Transcript Slide 1

THE REGULATORY HORIZON
Pharmaceutical Education Associates
Nasal Drug Delivery Conference
Philadelphia
October 4, 2007
Michael A. Swit, Esq.
Vice President, Life Sciences
ANCIENT 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
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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
– 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
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“Required” Drug Advertising Reviews
• New Section 503B of 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
• Adds Section 303(g) 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 insure 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
• 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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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 – 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 – a timetable for assessments
– 18 + 36 months
– During seventh year
• 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:
– $250,000 per violation
– $1,000,000 maximum 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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ClinicalTrials.gov – Data Sets
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Unique protocol ID #
Sponsor
Verification Date
Brief Title
Brief Summary
Study Design, Phase and
Type
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Condition or disease
Intervention
Study status
Eligibility criteria,
gender, age
• Trial location
• Contact Information
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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 …
• 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
• 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 FDA Data
– 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 – NIH to post:
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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
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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 = “Prohibited Act” under FDCA
• More on “Prohibited Act” – new Section 301(jj) of
the FFDCA
– Failing to file the required information
– Filing false information
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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
additional penalty
• 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
• Reminder – not applicable to medical devices
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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:
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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
• Title III – Pediatric Medical Device Safety &
Improvement Act of 2007
• Sec. 302 – Tracking Pediatric Device Approvals
– Applies to PMAs, Product Development Protocols
and Humanitarian Device Exemptions (HDE)
– Application must:
• describe “any pediatric subpopulations that suffer from the
disease…”
• Identify # of patients
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FDAAA & Pediatric Research –
Medical Devices ….
• Section 303 – Modification of HDE
– Can make a profit if for pediatric population
– Must restrict number of devices distributed to an amount
specified in the HDE
– Pediatric population defined as 21 or less (PREA is 18)
• Section 304 – Encouraging Medical Device Research –
HHS to come up with a plan within 180 days of
enactment
• Section 305 – Grants to Improve Pediatric Device
Availability -- $6,000,000 authorized
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FDAAA & Pediatric Research –
Medical Devices ….
• Section 307 – Postmarket Surveillance – Amends
Sec. 522(a) of FDCA:
– Sec’y may order manufacturer to do postmarket
surveillance of any Class II or III device
• The failure of which would be reasonably likely to have
serious adverse health consequences; or
• Expected to have “significant use” in pediatric patients;
or
– Can be ordered for more than 36 months if needed
• [previously, Sec. 522 only applied if intended to be (a)
implanted for > 1 year or (b) life-sustaining/ life-supporting
and used outside a device user facility]
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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
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Committee
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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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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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 “conventional wisdom” – not this year
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Questions?
Call, e-mail, fax or write:
Michael A. Swit, Esq.
Vice President, Life Sciences
THE WEINBERG GROUP INC.
336 North Coast Hwy. 101
Suite C
Encinitas, CA 92024
Phone 760.633.3343
Fax 760.633.3501
Cell 760.815.4762
D.C. Office 202.730.4123
[email protected]
www.weinberggroup.com
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About your speaker…
Michael A. Swit, Esq., is Vice President, Life Sciences at THE WEINBERG GROUP, where he develops and ensures
the execution of a broad array of regulatory and other services to drug and biologics clients seeking to market
products in the United States. His expertise includes FDA and CMS 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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