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1 FDA Resources and Meetings Larry Bauer Senior Regulatory Project Manager Rare Diseases Program Office of New Drugs/CDER Orphan Designation Workshop October.

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Presentation on theme: "1 FDA Resources and Meetings Larry Bauer Senior Regulatory Project Manager Rare Diseases Program Office of New Drugs/CDER Orphan Designation Workshop October."— Presentation transcript:

1 1 FDA Resources and Meetings Larry Bauer Senior Regulatory Project Manager Rare Diseases Program Office of New Drugs/CDER Orphan Designation Workshop October 12, 2012 Genentech Site Tour September 26-28, 2012

2 22 Overview Navigating the web Guidances Rare Disease support Meetings Tips

3 3 William Harvey 17 th century physician who discovered blood circulation: “Nature is nowhere accustomed more openly to display her secret mysteries than in cases where she shows traces of her workings apart from the beaten path; nor is there any better way to advance the proper practice of medicine than to give our minds to the discovery of the usual law of Nature by careful investigation of cases of rare forms of disease.”

4 Navigating the Web 4 Trying to find specific information can be challenging! Tip- When wanting to search a specific website, i.e., accelerated approval information found at the FDA.gov website: Type: accelerated approval site=fda.gov” Or: regulations site=fda.gov” Works for any site! site=fda.gov site=hhs.gov

5 5

6 Navigating the Web (2) Developing Products for Rare Diseases & Conditions eDiseasesConditions/default.htm –Office of Orphan Products Development (OOPD) Orphan Designation database –Center for Drug Evaluation and Research- Rare Diseases Program (RDP) –Center for Biologics Evaluation and Research (CBER) –Center for Devices and Radiological Health (CDRH) –Conferences 6

7 Navigating the Web (3) PDUFA Goals Letter –http://www.fda.gov/downloads/ForIndustry/UserFees/Presc riptionDrugUserFee/UCM pdfhttp://www.fda.gov/downloads/ForIndustry/UserFees/Presc riptionDrugUserFee/UCM pdf The Program –http://www.fda.gov/downloads/ForIndustry/UserFees/Presc riptionDrugUserFee/UCM pdfhttp://www.fda.gov/downloads/ForIndustry/UserFees/Presc riptionDrugUserFee/UCM pdf Guidance for Industry: Formal Meetings Between the FDA and Sponsors or Applicants –http://www.fda.gov/downloads/Drugs/GuidanceCompliance RegulatoryInformation/Guidances/UCM pdf Will be updatedhttp://www.fda.gov/downloads/Drugs/GuidanceCompliance RegulatoryInformation/Guidances/UCM pdf 7

8 Guidance –They reflect FDA’s current thinking on an issue. –A guidance 1 refers to any written communication that explains an Agency or Center policy or procedure. The term guidance generally refers to guidance for regulated entities (e.g., the pharmaceutical industry). –However, a guidance document can also be a stand alone document, that is, not tied to any regulation. –Guidances are prepared to establish clarity and consistency in FDA policies, regulatory activities, and inspection and enforcement procedures. 8 1 MaPP

9 Guidance (2) –Guidance documents usually are written to explain specific details of a regulation. –Guidances are intended to assist the pharmaceutical industry in carrying out its obligations under laws and regulations on subjects such as the processing, content, evaluation, and approval of drug product applications and the design, production, manufacturing, and testing of regulated products. –Can use an alternative approach if the approach satisfies the requirements of the applicable statutes and regulations. 9

10 Guidance (3) mation/guidances/default.htm –Drugs –Bioequivalence –CMC –Combination Products –Drug Safety –International Conference on Harmonisation (ICH)- quality, safety, efficacy –Procedural (meetings) –Pharm/Tox 10

11 11 FDA Programs to Support Rare Disease Drug Development FDA Rare Disease Council (New!) Office of Orphan Products Development (OOPD) CDER, Office of New Drugs (OND) – Rare Diseases Program (RDP) CBER rare disease liaison (PDUFA V-coming soon) CDER, OND - RPM Enrichment and Communications Team (PDUFA V-coming soon) Office of Special Health Issues (OSHI)

12 12 Office of Orphan Products and the Rare Diseases Program- Same? Different? OOPD –Administers Orphan Drug Act Orphan Designations Exclusivity Orphan grants –Device programs Pediatrics HUD Humanitarian Use Device designation –Strong advocacy work and outreach with RD stakeholders RDP –Facilitate communication within CDER/OND review divisions – Focus on complex regulatory requirements for INDs, NDAs and BLAs – Develop policy, procedures, and advice for RD clinical development in CDER

13 13 Rare Diseases Program Update 13 The current team –Anne Pariser –Larry Bauer –Kathy O’Connell –Gumei Liu Commissioner’s Fellow –Salvatore Pepe and Hong Vu Regulatory Research Staff New

