9 min reading time

As originally asked by Brad Brenner.

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Jennifer Finetti
Communications | Writing | Advocacy | Marketing | Outreach for Education / Higher Ed, EdTech and more
Marketing and promotion of off-label uses is strictly prohibited and highly regulated. The only real “discussion” of off-label uses should relate to physician education in the form of CME courses, publishing of peer review journal articles, results/discussion of clinical studies etc. And of this should come from physicians/clinical investigators – NOT from the device or drug manufacturer. And also the device/drug manufacturer cannot in any way attempt to direct/influence physicians & clinical investigators from behind the scenes. And I agree with Tom Albright above that the words “marketing” and “off-label” should not appear in the same sentence.

We have developed and launched web-based CME programs and understand how critical it is to ensure that CME activities are scientifically rigorous, evidenced-based and free from commercial bias. Adhering strictly to ACCME guidelines protects both the manufacturers and accredited providers – and ensures that physicians who do choose to be early adopters and use devices or drugs off-label have access to the latest research and information regarding safety and efficacy about both on-label and potential off-label uses, as well as a review of other therapies currently available for treatment, and the advantages and disadvantages of all options.

CME provides such an important resource for physicians. We developed a course that discussed soft tissue augmentation with an injectable that was already being used off-label by thousands of plastic surgeons and dermatologists. But due to off-label status of those applications, physicians had few resources to access information about safety, efficacy and appropriate technique of the procedures. I literally had physicians calling in to our office who would say “I have my first patient for this procedure coming to my office in 2 hours. Can you get me registered right away so I can take the course before she arrives?” This happened to me more than once so I know this must be at least somewhat common…

Bottom line – manufacturers must absolutely avoid any and all activities related to marketing and promotion of off-label applications, and must avoid any and all activities that could be construed as such. But physicians involved in the development and use of the off-label application can lead educational discussions/presentations about off-label uses, and ACCME-accredited CME activities can discuss off-label uses as well. If you would like additional information about this, send me a LinkedIn message:)

Guy Hibbins
Medical Officer
Even if you do manage to get people to use the device off-label, it is not a good commercial proposition as the device will have a limited life expectancy and in order to maximize potential sales you would want to get the indication on label as soon as possible. The device with the on label indication will win out. Looking for ways to promote off label use is a bit like looking for ways to catch fish in a small pond.

Sumathy Ramesh
Founder, lzerobzero
Instead of exploring legal ways to “promote” off label use- for there are none, as many members have eloquently expressed- why not explore ways to get those uses on the label effectively?

In the absence of particular knowledge of the device, let me outline a generic possibility:

Lets call the features of the device that are in the label as “510ked features” and the features you want to promote that are not in the current label/literature as “new features” for the purpose of this discussion.

The fact you want to promote the “new features” implies that you have some evidence or basis for believing that they work.
a) Expend the effort to clearly list the features and formalise/document this evidence; (sometime documenting the evidence may give you ways to gather and subsequently document further evidence)
b) expend the effort to do a detailed risk analysis clearly and sincerely listing what you know and what you do not know about the safety and efficacy of the “new feature”; identify potential hazards that may emanate from what you know AND what you do not know;
c) prepare an executive summary of steps a) and b).
d) use the executive summary to solicit and recruit physicians who may be willing to review your detailed evidence and risk analysis;
e) provide the documents from steps a) and b) along with samples of the device to each of the physicians recruited in step d) and request an evaluation. This will give an opportunity to the physician to critically evaluate the device and use it if they see fit, with full awareness of the risks and benefits as identified by the manufacturer.
f) use the evaluation feedback you receive from the physicians to bolster your original evidence document and risk analysis and draw a final list of “new features”
g) simultaneously complete the rest of the V&V as appropriate and prepare a new full/special 510k as appropriate for incorporating the “new features” in the label so you can sell the device freely.

P.S. As the original device was 510ked I assume at most you may only need another 510K to introduce the new features- but this could be a wrong assumption. In any case the previous exercise will only help strengthen any regulatory path you might have to take.

Michael Dayton
Biomed Research, Inc.
Off label promotion of a 510(k) cleared medical device is against the law. While a licensed physician may legally use any drug or device off label, ala the practice of medicine, they personally assume liability should something go wrong. Any company that attempts to promote off label uses is not a company that you want to work with, as they are headed into stormy weather.

