Welcome to this week’s installation of Warning Letter of the Week (WLOTW). This week, we will be continuing our series on a Warning Letter issued to Olympus Medical Systems (full Warning Letter).
Last week, we discussed the first finding listed in the Warning Letter, which was related to not correctly handling NCR and complaint data related to one of their products “distal end cover”. Be sure to check out that article here if you want to learn more about those subjects or get the full context for this article.
Also, if you want to learn more about Warning Letters, check out FDA Warning Letters: Everything You Need to Know.
This week, we will be reviewing findings related to validations/re-validation and complaint handling, including a graphic detail that raises serious doubts about Olympus Medical’s entire complaint handling process.
Table of Contents
Validation Concerns
The second finding in the Warning Letter is related to the last example we discussed last week. As a reminder, that example was about allowing wrinkles in the packaging seal without going through the full NCR process.
The finding starts by mentioning the “air bubbles in the package seal of MAJ-210/Lot H2410 a sterile product“. Olympus then tried to correct the sealing by modifying the equipment to “increase the cooling rate of the package after sealing“.
The FDA has already stated that the sterilization of the packaging is a validated process, and any concerns which might jeopardize the sealing would be considered high risk. Do you want to guess whether Olympus performed re-validation after changing the manufacturing process?
Of course not. While they did perform some testing to “demonstrate seal integrity, no re-validation of the process was made.” This is really a follow-up to the initial finding, to stress the importance of validation and re-validation for a sterilization process. The FDA specifically says that sterilization is a critical process and “cannot be fully verified by subsequent inspection and test”, referencing the language found in 21 CFR 820.75.
As a rule, sterilization is always going to be validated, as it is not typically feasible to test for sterilization without compromising the barrier. And because it is validated, when any changes or deviations occur, the process needs to be evaluated and possibly re-validated.
Follow-Up Validation Concerns
Based on the FDA Warning Letter, it looks like Olympus did take some actions in response to the initial 483 finding. They stated they were going to re-validate the packaging process. They also said they would revise “Process Validation” procedures “to clarify when revalidation is necessary and to specify who is necessary to review and approve changes to ensure revalidation decisions are appropriately made“. Olympus planned to update its “Assembly/Processing Equipment Control“ procedure as well.
The FDA determined the response was not adequate for some fascinating reasons.
First, Olympus conducted a review of all complaints and MDRs for the “last two years associated with all products distributed to the US to determine if any signals exist to suggest sterility was compromised as a result of the modification made to the sealing process.“
This was a good first step, however, the FDA stated “it is not clear whether your firm evaluated devices shipped to other markets as well that would have the same concern or could possibly be imported into the US by a third party.“.
I think this is a useful thing to see for medical device companies. If you are doing a complaint investigation as the result of an MDR or 483 findings, what we see is that the FDA wants you to check other markets as well, and anything that could be imported into the US. This is especially true with importers.
This way, the FDA has a further grasp on the extent of the issue and the effects of not re-validating the packaging sterilization. While you may have no issues in the US, there could be dozens of injuries caused by the device in a different country, which would impact their status in the US.
“Your firm should clarify this”.
Second, in response to Olympus implementing new procedures, the Warning Letter states that Olympus “did not mention a plan to train its personnel on these new procedures“.
That is another thing to think about if you need to respond to the FDA or an auditor in general about updating procedures. You not only need to update the procedures, but you also need to provide a training plan for those procedures.
Finally, in response to the re-validation, the Warning Letter states that Olympus did not “clarify that the retrospective reviews that were done were in line with the new requirements of its procedures“. Yet another helpful thing to include if you are ever in a position to respond to a similar finding.
Esophageal Trauma
Last week, we looked at the first finding in the Warning Letter related to improper complaint handling. This included not taking action on trending data, and creating a complaint procedure that excluded complaints that required reporting from generating CAPAs.
However, the concerns with Olmypus’ complaint handling procedures did not stop there. This finding is also the most damning of the findings in the Warning Letter.
