Center for Drug Evaluation and Research (CDER)
Program Background and Preparation for FY 2006 Appropriations Hearings
RADM Steven Galson Acting Center Director
February 11, 2005
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Contents
• CDER Organization Chart • CDER Programs -- Background
• • • • • • • • • • New Drug Review Generic Drug Review Post Marketing Surveillance Pediatrics Counterterrorism Compliance Training and Communication Regulatory Policy Executive Programs International Programs
• • • • •
Reorganizations and Changes Significant Initiatives FY 2006 Performance Goals/Targets Priorities Message for Congress
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Organization Chart
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Key Center Facts
• • • • • 2174 employees on board - end of FY 2004 Highly scientific work force Very high average salary compared to rest of Agency Nearly 85% of Center budget to cover salary (FY 05) 54/46 percent split appropriated vs PDUFA (FY 05)
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New Drug Review
(Office of New Drugs, Office of Pharmaceutical Science, Office of Pharmaceutical Epidemiology and Statistical Science (OPaSS))
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NMEs - Number Filed and Approved
Approved Filed
60 55 50 45 40 35 30 25 20 15 10 5 0
40 28 31
44
44
40
Number Approved
37 30 32 22 26 27
26
1993
24
1994
26
1995
46
1996
44
1997
38
1998
27
1999
39
2000
15
2001
22
2002
21
2003
23
2004*
60 55 50 45 40 35 30 25 20 15 10 5 0
Number Filed
Fiscal Year
* As of August 31, 2004 ** Approvals in a given year are not necessarily related to the applications filed in that same year
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A
Reasons for Optimism About Drug Development: FDA Review Times
CDER NM E M edian Approval Times by Calendar Year
Median Approval Time (Months)
50.0 45.0 40.0 35.0 30.0 25.0 20.0 15.0 10.0 5.0 0.0
80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01 02 20 19 19 19 19 19 19 19 19 19 19 19 19 19 19 19 19 19 19 19 19 20 20 20 03
Standard (1992 - 2003) Type C (1981 -1991)
Priority (1992 - 2003) Type A or B (1981 -1991)
* Prior to 1992, therapeutic gain was classified as type A, B, or C (defined below). Starting in 1992 Priority and Standard designation was used to represent therapeutic Research for new drug approvals. Center for Drug Evaluation and potential
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The PDUFA Cycle
Renegotiations begin 18 months prior to expiration
2002
2003
2004
2005
2006
2007
PDUFA III Signed June 12, 2002
February 2005
PDUFA III Expires October 1, 2007
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PDUFA III
• Continuous Marketing Application (CMA)
• Pilot 1 (#7) and Pilot 2 (#7) applications enrolled
• Postmarketing Study Commitments
• Enhanced website data quality from OND process improvements
• Industry Meeting Tracking System (IMTS)
• New system for tracking PDUFA meeting management goals successfully rolled out 12/2003
• NDA Regulatory Filing Review
• Template for quality improvement
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Percentage of Applications Reviewed Within Goal
FY 2003 Cohort (as of August 31, 2004)
100
80
60
40
20
0
St andard NDAs (10_mont h goal) Priority NDAs (6_mont h goal) St andard Ef ficacy (10_month goal) Priorit y Ef f icacy (6_mont h goal) Prior Approval M anuf acturing (4_mont h goal) CBE M anuf acturing (6_mont h goal) Class 1 NDA Resubmissions (2_month goal) Class 2 NDA Resubmissions (6_month goal) Class 1 ES Resubmissions (2_month goal) Class 1 ES Resubmissions (6_month goal) Class 2 ES Resubmissions (6_mont h goal)
n = 82
n = 19
n = 103
n = 35
n = 618
n = 1078
n = 24
n = 38
n = 16
n = 16
n = 40
Potential Performance
Performance to Date
Performance Goal
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PDUFA III -- Performance Management/Quality Systems
• Collaboration of CDER, CBER, Office of Planning • Defining scope for initial projects to examine and improve
• Product Review Meeting Management • Assigning and managing Post Marketing Commitments process • Drug Safety Communication and Processes
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Role of Office of Pharmaceutical Science (OPS)
• Significant involvement in CGMP initiative • Establishing a new risk-based pharmaceutical quality assessment system • PDUFA goals – integral player • CT and FDC for HIV – key role • Office of T & R – aligning research, Dr. Kahn, White Oak
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Office of Biotechnology Products
• Completed first year in CDER • Leading key scientific and regulatory issues – example = anthrax • Four NMEs – key role • Follow-on proteins – critical policy development participant
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Generic Drug Review
(Office of Pharmaceutical Science/Office of Generic Drugs (OPS/OGD), OND, OPaSS)
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Office of Generic Drugs
• One cycle approval goal - Enhanced communications (dissolution methods and bioequivalence criteria, productspecific interactions) • Generic drugs education programs • Streamlined operations - reduce time to approval while meeting the increasing workload
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Receipts of Original Generic Drug Applications (ANDAs)
600 553 500
Number of Submissions
449 400 361 326 335 307
346 300
200
100
0 1998 1999 2000 2001 2002 2003 2004
Projection of FY 04 Total
Aug31, 2004
Fiscal Year
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Original Generic Drug Median Approval Times
30 25 20
28.2 24.7
19.6
18.7 17.3
18.9
18.4
18.3
Months
17.3
16.4
15 10 5 0 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004
As of August 31, 2004
Fiscal Year
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Post Marketing Surveillance
(Office of Pharmaceutical Epidemiology and Statistical Science (OPaSS)/Office of Drug Safety)
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Role of Office of Pharmacoepidemiology and Statistical Science • FY 2004 accomplishments
• Completed 1759 “safety” reviews • Reviewed 26 “Risk MAPs” (5 NMEs) • RA, RM, & Pharmacovigilance guidance • 150 NDA/BLA & 790 IND statistical reviews
• Manage the Adverse Event Reporting System (AERS) • Future for FY 2006
–$5M increase –Secretary announcement
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CDER Post-Marketing Adverse Event Reports Received
AERS Database/PSI Reporting for January 3, 2005.
