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Michael A. Swit, Esq.Vice President

FDAAA – An Abbreviation in Search of Meaning

Impact of the Food & Drug Administration Amendments Act of 2007

on theDrug and Biologics Industries

San Diego Regulatory Affairs NetworkFebruary 26, 2008

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Standard Disclaimers Views expressed here are solely my own and

do not necessarily reflect those of my firm or any of our clients.

These slides support an oral briefing and may not be relied upon solely on their own to support any conclusion of law or fact.

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ANCIENT (Possibly Chinese) CURSE

May You Live in Interesting Times …

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These Are Interesting Regulatory Times

September 30, 2004 – the beginning of the current era of drug regulation Vioxx SSRI’s and suicidal ideation

Since then: Tysabri Avandia

New Lynchpin of Regulatory Process – Drug Safety

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Interesting Regulatory Times …

FDA Leadership Top -- In disarray

2004 -- McClellan left to go to CMS; Crawford interim Commissioner

Summer 2005 – Crawford confirmed by Senate Sept. 2005 – Crawford abruptly resigns 2006 – Andrew von Eschenbach becomes acting December 2006 – von Eschenbach confirmed Sept. 2007 – General Counsel resigns

Deputies & Associates – many leave at end of 2006

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The Perfect Storm? The Current FDA Regulatory Equation -- (Drug Safety

Lynchpin) + (Leadership Vacuums) = an approval process mired in uncertainty, fear and decision paralysis

PLUS A Democratic Congress

PLUS September 30, 2007 – Deadline Day

PDUFA Reauthorization Sunsets Pediatric Exclusivity and Pediatric “Rule” Sunsets

EQUALS Congress in driver’s seat to drive change??

But, still have 2 more years of Bush

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The Result – FDAAA FDAAA -- Food and Drug Administration

Amendments Act of 2007 -- H.R. 3580 (422 pages) Originally H.R. 2900 –

Introduced in House on June 28 by John Dingell Passed House on July 16

Negotiated compromise – passed House on September 20 and Senate on September 21

Signed by President on Thurs., September 27, 2007 Public Law 110-85

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Key Provisions for Drug Industry

PDUFA Reauthorization Prescription Drug Advertising Review Fees DTC Advertising Penalties Drug Safety Provisions Clinical Trials Registry & Results Data Base Critical Path Initiative – Reagan-Udall Foundation Pediatric Exclusivity and Pediatric “Rule” Reauthorization Citizen Petitions – limits FDA authority to delay approvals Biosimilars – NOT COVERED by FDAAA

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PDUFA Reauthorization – Title I

Goals Expedite drug development process Expedite application review process Postmarket Drug Safety

Gross Fees (not including inflation adjusters) $393 MM annually in User Fees

plus Drug Safety Fees Over 5 Years -- $225 MM

(starting at $25 MM; increases $10MM per year thereafter)

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Prescription Drug Advertising “Advisory” Review Fees

FDAAA Section 104 -- Must pay if you submit a TV ad for “advisory review” (but, don’t have to submit for review)

“Advisory review” = “reviewing and providing advisory comments regarding compliance of a proposed advertisement

If required to submit, you do not have to pay, unless you say it’s for “advisory review” No separate authority given FDA to require submission

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Prescription Drug Advertising “Advisory” Review Fees …

Annual Fees Generated Under DTC Review Authority -- $6.25 MM

FY 2008 – maximum fee is $83,000 per ad submission

Sunsets – October 1, 2012 Problem – the necessary user fees for the

program were not "provided in advance in appropriations Acts" as required by FDAAA; thus, FDA scratched program

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“Required” Drug Advertising Reviews

Section 503B – added to Federal Food Drug, and Cosmetic Act (FFDCA) -- added by Section 901 of FDAAA (the Drug Safety provisions)

FDA “may require” submission 45 days before dissemination

FDA “may make recommendations” on changes “necessary to protect the consumer good and well-

being”, or Consistent with prescribing information And, if available, to address specific populations

FDA can not require changes Constitutionality ???