14 14 RDP Priorities Scientific Development Biomarkers/ PROs/CROs Advice/guidance Natural history Disease specific areas Regulatory science Communications Patient advocacy groups NORD, Genetic Alliance Industry Regulatory Science Database Issue identification & tracking Data analysis Trend reporting Advice generation Collaborations NIH rare disease initiatives Drug Information Association Rare Disease Council Academia/consortia Education and Training Annual internal FDA reviewer training Science of Small Clinical Trials FDA Patient Advocacy Day NORD/DIA Rare Disease Summit

15 15 Orphan Drug Development Clinical Investigations are usually conducted under IND Orphan Drug Act does not define separate regulatory standards for the safety and effectiveness of drugs to treat rare diseases Requires at least one adequate and well-controlled trial (§ ) FDA is required to exercise its scientific judgment to determine the kind and quantity of data and information an applicant is required to provide for a particular drug to meet the statutory standards (§ )

16 16 For the 20 rare disease products approved in 2011, the number of patients included ranged from less than 20 to 1,266 (median 270) Most have received Priority Review designation Breakthrough Therapy designation (new!)  Yet, most of these products are novel ground breaking first-in-disease  Often new clinical endpoints and outcome measures have been developed  The spectrum of rare diseases is incredibly diverse and complex

17 Meetings with the FDA 17

18 18 Meeting Types Type A – immediately necessary for an otherwise stalled drug development program to proceed –Clinical Holds –Special Protocol Assessments –Dispute resolutions Timeline, goals –Response in 14 Days –Meeting in 30 Days (or within 14 days of requested date if beyond 30 days)

19 19 Meeting Types (2) Type B (milestone) –Pre-IND (21 CFR ) –Certain End of Phase 1 (21 CFR ) –End of Phase 2 (21 CFR ) –Pre-NDA/BLA (21 CFR ) Timeline, goals –Response in 21 Days –Meeting in 60 Days (or within 14 days of requested date if beyond 60 days) Meeting package due 1 month prior to meeting

20 20 Meeting Types (3) Type C (Everything else) –General advice –Under PDUFA V, a sponsor can request, or FDA can decide, for the questions to be addressed in a written response in lieu of a formal meeting Timeline, goals –Response in 21 Days –Meeting in 75 Days (or within 14 days of requested date if beyond 75 days)

21 21 FDASIA Impact on Meetings Type A meeting requests must include the meeting package Pre-IND and Type C meetings can be addressed by ‘written response only’ (WRO) –Upon applicant request (grant/deny as usual) or FDA discretion –Meeting package is due at least 1 month in advance of response goal date –FDA response to questions issued within respective meeting goals (e.g., 60 days or 75 days)

22 22 Statistics Last year CDER received approximately 2,000 requests for meetings Meeting workload varies widely between review divisions, (60 on the low end and 160 on the high end) † Source: FY 2011 Performance Report to the President and Congress for the Prescription Drug User Fee Act

23 23 Tips for Productive Meetings Give your project manager a heads up before submitting a new request Limit the number of questions to a reasonable number –Yes, subparts of a question are additional questions… Ask clear questions to help focus answers Keep most questions applicable to your current state of development –But, keep overall clinical plan in mind

24 24 Tips for Productive Meetings (2) Talk with your Project Manager, set an agenda Arrive minutes early to allow time to check in Minimize presentations Ensure you are getting what you need from the meeting Summarize what you think you’ve heard

25 25 Approval rates similar for rare and common disease applications 5 5 Pariser AR et al. Drug Discov Today 2012;17(15-16):

26 26 Frequency (#) Yes No NMEs and New BLAs Pre-NDA Meetings v. Regulatory Actions Approval Complete Response Refuse-To-File Withdrawal Pre-NDA meeting?

27 27

28 28 Drug Development Recommendations: Contact the FDA early and avail yourself of all opportunities for meetings and communication 2. Map out your clinical development program as early as possible 3. Don’t overlook value of early phase trials -Animal models -Exploratory endpoints -PK/PD parameters -Surrogates, biomarkers, clinical outcome measures 4. For pivotal study recommend submitting a Special Protocol Assessment (SPA)

29 29 Drug Development Recommendations: Rigorously control study conduct -Make the most of available information -Study personnel training and comprehensive study manual decrease variability in study-related procedures -Possible advantage for smaller trials/rare diseases, i.e., fewer sites, specialized investigators, better inter-site quality control 6. For rare diseases, recommend conducting a natural history study -Can inform many aspects of your development program -Can be retrospective or prospective -Published literature (i.e., case reports) often inaccurate for rare diseases – severe end of disease spectrum tends to get published and may not be representative of broader affected population and/or attenuated presentations

30 30 Drug Development Recommendations: Respect the vulnerability of patients: -Crucial to engage the patient community -Consider an independent Data Safety Monitoring Board or other oversight committee 8. Drug will only be labeled for populations/indications studied – consider early-on -target population (e.g., pediatrics) -likely use 9. For biologics: discuss characterization, assay, antibody testing, etc. with CMC as early as possible

31 31 Questions?


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