
Dan

[JGK]

Work in a GLP not GMP environment but or default SST is similar to yours

5 consecutive injections prior to the sample run with CV criteria on peak response and RT. Subsequent run integrity is monitored by in-run STDs and QCs

Peak tailing and/or resolution may be added to the SST deprending on client.

I've also run methods where the criteria is based on data from pre(4 inj) and post (3 inj) sequence STDs or duplicate prior to, every 12 th inj during and duplicate after the sequence. These methods involve entire sequence repetition for failures though.

[wrxtotoro]

(1) Yes, in all 3 companies that I have worked in.
(2) Both the %RSD of the 5 Std and the Overall Std (7 injection in your case) will have to pass. Std 2 recovery is only calculated against the first 5 standard injections. Other criteria such as Resolution, Tailing and RT window are also required to pass in all Std injections. But for the sample calculation, we only use the bracketing standards. I don't think there's a clear-cut right and wrong in these requirements/practice. Certain consulting firm in my current company is trying to change the Std Recovery and %RSD Limit to 1.0%, just to impress the FDA. Oh well...