Somashekar BV Hi.. We are not in the USA, but are CM to many USA principles. We are aware that we can be inspected by FDA from years, but have never been visited even once. The big thing here is that our principles are doing fine with FDA, and we are doing fine with our principles. The focus has been always on higher class devices and controls of principles over the CM's. When the 483's of principles indicate lack of control over the CM, and the principles response to FDA seems poor, we are up on their radar for inspection. In more ways than one, our procedures and records are inspected by FDA during the principle's FDA inspection.

Jim Kandler The message by Somashekar reflects my experience also. Another way of saying it is that Somashekar is supporting his customer well so the FDA does not feel at risk and need to visit him themselves.

Julie Omohundro I think the term "routine" is probably more accurate than "random." FDA does have a program of routine inspections of device manufacturers, but the frequency of inspection for any particular company is determined by FDA's risk-based approach to inspections. This means that Class III manufacturers will be inspected more frequently than Class I companies, but other factors are considered, such as history of recalls, changes to manufacturing facility, etc.

Perhaps someone here can give a more definitive answer, but I think contract manufacturers are probably treated similarly to CROs...unlikely to be inspected in their own right, but more likely to be included as part of an expanded inspection of a manufacturer that is their customer. In these cases, the inspection is likely to focus on the manufacturing activities directly related to the one customer's product, rather than a broader inspection.

I also think contract manufacturers would be more likely to be drawn into an FDA inspection of a manufacturer is the inspection is a pre-approval inspection of a Class III device, or a "for cause" inspection. For routine inspections, I think FDA is more likely to focus on the manufacturer's internal procedures for assuring the quality of the product it receives from its contract manufacturers than on the contract manufacturers themselves.

For more than you ever wanted to know about FDA inspections, you can peruse the FDA's own guidance manual on inspections:

http://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm244277.pdf

Hans Jörg Müller My experience is that also FDA prefers more to have planned audit rather than random ones because the customer ist better prepared with examples and papers ready
I experienced in one big medtech company the preparation phase of an FDA audit - there the management has many negotiations which sites and which production lines will be audited - and at the end it was a succes for both

Victoria Trafka I have experienced FDA inspecting medical device contract manufacturers (CM) and medical device firms (the original designers and distributors) in the US. These were producers of class I and class II devices, with no major complaints or recalls, and some were not FDA registered (before FDA registration was mandated for CMs). In all cases, the companies were given a couple days notice via phone call and FDA inspectors indicated that the inspections were random. I believe that the FDA has been increasing inspections and monitoring of all medical device companies, including CMs since FDA mandated registration and device listing a few years ago. It makes sense that the data and fees generated from registration would support this effort.

I somewhat agree with other comments that the inspections are risk-based in the fact that inspections are more likely if there are "causes" like adverse events, complaints, recalls, negative inspection findings or other negative events. But I can say from personal experience that FDA does simply inspect randomly without an obvious "cause" .

Julie Omohundro Hans and Victoria, thanks for clarifying one point I wasn't sure about. If CMs are now required to register, then they are now eligible for routine inspection.

I know a lot of people working at CROs who think that CROs are subject to routine inspection, but, as far as I know, this simply isn't possible, because FDA's inspection authority is limited to registered establishments. Most CROs can't be registered establishments, because they don't engage in any activities (manufacturing, specification development, repackaging/relabeling) that meet the criteria for "establishment." They do get inspected, but I'm pretty sure this is only because they manage clinical trials on behalf of an "establishment." In that case, it is really the "establishment" that is the subject of the inspection.

I started on the pharma side years ago, and my recollection is that FDA is (or was) "required" to inspect drug establishments every 2-3 years, but that there is no equivalent set timeframe for routine inspections of device establishments. Probably because, by the time they implemented device inspections, their experience with drug inspections had shown that such timeframes were largely pointless, as FDA rarely had the resources available to keep up with the "required" schedule. So now they use a risk-based approach, which I think is a better allocation of their resources..