450000
Follow Up Adjustments (SRS only)
400000
*Non-Serious Periodics (non-AERS)
SRS
AER S
350000
Number of Reports
MFR Periodic MFR 15-day MedWatch Direct
300000 250000 200000 150000 100000 50000 0
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
FDA Calendar Year Received
$12,000,000
$10,000,000
$8,000,000
TRENDLINE
$6,000,000
$4,000,000
COSTS
FY 1998 FY 1999 FY 2000 FY 2001 FY 2002 FY 2003 FY 2004
$2,000,000
$0 FY 1997
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Counterterrorism and Pediatric Drug Development
(Office of Counterterrorism and Pediatrics (OCTAP))
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Pediatric Drug Development
• FY 2004 Accomplishments:
14 new labels as a result of BPCA (79 total) 17 Exclusivity labeling changes approved 11 Exclusivity Determinations 4 Off-patent drug Written Requests issued
1 Referred to NIH (10 total)
5 On-patent drug Written Requests referred to Foundation for NIH Pediatric Adverse Event Monitoring – 18 drugs presented Pediatric Advisory Committee established Dissemination of new labeling information through the American Academy of Pediatrics (AAP)
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CT Activities/Accomplishments
• Collaborations on product approvals (prussian blue, chelators), guidances (smallpox, KI) • Research (plague) • IA Working Groups • Inter-Center Working Groups • Strategic National Stockpile • Procuring Medical Countermeasures/EUA
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Compliance
(Office of Compliance)
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Office of Compliance
• Developing risk management expertise for application to all aspects of Compliance programs, including
Unapproved drugs, including DESI, internet and health fraud Sampling and analytic testing programs to evaluate quality of drug supply
• Pioneered development of a sophisticated quantitative risk model to prioritize sites for GMP manufacturing inspections • Playing a leading role in the Agency’s GMP initiative, including
Development and training of a new specialized “Pharmaceutical Inspectorate” Modernized regulatory approach to electronic records Piloting implementation of draft guidance on scientific and technical disputes that arise during GMP inspections
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Support Offices
(Office of Regulatory Policy (ORP), Office of Medical Policy, Office of Training and Communications (OTCOM), Office of Executive Programs, Office of Information Technology)
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Office of Regulatory Policy (ORP)
• Involved in every major CDER initiative: follow-on biologics; critical path; CGMP • Critical role in drafting regulations and guidances and answering citizen petitions • FY 2004 accomplishments:
10 proposed and final rules 38 draft and final guidances 51 citizen petition responses (55 new petitions submitted) FOI Requests: 4286 received; 6278 answered; 4648 pending. Backlog decrease of 1630. Document production for 5 FOIA lawsuits and 4 third-party subpoenas.
