1. OPDP Update on Oversight of Prescription Drug Promotion Thomas Abrams Director Office of Prescription Drug Promotion Food and Drug Administration October 1, 2015 1

2. Goal and Objectives Goal –To protect and promote public health Objectives –Ensure that RX drug promotion is not false or misleading –Ensure that balanced picture of drug is conveyed –Aid in the communication of more useful information about drugs and diseases to the American public

3. Surveillance and Monitoring Disseminated materials submitted to FDA –Post-marketing submission requirements (Form FDA 2253) Conference attendance Complaints Healthcare Professional Outreach Initiative –Bad Ad Program 3

4. The Bad Ad Program FDA-sponsored outreach program designed to increase awareness of healthcare professionals (HCPs) about the role they can play in helping FDA ensure that prescription drug promotion is truthful and not misleading When HCPs have concerns about prescription drug promotion, they can report it to FDA: –Call 855-RX-BadAd –E-mail BadAd@fda.gov Continuing Education Program for HCPs –Physicians, pharmacists, nurses, physician assistants, nurse practitioners

5. Risk Based Enforcement Approach FDA’s allocation of resources and priorities based on impact on public health –Promotional campaigns that have potential to harm patients the most High priority areas include –Newly approved products –Products with significant risks –Products cited for violations in the past –Products cited in complaints –Products promoted with far reaching campaigns 5

6. Most Common Violations Cited in Regulatory Letters in FY 2015 Omission and minimization of risk information Omission of material facts Unsubstantiated comparative claims Overstatement of efficacy claims 6

7. TussiCaps Warning Letter Professional sales aid Violations included –Omission of material facts –Omission of risk information Indication: –TussiCaps is indicated for relief of cough and upper respiratory symptoms associated with allergy or a cold in adults and children 6 years of age and older. Contraindicated in children less than 6 years of age –Due to the risk of fatal respiratory depression Also PI indicates that caution should be exercised when administering to pediatric patients 6 years of age and older.

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10. TussiCaps Warning Letter Omission of material facts –Page 1: For the relief of cough and upper respiratory symptoms associated with colds or allergies Omission of “in adults and children 6 years of age and older” –Page 2: Image of coughing young child Contraindicated in children less than 6 years of age –Due to the risk of fatal respiratory depression Also PI indicates that caution should be exercised when administering to pediatric patients 6 years of age and older.

11. TussiCaps Warning Letter Omission of Risk Information –Efficacy claims made for TussiCaps but failed to present: Any of the contraindications Warnings and precautions about respiratory depression, head injury and increased intracranial pressure, acute abdominal conditions, obstructive bowel disease, and pediatric use Association with drug abuse and dependence Adverse reactions such as nausea and vomiting, sedation, drowsiness, mental clouding, impairment of mental and physical performance, anxiety, fear, dizziness, mood changes

12. OPDP Web Resources OPDP home page –http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/ CDER/ucm090142.htmhttp://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/ CDER/ucm090142.htm OPDP organization listing –http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/ CDER/ucm154886.htmhttp://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/ CDER/ucm154886.htm Guidances –http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/ CDER/ucm109905.htm#Guidanceshttp://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/ CDER/ucm109905.htm#Guidances Warning and untitled letters –www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/EnforcementActivit iesbyFDA/WarningLettersandNoticeofViolationLetterstoPharmaceuticalCompanies/ default.htmwww.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/EnforcementActivit iesbyFDA/WarningLettersandNoticeofViolationLetterstoPharmaceuticalCompanies/ default.htm 12

13. OPDP Contact Information Telephone Number –301-796-1200 Fax Numbers –301-847-8444 –301-847-8445 Submission Address –Food and Drug Administration Center for Drug Evaluation and Research Office of Prescription Drug Promotion 5901-B Ammendale Road Beltsville, MD 20705-1266 13

15. FDA, Center for Veterinary Medicine Advertising & Promotion Update Food and Drug Law Institute - 2015 Thomas J. Moskal, DVM, MLIS, Dipl. ACLAM FDA Center for Veterinary Medicine October 1, 2015

16. CVM’s Vision / Mission Vision Excellence. Innovation. Leadership. Mission Protecting Human and Animal Health

17. Overview Material Review ProcessMaterial Review Process Special ConsiderationsSpecial Considerations Particular ConcernsParticular Concerns © User:Colin / Wikimedia Commons, via Wikimedia Commons

18. CVM’s Review Process Form FDA 2301  Promotional Materials  Clinical Data  Quantity Marketed  Adverse Drug Experience trends Complaints  Industry  Consumers  Animal owners  Veterinarians Product Manager [triage & review] Surveillance  Professional Meetings  Internet

19. Special Considerations Variation in Animal Patient Populations –Number of Species –Disparity in size Food Animals –Drug residues in food –Drug depletion not the same in all species