Richard Brown I would agree that the proper term most likely is routine inspection as Julie O indicates. I have been involved in an FDA inspection of a contract manufacturer. We were told directly by the FDA that we were on the list and our time had come to be inspected. We were informed on a Thursday and I believe they arrived to start the inspection on the following Tuesday. The company produced class I & II devices for several of the world leaders in the industry.

The FDA inspectors also told us that the FDA was starting to increase inspections of contract manufacturers. The information on who was manufacturing product as suppliers to the industry was being cataloged from inspections of the original device companies and the FDA’s inspections of those facilities. The point was, at that time, it didn’t matter whether the contractor was registered with the FDA or not, they would sooner or later end up in the FDA database for routine inspections.

Victoria Trafka Julie - I have been told by FDA representatives that inspection for medical device companies is NOT limited to those that are FDA registered, and I've seen this happen. As Richard stated, once a company gets in a FDA database it is on the radar. Also, there are companies that (unfortunately) do not comply with regulations of registration although they should and they may also be inspected. If a company gets on the FDA radar, they are subject to inspection.

If anyone has questions about registration or regulations that apply to their company, the FDA has phone and e-mail support and will gladly answer questions. Generally, they do wish to help companies comply with regulations rather than policing them.

Denise Dion Contract manufacturers are inspected just as any other manufacturing facility. FDA does not distinguish between these types of manufacturing locations. If you make a finished medical device, you are subject to a 2 year statutory inspection. FDA does use a risk-based approach and does not always meet their statutory obligations. Class III manufacturers are first on the list, next sterile devices, next would be devices with known issues (companies with W/Ls from previous year or class I recalls or significant issues from any FDA surveillance), then all other class II (high on FDA's risk list are manufacturers of condoms and sterile exam gloves and blood bank systems). FDA can inspect any company that manufactures components for a finished device but will only do so if that component is adulterating or misbranding numerous medical devices - it is unusual for them to visit a component manufacturer but they can.

Gordon Millar At times I wonder if the FDA thinks itself to be the FBI. They seem to rule the world and have jurisdiction everywhere. Needless to say, as the US is the biggest healthcare market in the world and litigation is commonplace, this is inevitable. Having ISO 13485 for example is fine up to a point but without FDA compliance, you block out a huge potential market. In terms of scheduled audits, that's fine - that's easy to deal with but FDA does occasionally do short notice or spot audits just to catch companies off guard. And why not? You should operate on a day to day basis to the same standard as you would if you were forewarned of an impending audit. One truism is that if you don't come up to scratch, you will be on the radar and they will be like a dog with a bone.
I recently exited a contract for a number of reasons. One of these was the fact that the owner and his management team really had no understanding of ISO13485 which the company had been granted through having worked with a consultant and were in daily breach but were keen to file for FDA compliance in a gung-ho fashion without any appreciation of what is involved or required. Although QA was not my specific remit, I was the only person involved with any experience of Class 2 devices and asked to contribute but they were deaf to advice. I knew full well that I would get sucked into a mire and didn't want to become the FDA's "bone".

Be aware also that the Notified Bodies for the EU Medical Device Directive when performing ISO 13485 Audits can review key suppliers to Medical Device Manufacturer's and, when deemed necessary perform an audit of the supplier.
John Tugwell

Julie Omohundro Denise, you inspired me to seek out statutory authorization. I actually hate having to look at the statutes themselves; I much prefer the regulations. I didn't find anything about a 2-year inspection, but I did find the scope of FDA's inspection authority, I think:

§374. Inspection

(a) Right of agents to enter; scope of inspection; notice; promptness; exclusions

(1) For purposes of enforcement of this chapter, officers or employees duly designated by the Secretary, upon presenting appropriate credentials and a written notice to the owner, operator, or agent in charge, are authorized

(A) to enter, at reasonable times, any factory, warehouse, or establishment in which food, drugs, devices, tobacco products, or cosmetics are manufactured, processed, packed, or held, for introduction into interstate commerce or after such introduction, or to enter any vehicle being used to transport or hold such food, drugs, devices, tobacco products, or cosmetics in interstate commerce; and

(B) to inspect, at reasonable times and within reasonable limits and in a reasonable manner, such factory, warehouse, establishment, or vehicle and all pertinent equipment, finished and unfinished materials, containers, and labeling therein.