Jean Bigoney, RAC, CQE
Regulatory Affairs Specialist.
Ditto testimonials from third parties that are posted on a website whose content you control.

Michael Strauss
Vice President of Scientific Affairs at CBR International Corp.
Keep in mind that all advertising materials are essentially part of your labelling for devices.

Sarah H. Stec
Senior Counsel, Medical Device Regulatory Law at Johnson & Johnson
I was previously involved in device/pharma enforcement (not what I do now). To find “off-label claims,” I compared the indications for use with essentially anything anyone who represents the company in any way said about the product, including internal communications and claims made by sales reps. If it promoted an off-label use, or even if it implied a promotion of off-label use, regardless of what the disclaimers at the bottom of the page said, we used it. Having been on the other side of things, I agree with pretty much everyone else in saying that you may want to stop thinking about it and follow the rules.

Disclaimer: That wasn’t legal advice.

James Stout
Vice President of Quality Systems at Excorp Medical, Inc.
It can be a felony if the off-label use causes injury, and the manufacturer knew and kept quiet about the off-label use. I have found it usually less expensive (and less stressful!) to go ahead and get clearance for the additional indication for use.

James Erickson
Vice President at Ferghana Partners
Yes. There is no such thing as a 510(k) product “with” off-label use. Either you have clearance or you don’t.

Chris Gustilo
Vice President Global Marketing at Orthopaedic International, Inc.
I agree with most of the commentators — a company should stay very, very far away from any marketing of an off-label use. In general, it is just not worth it given the fines and the potential for future litigation.

I do think it gets a little tricky when a company’s product has expanded indications in other countries. But, once again, I think you need to be very disciplined and extremely explicit in communications to the market (including giving very clear guidance to your sales team).

Yuri Sokolov, MSc, PhD, MBA
Entrepreneur, Investor, Business Advisor
Colleagues, I fully concur with those who said NO to any marketing of off-label use.
As President & CEO, I saw it as a duty of mine to ensure that regulatory compliance was met in each market we intended to enter, and no off-label marketing was done in any form which was made a company policy.
If the use is uncertain, the company may clarify the matter by filing a request under Section 513(g) Requests for Information under the Federal Food, Drug, and Cosmetic Act – see at: [http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm209841.htm|leo://plh/http%3A*3*3www%2Efda%2Egov*3MedicalDevices*3DeviceRegulationandGuidance*3GuidanceDocuments*3ucm209841%2Ehtm/XNWH?_t=tracking_disc]

Tom Albright
President and CEO, Board Member at Recros Medica
To begin with, the words “marketing” and “off-label” should not even appear in the same sentence. We must market our devices for the uses for which they are cleared. If we become aware of significant off-label uses of a device, then we should encourage proper studies to determine the safety and effectiveness of the device for that use. If we don’t believe that a research investment is warranted, then the risks of that use should be monitored for risks, without any communication to suggest expansion of that unapproved use. We can only promote or market what we know works, and only if that use is properly cleared.

Kiu Leung, Ph.D. – Executive Forums, Western Wisconsin
President/Owner (Peer CEO Advisory Group, CEO Roundtable, Facilitator)
To promote off-lable use of a regulated medical product by a firm is misbranding, illegal and costly to the firm. The announcement of Abbott Laboratories $1.55 billion fine imposed by FDA and Department of Justice in May 2012 on off-lable promotion of Depakote, a psychiatric drug is a recent exmaple. Please note that in addition Abbott has to sign a Corprate Integrity Agreement with the US Government.

Jean Bigoney, RAC, CQE
Regulatory Affairs Specialist.
My advice? Don’t even think of it.