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DTC Advertising – Civil Penalties

Section 303(g) – added to FFDCA – civil penalties for false or misleading DTC ads for a prescription drug (not a device)

Penalty – Up to $150,000 on first offense in a 3-year

period Up to $300,000 on later offenses

FDA must give a chance for a hearing “Safe Harbor” – if you complied with all FDA

recommendations given in a review of the ad

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FDAAA & Enhanced Authorities Regarding

Postmarket Safety Originally S.484 or Kennedy-Enzi (Feb 1, 2007) Designed to improve drug safety monitoring

and evaluation Applies to Drugs and Biologics Subtitle A: Postmarket Studies and Surveillance Subtitle B: Other provisions to ensure drug

safety and surveillance

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Drug Safety – Phase IV Studies

FDAAA Section 901 – adds power of FDA to require post-approval “studies” or “clinical trials” – per new Section 505(o) of the FFDCA

Allows the FDA to require a post-approval clinical study or trial to assess: A known serious risk A “signal” of a serious risk To identify an unexpected serious risk when

available data suggests one

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New Safety Terminology

Serious Risk – the risk of a serious adverse drug experience Unexpected Serious Risk – not in labeling or related to a

labeled risk, but differs due to “greater severity, specificity, or prevalence.”

Signal of a Serious Risk: information related to a Serious Adverse Drug Experience associated with use of a drug derived from - A clinical trial, adverse event report, postapproval study, peer-

reviewed biomedical literature, from a postmarket risk identification system, or other scientific data

New Safety Information – relates to a serious risk or unexpected serious risk; may be based on new analysis of existing data or even an assessment of the effectiveness of an approved REMS (see next slides).

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Drug Safety – Phase IV Studies …

Study -- May not be required if available surveillance methods are adequate – FDA must make an “affirmative negative” (my words) determination before requiring

Clinical Trial – May not be required unless a Study is not adequate – “affirmative negative” determination also required

Already approved drugs – can only require if “new safety information” is available

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Drug Safety – Risk Evaluation and Mitigation

Risk Evaluation and Mitigation Strategies (“REMS”) Section 901 of FDAAA – adds a new Section 505-1 to FFDCA –

If a REMS is OK’d for an application, must follow it or sale of drug is illegal

You can voluntarily submit a REMS FDA may require if viewed as needed to ensure benefits of drug

outweigh risk Must be provided within 120 days of request Can be required later, after initial approval, if new safety info exists

Decision to require a REMS must be made at or above the division director level in CDER

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Content of a REMS Minimal Elements:

a timetable for assessments of the strategy set forth in REMS 18 + 36 months During seventh year

Some additional elements Additional Potential Elements

Medication Guide, Patient Package Insert Communication Plan, such as:

Disseminating info about the REMS to ensure REMS is being done correctly (e.g., medical monitoring elements)

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Content of a REMS … Assuring safe use …

Requiring specialized training or certifications for health care providers

Required certifications of dispensing pharmacies

Dispensing only possible if certain info supplied regarding patient (e.g., lab tests)

Patient monitoring Patient registry enrollment

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Civil Penalties for Drug Safety Violations

Section 902 of FDAAA -- If fail to conduct required post-approval studies or trials, or to follow a REMS, can face civil monetary penalties: Initial violations

$250,000 per violation $1,000,000 maximum in “single adjudication”

Continuing violations $250,000 per 30-day period Double in each 30-day period thereafter Maximum: $10,000,000 in “single adjudication”

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FDAAA & Clinical Trials Registries

Current U.S. Law – FDAMA §113 – Since Feb. 2000 All persons conducting clinical trials of experimental

treatments for “serious or life-threatening” diseases and conditions

Where the trial is to test “effectiveness” – i.e., Phase 2, 3 or 4 studies with efficacy endpoints

Must register certain information with U.S. government, within 21 days of study enrollment opening

Done via ClinicalTrials.gov No requirement for clinical trials Results

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Limitations of ClinicalTrials.gov

Only applies to “serious or life-threatening” diseases Drugs – not devices

No mechanism to ensure compliance by all performing clinicals

Inconsistent information in required data fields Only applies to studies under INDs Does not include actual results

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FDAAA & Clinical Trials Registries …

Section 801 -- Expands Trial Registry System Much more detailed information required on the

clinical studies Applies to drugs and devices

Devices – under 510k’s, PMAs or PDPs and HDEs or Section 522 Postmarket Surveillance

Drugs – “controlled clinical investigation” other than a Phase I

study Not pegged to serious or life threatening

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FDAAA & Clinical Trials Registries …

