Patient Protection and Affordable Care Act (PPACA) of 2010 .... Established and began development of 3 oncology data sta
Update From CDER Janet Woodcock M.D. Director, CDER, FDA
CDER 2011 • • • • •
Period of “consolidation” Many initiatives ongoing: require completion In the midst of user fee negotiations Likely time of financial austerity Overall priority of QMS implementation in the programs‐‐ongoing
NEW DRUG PERFORMANCE STATISTICS
2010 State of CDER
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Prescription Drug User Fee Negotiation
Reauthorizing PDUFA for FY2013‐2018 • New reauthorization requirements for PDUFA V – Prior public input – public meeting held on April 12, 2010 – Monthly consultations with public stakeholders while FDA negotiates with regulated industry – Posting of meeting minutes – google “PDUFA Meetings” to find them – Publication of recommendations prior to presentation to Congress (late Summer 2011) – Public input on recommendations (public meeting planned for Fall 2011) – Transmit recommendations to Congress by January 15, 2012
• FDA Negotiating Team – CDER: Theresa Mullin, John Jenkins, Debbie Henderson, Donal Parks, Jane Axelrad, Ed Cox, Patrick Frey – CBER: Bob Yetter, Chris Joneckis
• Ratifiers – Josh Sharfstein, Janet Woodcock, Karen Midthun, Russ Abbott, Ralph Tyler, David Dorsey 12
FDA and Industry Perspectives • FDA – – – –
Sound financial basis for operating review program Stick to fundamental goals that drive public health outcomes Stakeholders feel that their concerns are addressed Proposed enhancements focus on: • Increasing efficiency of current program • Strengthening science base • Increasing public confidence
• Industry – Develop more efficient process to deal with post‐FDAAA review challenges – Establish more transparent Benefit‐Risk standards – Ensure greater consistency across divisions (e.g., review process, meeting requests, GRMPs) – Establish more predictable timeframe for REMS requests 13
Patient, Consumer, and Health Professional Perspectives • Speed development of new drugs through greater focus on emerging regulatory science • Support development of innovative trial designs • Advance development of drugs for rare diseases • Provide clear information on benefits and risks • Obtain pharmacist and patient input on REMS design • Strengthen system for oversight and audit of clinical trials • Provide for easier, more consumer‐friendly Adverse Event reporting • Make REMS more standardized • Establish metrics to evaluate success of REMS • Assess REMS burden on healthcare system 14
Drug Safety
REMS Implementation Progress • Approved over 60 REMS, including 9 of the most complex programs with elements to assure safe use, and 3 “deemed” REMS • Issued 25 safety labeling change notification/order letters (each class labeling change is counted as one letter) • Intend to publish several FDAAA‐related guidance documents – Guidance that should reduce burdens on the healthcare system of “Medication Guide‐only” REMS, while preserving use of Medication Guides to present important information to patients as part of patent labeling – Guidance on safety related labeling changes – Guidance on Postmarketing Studies and Clinical Trials
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Recognizing Implementation Challenges • Since REMS provisions took effect 2.5 years ago, we have heard concerns from stakeholders • In July, 2010, FDA held a 2‐day public meeting – Over 70 individual presentations to obtain stakeholder views on the REMS program – Issues and Challenges associated with the development and implementation of REMS for drugs
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What we heard at Public Meeting • REMS are necessary to preserve access to drugs whose risks would otherwise exceed benefits • Multiplicity of unique REMS places burdens on the healthcare system – Particularly, REMS with elements to assure safety use (now totaling 20 different programs: 15 new and 5 “deemed”) – Also, “Medication Guide‐only” REMS
• Standardize REMS programs to reduce burden on the healthcare system 18
What we heard at Public Meeting • Consult with prescribers, pharmacists, patient groups, and others to get input – How to design REMS so that they preserve access while effectively addressing risk
• Integrate REMS into existing healthcare systems to reduce burden • Use developing informatics systems (e.g., e‐ prescribing, e‐health record) to implement REMS more efficiently and effectively 19
Next Steps for REMS • Developing a framework for improving REMS • Will be engaging in public outreach through a variety of different efforts to discuss various components of the framework • Objective: develop standardized REMS that can be plugged into existing healthcare systems to address particular risks and categories of risk
