fda 101: jason sapsin
TRANSCRIPT
Jason Sapsin, JD, MPHJason Sapsin, JD, MPH
C.U. Graduate SchoolC.U. Graduate School
1
November 4, November 4, 20152015
Colorado School of Public Colorado School of Public HealthHealth
FDA 101
Jason Sapsin, JD, MPHJason Sapsin, JD, MPH
C.U. Graduate SchoolC.U. Graduate School
• Agencies are Organisms
• Understand the genotype
• Interact and understand with whom you are interacting
• Understand the environment and the resulting “genetic expression”
Understand the organizational culture
Jason Sapsin, JD, MPHJason Sapsin, JD, MPH
C.U. Graduate SchoolC.U. Graduate School
In 1736 I lost one of my sons, a fine boy of four years old, by the small-pox, taken in the
common way. I long regretted bitterly, and still regret that I had not given it to him by
inoculation. This I mention for the sake of parents who omit that operation, on the
supposition that they should never forgive themselves if a child died under it; my example showing that the regret may be the same either
way, and that, therefore, the safer should be chosen . . . .
Jason Sapsin, JD, MPHJason Sapsin, JD, MPH
C.U. Graduate SchoolC.U. Graduate School
Benjamin Franklin: His Autobiography 1706-1757, Edited by Charles W Eliot Lld, P. F. Collier & Son Company, New York (1909) TWYFORD, at the Bishop of St. Asaph's, 1771.
Jason Sapsin, JD, MPHJason Sapsin, JD, MPH
C.U. Graduate SchoolC.U. Graduate School
Jason Sapsin, JD, MPHJason Sapsin, JD, MPH
C.U. Graduate SchoolC.U. Graduate School
Jason Sapsin, JD, MPHJason Sapsin, JD, MPH
C.U. Graduate SchoolC.U. Graduate School
Jason Sapsin, JD, MPHJason Sapsin, JD, MPH
C.U. Graduate SchoolC.U. Graduate School
• FDA regulates > 20¢ of every $1 spent by U.S. consumers
• The Agency has enforcement roots
• Has the only federal law enforcement agency exclusively devoted to public health (OCI)
• 16, 738 total employees (FY 2015 Budget Justification)•CDRH: 1723 CDER: 4508 ORA: 5250
Jason Sapsin, JD, MPHJason Sapsin, JD, MPH
C.U. Graduate SchoolC.U. Graduate School
Office of the CommissionerOffice of the CommissionerOffice of FoodsOffice of Foods
Structure
Office of Global Regulatory Office of Global Regulatory Operations and PolicyOperations and PolicyOffice of Medical Office of Medical Products and TobaccoProducts and Tobacco
CFSAN CDRHCBER CTPCDERCVM
ORA OCC
Jason Sapsin, JD, MPHJason Sapsin, JD, MPH
C.U. Graduate SchoolC.U. Graduate School
CFSAN ORA
OCCOF
CDER
CBERCDRH
CVM CTP
OC
OGROPOMPT
Structure (cont’d)
Jason Sapsin, JD, MPHJason Sapsin, JD, MPH
C.U. Graduate SchoolC.U. Graduate School
• CDRH• CDER• CVM• CBER• CFSAN
• OCC• ORA
EnforcementEnforcement
Evaluation Offices
• CDRH• CDER• CVM• CBER• CFSAN
• OCC• ORA
Compliance Offices
Product DevelopmentProduct Development
Jason Sapsin, JD, MPHJason Sapsin, JD, MPH
C.U. Graduate SchoolC.U. Graduate School
1.1. ConstitutionConstitution
2.2. Statutes Statutes (Federal Food, Drug, and Cosmetic Act)(Federal Food, Drug, and Cosmetic Act)
3.3. RegulationsRegulations
4.4. The Common LawThe Common LawJacobson v. MassachusettsJacobson v. Massachusetts
5. Guidance documents5. Guidance documents
6. Policy documents6. Policy documents
Places to look for Authority or Guidance
Jason Sapsin, JD, MPHJason Sapsin, JD, MPH
C.U. Graduate SchoolC.U. Graduate School
1. Pure Food and Drug Act (1906)• Food and Drugs must be safe
2. Food, Drug, and Cosmetic Act of 1938• Drugs must be proven safe• Devices can be regulated (post-market)
3. Kefauver-Harris Amendments (1962)• Drugs must be proven safe and effective
4. Medical Device Amendments Act (1976)• Devices required to meet performance standards
or receive pre-market approval
Notable Statutes
Jason Sapsin, JD, MPHJason Sapsin, JD, MPH
C.U. Graduate SchoolC.U. Graduate SchoolStatutory example: “Device”§201(h) (FDCA): “An instrument, apparatus, implement, machine, contrivance . . . Including a component part, or accessory which is . . . Intended for use in the diagnosis of disease . . . or in the cure, mitigation, treatment or prevention of disease . . . or intended to affect the structure or any function of the body . . . and which does not achieve any of its primary intended purposes through chemical action and . . . is not dependent on being metabolized.”