Since the list of facilities that FDA is authorized to enter and inspect is the same as the establishments that are expected to register (right?), I come back to my thinking that they are not authorized to inspect any facility that is not a registered establishment, and I'm interested to know if anyone else here can shed further light. (And where is a device lawyer when you really need one?!?)

Richard Brown Julie, I believe the confusion comes from the fact that Contract Manufactures involved in manufacturing of medical devices are required to register. The fact that a lot of CMs don't is not a way around needing to follow the regulations or from being inspected. The analogy I would propose would be I can drive a car without a valid drivers license but the fact that I don't have a license in no way prevents the police from pulling me over and enforcing driving regulations. In the same sense the FDA is required to oversee manufacturing of medical devices. The definition of a medical devices as defined by the FDA is quite broad, it includes everything from tongue depressors and bed pans to the most technologically advanced laser robots. It is for this reason the FDA has the authority to inspect any facility that they believe are producing medical devices for distribution.

As I had stated earlier I worked at CM that was inspected that at the time was not registered with the FDA nor at the time were CMs required to register. I believe the actual requirement for registration of CMs was changed a year or two later.

Under the current requirements the fact that a facility isn't registered already puts them in violation of the current rules and is a reason for the FDA to come knocking.

Julie Omohundro Richard, I agree that this is a central point of confusion, one which I think I initially injected into the discussion myself, because I wasn't aware that CMs were now required to register.

I think another point of confusion may be the (potential) difference being physically inspected and being the subject of an inspection.

I go back to CROs that are contracted by manufacturers to manage and monitor clinical trials on behalf of the manufacturer. They are suppliers and are not (I'm pretty darn sure) required to register with the FDA. Therefore they cannot (I'm pretty darn sure) be the subject of an inspection. However, when FDA is inspecting a manufacturer that contracted a CRO to manage and monitor one or more of its clinical trials, FDA can and does go into the CRO to inspect their records related to those trials.

This is not an inspection of the CRO, but of the manufacturer. Any findings will show up on a 483 issued to the manufacturer, not to the CRO. These are most likely to be pre-approval inspections. They might also be for-cause inspections, if FDA had reason to think the manufacturer was doing funny things with its clinical data. I think FDA would rarely include a CRO in a routine inspection of a manufacturer.

Until CMs started registering, I think they were in the same situation as a CRO. Now that they are required to register, I agree that they are indeed in the same situation as a manufacturer.

Final caveat....this is regulatory, so just because I'm pretty darn sure doesn't make it so. However, I was not surprised to learn that CMs are required to register. Given the statutory wording, it's not clear to me why they weren't required to register from the start. But I don't see how a CRO meets the statutory criteria for being either required to register with the FDA or being the actual subject of an FDA inspection. So I would be very surprised to learn that the situation is otherwise for CROs.

Lakshman Srinivasan Just had one last week. Couple of days notice, without indication of what would be audited. We produce Class 2 devices and there were no recalls or quality issues from past audits that would have triggered the audit. It appears to have been truly random.

Bruce Youngman Useful for looking at FDA trends and inspections. You can drill down into the data shown on the dashboard.

http://govdashboard.fda.gov/

CEO -Shuky- Liat Nadel-Isr.Reg.Holder As far as I know the unexpected audits are not only for class III.Depends on auditor.Moreover since there are new strict regulations worldwide ,the unexpected visits are also done by Notified Bodies EU

Lakshman Srinivasan Ms Nadel, please see above - we just had one for a class 2 device.

Julie Omohundro Bruce, thanks for posting the link, now bookmarked!

