november 4, 2009 michael a. swit, esq. vice president sdran/ocra marketing applications conference
TRANSCRIPT
November 4, 2009
Michael A. Swit, Esq.Vice President
SDRAN/OCRA
Marketing Applications Conference
Drug Safety –
An Overview of FDA Powers under
FDAAA
Standard Disclaimers
Views expressed here are solely mine and do not reflect those of my firm or any of its clients.
This presentation supports an oral briefing and should not be relied upon solely on its own to support any conclusion of law or fact.
FDAAA
Vioxx, FDA and the “Perfect Storm” for Drug Safety Reform
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
Key Provisions for Drug Industry
PDUFA Reauthorization Prescription Drug Advertising Review Fees DTC Advertising Penalties Drug Safety Provisions – Our Focus Today 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
FDAAA & Enhanced Authorities Regarding
Postmarket Safety
Originally S.484 -- 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
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
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).
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
Drug Safety – Risk Evaluation and Mitigation Strategies
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
Content of a REMS
Minimal Elements: 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)
Content of a REMS …
Elements to Assure Safe Use (ETASU) … Requiring specialized training or certifications for
health care providers Required certifications of dispensing pharmacies Dispensing only possible if certain info supplied
regarding patient and documentation of safe use (e.g., lab tests such as pregnancy – Accutane®)
Dispensing only in certain health care settings (e.g., hospital)
Patient monitoring – e.g., at specific times Patient registry enrollment
REMS in Action – Pre-FDAAA Several products were subject to voluntary risk
minimization action plans (RiskMAPs) 1988 - Accutane® (pregnancy prevention
program including monthly tests, limit to one month supply, HCP and patient surveys)
1998 - Thalomid® (thalidomide) (STEPS Program, registered HCP prescribing, pregnancy tests)
Products with RiskMAPs include: Clozaril, Tysabri, Exubera
RiskMAPs typically reserved for products with unpredictable and potentially deadly risks
REMS in Action -- FDAAA When required
Unapproved Products FDA may require a REMS where one is necessary for the
benefits of the product to outweigh the risks Approved products
Deemed to have a REMS if the product is already subject to restrictions on distribution
and use; or FDA and the manufacturer agree as such
FDA may require a REMS if new safety information becomes available; and a REMS is necessary for the benefits of the product to
outweigh the risks Guidance issued on March 27, 2008 that lists 16 products
determined to have REMS already (e.g., Accutane®, Thalidomide)
FDA’s determination that a product is subject to a REMS is not subject to administrative review
REMS in Action -- FDAAA In making a REMS determination,
FDA must consider: The size of the patient population involved; The seriousness of the disease or condition to be
treated; The expected benefit of the drug; The duration of treatment; The seriousness of adverse events associated with
the drug; and Whether the drug is a new molecular entity
REMS in Action Medication Guides are by far the most common
component of new REMS; many REMS require only a Medguide and periodic assessment Required if FDA finds one or more of the
following: Drug product is one for which patient labeling could
help prevent serious adverse events Drug is one with serious risks (vs. benefits) and
patients should have information in deciding whether to use (or continue to use)
Drug is important to health and patient adherence to directions for use is crucial to drug’s effectiveness
Applicant must ensure the Medguide is available to patient when drug dispensed
Occasionally -- may also be a Patient Package Insert (or FDA may convert a PPI to a Medguide)
REMS in Action Elements To Assure Safe Use (“ETASU”) –
Before requiring, FDA must determine: Drug is effective but is linked to a serious adverse drug
experience, can be approved (or not withdrawn) only if elements are required
For a drug initially approved without ETASUs, other elements of a REMS are not sufficient to mitigate risk
Need a validated system to monitor effectiveness Now -- required for 8 “new” products and 1 product class
(opioids; under development) Entereg:
Only in certified hospitals that perform bowel resections and are in E.A.S.E. program Entereg Access Support and Education – www.entereg.com
Limited to 15 uses
REMS in Action Statistics – 89 -- Approved Under FDAAA (does
not include “deemed” REMS such as Accutane®) MedGuides – 66 MedGuides + Communication Plans – 15 MedGuides + CP + ETASU – 3 MedGuides + CP + ETASU + Implementation Plan –
3 CP + ETASU + Implementation Plan – 2Source:
http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm111350.htm [as of 11/3/09]
Development/FDA approval of a REMS -- may add 2-9 months to the product approval process (Pink Sheet, Jan. 12, 2009)
Guidance on REMS September 2009 – “Format and Content of
Proposed Risk Evaluation and Mitigation Strategies (REMS), REMS Assessments, and Proposed REMS Modification” Good overview of REMS requirements Covers:
Format and content of a proposed REMS plus supporting documentation (both must be in REMS submission)
Content of Assessments and proposed Modifications to approved REMS
What identifiers to use on REMS documents How to communicate with FDA on a REMS
REMS – submitted as prior-approval supplements if to an approved NDA/BLA
Additional FDA Resources FDA.gov -- Index to Drug-Specific
Information http://www.fda.gov/Drugs/DrugSafety/Postmar
ketDrugSafetyInformationforPatientsandProviders/ucm111085.htm
FDA.gov – Medication Guides (includes pre-FDAAA guides) http://www.fda.gov/Drugs/DrugSafety/ucm0857
29.htm
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”
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
Questions?
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 and biologics clients seeking to market products in the United States. His expertise includes FDA 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.