One of the benefits of working in New Zealand over the US is scheduled FDA inspections - a refreshing change from the days of RED ALERT mode when the inspectors show up unannounced. :)
However, I'm curious about the logistics... If you're located OUS and have been subject to a recent FDA inspection - how long did it take to schedule an actual audit date from the time you were notified? How much time between the date finalisation and the actual audit? How many auditors and how many days?
I've already reviewed the FDA materials for foreign manufacturer inspections, but want to know how things REALLY go down. Thanks in advance for any info!
I’ve assisted OUS clients with three OUS FDA routine inspections in the last year or so. One was in your region (i.e., over in Sydney, Australia). FDA will typically pre-announce the OUS inspection in writing (by email) approximately 3 months in advance of specific audit dates proposed by FDA. You will usually be given 5 days within which to respond to FDA’s inquiry by giving FDA an inspection contact person and starting discussions about the proposed dates.
If you fail to respond within 5 days, FDA states that it will consider its regulatory options, including taking this into account in determining whether to sample or otherwise examine products from your facility when offered for import into the U.S. and in determining whether such products are subject to refusal of admission into U.S. commerce.
FDA expects that finalizing the inspection dates is a simple administrative act on your part, and I have always responded commensurately. Specifically, I responded within the 5-day timeframe, and then had final agreement with FDA regarding the audit dates within a week or so thereafter. If it takes a firm much longer than that to settle on the proposed audit dates, then the FDA will likely think the firm is being evasive. Being evasive (or being viewed as evasive) is not a good way to start off any FDA inspection.
Typical OUS FDA inspections are what FDA calls “Level 2” inspections. Level 2 inspections are “Comprehensive Inspections”, meaning that they will cover all four major subsystems (Management Controls, Design Controls, CAPA, and P&PC) (see the FDA’s QSIT Guide). FDA considers a Level 2 inspection to be a comprehensive review of the compliance status of the firm.
The Level 2 OUS “routine” inspections I’ve participated in were all 4 business days in duration for small to medium-sized firms. They typically have one Investigator. However, “for cause” inspections, other non-routine inspections, or larger firms could certainly dictate that the inspection go longer than 4 days, and involve more than one Investigator.
Hope this helps,
Thanks Kevin! If it took longer than that (on the FDA's part), what do you think would be the cause - simple logistics or something related to review of the firm's data?
I infer that by "longer than that”, you mean the 4-day duration. Each scenario really needs to be considered carefully on its own merits to identify if there could be any triggers that might warrant longer than 4 days of inspection. Firm size and past compliance history would be the key drivers for longer durations.
In any event, my experience has been that FDA is quite committed to maintaining its pre-arranged dates and audit durations. The OUS inspections usually start on a Monday or Tuesday, and then end on Thursday or Friday. FDA's own OUS logistics and schedules are very demanding. I recall an OUS inspection where the inspector had to rush off to do another OUS inspection very soon thereafter in a different country. Rescheduling or cancelling such arrangements would be very troublesome for all stakeholders.
In general scheduling seems to be very difficult for FDA with respect to OUS inspections. For example, in the initial inquiry/notification, the FDA has typically asked right away for help with certain travel accommodations, to which we provided assistance. But then later, literally within a few weeks before the inspection, I had frantic emails from an FDA “travel coordinator" who was still having trouble finding flights and hotel arrangements, even though the inspection was scheduled months earlier. I think the FDA’s foreign inspection cadre is overtaxed and under-resourced.
I would say that an inspection originally scheduled for a 4-day duration would only go longer in the event of discovery of an extreme serious U.S. public health threat. But even then, the routine inspection would probably end as scheduled, with the situation being quickly handed over from the FDA’s ORA DMPTI device inspections branch (handles routine OUS medical device inspections) to the Foreign Enforcement Branch of the Office of Compliance (handles OUS inspection enforcement actions when necessary) who would then expedite further actions as necessary. For example, I had an OUS client recently go through a similar process where the routine ORA inspection ended on day 4 as planned, even though evidence/data was uncovered that ultimately led to a significant Warning Letter from the Office of Compliance. (I wasn’t hired until after the Warning Letter). Then the Warning Letter follow-up inspection was, you guessed it, 4 days in duration. But every scenario can be different, so other Forum members may have additional examples to share that might have gone longer than 4 days.
Actually I am more curious about the time to schedule the actual audit date. Another NZ company had an experience in 2011 where it took 11 months after being notified of the inspection to actually settle on a date, which took place 9 weeks later. However, I'm very happy with the other detail you provided - very helpful!
