Presentation Transcript

1. Food and Drug LawNovember 22, 2010

   Ralph F. Hall
2. Overview Current events QSRand post market matters Recalls Biologics Cosmetics Product liaiblity
3. Complaint Handling, MDR Reporting and Recalls
4. Overview Post market approval obligations Inform FDA of product changes sPMAs or 510(k)s Track and assess complaints Report adverse events Update warnings as appropriate Remove violative or unsafe product from the field Assessing and analyzing actual product performance Rare or unknown risks Product problems
5. Inquiries, Complaints, MDRs and 806 Device information Complaint Root Cause Trends Investigation Inquiry Corrective Action Non FDA matter Regular Business Effectiveness MDR Customer Contact 806 Report
6. Hypothetical An Acme sales representative is talking to a doctor about a new pulmonary device. The doctor tells the sales representative that earlier that week, she had heard about another doctor at the hospital who had hooked a nitrogen line into the oxygen port on another product made by Acme. The doctor is not sure that the story is true. What she heard was that a nurse recognized the problem before the product was used on a patient and no one was harmed. The labeling clearly states that nitrogen lines should not be connected into the oxygen port. There is a warning sticker on the machine itself and the lines are also color coded to make it clear. There are over 75,000 devices of this type on the market and this has only been reported twice before. Is this a reportable event?
7. Event Reporting Mechanisms PMAs, sPMAs and annual reports MDRs (803) 806 correction and removal reports Medical Product Surveillance Network MedSun Sampling approach International reports Inspections Lifescan and EVT Press reports and “tips”
8. Recalls Part 806 (Reporting and Recordkeeping Requirements) Part 7 (Guidance on conducting health hazard evaluations, implementing recall strategy, and writing recall communications) Vast majority of recalls voluntary FDA has authority for mandatory recalls
9. Recall Decisions Unanticipated increase in rate or severity of adverse events Substantially violative product Structured internal procedure including Health Hazard Evaluation
10. What Needs Reporting? Any correction or removal of a device undertaken either to: Reduce a risk to health posed by the device; or Remedy a violation of the FDA Act when health risk exists or is remote
11. Key Reporting Definitions “Correction”: the repair, modification, adjustment, relabeling, destruction, or inspection (including patient monitoring) of a device without its physical removal from its point of use to some other location “Removal”: the physical removal of a device from its point of use to some other location for repair, modification, adjustment, relabeling, destruction or inspection
12. Key Reporting Definitions (cont’d) “Risk to health”: A reasonable probability that use of, or exposure to, the product will cause serious adverse health consequences or death; or That use of, or exposure to, the product may cause temporary or medically reversible adverse health consequences, or an outcome where the probability of serious adverse health consequences is remote
13. Recall Classification Class I recall – use of the product could lead to death or serious injury Class II recall – risk of death or serious injury is remote Class III recall – violative product but no measurable risk to human health FDA assigns the class
14. What Does Not Need Reporting Actions undertaken to improve the performance or quality of a device but that do not reduce a risk to health posed by the device or remedy a violation of the FDC Act caused by the device Other market actions Market withdrawals Routine servicing Stock recoveries
15. Hypothetical In response to the event in which a doctor may have connected a nitrogen line into the oxygen port, Acme makes a new collar for the oxygen line which physically prevents a nitrogen line from being connected. Acme adds this part to its price list and informs customers that this part is available should the customer want the extra protection. Is this addition to the price list reportable? What if Acme simply adds a new warning in bold letters to the physician’s manual for this Is this a reportable event?
16. Complaint Handling and MDRS Current Focus Adequacy of MDR filings Adequacy of CAPA system Relationship of complaints/MDRs to device changes Complaint handling and investigation Off label uses as “complaints” Recall decisions Growing connection to False Claims Act
17. Hypothetical An orthopedic surgeon calls Acme’s Chief Medical Officer (CMO). The surgeon reports that he recently performed a hip replacement on a 62 year old woman in good health. 3 weeks post implant, he determines that there is no bone growth into the new hip implant. That means that the implant is unstable and may require replacement. What should the CMO do? What should the company do?