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Office of Medical Policy
• Labeling Initiatives Physician Labeling Rule & Guidance • Clinical Trials and HS Protection Expanded Access, Charging, Foreign Rules Available Therapy, misconduct Guidance • Drug Marketing and Advertising Brief Summary, Help Seeking guidance Research & Enforcement
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OMP Division of Scientific Investigations (DSI)
FY 2004 Accomplishments • Clinical Investigator Inspections: 368 • Foreign Inspections: 44 • Sponsor/Monitor Inspections: 17 • Complaints: 139 (193 to date in 2004) • IRB Inspections: 169 • GLP Inspections: 75 • Bioequivalence Inspections: 83
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Office of Training and Communication
• Drug Information 7000 e-mails, calls, letters • Training 108 courses, seminars, rounds, lectures 200 CDER and FDA faculty • Provided CDER web services Internet - Reaching 1.2 million visitors who make 21 million page hits a month Launched Drugs@FDA • Library – consolidation and agency leadership
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OTCOM continued
Ongoing Public Relations Campaigns
Generic Drugs Buying Drugs On Line Importing Drugs from Outside the USA Medicines and the Elderly Antibiotic Resistance Driving and Sedating Drugs Managing the Benefits and Risk of Medicines • Misuse of Analgesics • Misuse of Prescription Pain Relievers
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• • • • • • •
Office of Executive Programs
• 31 Advisory Committee meetings • RSR Program for FY 2004
Received 66 concept papers/55 full proposals Funded 27 projects
• Managing Strategic Objectives initiative for Center • CDER Cultural Survey • Ombudsman
54 Request for Determinations (RFDs) for Combination Products (since January 2004) Continuing to provide assistance to external constituents (more than 1500 contacts received last year)
• Quality Assurance
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Executive Operations Staff (EOS)
• Providing Support to Center-wide initiatives
CGMP initiative PDUFA 3 Implementation RIHSC/Research Database Development
• GAO/OIG Evaluations
14 new GAO studies 2 new OIG studies
• Coordinating communications on drugs of interest • Weekly/Forecast Report
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International Activities
• International Conference on Harmonisation (ICH) Harmonized over 50 guidelines • Regulatory partnerships EU, Canada, Switzerland • EMEA – confidentiality arrangement 1/05 • PAHO, WHO, PEPFAR
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Reorganizations and Changes
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Reorganizations and Changes
• OND Re-org
Improve workload and resource balance Improve logical groupings of products within division and offices Complete the integration of therapeutic biologics into OND division/office structure
• Changes to OPS Office of New Drug Chemistry • White Oak Move
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Significant Initiatives
• Drug Safety • Critical Path
Participating in Agency cross-cutting projects and leading several CDER specific projects Currently absorbing the costs
• Pharmacogenomics (PGx)
Guidance for industry published Better understand the current use of PG in drug development and gain experience in handling and evaluating genotype and gene expression data
• cGMPs for the 21st Century
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cGMPs for the 21st Century Initiative
• Initial 2-year phase – final report published 9/04 • Next phase
• • Reaffirm and expand upon the vision of the initiative Provide progress update, including steps to be taken to implement and “institutionalize” the path forward Facilitate implementation of continuous improvement Facilitate adoption of the best manufacturing science and technology Facilitate implementation of world class quality systems Remove unnecessary regulatory barriers Provide greater regulatory flexibility where warranted Continued close oversight and enforcement where regulatory flexibility not appropriate Closely linked to more risk-based oversight
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• Objectives
• • • • • • •
• Strategies
Significant Initiatives
• Structured Product Labeling (SPL)
Collaboration with ARHQ and NIH for standards and realization of “DailyMed”
ARHQ IAG helping to fund our efforts
Major IT initiative
• Follow-on Proteins
a.k.a. follow-on or generic biologics DIA Workshop next week in Arlington
• PEPFAR
President’s Emergency Plan for AIDS Relief Negotiated budget – IAG with DHHS
Center and Field Activities
$400K for FY 2004 $3.4M for FY 2005
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FY 2006 Performance Goals and Targets
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Human Drugs Program
1. New Drug Review Improve the efficiency and effectiveness of the new drug review program to ensure a safe and effective drug supply is available.
FY 06: Review and act upon 90% of original standard NDAs within 10 months of receipt.
2. Pediatric Drug Review Increase the number of drugs that are adequately labeled for children and ensure the surveillance of adverse events in the pediatric population.
FY 06: Issue at least 10 written requests (WRs) for drugs that need to be studied in the pediatric population and report to the pediatric advisory committee on adverse events for at least 10 drugs that receive pediatric exclusivity.
3. Generic Drug Review Improve the efficiency and effectiveness of the generic drug review program to ensure safer and more effective generic drug products are available for Americans.
FY 06: Decrease the average FDA time to approval or tentative approval for the fastest 70% of original generic drugs applications by 0.5 months.
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Human Drugs Program
4. Over the Counter Drug Review Improve the efficiency and effectiveness of the over-the-counter (OTC) drug review program to ensure a safe and effective drug supply is available.
FY 06: Complete review and action on 100% of Rx-to-OTC Switch applications within 10 months of receipt. Make significant progress on completing 6 OTC monographs.
5. Counterterrorism Enhance the protection of the American public against the effects of terrorist agents by facilitating the development of and access to medical countermeasures, providing follow-up assessments on therapies, and engaging in emergency preparedness and response activities.
FY 06: Coordinate and facilitate development for at least 6 medical countermeasures.
6. Patient Safety Improve the Safe Use of Drugs in Patients and Consumers
FY 06: Review and provide comments on 100% of Risk Minimization Action Plans (RiskMAPs) for NMEs and for those products for which the sponsor or FDA initiated discussions, in accordance with applicable PDUFA goal dates.
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Priorities
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Priorities
Drug Safety
$5M FY 2006 Increase targeted for Office of Drug Safety (ODS) Upcoming Announcement
Drug Safety Board Med Net
White Oak Move PDUFA III PDUFA IV Critical Path
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Message for Congress
• Drug safety
Scope
Accounts for at least half of the Center’s mission Far more than just the Office of Drug Safety (ODS)
We’re being proactive
Drug Safety Announcement
Legislative and budget implications
• Base erosion threatens PDUFA progress
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