Regarding the inspection lead time, I would say that it is most likely related to FDA logistics and resources. I've not heard of a scenario where FDA scheduled the inspection a long way out in order to allow itself a certain amount of preparation time; but that doesn't mean FDA has never done so. The 11-month scenario you mentioned is certainly different than what I’ve experienced.
There could have been a number of factors unique to the 11-month scenario and/or FDA’s schedule at that point in time. My guess is the timeframe was related to getting the firm’s and FDA’s schedules to align, or it was related to something of unusual scope about that particular inspection. For example, if the inspection was a “For Cause” inspection instead of a Level 2, then it may necessarily be more in depth than a routine inspection, and could have inspection preparation time that might be extended accordingly.
I have seen this happen a couple times - once OUS and once actually after the "pre-announced" a US inspection. In neither case did it have anything to do with the firm. As it happened, there were outside "crises" that the FDA pulled the inspector on to (in one case it was the big dog food poisoning scandal and I can't remember the other right now).
Kevin's overall summary was spot on for all the OUS inspections my various employers had at our OUS plants. They always finished in 4 days and at least part of that is due to how FDA staffs overseas inspections. They have an incredibly small group of dedicated OUS inspectors. Instead, they usually "pull" inspectors from their various US Districts for "overseas assignments" that typically seem to be about a month long. These inspectors literally have an inspection scheduled at a different facility each of those weeks, and by the end of the month want to get home, so something pretty big would have to happen to make them run long.
And though I gave my insights about OUS inspection duration based on actual experience in light of your inquiry about "how things REALLY go down", it's still important to always stay up to speed on FDA's written policies, such as those to which you referred (i.e., the FDA's materials for foreign manufacturers inspections). For example, therein FDA states, "The time allotted for each inspection varies depending on the type and number of products to be covered. Inspections of firms producing less critical products may be assigned less time than those making more technically complex items."
Do you have specific questions that you would like to ask an FDA investigator? The NJ NY RAPS Chapter will be hosting a face to face meeting entitled, "The Changing Environment of National and International Inspections." This is an evening event on Thursday October 20, 2016 at the Bridgewater Manor. Our speaker is Helen Verdel, drug specialist, investigator, consumer safety office, FDA New Jersey District Office.
Additional information is available at http://www.raps.org/EventDetail.aspx?id=25259.
Great start to an "Elephant-in-the-Room" topic.
The US FDA has perpetuated an unequal playing field between US domestic manufacturers and manufacturers in the RoW (Rest-of-World).
While I fully understand and empathize with the resource limitations the agency is under, that is no excuse for holding domestic US manufacturers to a higher level of compliance scrutiny than RoW manufacturers designing, manufacturing, and distributing similar competitive products. This disparity of oversight allows some RoW manufacturers to "go light" on processes and activities thus avoiding the overhead costs that unfortunately go along with robust prevention based systems. This disparity in oversight, unfortunately, allows some RoW manufacturers products to have a cost advantage versus their US domestic competitors.
While working at several multinational organizations over the last 35 years, I can attest that domestic facilities are often subject to multi-week investigations resulting in only minor 483 observations, while our international facilities were never or "lightly" inspected in the decades I was managing compliance activities. This disparity in investigational oversight and monitoring only perpetuates a dangerous mindset that FDA requirements can be "shorted" because the likelihood of those shortcuts being discovered is minimal.
And while most RoW organizations pride themselves on robust processes and a compliance mindset, like many of us, I have visited and audited RoW suppliers and contract manufacturers that possess sub-standard systems that would never be tolerated in a domestic facility and could very likely result in significant warning letters, import detentions, consent decrees, or at worst product recalls.
I have found myself warning RoW facilities that the US FDA is coming, and when FDA failed to show up, I was painted as "Chicken Little", reacting with alarm when there was no perceived threat. This only served to undermine the value of robust risk-based systems of prevention, creating paradigms that put organizations and patients at risk.
With the new EU Medical Device Regulation coming shortly, Notified Bodies will have many of the same resource constraints as US FDA (despite the fact that they are directly paid by the manufacturers rather than through taxation and fees). Already many Notified Body "audits" are limited to less than a week, and it is unlikely that this will change in the near future.
With globalization a reality, harmonized, consistent and equal application of compliance oversight of all manufacturers is necessary to ensure patient safety and device effectiveness while maintaining a level playing field to ensure equal competition in the global marketplace. The concept of MDSAP is a good start, but nuances in interpretation, and the conflicts of interest inherent in "Paid" auditors having a fiduciary relationship with the organizations they are providing oversight for vs. independent oversight agents will still allow for the continued proliferation of an unequal playing field.
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