18. Biologics

19. Biologics Overview Regulated under PHSA 42 USC § 262 Historical development Vaccine programs Small pox, etc Predates FFDCA of 1906 Different product and distribution systems Batch issues
20. Biologics RegulationDefinition 42 USC § 262 (i) “Biological product means a virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product … applicable to the prevention, treatment or cure of a disease or condition of human beings. Definitional aspects Not intent based Not applicable to animals No mention of structure
21. Biologics Regulation Key issues Blood donations and transfusions Blood products Vaccine matters New strains AIDs vaccines Tissue regulation Whole organs Tissue (21 CFR §§ 1270, 1271) Adverse event reporting (VAERS)
22. Biologic Regulation Requires biologics license Biologics license application (BLA) Analogous to NDA Approval based on Safety Purity and Potency GMPs required Regulated by CBER Similar pediatric push
23. Biologics Regulation Recall authority § 262 (d) Imminent or substantial hazard to public health False labeling provision Inspection authorization FDCA “savings clause” Nothing modifies, affects, etc. the FDCA
24. Biologics Regulation Adoption of FDCA § 262 (j) FDCA “applies to a biological product … except that a product for which a license has been approved … shall not be required to have an approved [new drug] application …” Incorporates classical FDCA provisions and structures GMPs INDs Enforcement
25. Emerging Issues Gene therapy Clinical trial safety Patient protection Gene transfer processes Tissue regulation Excludes organ transplantation Synthetic biology biosimilars Xenotransplantation

26. Cosmetics

27. Cosmetic Regulation Definition of a “cosmetic” “articles intended to be rubbed, poured, sprinkled, or sprayed on, introduced into, or otherwise applied to the human body … for cleansing, beautifying, promoting attractiveness, or altering the appearance” Components of such articles Except soap
28. Cosmetic Regulation Definition based on intended use Similar approach to drugs and devices Relationship to food Differentiating drugs and cosmetics What is botox? Treat disease or affect structure Determining intended uses Direct action (labeling and advertising) Indirect (common knowledge) Combination products – but not the statutory type
29. Possible Cosmetic Risks Safety Poisonous components Allergic reactions Contamination Foreign material Internal ingestion Efficacy? Economic issues Fraud Misrepresentation
30. Applicable Regulatory Structures? General adulteration provisions Contamination Poisonous substances General misbranding False or misleading in any particular Labeling General manufacturing controls 21 U.S.C. §§361, 362
31. Key Cosmetic Issues Interface with drug world When does a cosmetic become a drug? Role of objective intended use Function/structure claims How close can one advertise? Linkage of appearance issues to mental health & physical health Weight loss products Health or appearance issues Rise of more “exotic” ingredients Economic fraud
32. Cosmetic Hypothetical Acme’s product is advertised to remove wrinkles Acme’s product is advertised to make wrinkles invisible “Feel better, look better” claims U.S. v. French Bronze Tablets Silicone breast implants Reconstructive v. non-reconstructive use
33. Cosmetic Regulation No premarket approval process Except for color additives Use of GMPs or QSR General requirements No specific provisions such as 21 CFR 820 Voluntary registration Facilities Products
34. Cosmetic Regulation Ingredient listing Retail products Several banned ingredients Mercury compounds FTC jurisdiction over unfair and deceptive advertising or promotional practices Adverse event reporting
35. Cosmetic Enforcement General inspection authority §361 – adulteration Poisonous or deleterious substance Filthy, putrid or decomposed substance Prepared under insanitary conditions §362 – misbranding Labeling that is false or misleading in any particular Inadequate labeling

36. Veterinary Products

37. Veterinary Product Regulation §321 v – new animal drug Used in animals other than man Used in animal feed GRAS concept for “old” animal drugs Subset of “drug” definition § 321 (w) animal feed Not sole source of nutrition
38. Veterinary Product Regulation Animal food regulation Animal feed (321 (w)) Contains regulated products Antibiotic containing feed Hormone additives BST and similar products Basic food Animal food additives
39. Veterinary Product Regulation Premarket animal drug approval § 360(b) Non-GRAS substances New Animal Drug Application (NADA) Similar concept to NDA Standard is safety and efficacy Affect on animal Affect on humans Animal feed regulation Overlap with food safety
40. Veterinary Product Regulation Other regulatory structures Labeling requirements GMP compliance Adverse event reporting Corrections and removals Adulteration and misbranding concepts Lack of required approvals Labeling issues Traditional adulteration issues