Antonin Cuc In the Czech Republic there are the radilogists and radiologic technicians carefully covered with the regulations for designing workplaces with RTG emiters, carefully testing of staff and processing with duties for measurement personal risk of radiation - but the patients are full out of summarísed radiological risk of radiation of parallely and extremal dangerous radiation in duration for example the last 3 years with multilateral repeated CT, RTG, PET testing on specific medical Ambulancies of CT Head neurology, Kidneys Urology, RTG Orthopaedic implants, Spinal or Cancer Testing, etc. There are only the banal recommendation to optimize all next radiological testing of the separate view of the individual medical Ambulancy...THERE ARE NO COORDINATION, NOBODY SUMMARISED RADIATION RISKS FOR THE INDIVIDUAL PATIENT UNDER THE DEFFINED LIMITS...there are the perfect reason to produce the Mass new cases with the Dg. Leukemia CLL in the Czech Republic yearly! There are nonsence against to minimize patient repeated and summarised risks against the rules Based evidenced Science in the long being Transformal processing. Have you in your country the better rules for standard Health and Safety of managing medical patient repeated and summarised radiologic risks? I am just dying on the inforced Leukemia B-CLL after many parallel radiologic and so as sequential orthopaedic systematic daily medical serious illegal mistakes in medical daily workflow - despite I have patented the dicision making Method S_T_A_R_S-Statistical Retrieval and Search of information to reuse for repeated strategic similar decision making with risk and computer support, Utility model 21532 Czech Republic 2010. The milions of Medical Devices there are daily used illegal way contrary being Technician Requirements of Law for Safety usage, without supervision of Technician requirements Law in medical workflow.

Julie Omohundro Antonin, if I understand your question, it is possible that there are systems in place in the US to assure that patients are not overexposed to radiation across multiple practitioners and therapies, but I think that would be a question to put to our healthcare provider community. This LinkedIn Group seems to be dominated by medical device manufacturers. Here are two Groups on LinkedIn that focus on radiology; I suggest that you join them and pose your questions there:

Radiology Imaging Community
Radiology Imaging Professionals

Antonin Cuc Julie, there are lack defined duties for the Physicians to respect the Safety interess to choice only the adequated next way for the intend radiologic testing of defined patient "with optimize risk of radiation, as the comparation Efficiency and Lost". This is full idealistic situation of medical decision making...when the orthopaed could take maybe 6 RTG imaging of complicated femural bone breacking and he decided maybe with regards to the older patient to accept only 2 RTG imaging with supplement 2 ultrasonic testing on the screen. as the sufficinet compromise. When I have in my individual Health documentation declared the first diagnoses from my skin problems...as the defined Radiation overflow effects....there are the penalty crimi medical decision to applicate form me hard radiologic complex orthopaedic series RTG imaging all my body and skelet with intensity "hip bones" without safety covering my sexual organs, etc. My doctor had got now information about all previous radiologic testing, but with the information about Dg. overflow of radiation on my skin...it was namely sure to cause my Leukemia B-CLL...there are false arguments "we are working on Orthopaedy allways the same consequents ways"! Yes, you are allways without backwards information - How many patient were needless dying with the Leukemia CLL". Physicians are not the objective measurement or algorithmic caunt the summary growing radiation patient risks and excluded the next radiation for extremaly dangerous risk in time. The physicians are with local medica specific view, despite there are in patient Health documentation easy to find the suspicious markers....the physicians are working in daily workflow without regards to the interdisciplinaire medical evaluating the disponsable patient Health information in EHRs. In the countries OECD there are many thousands of patients - which they are needless yearly dying or heavy injuring under Criminal analyses contextual creating by my patented decision making Method "S_T_A_R_S-Statistical Retrieval and Search of sufficient information to reuse for repeated strategic decision making with risk and computer support", 21532 Czech Republic.There are absurd the undertaking legal technician requirements usage of Medical Devices, sufficient statistic disponseable evidences, criminal evidences, multidisciplinaire medical knowledges, repeated usage of intuitive decision making when there are mandatory duties to respect Law, right praxis, managing of patient Health and Safety. We should prefere "Based Evidence Science Transformal processing in long beeing Transformal Channel" as more complex scientic aspects for safety medical decision making as todays praxis in "Based evidence Medicine" only! There must be create the new population of the processing Medical Standards for safety usage the technician products "Medical Devices"!