21 CFR §807.20: “An owner or operator who is engaged in the manufacture [etc.] of a DEVICE . . . shall register and submit listing information for those DEVICES.”
Regulation: Registering a device
Jason Sapsin, JD, MPHJason Sapsin, JD, MPH
C.U. Graduate SchoolC.U. Graduate School
Policy example: Enforcement Policy (2010)
Guidance example: Draft Guidance – “Premarket Notification Submissions for Medical Devices that Include Antimicrobial Agents” (July 19, 2007)
Jason Sapsin, JD, MPHJason Sapsin, JD, MPH
C.U. Graduate SchoolC.U. Graduate School
Enforcement Philosophy: July 15, 2010
• “One of the highest priorities”• Some will disregard or exercise inadequate vigilance• Ensure firms’ investment in quality systems• Maintain level playing field for good actors
Product Categories and Pathways
Jason Sapsin, JD, MPHJason Sapsin, JD, MPH
C.U. Graduate SchoolC.U. Graduate School
DrugsDrugsAchieve effect through chemical interactionAchieve effect through chemical interaction
• OTCOTC• RxRx
• MonographMonograph• NDANDA• ANDA (generic)ANDA (generic)
Jason Sapsin, JD, MPHJason Sapsin, JD, MPH
C.U. Graduate SchoolC.U. Graduate School
Drugs:Drugs:PathwaysPathways
Monograph
“Recipe”
Ingredients
Indications
Non-Monograph
NDAPre-Clinical
IDE
Phased Trials
Millions x 100
10 years
ANDAPre-Clinical
BioE
IDE? Trial?
Millions x 10
<10 years
Jason Sapsin, JD, MPHJason Sapsin, JD, MPH
C.U. Graduate SchoolC.U. Graduate School
• Class I
• Class II
• Class III
DevicesDevicesAchieve effect through physical / mechanical Achieve effect through physical / mechanical interactioninteraction
No 510k*510kPMA
Jason Sapsin, JD, MPHJason Sapsin, JD, MPH
C.U. Graduate SchoolC.U. Graduate School
DevicesDevicesClass I & II
“510k” or “De Novo 510k”
Substantial Equivalence
Descriptive and / or Trials (IND)
Class III
PMA
IND / Trials
Safe and Effective
Class I exempt
Quality systems compliance
Standards
Records and reporting
Jason Sapsin, JD, MPHJason Sapsin, JD, MPH
C.U. Graduate SchoolC.U. Graduate School
Development ConsiderationsDevelopment Considerations• Time to marketTime to market
• IndicationsIndications• Influence difficulty to marketInfluence difficulty to market• Marketing implicationsMarketing implications
• Study Design / LogisticsStudy Design / Logistics
• Early engagementEarly engagement• Informal and formal development Informal and formal development
approachesapproaches
Jurisdiction, Adulteration, Misbranding, Label(ing)
Jason Sapsin, JD, MPHJason Sapsin, JD, MPH
C.U. Graduate SchoolC.U. Graduate School
FDA’s power to regulate stems from Congress’ determination of what constitutes unlawful activity
§ 331. Prohibited acts The following acts and the causing thereof are prohibited: (a) The introduction or delivery for introduction into interstate commerce of any food, drug, device, tobacco product, or cosmetic that is adulterated or misbranded. (b) The adulteration or misbranding of any food, drug, device, tobacco product, or cosmetic in interstate commerce. (c) The receipt in interstate commerce of any food, drug, device, tobacco product, or cosmetic that is adulterated or misbranded, and the delivery or proferred delivery thereof for pay or otherwise.
