fda aa - title i pdufa iv

FDA AA - Title I

PDUFA IV & FDA’s Performance Goals

Friday, 30 November 2007

MBC

Naseem KabirAssociate Director

Regulatory Affairs

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FDAAA & FDA’s PERFORMANCE GOALSFDAAA (Title I) Performance Goals

Section 103 (Authority to Assess & Use Drug Fees)

Section A

I. Review Performance Goals

II. NME Performance Goals

III. Meeting Management

IV. Clinical Holds

V. Major Dispute Resolution

VI. Special Protocol Assessments

VII. Additional Procedures

VIII. Enhancement and Modernization of the FDA Drug Safety System

IX. Review of Proprietary Names to Reduce Medication Errors

X. First Cycle Review Performance

XI. Expediting Drug Development

XII. Post-Marketing Study Commitments

XIII. Improving FDA Performance Management

XIV. Information Technology Goals

Section 104 (Fees Relating to Advisory Review of Prescription Drug TV Advertising)

Section B

Performance Goals & Procedures for Advisory Review of DTC Television Advertising

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PDUFA IV (Parts I-VII): What is New?

FDA’s fee revenue amounts have increased

Type of Fee Revenue Fiscal Year 2007 Fiscal Year 2008

Total Fee Revenue $259.3 million $392.7 million

Establishment $86.433 $153.137

Product $86.433 $153.137

Application/Supplement $86.434 $153.137

Drug Safety -- $25 million

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Additional $225 million of revenues for drug safety reflected in user fees

$25,000,000 for fiscal year 2008;

$35,000,000 for fiscal year 2009;

$45,000,000 for fiscal year 2010;

$55,000,000 for fiscal year 2011; and

$65,000,000 for fiscal year 2012

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Additional criteria for orphan drugs to request exemption from product and establishment fees

The drug is owned / licensed and is marketed by a company that had less than $50,000,000 in gross worldwide revenue during the previous year

Must submit certification that gross annual revenues < $50,000,000 for the preceding 12 months before the exemption was requested

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PDUFA IV (Parts I-VII): What Remained the Same?

FDA’s performance goals for application reviews

Orphan drugs continue to remain exempt from user fees for review of applications

Performance goals for clinical holds, major dispute resolution and SPAs

Requirement to pay annual prescription drug establishment fees and product fees

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PDUFA IV (Parts I-VII): What Remained the Same?

SUBMISSION COHORT Standard Priority

Original Applications 90% in 10m 90% in 6m

Class 1 Resubmissions 90% in 2m 90% in 2m

Class 2 Resubmissions 90% in 6m 90% in 6m

Original Efficacy Supplements

90% in 10m 90% in 6m

Class 1 Resubmitted Efficacy Supplements

90% in 2m 90% in 2m

Class 2 90% in 6m 90% in 6m

FY 2008-2012 90% in 6m (CBE) 90% in 4m (PAS)

Manufacturing Supplements

Original & Resubmitted NDAs/BLAs & Efficacy Supplements

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PDUFA IV (Parts I-VII): What Changed Slightly?

An application/supplement that is submitted but refused for filing, or withdrawn before being accepted/refused for filing is subject to full review fee upon resubmission (unless waived/reduced)

FDA’s performance goals for meeting management remain unchanged except:

Type B and C: 90% within 21 calendar days of FDA receipt

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PDUFA IV (Parts I-VII): What Changed Slightly?

Submission Type Fiscal year 2007 Fiscal year 2008

Applications

Requiring clinical data

Not requiring clinical data

Supplements requiring clinical data

Annual Establishment Fee

Annual Product Fee

896,200

448,100

448,100

331,100

49,750

1,178,000

589,000

589,000

392,700

65,030

User fee increases

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Part VIII: Enhancement and Modernization of the FDA Drug Safety System

FDA to develop a 5-year plan to modernize drug safety activities & systems, emphasizing:

A. new methodologies in the collection of AE info throughout the product life cycle;

B. epidemiology best practices and guidances;

C. CDER/CBER database acquisition and expansion;

D. validation, development of risk management / communication tools;

E. improved post-market IT systems / linkages, and

F. enhanced coordination between FDA offices and teams (CDER and CBER, pre-market and post-market)

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FDA will conduct and support activities designed to modernize PV by:

A. Maximizing public health benefit of AE collection throughout product life cycle

RFP published in 2008, awarded 2009, completed by 2011

Contractors will critically review US, ex-US AE collection

B. Developing an epidemiology ‘best practices’ and guidance document

Public workshop in 2008; review current practice in US, ex-US

CDER and CBER to release joint guidance in 2010

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FDA will conduct and support activities designed to modernize PV by: (cont..)

