medical device promotion: special considerations · •the indications for use statement in the...

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Promotional Review Compliance for Drugs and Devices

Anne K. WalshDirector

Hyman, Phelps & McNamara, P.C.202-737-4592

[email protected]

Medical Device Promotion: Special Considerations

January 11-13, 2016

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Topics for Discussion1. Regulatory Authority

• What regulatory authorities govern device promotion: FTC, FDA, or both?

2. General v. Specific Uses• Can a company promote a specific use for devices with a general

clearance?

3. Education v. Promotion• How can companies teach doctors how to use its medical device?

Can reps be in the OR?

4. Reimbursement Discussions• What can a company say about reimbursement of specific

procedures? 2

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Regulatory Authority3

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Regulatory Authority

• Federal Trade Commission

• FTC has the authority to regulate:

• All medical device advertising except those concerning restricted devices.

• Food and Drug Administration

• FDA has the authority to regulate:

• Advertising of all restricted medical devices

• Labeling of all medical devices

Key is Advertising vs. Labeling4

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Regulatory Authority• What is a restricted medical device?

• A device that is deemed restricted either…• By regulation - Sec. 520(e);• As a condition of approval of a Class III Device – Sec.

515(d)(1)(B)(ii); OR• As part of a performance standard – Sec. 514(a)(2)(B)(v)

• Most restricted devices are prescription devices (but not all prescription devices are restricted devices).

• Virtually all Class III devices with a PMA approval are restricted devices.

• Examples of restricted devices include:• Analyte Specific Reagents (ASRs)• Hearing Aids• Over the Counter (OTC) test sample collection systems for

testing drugs of abuse5

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• What is advertising?

• Generally defined as promotional materials found in electronic media and print media.

• ELECTRONIC: television, radio, and internet (pay for placement).

• PRINT: product brochures, magazines, journals, newspapers, and billboards.

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• What is labeling?

• All labels and other written, printed or graphic matter upon any article or any of its containers or wrappers or accompanying such article.

• “Most, if not all advertising, is labeling. The term 'labeling' is defined in the FD&C Act as including all printed matter accompanying any article. Congress did not, and we cannot, exclude from the definition printed

matter which constitutes advertising.“• United States v. Lee, 131 F.2d 464 (7th Cir. 1942).

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Medical Device?

Is it a different FDA regulated

product?

Other laws may govern

FDA may evaluate labeling

Is is a restrictedmedical device?

Is the conduct advertising?

Is the conduct labeling?

Other laws may govern

FDA may evaluate labeling

Is the conductalso labeling?

FTC may evaluate

FDA and FTC may evaluate

FDA may evaluate

Step-by-Step Analysis of

Which Agency Governs

Promotional ActivityNo

YesNo

No

Yes

No

YesNo

Yes

No

YesYes

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TYPE OF DEVICE ADVERTISING LABELING

Non-RestrictedMedical Devices

RestrictedMedical Devices


Key is Advertising vs. Labeling

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Regulatory Authority• Who regulates the following?

• Device: “Discreet” HIV/AIDS Test Kit

• Medium: Internet

• Promotional Claims: 99.4% accurate, despite the fact that 59.3% of kits tested showed inaccurate results, including both false positives and false negatives.

• Result: Because this case involved an advertising claim over a non-restricted device, FTC, not FDA, has authority to regulate. • Chronology: FTC filed a complaint seeking PI, the District Court

issued a TRO banning the importation, advertising and sale of the kits. Company settled with FTC. See FTC v. Seville Marketing, Ltd. No. C04-1181L (W.D. Wash., Filed May 14, 2004). 10

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• Device: “Analyte Specific Reagent (ASR) Probe Mix” designed to be used in genetic tests to detect sensitivity to blood thinner, Warfarin.

• Medium: Package label

• Promotional Claims: Marketed device as ASR Probe Mix when it should have been marketed as an In Vitro Diagnostic (IVD).

• Result: Because this case involved a labeling claim over a non-restricted device, FDA, not FTC, has authority to regulate. • Chronology: FDA issued a Warning Letter to Paragon Dx, LLC

stating that the device is adulterated and misbranded. Paragon agreed to stop of device. See FDA Warning Letter (March 18, 2010) and FDA Close Out Letter (May 11, 2010).

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• Device: Mechanical dilator sheath intended for percutaneous dilation of tissue surrounding cardiac leads, indwelling catheters and foreign objects.

• Medium: Product brochures

• Promotional Claims: Marketed with design features and uses that were not part of the originally cleared 510(k): K061000.