20. Particular Concerns Appropriate Risk Communication –Human food safety information including drug withdrawal time –Human exposure safety information –Target Animal Safety Unsubstantiated Claims and Conclusions http://www.ars.usda.gov/SP2UserFiles/photoResize/80420530_sitelogo.jpg

21. CVM Contact Information Center for Veterinary Medicine, Division of Surveillance Telephone:(240) 402-7082 Email: CVMSurveillance@ fda.hhs.gov CVMSurveillance@ fda.hhs.gov Form FDA 2301 and Form FDA 1932 (adverse drug experience reporting) may be obtained on the Internet at http://www.fda.gov/cv m/forms/forms.html, by telephoning the Division of Surveillance (HFV- 210), or by submitting a written request to the following address: Food and Drug Administration, Center for Veterinary Medicine, Division of Surveillance (HFV- 210), 7500 Standish Pl., Rockville, MD 20855-2764. http://www.fda.gov/cv m/forms/forms.html (Background image by Shannon Jordre, HFV-230, © 2010)

22. 2015 CBER Update: Advertising & Promotional Labeling Compliance Sonny Saini, PharmD, MBA Senior Regulatory Operations Officer Advertising & Promotional Labeling Branch Division of Case Management Office of Compliance and Biologics Quality

23. Advertising & Promotional Labeling Branch Lisa Stockbridge, Branch Chief Michael Brony Oluchi Elekwachi Kristine Khuc Dana Martin Loan Nguyen Alpita Popat Sonny Saini

24. CBER Office of Compliance OFFICE OF COMPLIANCE AND BIOLOGICS QUALITY DIVISION OF BIOLOGICAL STANDARDS AND QUALITY CONTROL DIVISION OF CASE MANAGEMENT ADVERTISING & PROMOTIONAL LABELING BRANCH BIOLOGICAL DRUG AND DEVICE COMPLIANCE BRANCH BLOOD AND TISSUE COMPLIANCE BRANCH DIVISION OF INSPECTIONS AND SURVEILLANCE DIVISION OF MANUFACTURING AND PRODUCT QUALITY

25. CBER Products Blood and Blood Components Vaccines Allergenic Extracts Human Tissue & Cellular Products (cord blood) Gene Therapy Products Biological Devices and Test Kits

26. Regulations for CBER Product Labeling 21 CFR §201.56 and §201.57 21 CFR §208.20 21 CFR §610.60 - §610.67 (container and package) 21 CFR §660.28, §660.35 and §660.55 (blood reagents) 21 CFR §801 and §809 (biological devices) 21 CFR §1271 (cells, tissues)

27. Promotional Material FY10 - FY14 (through August 28, 2015)

28. Recent Compliance Actions

29. Common Issues Absence of Risk Information Unapproved Use Unsubstantiated Comparison/Superiority 29

30. FLUBLOK Untitled Letter March 2015 Video interview posted on Protein Sciences Corporation’s website, www.flublok.com, entitled ‘Watch us on Lifetime – The Balancing Act.’ www.flublok.com CEO Dr. Manon Cox states that FLUBLOK has ‘three times more protein in there, so it is also a high dose vaccine. More protein means your body will form more antibodies that will help you fight the flu.’

31. FLUBLOK Untitled Letter (cont.) Suggestion that the higher antigen content translates into greater protection Suggestion that FLUBLOK is comparable to a high dose flu vaccine because of higher antigen No data to substantiate the above claims Omission of risk information in the video

32. Intended Use Intended for the safe and rapid preparation of autologous platelet-rich plasma (PRP) from a small sample of blood at the patient’s point of care. The PRP is mixed with autograft and/or allograft bone prior to application to an orthopedic surgical site as deemed necessary by the clinical use requirements.

33. RegenKit ® -THT Website Patient brochure – RegenPlasma TM Unleashed! Professional Brochure – RegenPlasma TM Unleash the Power of PRP in Your Practice!

34. Claims RegenKit ® -THT Claims “With a simple, quick and advantageous RegenLab™ process, your own blood is safely prepared on the physician’s premises and is delivered to your skin within the same treatment session.” “RegenPlasma™ is regenerative medicine and works best aesthetically when it is introduced into the skin.” “The use of RegenPlasma™ has long been known in a variety of aesthetic, surgical and wound care fields of medicine. RegenPlasma™ is a carefully designed leading edge product that has been scientifically verified for aesthetic applications…The results have proven to be superior!”

35. RegenKit®-THT The RegenKit®-THT is designed to be used for the safe and rapid preparation of autologous platelet-rich plasma (PRP) from a small sample of blood at the patient’s point of care. The PRP is mixed with autograft and/or allograft bone prior to application to an orthopedic surgical site as deemed necessary by the clinical use requirements.