Timing -- where “applicable clinical trial” is ongoing on date of enactment or initiated after enactment 90 days after enactment if ongoing 21 days after first patient in if initiated after enactment if ongoing at enactment, but not for serious or life

threatening, you have 1 year to post Posting of data –

Drug – within 30 days of submission Device –

If not previously cleared, not earlier than date of clearance or approval

If previously cleared, not until 30 days after clinical trial results data is to be submitted

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FDAAA & Clinical Trials Results

Linking to Existing Data – within 90 days of enactment -- for clinical trials that form “the primary basis for an efficacy claim” or are post-market trials

Data Advisory committee (if any) consideration – any summary by

FDA Posted pediatric assessments or reports Public Health Advisories Drugs -- FDA Action Package required under 505(l)(2) Devices

Detailed Summary of Safety & Effectiveness info for PMAs 510k summary of safety & effectiveness data

Medline citations NIH Database of structured product labels

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FDAAA & Clinical Trials Results …

Phase-In of Data Results 1-Year

Demographic and baseline characteristics of patients

Primary and secondary outcomes Point of contact Any agreements between sponsor and investigator

that “squelches” the investigator 3-Year – Rulemaking required not later than 3

years post-enactment for greater expansion of results database

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FDAAA & Clinical Trials Results …

Expanded Registry and Results Database under Rulemaking Would cover trials on both approved and unapproved products Required

Summary in lay language Summary in technical language Full study protocol Submission date – generally 1 year after completion date or

estimated completion date of study Public Meeting – within 18 months of FDAAA Adverse Events – how to incorporate into databanks?

Within 18 months, rulemaking needed on how to do If not, default provisions will go into effect

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FDAAA & Clinical Trials Results …

FDA Submission Certification – NDAs, PMAs, BLAs, 510k’s and HDEs will have to include certification that all applicable requirements on trials information have been submitted Noncompliance or false information in a

certification = “Prohibited Act” under FDCA Form 3674 – vehicle for compliance

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FDA Submission Certification -- 3674

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FDAAA & Clinical Trials Results …

Civil Money Penalties – up to $10,000 for all violations in a single

adjudication Failure to correct within 30 days, $10,000 per

day Preemption – “upon the expansion,” no

state may establish or continue in effect any requirement on registries or results

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Critical Path Initiative – Reagan-Udall Foundation

Sec. 601 of FDAAA Not part of U.S. Government, but funded in

part by FDA budget “To advance mission of FDA to modernize

medical, veterinary, food, food ingredient, and cosmetic product development, accelerate innovation, and enhance product safety.”

Promote research into unmet needs in those areas

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Pediatric Exclusivity & The Best Pharmaceuticals for

Children Act How to Get Exclusivity:

If FDA requests a sponsor to do clinical studies on a children’s age group for a particular drug

Sponsor does studies and submits data to FDA Get 6 months tacked on to an existing period of

a patent or Waxman-Hatch Exclusivity Get the exclusivity regardless of the results of

the study as long as you did what FDA wanted

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Other Key Aspects of Pediatric Exclusivity

Can Qualify for Pediatric Exclusivity up to two times Studies Done Under PREA also qualify for

exclusivity, even though not specifically requested by FDA -- §505A(h) of FFDCA

Reminder – not applicable to medical devices

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FDAAA & Pediatric Research – BPCA Reauthorization

Major Changes No pediatric extension if 9 months or less left on underlying

patent or Waxman-Hatch exclusivity Internal Committee – also reviews request for studies under

BPCA Adverse Event Reports –

If relating to drugs for which labeling changes have been made,

Submitted to Office of Pediatric Therapeutics Consider handling Shall seek recommendations from Pediatric Advisory Committee

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Pediatric Research Equity Act (“PREA”)

Enacted 2003 Requires “Pediatric Assessments” on most new drug

applications and supplements that are for a: New active ingredient New indication New dosage form New dosing regimen New route of administration

RESULT – applies to ANDAs and Citizen Petitions Already-marketed drugs – FDA could order studies if

agency request under BPCA denied by application holder

Same requirements for biologics Not applicable to medical devices

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PREA – Required Assessments

Adequate Data to show: Safety and effectiveness of the

drug/biologic for the claimed indication in all relevant pediatric subpopulations; and

