Missed Quarterly Dose Audit! Sterilization Validation of Medical Devices

[Tara QA]

Hello to All ..

I was wondering if somebody, more learned than I on sterilisation validation of Medical devices could help me out!

Having reviewed the schedule, I have 4 sucessful dose audits but i've noticed that one particular dose audit was missed meaning there is a gap of 6 months between the two. I am hoping to pull together a justification for the delay, and I am hoping to get a sanity check from someone.

Provided we can demonstrate the validation did not go out between the two dates (boths reports are fine), that we've controlled our environments, and that bioburden has been determined for each batch released in this time period complied (and were well with initially used for dose setting).. would this be sufficient to demonstrate control?

T.

 

[Marcelo]

I'm not a sterilization expert, so i will also wait for the opinion of others....anyone?

 

[jscholen]

We do quarterly dose audit reports and I believe that if you can show that the process hasn't changed (product or process) with some high level of assurance then you should be fine. I don't think anyone will push back. Mistakes happen but...you need to open a CAPA to investigate why it happened and establish a corrective action to prevent it from happening again. This will close the loop on your quality system showing it to be effective.

 

[JaxQC]

“sufficient to demonstrate control?”

The only problem is that it’s not in control. Otherwise the audit would not have been missed. Normal mistake, yes but a robust system prevents this through checks & balances. The risk might be low based on the overlap of the others but basically the “we do what we say” did not occur regardless if the testing results were bad or not.

The important item is to ask why. What part of the system allowed that to occur (notification, follow-up, closure etc) in the first place? Opening a corrective action and follow-up with finding out how to not allow a miss to occur again. Most auditors would not gig, other than a observation note, where an oversight was identified in-house and a long term fix put in place. Expect them to look a little closer in this area but if the ducks are all in line, it shouldn’t be a problem. Have a good day.

 

[MIREGMGR]

Note that if you were asking in an FDA context instead, failure to perform required sterilization control probably would mean a recall.

If you have some product going to the US, you need to consider this problem from both perspectives.

 

[Tara QA]

hello

Thank you so much for all your replies, they have been really helpful.

we have opened up an investigation to try and establish why it happened. Essentially it wasn't picked up until the yearly schedule was combined into one big two year schedule. It should have been spotted, and it wasn't. There's no excuse for it. In terms of corrective actions the schedule has been updated to make it easier to spot this in the future, and also review of schedule has been built into monthly QA meetings.


MIREGMGR -We sell the product into the US so the FDA point is applicable too... Please excuse my ignorance! but from what aspect would it be considered a recall? Yes, there was an oversight, we've identified CA's.. and have also assessed what the risk of us having an increased interval between audits.. we have strong data to demonstrate there was no change in bioburden that could affect the validity of initial dose set, for each batch released during this interval.. and also, we continued to manufacture it in a controlled environment.

Surely the point of doing the audits is to demonstrate the above, if we missed the audit we have to be able to demonstrate this by some other means, if we can't.. then we'd be on recall territory, right?

 

[MIREGMGR]

We sell the product into the US so the FDA point is applicable too... Please excuse my ignorance! but from what aspect would it be considered a recall? Yes, there was an oversight, we've identified CA's.. and have also assessed what the risk of us having an increased interval between audits.. we have strong data to demonstrate there was no change in bioburden that could affect the validity of initial dose set, for each batch released during this interval.. and also, we continued to manufacture it in a controlled environment.

Surely the point of doing the audits is to demonstrate the above, if we missed the audit we have to be able to demonstrate this by some other means, if we can't.. then we'd be on recall territory, right?

The FDA historically has taken action against failures to conduct quarterly gamma verification. See for instance the 2005 Warning Letter to Charter Medical, https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2005/ucm075427.htm .

As you may be aware, the FDA terminology for "oversight" would be "failure", and the FDA does not place the same conceptual importance on Corrective Action as an indication that an already-occurred failure is excusable. As to your risk assessment, you might want to be aware of the institutional split within the FDA between the pro-harmonization faction, which regards risk management as key, and the traditionalists. The traditionalists hold most power regarding device compliance, as far as I can tell. I wouldn't count on them giving much weight to your risk assessment.

You haven't detailed the nature of your products. Generally the FDA has been intolerant of distribution of devices without completely assured sterilization, particularly for devices presenting risks beyond no patient contact or intact skin contact only.

Additionally, if your devices have higher risk and have been used in procedures, I think the FDA interpretation might be that you were/are required to file an MDR in regard to the situation.

That's what your situation seems like to me, based on what you've told us. I appreciate that you have an explanation that you think justifies an exception.

If you wanted to be proactive, you could call the Recall Coordinator responsible for your location and initiate a discussion of how you should interpret the gray-area situation. My guess is that that person would want to see an MDR, and initiate a discussion with HQ.

 

[Tara QA]

Thanks for your response MIREGMGR, it was very informative. I accept your point about FDA considering this issue to be a failure, and at the very least it would be picked up as an observation, but I don't believe ultimately we have put anybody at risk. For info we manufacture a Class 2b product.

Generally the FDA has been intolerant of distribution of devices without completely assured sterilization, particularly for devices presenting risks beyond no patient contact or intact skin contact only.
.

You mention 'completely assured sterilization', my point is that I strongly believe we have the data to provide this assurance. We release a product on it meeting bioburden criteria, this criteria is way below that used to set a dose initially (by about 700cfu's), thereby showing the initial dose continues to be valid, and we have this data for all batches that were released during this increased interval. Or am I missing something??

Is it a potential recall because i have put patients at risk, or because we have not followed 11137 down the very letter, where it states three months, or another justified interval?

Where sterilization couldn't be assured, then yes I can completely understand why it would be going down recall Lane. In my specific instance, I just can't see why it could be considered to be so.. nevertheless I have had the risk assessment reviewed by regulatory, and also a consultant who used to work as a field investigator.


Any other comments would be appreciated.

 

[Jimmy the Brit]

Any other comments would be appreciated.

I disagree with MIREGMGR on this - there is no way that this would be grounds for a recall. The warning letter cited was for a firm that had not done any dose audits for two years, a very different prospect from a validated cycle with a single missing event, with valid evidence of sustainable process control over the missing period. Numerous medical device manufacturers choose not to follow the restrictive quarterly dose audit, but instead demonstrate that their process remains in control, that bioburden speciation remain stable and predictable, and that there is adequate historical data to back up their choice. Unless you are running a very low exposure cycle (which I don't think you are - from your comment about bioburden limits I assume you are using VDmax25) then you have a huge overkill built into your validated cycle (I assume an audit dose in the region of 9 to 10 kGy?), and there is no reason to suspect that this will have changed, just because you missed an audit interval.

This is a failure to follow an internal procedure, it needs to be covered with a well thought out scientific justification for why the sterility assurance level will not have been affected (which it sounds like you already have), and of course a root cause analysis of how the committed audit period was missed, and an action to ensure it will not be missed again.

If in doubt raise this as a question to a consultancy that the FDA trusts, like Joyce Hansen Associates, before raising it as an MDR or recall. I am pretty confident it is neither.

Jimmy

 

[Tara QA]

^ Thanks Jimmy, those were precisely my thoughts on the issue.. I was just trying to understand MIREGMGR point of view.