Here is the FDA Guidance on that subject:
[http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM285145.pdf|leo://plh/http%3A*3*3www%2Efda%2Egov*3downloads*3Drugs*3GuidanceComplianceRegulatoryInformation*3Guidances*3UCM285145%2Epdf/bRxD?_t=tracking_disc]

If a request for off-label use is made to your company, you are permitted to respond in certain limited ways. But as part of your marketing? You might get away with it for a while. Most likely one of your competitors would blow the whistle on you and then you would be on the receiving and of one of these
[http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2012/ucm310790.htm|leo://plh/http%3A*3*3www%2Efda%2Egov*3ICECI*3EnforcementActions*3WarningLetters*32012*3ucm310790%2Ehtm/vNdh?_t=tracking_disc]
[http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2012/ucm306771.htm|leo://plh/http%3A*3*3www%2Efda%2Egov*3ICECI*3EnforcementActions*3WarningLetters*32012*3ucm306771%2Ehtm/d289?_t=tracking_disc]
at which point your regulatory affairs specialist would get to work overtime. Plus you are now on an internal FDA list that you do not want to be on. Plus when someone does an internet search on your company, it will pull up the FDA nastygram.

Is it worth it when you compare that to the cost of getting the device cleared for what you want to market it for?

John D. Miller
Principal at Private Consulting
with a previously registered 510K device, off label marketing is not an avenue I would suggest pursuing. Now surgeons/Dr’s will at times discuss among their professional community off label uses, but, as the registered 510K manufacturer/distributor you are not allowed to do this.

Glenn Neuman
Director of Scientific Affairs at New World Regulatory Solutions, Inc.
It’s not just what you say or write, but it’s also your intent, whether said or not, that constitutes off-label use. Under 21 CFR 801.4, intended use includes “objective intent,” which is determined by expressions or may be shown by the circumstances surrounding the distribution of the product. Your objective intent appears to be to market off label. If FDA were mind-readers (and they often think they are) they would bust you for thinking about it! I wrote an article on this for Clinica last year, which I am allowed to share (but I did not post it on our website), so here is a link you can use to access it:

[https://dl.dropbox.com/u/35784625/Clinica%20March%2011%2C%202011%2C%20Off-label%20Promotion.pdf|leo://plh/https%3A*3*3dl%2Edropbox%2Ecom*3u*335784625*3Clinica%2520March%252011%252C%25202011%252C%2520Off-label%2520Promotion%2Epdf/VgQo?_t=tracking_disc]

Mario Martinez
Managing Partner at Tecnix, LLC
My understanding is that off-label use is relative to geography, some countries have different requirements so while you do have restrictions on off label promotion in the U.S. those same restrictions do to apply in other geographies.

I don’t believe there is any law preventing a subsidiary or distributor from posting this information on the Internet as long as appropriate warnings are used. But I am not a regulatory or legal expert and perhaps others can comment on this.

Jon Speer
Founder of Greenlight Guru – Helping medical devices get to market faster with less risk
This is a slippery slope. Sometimes physicians publish about off-label usage of a device. But a medical device company should in no way promote off-label uses. Many would even suggest that if a company becomes aware of off-label use, then the company should:

1. Update risk management documentation to account for off-label risks
2. Contact those using device off-label and remind them you do not have proper clearance for this.
3. File a new submission to FDA to get proper clearance.

Christophe Cognard
European Marketing Manager HDS (Hazardous Drug Safety)
One of the key questions to ask is whether the off-label is linked to a safety risk as in the case of the pain pumps or simply delay in approval.

In the first case, clear pro-active communication should be done to highlight the risks and prevent future liability. In the second case, be sure that physicians or potential customers will find their way without having your company to be involved at all.

Some years ago, I was working in the field of electrophysiology where a new procedure was not officially approved: AF ablation (atrial fibrillation ablation). The trick was that, as frequently the case, the procedure was already performed routinely in Europe. And that it could be used using catheters and other equipment available on the US market. A typical example of off label.

All companies were very careful in their communication after FDA sent warning letters to some of them. Numerous literatures were also available but we couldn’t even mention it. As for customers quotes, as soon as a company mentions it, it endorses it. At least that’s the position of our legal department.

However physicians aren’t stupid. They simply had to visit the international version of web sites or to attend overseas congresses. Which they did extensively. Once the procedure was finally approved, it was already performed in many sites.

I would always recommend to remain on the safe side because the benefits/risks ratio is too high and anyway not necessarily needed.

Brad Brenner
Founder, Brenner Associates Marketing Communications
Thanks for this thoughtful input. I know this is a delicate issue to say the least. Anyone have thoughts regarding factual mentions of off label uses in say, a press release – perhaps specifying also that the company does not endorse or supports off label uses? Other possible gray area (but legal) ways to educate the medical community that these uses are a reality?