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DRUG SAFETY: Institutionalizing policies, processes, and procedures • Developing framework for prioritizing and setting timeframes for addressing the multitude of post‐ marketing safety issues • Continuing to work on processes and procedures for applying multi‐disciplinary review teams to review and manage post‐market safety issues
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DRUG SAFETY • Safety First Steering Committee – Focusing on improving oversight and accountability for managing safety issues – Providing more oversight for responding to safety‐related Citizen Petitions – Evaluating processes for determining what issues go to external groups (e.g., Advisory Committees, Drug Safety Board) for advice – Updating the Drug Safety Communication guidance
• Additional Center coordination • Further defining office roles in our drug safety decisions, • Clarifying our safety decision‐making process, identifying how decisions are made, and • Identifying need for additional drug safety policy and guidance to ensure appropriate and timely handling of drug safety issues
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DRUG SAFETY • Safe Use Initiative – Reduce preventable harm from medications – Collaborate with external stakeholders – Recently conducted public meeting to develop projects
• Scientific Collaborations – Prevent drug‐induced organ toxicity – Draft guidance published on “Qualifying Drug Development Tools” includes biomarkers and patient‐reported outcomes— in comment period
• IOM Study: Using results of controlled, observational and other studies for regulatory decision‐making on drug safety 23
Patient Medication Information (PMI) • Current multiplicity of Medguides, voluntary “consumer medication information” and patient package inserts • Near‐consensus that US needs a “single document solution” to PMI • FDA has held multiple meetings on this topic to get stakeholder input • Plan to initiate pilots/move towards implementation
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SENTINEL ‐ Potential Capabilities • Safety issues may be identified and evaluated in near real‐time • Sentinel may expand current capacity for evaluating safety issues – Improved access to subgroups, special populations – Improved access to long‐term data
• Active surveillance may identify an increased risk of common AEs (e.g., MI, fracture) that health care providers may not suspect are related to medical products
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Sentinel Initiative – FDA Organization Agency/Center Agency Sentinel Core Team – led by CDER Office of Medical Policy • Leads agency development of tools/resources for medical product active surveillance – – – – –
Janet Woodcock – Senior Executive Sponsor Rachel Behrman – Executive Sponsor Melissa Robb – Project Director Judy Racoosin ‐ Scientific Lead Mitra Rocca ‐ Medical Informatics Lead
CDER Sentinel Related Activities – led by CDER Office of Surveillance and Epidemiology • Leads Center implementation of Sentinel tools/resources and their integration into existing CDER surveillance procedures – Gerald Dal Pan ‐ Director, Office of Surveillance and Epidemiology – Marsha Reichman ‐ CDER Lead for Sentinel Activities 26 26
CDER Sentinel Steering Committee Policies • Short/long long term CDER goals for active surveillance using Sentinel • Determine how to use results of post‐market surveillance investigations in formation of regulatory decisions • Integrate use of Sentinel data in CDER post‐market safety processes • Communicate about Sentinel to CDER Priorities • Establish priorities for areas of greatest concern for post‐market active safety surveillance • Determine types of data most relevant for active post‐market drug safety surveillance • Decide priorities on active surveillance related questions as they arise Procedures • Review procedures for determining – Which active surveillance questions are addressed – Follow‐up of active surveillance results – Identification of CDER staff participating in various Sentinel Initiative activities 27
2010 State of CDER
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CDER Employee Morale
OPM Government Employee Viewpoint Survey • Email survey of government employees • Variety of questions about employee perceptions of organization, management, leadership, environment, etc. • Repeated every two years
OPM EMPLOYEE VIEWPOINT SURVEY % Positive Responses
OVERALL AVERAGE 67%
GOV'T
54%
CDER
40% 2006
2008
2010
Survey Year
In 2010, CDER returned 1,116 surveys (770 in 2008, 942 in 2006), a 37% response rate.