To support dosing and administration for each pediatric subpopulation for which the drug/ biologic is safe and effective

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FDAAA & Pediatric Research – PREA Reauthorization

Major Changes and Additions: Reviews by FDA “Internal Committee” – established by Section

403 of FDAAA “shall” be used to consult with reviewing divisions relative to

pediatric plans and requests for deferrals and waivers Will recommend if pediatric supplements shall get priority review

Deferrals – have to include a timeline for completion of the studies

If waiver sought because pediatric formulation not possible, your submission will be posted on FDA’s website

Labeling disputes – to be referred to Pediatric Advisory Committee

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FDAAA & Pediatric Research – PREA Reauthorization …

Disseminating “Pediatric Assessments” 210 days after submission – FDA posts on its

website: Medical, statistical and clinical pharmacology

reviews of those assessments Sec’y shall require sponsors of assessments

that result in labeling change to distribute information on labeling changes reported to FDA in the form of an annual summary to physicians & other health care providers

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Citizen Petitions Section 914 of FDAAA -- Adds a new Section 505(q) to

the FFDCA FDA cannot delay approval based on a citizen petition

unless FDA determines that a delay in necessary to protect the public health

If FDA so determines, must, within 30 days of the determination: Notify the affected applicant(s) either via a meeting or

document Petition decisions must be made in 180 days and can not

be extended for any reason

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Biosimilars – “Sense of Senate” Endorsement

Had been in Senate Version; not in FDAAA to give FDA authority and flexibility to approve

biopharmaceuticals subject to an abbreviated approval pathway

ensure patient safety remains paramount establish a pathway that is “efficient, effective and

scientifically-grounded and includes measures to ensure timely resolution of patent disputes

provides appropriate incentives for R&D of biopharmaceuticals Current Generic “conventional wisdom” – not this year;

But, BIO -- pushing -- to avoid 2009

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Summary FDAAA = the Food & Drug Lawyer’s

continued full employment act Complicated Detailed Still much to be implemented Assume conservatism in FDA going forward,

particularly due to acute Congressional oversight

Impact of Democratic President???

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Call, e-mail, fax or write:

Michael A. Swit, Esq.Vice President

The Weinberg Group Inc.336 North Coast Hwy. 101

Suite CEncinitas, CA 92024

Phone 760.633.3343Fax 760.454.2979Cell 760.815.4762

michael.swit@weinberggroup.comwww.weinberggroup.com

Questions?

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About your speaker…Michael A. Swit, Esq., is a Vice President at THE WEINBERG GROUP, where he develops and ensures the execution of a broad array of regulatory and other services to drug, biologics and medical device/diagnostic clients seeking to market products in the United States. His expertise includes product development strategies, compliance and enforcement initiatives, recalls and crisis management, submissions and related traditional FDA regulatory activities, labeling and advertising, and clinical research efforts.

Mr. Swit has been addressing critical FDA legal and regulatory issues since 1984. His multi-faceted experience includes serving for three and a half years as corporate vice president, general counsel and secretary of Par Pharmaceutical, a prominent, publicly-traded, generic drug company and, thus, he brings an industry and commercial perspective to his work with FDA-regulated companies. Mr. Swit then served for over four years as CEO of FDANews.com, a premier publisher of FDA regulatory newsletters and other specialty information products for the FDA-regulated community. His private FDA regulatory law practice has included service as Special Counsel in the FDA Law Practice Group in the San Diego office of Heller Ehrman White & McAuliffe and with the Food & Drug Law practice at McKenna & Cuneo, both in the firm’s Washington office and later in San Diego. He first practiced FDA regulatory law with the D.C. office of Burditt & Radzius.

Mr. Swit has taught and written on a wide variety of subjects relating to FDA law, regulation and related commercial activities, including, since 1989, co-directing a three-day intensive course on the generic drug approval process and editing a guide to the generic drug approval process, Getting Your Generic Drug Approved. A former member of the Food & Drug Law Journal Editorial Board, he also has been a prominent speaker at numerous conferences sponsored by such organizations as RAPS, FDLI, and DIA. A magna cum laude graduate of Bowdoin College, he received his law degree from Emory University Law School and is a member of the California, D.C. and Virginia bars.

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