36. RegenKit ® -THT Untitled Letter Adulterated –Because there is no approved premarket application (PMA) or an approved application for an investigational device exemption (IDE) under section 520(g) of the Act, 21 U.S.C. §360j(g) for the new intended uses of this device. Misbranded –Because there has been no notice or other information with respect to the new intended uses for the device provided to FDA, as required by section 510(k) of the Act, 21 U.S.C. §360(k). –Claims concerning use in cosmetic surgery are evidence of intended uses that are not consistent with the 510(k) clearance for RegenKit®- THT and represent a major change or modification in the intended use that requires the submission of a PMA or a 510(k).

37. Resources Guidances http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRe gulatoryInformation/default.htm http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformatio n/Guidances/default.htm Compliance Letters http://www.fda.gov/cber/efoi/adpromo.htm APLB Website http://www.fda.gov/BiologicsBloodVaccines/DevelopmentApprovalPr ocess/AdvertisingLabelingPromotionalMaterials/ucm164120.htm

38. NEW Contact Information Food and Drug Administration Center for Biologics Evaluation and Research Document Control Center 10903 New Hampshire Ave WO71 - G112 Silver Spring, MD 20993-0002 Phone: 240-402-9158

40. CDRH Advertising and Promotion Update FDLI Toni Stifano October 1, 2015

41. DPLC Responsibilities Enforcement of regulations related to: –the submission of premarket applications and –labeling requirements including promotion and advertising materials and practices Jurisdictional Determinations –Device Determinations –Pre-amendment Device Determinations Custom Device Program –Annual Report Reviews

42. IMPACT I nformed –Decisions are based upon the best available data, evidence, and information. Sources of data, evidence, and information are regularly improved and new sources are identified and used. M eaningful –Decisions improve device safety and effectiveness. Decisions increase industry compliance. P roportional –Decisions are well-matched to the nature & significance of the problem or violation. Resource allocations and expenditures are well-matched to the nature/significance of the problem or violation. A ctive –New & emerging problems or violations are proactively prevented or identified. Problems or violations are driven to resolution. Corrections are monitored for long-term compliance. C onsistent –Decisions and work products are repeatable and accurate. T imely –Problems or violations are identified early and resolved promptly.

43. IMPACT-Based Priorities Focus on resolution of violations or issues not taking “action” –Meaningful, Timely Use of non-enforcement actions (outreach) to resolve less significant issues –Proportional, Timely Consider All-at-Once rather than One-at-a- Time strategies –Informed, Proportional, Consistent

44. Common Problems Third Party Sellers Claims for products intended to remedy the latest outbreak or natural disaster Breaking commitments made during the premarket review process Exceeding boundaries of enforcement discretion Misuse of exempt product classifications

45. Recent Actions Warning Letter – Quotient ADHD System Cleared to aid physicians by providing objective measurements of hyperactivity, impulsivity and inattention… Promoted for: –Determine the effectiveness of a new treatment and achieve clinical efficacy sooner –Optimize treatment in weeks instead of months –Follow-up tests help to assess whether the patient is getting the right intervention –Objectively measure micro-motion and analyze shifts in attention state

46. Resulted in: 9 Warning Letters for unapproved or un- cleared medical devices and 814 detained parcels in total Operation Pangea VIII

47. Surgical Mesh Cleared use (general): For reinforcing soft tissue or bone where weakness exists Each of the three products were being promoted specifically for use in surgery of the breast including mastopexy with or without augmentation, reconstruction and revision. One of the products included the use of abdominal, inguinal, femoral diaphragmatic, scrotal and umbilical hernia repairs.

48. Colon Hydrotherapy Promoted to see improvements in the following: –Removal of ‘autotoxins’ –Psoriasis –Lupus –Multiple sclerosis –Chronic intestinal psueduobstruction –Congenital dysautonomia –Ovarian cancer –Parasitic infections

49. The ONDAMED System A biofeedback device? The device was being marketed to treat or cure: –Multiple sclerosis –Breast cancer –Blindness –Lyme disease –Osteoporosis –…and smoking cessation

50. Dermal Fillers Dermal fillers are Class III – PMA injectable “implants” The approved uses are for use in the face e.g.,nasolabial folds, cheek and lip augmentation (20+ approved products) Unapproved uses include: –Breast augmentation –Increase the size/shape of the buttocks

51. Dermal Fillers The unapproved polyacrylamide hydrogel was being marketed for use in the face, lips and buttocks to increase their size and for breast, genital and whole body shaping. The combination product for shaping the face, genitals, mammary glands and buttocks and for use as an endoprosthetic for vocal chords in cases of paralytic stenosis of the larynx…as well as a number of other indications

52. INTERESTING USE OF POLYACRYLAMIDE….THE TEST TUBE ALIEN

53. Keisha Thomas, Acting Director Deborah Wolf, Regulatory Counsel LaShanda Long, Branch Chief Debbie Demeritt, Branch Chief Kareem Burney, Jurisdictional Officer DPLC Contact Information

54. Questions? 54