2010 Employee Viewpoint Results
31
OPM EMPLOYEE VIEWPOINT SURVEY MY WORK EXPERIENCE (AVG) 77%
76%
70
74%
74% 72% 70%
70%
GOV'T
68%
CDER
68% 66% 64%
% Positive Responses
78% Positive Responses
MY AGENCY
62%
64
65 60
60
55
CDER
50 45
2010
2008
Survey Year
2010 Survey Year
SUPERVISOR/TEAM LEADER
MY WORK UNIT 85
65
62
60
Gov't 53
55
53
49
45
CDER
% Positive Responses
70 % Positive Responses
Gov't
40 2008
50
58
57
77
80 72
75
69
70 65
64
Gov't CDER
60 55 50
40 2008
2008
2010
2010 Survey Year
Survey Year
2010 Employee Viewpoint Results
32
OPM EMPLOYEE VIEWPOINT SURVEY MY SATISFACTION (AVG)
LEADERSHIP (AVG) 70%
70%
70%
66%
65% 60%
57%
55%
GOV'T CDER
55% 50% 45% 40%
Positive Responses
Positive Responses
75%
65%
62% 58%
60% 55%
56%
GOV'T CDER
53%
50% 45%
2008
2010
2008
2010 Survey Year
Survey Year
% Positive Responses
WORK/LIFE 65 60
56
55 47
50 45
42
Gov't CDER
40
40 35
Our only decrease - satisfaction with childcare programs, elder care programs, employee assistance program
30 2008
2010 Survey Year
2010 Employee Viewpoint Results
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Other CDER Initiatives
Biological Products Biological products are generally produced using a living system or organism. Such products may be manufactured through biotechnology (e.g., recombinant DNA technology), derived from natural sources, or, in some instances, produced synthetically.
Example: Monoclonal Antibody
Aspirin
2010 State of CDER
35
BIOSIMILARS • Patient Protection and Affordable Care Act (PPACA) of 2010 created a pathway for regulation and approval of: – Biosimilar biological products – Interchangeable biological products
• Have chartered internal committees to collaborate on policy issues and address product specific review and science • Part 15 Hearing on November 1st & 2nd • Many challenges: – Definition of protein, Transition provisions, Standards for interchangeability, Standards for naming, “Publicly‐ Available Information” 36
“GDUFA” Generic Drug User Fees • Only CDER program not supported by user fees • Approx. 80% of RXs; estimated $10 billion in annual cost savings • Backlog of over 2000 Originals; 4000 Supplements • FDA receives ~800 Originals, ~1600 DMFs annually • Impacts all of CDER – – – – –
Review Inspection Petitions Medical/clinical consults Post‐marketing safety 37
GDUFA Status • Second attempt to negotiate; first in 2007 • Public meeting held in 3rd Quarter 2010 • Broad range of industry proposals – Traditional to innovative – $70 to $250 million plus
• Challenging environment • Expect to enter meaningful negotiation in 1st Quarter 2011 • CDER and Agency teams formed and active
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Clinical Trials Transformation Initiative (CTTI) • Public‐private partnership between Duke University and FDA • Aim: To improve the quality and efficiency of clinical trials • Comprised of over 50 organizations, including government agencies, industry representatives, patient and consumer representatives, professional societies, investigator groups, academic institutions, and other interested parties 39
Current Clinical Trials System • Often paper‐based, slow, and costly • Poor quality and inefficiency in clinical research can – Seriously limit the number of questions that we can answer about the appropriate uses of approved or licensed medical products – Significantly delay access to new therapeutic innovations
• CTTI was created to address a crisis for US clinical research, however: – Trials and issues are global – CTTI seeks to identify practice improvements that can be applied internationally – CTTI is engaging international collaborators 40
CTTI Projects • Effective and Efficient Monitoring – Goal: to identify best practices and develop sensible criteria to help sponsors choose the most appropriate monitoring methods for a trial
• Improving Unexpected SAE Reporting to Investigators – Goal: to generate empirical evidence about the current U.S. system for reporting serious adverse events (SAEs) to investigators under an IND application, and to identify potential system modifications to more efficiently and effectively inform investigators of such events 41
Regulation of Pharmaceutical Quality • CDER Vision for Pharmaceutical Quality – guiding principles – Single pharmaceutical quality oversight system at FDA – We will have an integrated quality systems orientation – We will use science‐based and risk‐based policies and standards – Our actions are taken in a global context – We will use all the tools at our disposal to ensure that the US drug supply is safe and of high quality
• Two facilitated 2‐day retreats – September and November, 2010 – Managers and leaders from OPS and OC
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Pharmaceutical Quality – Next Steps • Engage OC and OPS staff in vision, direction, and messages from the retreats • Form CDER Council on Pharmaceutical Quality • Create task groups to focus on developing detailed SOPs for major topic areas – – – – –
Review of Innovative Technologies Change Management Recalls, Defect Evaluation, and Drug Shortages Change Management Conditions of Approval 43
Globalization of Pharmaceutical Manufacturing • Movement toward ex‐US manufacturing continues • Just one facet of overall trend for FDA‐regulated products • FDA is continuing to evaluate additional ways to deal with the large number of non‐US drug manufacturing sites