• Result: Because this case involved labeling claims, FDA, not FTC, has authority to regulate. • Chronology: FDA issued a Warning Letter to Cook Vascular, Inc.,

stating that the device is adulterated and misbranded because the new design features represent a new intended use. See FDA Warning Letter (April 15, 2014). 12

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Regulatory Authority• FTC enforcement standard:

• Adequate substantiation (competent and reliable scientific evidence)

• No deception (misrepresentation or omission likely to mislead a reasonable consumer)

• No unfairness (causes or likely to cause substantial injury to a reasonable consumer)

• FDA enforcement standard:• A product is misbranded if it:

• Bears false or misleading labeling

• Bears inadequate directions for use in the labeling

• Lacks general labeling requirement, including but not limited to statement of intended uses and warnings, precautions, side effects and contraindications; the generic name of the product; and if necessary, a description of the device’s components. 13

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• Bottom Line: • Medical device promotion could be regulated by FTC, FDA, or

both, depending on whether the promotional activity constitutes labeling.

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General v. Specific Uses 15

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Promotion of Specific Uses

• Situation: • Medical devices commonly are cleared with a general clearance

• For example, ablation of soft tissue, or removal of soft tissue or fluid from the body during surgery

• Manufacturers frequently promote these devices for specific applications due to:

• Minor technological changes to the device that make it more applicable to a specific use

• Ability to compete with a product that has the specific indication

• Evolution of medical practice

• The addition of a specific indication for use could trigger the need for separate pre-market approval (PMA) or 510(k) clearance.

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• Question:

• How can a company promote a specific use for devices with a general clearance without running afoul of off-label promotion?

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• The Indications For Use statement in the product labeling defines the scope of FDA’s clearance.

• According to FDA: “Changes in the indications for use section of labeling raise more agency concern than any other aspect of labeling. In fact, most changes in this part of the labeling will require the submission of a 510(k).”FDA Guidance Document: Deciding When to Submit a 510(k) for a Change to an Existing Device

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• The company’s intended use determines whether a product has added a new specific indication for use.

• FDA evaluates the company’s objective intent based on evidence from:

• labeling and promotion

• sales calls, site training, trade shows or speeches

• statements by third parties (e.g., testimonials)19

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• FDA has identified factors it uses to evaluate whether a specific use becomes a new intended use that falls outside the general clearance for a device:

• Risk

• Public Health Impact

• Knowledge Base

• Endpoints

• Tool or Treatment

• Adjunctive Therapy

• Design changes

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• If the change “limits use to within the currently cleared indication,” then no new 510(k) clearance or PMA approval is needed.

• Marketing for only 2 of the 3 cleared indications

• Marketing only to adults over 60 years of age when cleared for use in adults

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• If the change “expands use to closely related populations,” then separate clearance or approval may be necessary.

• Less likely if the expansion is to a population with similar demographics, diagnosis, prognosis, comorbidity and potential for complications as the original

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• If the company’s promotion does any of the following:• introduces new risks;• dramatically broadens the patient population;• leads to a major qualitative difference in device use

(e.g., diagnostic vs. screening, cutting soft tissue vs. treating breast cancer);

• involves different set of clinical endpoints; or • requires device modification that are not necessary for

the more general use;

FDA is likely to find that the company has created a new intended use requiring separate clearance or approval. 23

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• How would FDA regulate the following?• Product: DIAGNOdent Laser Fluorescence Caries Detection

• Intended Use: “…as an aid in the diagnosis of caries.”

• Conduct: Company’s print advertising claims that the device provides “accurate, reliable caries detection” and that the device is “the new standard of care in caries detection.”

• 510(k) submission: There is no support for “absolute” caries detection in company’s original submission.

• Result: FDA issues Untitled Letter in March 2005 advising KaVo Dental Corporation to cease marketing for absolute caries detection.

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• How would FDA regulate the following?• Product: Sleep Right Adjustable Night Guard

• Intended Use: for (i) protection against teeth grinding, bruxism and jaw clenching; (ii) short term pain relief from muscle spasm due to occlusal interference; and (iii) prevention of chronic tension and temporal mandibular syndrome caused by chronic jaw clenching.

• Conduct: Manufacturer’s website promotes device for non-prescription use and for use by children 12-18 years old.

• 510(k) submission: Clearance was granted for a prescription only device and for adults 18 years of age and older.

• Result: FDA issues Warning Letter in Jan 2007 to Power Products stating, among other things, that product is misbranded. 25

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• Potential for change in FDA enforcement due to recent settlement in Pacira Pharms., Inc. v. FDA

• October 2011 – FDA approved Exparel for use as a “post-surgical local anesthestic” – a general broad indication.• Two types of clinical studies were used to gain approval: (i)

bunionectomy; and (ii) hemorrhoidectomy.

• September 22, 2014 - FDA alleged that Exparel was misbranded • Promotional materials described uses in surgical procedures

beyond bunionectomies and hemorrhoidectomies (e.g., laparoscopic cholecystectomy and open colectomy) – specific uses. 26

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• September 2015 - Pacira sued FDA on First Amendment grounds.• Pacira cited published studies supporting the safety and efficacy

of Exparel’s use in surgical sites other than bunionectomy and hemorrhoidectomy.

