Presentation to Conference on Marketing Applications jointly sponsored by San Diego Regulatory Affairs Network (SDRAN) and the Orange County Regulatory Affairs (OCRA) Discussion Group, in November 2009. Talk focused on the new powers granted FDA under the 2007 Food and Drug Administration Amendments Act (FDAAA).

1. November 4, 2009
Michael A. Swit, Esq.
Vice President
SDRAN/OCRA
Marketing Applications Conference

2. Drug Safety –
An Overview of FDA
Powers under FDAAA

3. 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.

4. 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

5. 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

6. 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

7. 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

8. 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).

9. 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

10. 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

11. 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)

12. 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

13. 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

14. 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

15. 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

16. 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)

17. 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

18. 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 – 2
Source:
http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProvider
s/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)

19. 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

20. Additional FDA Resources
 FDA.gov -- Index to Drug-Specific Information
 http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInforma
tionforPatientsandProviders/ucm111085.htm
 FDA.gov – Medication Guides (includes pre-FDAAA guides)
 http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm

21. 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”

22. Call, e-mail, fax or write:
Michael A. Swit, Esq.
Vice President
The Weinberg Group Inc.
336 North Coast Hwy. 101
Suite C
Encinitas, CA 92024
Phone 760.633.3343
Fax 760.454.2979
Cell 760.815.4762
michael.swit@weinberggroup.com
www.weinberggroup.com
Questions?

23. 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.