Computational Science Center CSC Mission To support CDER in continually improving the optimal drug evaluation and review process for the entire drug lifecycle while addressing the dynamic nature of the healthcare system •
Current agency collaborations – – – –
•
Contracts/Support –
•
CDER (OND, OSE, OPI, OC, OCTEC, OM, OPS) CDRH CBER Office of the Commissioner
Better Data, Better Tools, Better Decisions
Approximately 20 contracts to support analytic capabilities including tool development, roll out, training, infrastructure, data conversion, data standards
Current projects/activities –
48 projects to support analytic capabilities
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Computational Science Center • Tools and Analysis/Infrastructure – Designed 6 prototype analysis panels (demographics/ AEs) – Upgraded infrastructure to be able to support WebSDM and JReview data analysis tools – Deployed and supported acquisition of multiple high‐end scientific workstations
• Data Standards (Computational Science Center) – Developed and refined a Data Standards Request Checklist to serve as a resource for reviewers and sponsors to facilitate the receipt of standardized data – Established Data Standards Liaisons within all review divisions in OND to serve as data standards leads – Established and began development of 3 oncology data standards domains with reviewers from the Office of Oncology Drug Products
• Legacy Data Conversion Efforts Underway – HIV Legacy Data Conversion: 7 drugs / 21 studies – Osteoporosis Legacy Data Conversion: 6 drugs/ 15 studies – Diabetes Legacy Data Conversion 46
Translational Medicine • Biomarker Qualification Program – Draft Guidance on process for qualification of Drug Development Tools (DDTs) published October 2010 • Process applies to biomarkers, Patient Reported Outcomes, and animal models
– Qualification decision for urinary clusterin and renal papillary antigen‐1 – Regulatory Briefing for nonclinical use of troponin, supportive of qualification – MaPP in development
• Biomarker Qualification Pipeline: – 7 projects in Consultation and Advice stage – 4 additional projects in BQRT formation step at start of Consultation and Advice stage 47
DATA STANDARDS!! We are all too familiar with this….
Boxes below comprise one paper-based NDA
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and this….E-Submission Data Needs Standardization Files Are Not Standardized …
Sponsor A
Variables Are Not Standardized
Sponsor B
Sponsor A
Sponsor B
Terminologies Are Not Standardized 49
Instead of … Looking for the relevant data
We would prefer… Thinking about the relevant data
A Data Driven Review Process Requires Transformation of Drug Regulatory Information 50
Lack of Clear Data Standards Results in… • Delays and inefficiency in review process – Difficulties integrating datasets – Lack of traceability in the Sponsor’s statistical analysis – Extremely demanding data manipulations to answer questions – Each reviewer creating code to answer a standard review question; limiting time to perform complex analyses
• Limited ability to ask in‐depth questions and address late‐emerging issues • Increased variability in quality of reviews • Reduced transparency and predictability 51
Need For a Data Standards Plan • CDER required a plan for data standards to meet its “end user” reviewer needs • Standardization of data submissions, policy changes, a robust infrastructure, and updated business processes would make significant improvements possible • Objectives of the plan: – Establish a comprehensive data standards program at CDER – Ensure development of data standards for all key data needed to make regulatory decisions, and – Ensure successful use of those standardized data
• CDER posted first draft of data standards plan in May 2010 52
Recent Highlights • Established CDER’s Data Standards Program Board – Oversee CDER Data Standards Plan execution – Oversee data standards projects and progress − Review center position on data standards work with outside organization to represent best interests of CDER
• Expanding engagement with all stakeholders – Implementation of the Data Standards Request Checklist – Data validation tools under development – Electronic submissions interest group (eSIG) revived – Collaboration with external partners (NIH, HHS, standards developing organizations) – Discussions with industry
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Priority Efforts for Next Two Years • Establish new regulatory requirements for electronic submissions of all study data – Plan to propose eSubmission rule for data submissions – Enhance existing guidance and reviewer resources
• Develop a baseline inventory of data standards needs – Current state of all data received – Available standards – Prioritize improvement efforts
• Establish a basic set of clear processes to support data standards development and implementation – Establish “lifecycle approach” for good data standards management 54
Summary • Multiple ongoing initiatives – Process improvement for new drug review, generics, postmarket safety – New mandated programs: biosimilars, Sentinel – Data standardization – Scientific projects
• Review performance relatively stable • Expect constrained fiscal environment
2010 State of CDER
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