fda 101: jason sapsin

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



• 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



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 . . . .



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.



• 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



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



CFSAN ORA

OCCOF

CDER

CBERCDRH

CVM CTP

OC

OGROPOMPT

Structure (cont’d)



• CDRH• CDER• CVM• CBER• CFSAN

• OCC• ORA

EnforcementEnforcement

Evaluation Offices

• CDRH• CDER• CVM• CBER• CFSAN

• OCC• ORA

Compliance Offices

Product DevelopmentProduct Development



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



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


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



Policy example: Enforcement Policy (2010)

Guidance example: Draft Guidance – “Premarket Notification Submissions for Medical Devices that Include Antimicrobial Agents” (July 19, 2007)



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



DrugsDrugsAchieve effect through chemical interactionAchieve effect through chemical interaction

• OTCOTC• RxRx

• MonographMonograph• NDANDA• ANDA (generic)ANDA (generic)



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



• Class I

• Class II

• Class III

DevicesDevicesAchieve effect through physical / mechanical Achieve effect through physical / mechanical interactioninteraction

No 510k*510kPMA



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



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)



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.



• 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



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



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



• 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.



ConsequencesConsequences

• FinesFines• Jail time (limited)Jail time (limited)• DebarmentDebarment• Subsequent exposure to felony Subsequent exposure to felony prosecutionprosecution

Park DoctrinePark Doctrine



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



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?



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.



THE ENDTHE END

fda 101: jason sapsin

Health & Medicine