C. Expanding database resources

Not just AERS, but population-based epidemiologic data

Targeted PM surveillance, signal detection

FDA to purchase epi (observational) DB, hire additional epi staff

D. Developing, validating risk management and risk communication tools

Evaluate effectiveness of RiskMAPs

Public workshop in 2009: assess current risk management / risk communication options

Annual systematic review of select risk management programs & tools

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Impact on Industry:

Outcome of the 5-year plan is likely to bring about a dramatic shift in PV, with consequences to all PV processes and procedures

Increasing importance of risk management PE will impact resources, training, and necessary skill sets

PE will become increasingly critical to support PM safety activities and commitments

IT systems thus created will need to be updated to accommodate new requirements

PDUFA IV represents a significant shift towards a life-cycle approach to risk management

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PART IX: REVIEW OF PROPRIETARY NAMES

Objective is to reduce medication errors

Opportunity to submit brand name during the IND process (instead of during NDA) and to obtain FDA feedback earlier

Pilot program to be implemented in FY 09

Allows companies to submit their research on the brand names, which FDA can evaluate to provide decision

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PART X: First Cycle Review Performance

Day-74 Letters: Notification of Issues Identified During Filing

Will identify substantive review issues during the filing review (for original NDA/BLA applications and efficacy supplements)

Notification also sent if no substantive issues identified

Not indicative of deficiencies that may be identified later in the review cycle

To include planned review timelines (including dates for feedback on labeling and post-marketing commitment discussions)

Allows companies to better plan workload

Solid strategy on submission content

Submission of major amendments may nullify timelines

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PART XI: Expediting Drug Development

FDA to develop guidance documents to further the Critical Path Initiative

Clinical Hepatotoxicity – FY 2008

Non-inferiority Trials – FY 2008

Adaptive Trial Designs – FY 2008

End of Phase 2(a) Meetings – FY 2008

Multiple Endpoints in Clinical Trials – FY 2009

Enriched Trial Designs – FY 2010

Imaging Stds for Use as an EP in Clinical Trials – FY 2011

Ongoing collaboration with scientific community to develop guidances on:

Predictive Toxicology

Biomarker Qualification

Missing Data

FDA participation in public workshops to explore new approaches to develop a structured model for benefit/risk assessment. Goal is to evaluate pilots and development of guidance documents

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PART XII: Post-Marketing Study Commitments FDA commits to: Developing harmonized (CBER/CDER) SOPs that articulate the

Agency’s policy and procedures (e.g., timing, content, rationale and vetting process) for requesting that applicants agree in writing to “voluntary post-marketing study commitments” What will “voluntary” mean to industry?

SOPs will be finalized prior to the end of FY 08

Training will be provided to all CBER and CDER review staff on the SOPs as necessary through FY 12

From industry perspective: Must strategically consider consequences of PMCs and negotiate

accordingly Part XII extends possibility of FDA requesting PMCs for previously

approved drugs

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PART XIII: IMPROVING FDA PERFORMANCE MANAGEMENT

FDA will conduct studies to:

Assess the impact of the electronic submission and review environment on the efficiency and effectiveness of the overall process for the review of human drugs

Assess the progress toward full implementation of Good Review Management Principles, focusing on both FDA reviewer practices and industry sponsor practices affecting successful implementation

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Part XIV: IT Goals

5-year plan will include:

new safety system (previously referred to under Drug Safety)

a roadmap for all IT plans intended to support the goal of end-to-end electronic communications

Plan will be updated as FDA deems necessary to achieve the IT objectives

Communications and Technical Interactions:

FDA and industry stakeholders will meet on a quarterly basis to discuss:

Discuss on-going implementation of the IT Plan

Status of IT metrics as available

Potential impacts of future activities on stakeholders

Revisions to the IT Plan

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Part XIV: IT Goals

Metrics & Measures Numbers and types of applications received (NDA, BLA, IND, etc.)

Total number of submissions categorized by type of submission

Total number of submissions in valid electronic format in compliance with FDA standards

The number and type of failure areas for electronic submissions out of compliance

Total number of submissions received through the secure electronic single point of entry versus other methods

Total number of submissions received substantially on paper.

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SECTION B FEES RELATING TO ADVISORY REVIEW OF DTC TV ADS

Overview of Legislation Authorizes FDA to assess/collect user fees for advisory review of drug DTC TV

ads

Medical device DTC TV ads not impacted at this time

Voluntary Program

Notify FDA in advance of # of DTC TV ads intended for next FY

FDA issued FR notice for companies wishing to participate in FY 2008

Legally binding commitment to pay fees

≤$83,000 per submission in FY2008

to be paid up front for # of reviews requested

FDA will commit to providing advisory review in specified period of time

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For Further Info

My contact [email protected]

FDAAA websitehttp://www.fda.gov/oc/initiatives/advance/fdaaa.html#actions

PDUFA websitehttp://www.fda.gov/oc/pdufa/

FDA Performance Goalshttp://www.fda.gov/oc/pdufa4/pdufa4goals.html

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Questions?

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