Jason Sapsin, JD, MPHJason Sapsin, JD, MPH
C.U. Graduate SchoolC.U. Graduate School
• A Strict Liability statuteA Strict Liability statute
• § 303(a): “Any person who violates a § 303(a): “Any person who violates a provision of provision of section 301 shall be imprisoned section 301 shall be imprisoned for not more than for not more than one year or fined not more one year or fined not more than $1,000 or both.” than $1,000 or both.” (Misdemeanor)(Misdemeanor)
• § 305: Notice and opportunity to present § 305: Notice and opportunity to present views views prior to reporting to DOJprior to reporting to DOJ
Jason Sapsin, JD, MPHJason Sapsin, JD, MPH
C.U. Graduate SchoolC.U. Graduate School
Park DoctrinePark Doctrine
““A positive duty to seek out and A positive duty to seek out and remedy violations when they remedy violations when they occur, but also, and occur, but also, and primarily, a primarily, a duty to implement measures that duty to implement measures that will insure that violations will not will insure that violations will not occuroccur.”.”SCOTUS 1975SCOTUS 1975
Jason Sapsin, JD, MPHJason Sapsin, JD, MPH
C.U. Graduate SchoolC.U. Graduate School
FDAFDA• AdulterationAdulteration
Product is not what it appears to be in quality, purity or Product is not what it appears to be in quality, purity or naturenature
• MisbrandingMisbrandingProduct is not what it is implicitly or explicitly represented to beProduct is not what it is implicitly or explicitly represented to be
Jason Sapsin, JD, MPHJason Sapsin, JD, MPH
C.U. Graduate SchoolC.U. Graduate School
• Adulteration (Drugs and Devices §351)Insanitary conditions; improper conditions of manufacture, packing or storage; does not meet performance standards; it lacks premarket approval; it is used outside its investigational exemption
• Misbranding (Drugs and Devices §352)Labeling is false or misleading in any particular; lack of prominence or conspicuousness; failure to report or conduct postmarket surveillance; failure to identify the manufacturer
• Label / Labeling (§321)“Label” is printed, written or graphic matter on the immediate container; “Labeling” is both labels and other written, printed or graphic matter on the article, its containers or accompanying the article.
Jason Sapsin, JD, MPHJason Sapsin, JD, MPH
C.U. Graduate SchoolC.U. Graduate School
ConsequencesConsequences
• FinesFines• Jail time (limited)Jail time (limited)• DebarmentDebarment• Subsequent exposure to felony Subsequent exposure to felony prosecutionprosecution
Park DoctrinePark Doctrine
Jason Sapsin, JD, MPHJason Sapsin, JD, MPH
C.U. Graduate SchoolC.U. Graduate School
Common Mistakes 1.Failure to communicate / failure to build
relationships2.Related: Shortcuts & “Adversarialism”3.Underestimating FDA reviewers /
Inspectors 4.Misunderstanding FDA’s population-
level (public health) focus
Jason Sapsin, JD, MPHJason Sapsin, JD, MPH
C.U. Graduate SchoolC.U. Graduate School
Common MisperceptionsCommon Misperceptions
1.1. FDA is slower to approve new drugs than FDA is slower to approve new drugs than EU?EU?
2. Average (actual) time to final decision for 2. Average (actual) time to final decision for 510ks is 1-2 years?510ks is 1-2 years?
3. Average (actual) time to final decision for 3. Average (actual) time to final decision for PMAs is 3-5 years?PMAs is 3-5 years?
Jason Sapsin, JD, MPHJason Sapsin, JD, MPH
C.U. Graduate SchoolC.U. Graduate School
Exercise1. You have an opportunity to join a new company. You will
either be pursuing a new medical device or a new drug. The device is a variation of an existing medical device; the drug is based on a known drug but with different indications and a new delivery system. Which do you pursue, and why?
2. In developing your product, the CEO suggests that you see how it performs with some of the patients who you – as a new, practicing physician – regularly see. These patients suffer from very difficult conditions and you think the new therapies could help them. What do you do? Why?
3. Your new product is about to go to market. The Chief Operating Officer tells you that there is a deviation from specification (non life-threatening) in some of the products, occurring very rarely. QA has only found one problem in a run of 20,000 units and it appears to be random. The products are being loaded off the shipping dock.
Jason Sapsin, JD, MPHJason Sapsin, JD, MPH
C.U. Graduate SchoolC.U. Graduate School
THE ENDTHE END