1. 1 Legislative Issues: Pediatric Research & Clinical Trials Registries/Databases 23 – 26 September 2007 Hynes Convention Center Boston Michael A. Swit, Esq. Vice President, Life Sciences THE WEINBERG GROUP, INC.

2. 2 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

3. 3 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

4. 4 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 request under BPCA denied by application holder Same requirements for biologics Not applicable to medical devices

5. 5 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

6. 6 PREA – Deferrals Deferral to post-approval of adult use possible if –Adult use approval ready before pediatric studies completed; or –Pediatric studies should be delayed until more S or E data has been collected; or –“ Other Compelling Reason ”

7. 7 PREA – Waivers Grounds –Needed studies impossible or highly impractical # of patients Geographic dispersion –Evidence “ strongly suggests ” drug would be ineffective or unsafe in all pediatric age groups –No “ meaningful clinical benefit ” over existing therapies by the new formulation and not likely to be used in large numbers Complete or partial possible –Partial – pediatric subpopulations Neonates Infants Children Adolescents –Meet one of grounds, but for a pediatric subpop

8. 8 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

9. 9 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

10. 10 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]

11. 11 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

12. 12 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

13. 13 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

14. 14 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

15. 15 ClinicalTrials.gov – Data Sets Unique protocol ID # Sponsor Verification Date Brief Title Brief Summary Study Design, Phase and Type Condition or disease Intervention Study status Eligibility criteria, gender, age Trial location Contact Information

16. 16 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

17. 17 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 –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

18. 18 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

19. 19 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

20. 20 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

21. 21 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 FDCA –Failing to file the required information –Filing false information 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

22. 22 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 michael.swit@weinberggroup.com www.weinberggroup.com Questions?

23. 23 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.