41. Product Liability Issues

42. Key Issues Practice of medicine Warnings To whom About what Preemption Drugs Devices Non-identification theories of liability
43. §396 “Nothing in (the FDCA) shall be construed to limit or interfere with the authority of a health care practitioner to prescribe or administer any legally marketed device to a patient for any condition or disease …” FDA still has the right to: Restrict sales of devices Establish labeling Prohibit promotion of unapproved uses of devices
44. Duty to WarnHistorical view Prescription drugs and devices require physician involvement Ordinary consumer not capable of understanding risks and benefits Physician acts as “learned intermediary” Warnings must be adequate for physician, not for lay person Content Complexity Read and rely requirement
45. Perez v. Wyeth Rise in direct to consumer advertising (DTC) Does DTC “bypass” the physician as the decision maker? DTC requires disclosure of major risks 30-60 second ad can’t provide “fair balance” and complete information Impact of DTC on the role of the physician Encourage prescription Read and rely Learned intermediary doctrine does not apply (at least in NJ) to products promoted through DTC channels
46. Patient Information DTC implications Available information Internet Clinical trial sites Direct patient notification of product issues HRS conference GDT Independent Panel Role of physician Abdication of responsibility? Role of patient
47. Preemption Product liability historically a state matter Interface between state product liability law and federal regulatory systems Express preemption Implied preemption Conflict preemption Field preemption Breach of FDA regulation as a private cause of action Action against FDA
48. Express Preemption 360(k) “(N)o state … may establish … with respect to a device … any requirement – which is different from, or in addition to, any requirement applicable under this chapter to a device and which relates to the safety or effectiveness of the device or to any other matter included in a requirement applicable to a device … No equivalent drug provision Prescription drug labeling rules state that there is preemption
49. Medtronic v. Lohr Pacemaker lead case Defective lead required emergency surgery 510(k) device Plaintiff asserted design defect, failure to warn and strict liability theories Medtronic asserted preemption as a complete defense Summary judgment motion
50. Medtronic v. Lohr Role of product liability actions Promote safety Compensation 510(k) is a “substantial equivalence” determination, not a safety determination Need for concrete, specific federal requirements, not general 510(k) requirements State requirement must conflict with federal requirement Violation of FDA regulation Stand alone cause of action per se negligence
51. Riegel v. Medtronic PMA case Tort cases can create “requirements” PMA creates device specific requirements “Parallel” claims permitted “different from or in addition to” claims preempted What is an FDA requirement? Guidance? What is parallel?
52. Implied preemption No direct statutory preemption FDA fully “occupies the field” Field preemption Any private litigation result in favor of claimant would necessarily impinge on regulatory structure Conflict preemption Adequacy of labeling (PMA or NDA product) Would any finding of inadequacy of labeling implicate adequacy of FDA decision
53. Wyeth v. Levine Pharmaceutical case Drug labeling Do not put IV in artery Stop if pain Risk of gangrene Drug administered into artery; patient report severe pain Amputated arm Suit against HCP settled Suit against Wyeth Inadequate warning
54. Wyeth v. Levine Jury verdict for Levine Product should not be on market Wyeth argued implied preemption on appeal Can’t change label without FDA approval Regulatory history supports (but not conclusive) that FDA wouldn’t change label Court relied on “changes being effected” regulation Wyeth could have changed label
55. Fraud on FDABuckman Orthopedic bone screw case 510(k) device Plaintiff sued asserting that the defendant committed fraud on the FDA But for the fraudulent statements, FDA would not have approved the device Fraud claim based solely on breach of FDA requirements Claims preempted FDA has specific provisions dealing with false statements Risk to applicants Conflicting requirements Increased cost and delays
56. Fraud on FDA Analyzed as preemption Any private cause of action for violation of law? What about False Claims Act? Violation as evidence of negligence Violation as way to avoid preemption Validity of theory Impact on discovery
57. Strict Liability Drugs as “unavoidably unsafe” products Restatement of Torts 2nd (402A comment k) Does that turn a strict liability case into a negligence case? State of the art as a defense Reasonableness of testing, development, etc.
58. Non-identification theories Statement of the problem Generic product Same chemical agent Allegation of injury Inability to determine actual manufacturer of product the particular person ingested Traditionally, had to show that defendant was responsible for (e.g. made) the product that caused the injury
59. Non-identification theories Alternative liability (Summers v. Tice) All tortfeasors present and equal accountability Concerted action/conspiracy Parallel action Enterprise liability (Hall v. DuPont) Industry standards Market share (Sindell) Defining and proving market shares Collins Sue one manufacturer who made DES of the type taken by mother Others can be joined (by defendant) Comparative negligence
60. Economic Liability Antitrust laws DOJ FTC Merger issues HSR premerger filings EU antitrust clearance Consumer fraud FTC Lanham Act State laws
61. Antitrust Issues Unfair competition Price fixing Control of raw or intermediate materials PBM issues Access to formularies Pricing and preferences Patent licensing/Hatch-Waxman related issues Collusive settlements Patent tie ins
62. Consumer Fraud FTC Deceptive advertising Jurisdictional MOUs Lanham Act Unfair competition Private cause of action Zeneca v. Lilly

63. Questions or Comments