System Suitability

Discussions about HPLC, CE, TLC, SFC, and other "liquid phase" separation techniques.

30 posts Page 1 of 2
This is more of a compliance question than a science question, but since a lot of people on this forum are in the Pharmaceutical industry I would like to ask the following question (we've been having a big debate about this at work).

My opinion is that System Suitability determines whether or not a set of data can be reported, but that system suitability does not need to be established before you run a set of samples. For example, if an analyst prepares standards and samples and sets up their sequence - and now it's 5:30 PM and they want to go home - it seems to me perfectly acceptable to let the sequence run and then evaluate the data the following day. And if it turns out that system suitability has failed, then the data will have to be invalidated; and if system suit has passed then the data may be used.

Others in my company firmly believe that system suit has to be shown before the samples are analyzed. So, in the example above our analyst would have to stay untill 8:00PM or could not start the samples untill the following day. I really don't see any logical reason for this. And I've already checked USP <621> and it does not say that system suit has to be evaluated before the samples are run. But it seems that many in the industry do it that way.

I am very interested in hearing feedback from others on this issue.

Thanks
Yes, This practice has followed in many labs in pharma companies (including my lab in India).I think there are two reasons behind this,
1. if the system suit fails the analyst need not to spend time to prepare the samples untill the system suitability passes
2. Since the criteria is mentioned in the USP and everybody wanted to go i to the safer side by doing this before they starting the analysis or they may be over cautious and unwanted questions by auditore. Apart form this i see no reason for why analysis can not be preformed if sys. suit fails. Good discussion lets get more people's opinion.

Regards
Vijayak
It is perfectly acceptable to run your samples alongside the system suitability and you do not need to wait for them to pass before you proceed, so there is absolutely no need for you to wait around to check this and leaving a run on overnight is pretty routine.

Your main question however will be in the REPORTING of the data, as you have now regardless of the system suitability, generated sample results, whether valid or invalid. Especially for GMP I believe you may need to report the "failed" run, perhaps not in detail but at least allude to the fact the run was done and why it was invalidated if the system suitability fails. As long as your data reporting and collection is completely transparent you should be alright by the MHRA/FDS.

Lynz x
ex-GLP/GMP auditor
ex-stability/validation study director
current-method development scientist
Either approach is acceptable. You just have to be clear if you are going to report any data generated and if not why you have not.

The approach of injecting the SST solution and check injection reproducability before injecting your samples is very useful where you may have limited sample quantity, limited stability in solution or a long complex sample preparation and you want to know the system is performing acceptably before running your samples.
Insanity: doing the same thing over and over again and expecting different results.
Albert Einstein, (attributed)
US (German-born) physicist (1879 - 1955)
We do the SS with the calibration standards, at the beginning of each sequence. The same injections are used for both SS and for calculating percent active, all automated, Agilent ChemStation A.09.

If - by some chance - SS fails, then there is no data to report, no OOS investigation, because sample results are only valid if the system passes SS.
Consumer Products Guy wrote:
We do the SS with the calibration standards, at the beginning of each sequence. The same injections are used for both SS and for calculating percent active, all automated, Agilent ChemStation A.09.

If - by some chance - SS fails, then there is no data to report, no OOS investigation, because sample results are only valid if the system passes SS.


We do the same with Chromeleon 6.80. As we have already entered the weight of the standards there will be results. The sequence is then marked as INVALID and submitted (by the technican) and reviewed (by a supervisor). Valid seuences are submitted, reviewed and approved.
I appreciate all the responses. But please remember the main question is: "Does system suitability have to be demonstrated before you run your samples."

To reiterate, I firmly believe that there is no reason why system suitability must be shown before the samples are run; instead what matters is that system suitability must pass for the data to be reported.

Agree or Disagree please.
Ah I see I understand now what you mean, in that case yes I think system suitability must be demonstrated before you can claim any samples run afterwards pass.

Whilst you can stick on your system suit, then samples and leave it to run (e.g. overnight) you still need to, when you process the run, show the system was suitable for use and repeatable BEFORE the samples went on i.e. passed. Also whilst you can run your standard verification and samples at any part of the run after your passed system suit, if you don't at least demonstrate the system is functioning repeatably and well beforehand how do you know the data collected for your stds/samples is accurate?

Does that make sense?

lynz x
Hi Adam,

A good question!

I agree that system suitability does not need to be proven before samples are run, but does for data to be reported

If you think about it standards are an integral part of the "system suitability" criteria (i.e. measures system precision) and these are run throughout the run (including at the end of the run). So in this case (for assay determination against external standard) it is impossible to show system suitability before the samples are run! You can only determine system suitability standard precision criteria after the whole run is finished!
The simplest system suitability test is analytical balance performance - and I always thought that if the balance fails then all the results since the last time that it passed are suspect. The logic being that it has gone out of spec sometime between the two tests, and there is no way of knowing when, and which samples were affected. I would have thought that, strictly, an analytical instrument is the same. - it needs to pass suitability both before and after a batch of samples, and for large batches there need to be check standards, calibrants or whatever run among the samples.

Peter
Peter Apps
It is not the best practice, especially if you continue to run at risk and generate a lot of failed suitability runs, as it then becomes more of a laboratory trend.

The risk can be reduced by test injections and if the system appears to be suitable I would proceed with the analysis.
adam wrote:
I appreciate all the responses. But please remember the main question is: "Does system suitability have to be demonstrated before you run your samples."

To reiterate, I firmly believe that there is no reason why system suitability must be shown before the samples are run; instead what matters is that system suitability must pass for the data to be reported.

Agree or Disagree please.


In the GLP lab where I used to work we would try and have the SST completed before the end of the day the activate the sample sequence if a pass was obtained (Most common practice)

However, if the run time was such that we couldn't do this during a working day we would keep our fingers crossed and go for it, checking the SST as soon as possible the next day. If it failed, we halted the run and repeated.

On some occaisions we were supplied methods where the full SST was not calculated until the sequence was completed (injections at the beginning and end of the run were used in the calculation).

In this case there was a criteria for the injections at the start of the sequence which, if met, allowed the run to proceed and a final set of critera incorporating all injections for full sequence acceptance.
Good judgment comes from bad experience, and a lot of that comes from bad judgment.
Here, a SST is included at beginning of every run. While samples are being prepared we will check on the SST, if it happens to fail we can stop the run. Otherwise, generally we just run with the SST and check the next day if it passed or failed, there is no reason to stay late, unless it is some sort of critical run with a deadline...then sometimes we can't help but make sure SST passes before leaving so we don't waste time/solvent etc.
USP <621> states that suitability has to be demonstrated throughout the run.
Before
during
after

The lab I work in performs all the replicate injections before the run to demonstrate initial suitability followed by regular injections of the SST solution to demontrate suitability throughout with bracketing standards for analysis.
Hi Adam

System suitability in itself says, the suitability of the system for the samples ur going to prepare. If that system is not suitable then there is no use of making samples or running those. Ultimately those samples are going to go in waste. And thats why our bracking std's also comes under system suit. so its better to chek sys suit first and then go for sample preparation.

If your lab is under GLP. then you have to inject your standard first, check the sys suit and then go for your samples.
but if you are working in non-GLP premises then you can check method's vital checks points


If incase in future, auditor ask for sys suit and that time if u dnt have any justification to your failed set then u'll be in a big trouble. U cannot say give the justification of office hours.
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