Olympus Medical received a complaint “on November 21, 2020. The complaint described that “a patient sustained esophageal trauma” and “tissue from the esophagus was caught up in the distal tip of the device.” The complaint also stated that the “customer attributes these events to cracked caps” and that they noticed a “few already cracked when coming out of the packaging.”
While it is reasonable (however unsavory) that a Medical Device company would receive a complaint of this nature, Olympus’ handling of the complaint is anything but reasonable.
“Your firm’s complaint handling procedure, OMBS (b)(4) requires investigations of complaints to be made within 30 days. The investigation of the complaint was not made until 2022.”
This is truly the worst action found in the Warning Letter. It is important to have good procedures related to trending data and validation. However, it is absolutely non-negotiable to investigate complaints that cause patient injury.
It also begs the question of Olympus’ response to the first finding, where they claimed that there were no risks related to an uncovered endoscope.
Follow-Up Complaint Handling
Yet again, the FDA did not find that Olympus Medical’s responses were adequate.
Olympus took a good amount of actions to try and address the issue, however, they failed to address the main concern of the FDA. The actions they took were:
- Initiating a CAPA to investigate the root cause of the complaint
- Revising their Complaint Handling Procedure to “(include) instructions for ensuring individual complaints are opened for all related/concomitant devices“
- Revising their Complaint Handling Work Instruction to include “detailed instruction(s) for ensuring individual complaints are opened for all related/concomitant devices while performing complaint investigation“.
- Olympus also trained their personnel on the updated procedures.
Another action that Olmypus took was to perform a “retrospective review of all complaints associated with MAJ-2315, expanding the search to other scopes that use the distal cap in addition to TJF-Q190V“.
During the review, they found “98 complaints not initiated according to their procedure during this retrospective review“. Even more evidence that Olympus was doing a terrible job with its complaint handling. It is shocking how many complaints Olympus received that were not handled properly, and not reported to the FDA.
All of these actions were needed, but as I mentioned, they did not address the root cause of the FDA’s concern.
As stated by the FDA: “it is not clear based on your firm’s CAPA and documentation whether they have investigated why the investigation into the complaint did not occur for two years, while your firm’s procedure requires it to be made within 30 days.“.
This is a time when re-writing a procedure and performing training is not going to cut it. Their complaint handling procedure already said that complaints would be investigated within thirty days. The question is why weren’t the complaints investigated?
Was this really just a training or procedure issue? Or was there something more systematic that prevented proper investigations from being completed? The company needs to let the FDA know exactly how it will prevent a similar situation from happening in the future.
If you would like to avoid this type of situation at your company, check out our article covering the creation of an ISO 13485 and FDA medical device complaint handling procedure.
Lessons Learned
As always, our goal with the WLOTW articles is to learn as much as possible in order to avoid mistakes made by other companies. While we covered some of the higher-level lessons in the first article, there are still some specifics to learn from the findings discussed today.
- Sterilization typically requires validation. And since it requires validation, any changes to the process need to be assessed to determine if the process needs to be re-validated.
- If you are reviewing complaints made about products, the FDA expects you to expand the search outside of the US. This includes complaints made for that product in foreign countries or products that might be imported into the US.
- If you are updating a procedure as part of a corrective action, you need a clear plan on how you are going to train personnel on the new procedure.
- When responding to a serious finding, the response needs to address the actual root cause of the finding. Simply correcting a procedure is not enough, especially if the information was already present in a procedure and did not prevent the issue in the first place.
Wrapping Up
That was our second WLOTW article covering an FDA Warning Letter given to Olympus Medical. We covered issues with validation, re-validation, and complaint handling, which are all essential elements of a medical device quality management system.
Next week will be our final article in this multi-part series, where we will review a finding related to improper MDR procedures.
As always, if you have any questions or thoughts on this Warning Letter, feel free to leave them in the comments below.