• December 2015 – the parties settled the litigation.• FDA clarified that the company could promote Exparel for uses

beyond the two specific studies used to support the approval.

• FDA approved a supplemental application, which removed the statement, “EXPAREL has not been demonstrated to be safe and effective in other procedures” from EXPAREL’s label.

• FDA’s reason for rescinding the Warning Letter: “..different statements in various parts of the approved labeling created ambiguity with respect to the scope of the approved indication.” 27

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• Question:

• How can a company promote a specific use for devices with a general clearance without running afoul of off-label promotion?

• Bottom Line:

• FDA may be more likely to deem a specific use covered by a broad general clearance.

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Education v. Promotion 29

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Educational Activities

• Situation: • Unlike administration of drugs, the use of a medical device

requires knowledge of the product’s unique technological and design characteristics. The manufacturer has the most intimate knowledge about its device, and doctors rely on the company to “educate” on the device.

• Medical device technology is constantly evolving, and even minor changes in the device or software improvements require training doctors about these new features.

• Doctors frequently use medical devices in unapproved applications. Medical device companies, however, have limitations on its dissemination of off-label information.

• Medical device companies must tread carefully when engaging in this training.

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• Question:

• How can companies teach doctors how to use its medical device without running afoul of off-label promotion?

• Can reps be in the OR?

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• Legal Framework

• In drug cases, the government has had to resort to a “backdoor new drug charge” to bring cases for off-label promotion based on oral statements by the company’s sales reps.

• Evidence of off-label promotion of medical devices can result in a more straightforward charge. • A sales rep’s discussion of off-label uses can be used as

evidence of the company’s objective intent to create a new intended use for the device.

• If the medical device requires, but does not have, clearance or approval for this new intended use, it is adulterated or misbranded.

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• Ways to mitigate risk:• FDA has long taken the position that firms can “respond to

unsolicited requests for information” • Information must be “truthful, balanced, non-misleading, and non-

promotional scientific or medical information” See FDA Guidance Document: Responding to Unsolicited Requests for Off-Label Information About Prescription Drugs and Medical Devices

• Companies may want to fully document requests for information

• Separate sales and marketing staff from clinical and medical liaisons

• Avoid preparation of stock materials that involve off-label uses

• Include peer-reviewed scientific studies or medical textbook chapters (not supported or otherwise influenced by a medical device company) describing successful use of the device for off-label uses with the disclaimer that FDA has not cleared the device for that specific use.

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• Historically, government prosecutors have looked skeptically at sales reps’ presence in surgical suites, patient rooms, hospital pharmacies, or other clinical settings.

• Viewed as evidence of intent to promote off-label uses.

• In reality, medical devices present different knowledge bases for clinicians than drugs.

• Doctors actually rely on sales reps to teach them how to use the device.

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• Question:

• How can companies teach doctors how to use its medical device without running afoul of off-label promotion?

• Can reps be in the OR?

• Bottom line:

• There is a practical need for sales reps’ attendance and participation in clinical settings.

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Reimbursement Issues36

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Reimbursement Issues

• Situation:

• Medical device company reps are frequently asked questions about reimbursement, both private and governmental programs. • Even if these discussions are referred outside of the sales

context, there can still be issues related to the scope of the information disseminated.

• Unlike drugs, the reimbursement of medical devices may be incorporate into the cost of a medical procedure.• If the medical procedure is an off-label use of the device, the

company’s discussion about specific reimbursement codes may impact the device’s intended use.

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• Question:• What can a company say about reimbursement of

specific procedures without running afoul of off-label promotion?

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• The same factors apply to the educational activities associated with training doctors on the use of a medical device in off-label settings.

• Ways to minimize risk:

• Limit discussions to “responses” to unsolicited requests for information

• Document requests for information

• Separate sales and marketing staff from reimbursement specialists

• Avoid preparation of stock materials that involve reimbursement codes for off-label uses of the device

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Questions

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Relevant Medical Device Guidance

• 510(k) Program: Evaluating Substantial Equivalence: http://www.fda.gov/downloads/MedicalDevices/.../UCM284443.pdf

• General/Specific Intended Use: http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm073945.pdf

• Deciding When to Submit a 510(k) for a Change to an Existing an Existing Device: http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm080235.htm

• Distributing Scientific and Medical Publications on Unapproved New Uses – Recommended Practices: http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm387652.pdf

• Responding to Unsolicited Request for Off-Label Information about Prescription Drugs and Medical Devices: http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm285145.pdf 41

http://www.fda.gov/downloads/MedicalDevices/.../UCM284443.pdf

http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm073945.pdf

http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm080235.htm

http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm387652.pdf

http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm285145.pdf