6th Annual Science and Standards SymposiumJanuary 16, 2013Istanbul

US Regulatory UpdatesRoger L. Williams, M.D.CEO and Chair, Council of Experts

The Washington, D.C. Area: USP and FDA

Food and Drug Administration, White Oak Campus

USP Homes

Food and Drug Administration

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The Latest

Generics ‘Super’ OfficeOffice of Generic DrugsMatches Office of New DrugsDirector: Dr. Greg GebaOffice of Product QualityBrings in new drug chemists (Office of New Drug Product Quality/ONDPQ)Brings in generic drug chemistsBrings in Office of Manufacturing and Product Quality (formerly with Office of Compliance)Review of CMC for new drugs, generic drugs and post-approval changes, together with inspection component

Signed into law July 2012Reauthorizes for five years user fee programs for

prescription drugs and medical devicesEstablishes new user fee programs for generic drugs

(GDUFA) and biosimilarsMakes further FDA reforms (in line with FDA global strategy)

–Emphasizes risk-based approach, foreign inspections (FDA will perform reviews and audits of foreign drug safety programs and standards), greater manufacturer accountability (know your supplier, testing–manage risk/establish safety of raw materials and finished drugs)

–Drug supply chain improvements (but no track and trace- possibly to be in a future bill)

–Drug shortages (manufacturer notification)

FDASIA (Food and Drug Administration Safety and Innovation Act)

GDUFA

S.3187 – “Food and Drug Administration Safety and Innovation Act” (FDASIA)

GDUFA is Section 301 of FDASIA Bipartisan effort – hardly see these days Fast approval – moved quickly thru House and Senate Reconciliation process rapid Signed by the President on July 9, 2012

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What’s New at the Office of Generic Drugs/Review Times

New ANDA Requirements– 3 batch requirements for ICH Stability conditions– 3 batch requirements coming for all ANDAs– Size, shape, color issues – Tightening ANDA filing requirements

• Monitor Completeness and Acceptability Checklist

Staff time re: GDUFA implementation– Daunting task – lots of meeting, training new employees

– takes staff and management away from review time

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Other Impacts of GDUFA on OGD Program

Coordination of inspections with Office of Compliance Complete response letter coordination New review practices…reorganization of CMC reviewers? Integrating New Drugs into the GDUFA program

– Consults – labeling carve out, toxicology, etc.– Office of Chief Counsel and Office of Reg Policy

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How Does OGD Get to 2015-2017 Metrics?

Last twelve months– Average receipts of originals 92/month (1103)– Average approvals 43 AP/month (479)

Backlog at OGD is at 2933* ANDAs as of 9/30/2012– To clear backlog at current rate – 2933/517 = 5.67years– If stream of ANDA continue at current pace (1000+/yr) and

with the phase in of staffing over 3 years there will be great pressure to meet the 3-5 year metrics

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User Fee Issues

New User Fees for FY 2013 (PDUFA) (BsUFA)**– Remember Fees for all (b)(2) applications*– Modestly higher fees Only 6.3% – New fees

• NDA with clinical data• $1,958,803

• NDA without clinical data• $979,600

• Establishment fees (+1.2%)• $526,500

• Product fees (actual decrease -0.6%)• $98,380

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* Small Business waiver for 1st NDA still possible Also Orphan drugs exempt from fee**BPD fee 10% and reactivation fee 20% of PDUFA NDA

Generic Drug User Fee “Guesstimate”

GDUFA Fees (estimate based on $299 million)– US Establishment $110-125,000– X US Estab. $125-140,000– US API Estab. $ 18 - 25,000– X US API Estab. $ 30 - 40,000– Orig. ANDA $ 51,520– PAS $ 25,760– Orig. DMF $ 21,340– ANDA Backlog Fee $ 17,434

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*- FDA FR 6/14/12 notice withdrawing about 400 old ANDAs

Generics Success Represents Unprecedented Challenge

$931 Billion in savings (2001-2010) has resulted in continued success and growth

While program funding has remained relatively flat…

Generics Industry success has come to represent an unprecedented Regulatory challenge in terms of..– Size– Scope– Geography

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2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011

2011 was another historic high

Continued Growth in ANDAs

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Combined, ANDAs and DMFs are approximately 10 X Plus, the NDA volume

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Multiple references, often years after filing

DMFs Also Rapidly Growing

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Increases in FDF Foreign Inspections

Original EER's by location - FDF profile group

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ANDA Domestic

ANDA Foreign

NDA Domestic

NDA Foreign

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Increases in Foreign API Inspections

Original EER's by location - API profile group

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ANDA Domestic

ANDA Foreign

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GDUFA Addresses Those Challenges

$299M per year is less than ½ of 1% of Generic Drug sales• And is expected to reduce costs considering the reduced

development/regulatory timelines

GDUFA results in less than doubling in OGD over the life of the program

• Efficiency enhancement are a critical component of GDUFA

GDUFA is modest size despite 10 X plus the application volume of brands

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GDUFA Goals Letter

Overview

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Goals Letter Overview

Scope, Assumptions, and Aspirations

Immediate Efficiency Enhancements

Metrics

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Key Achievements

The program advances critical values

• Timely access to generic drugs• Certainty for industry and FDA

• Safe, high quality generic drugs

• Maintains affordability of generic drugs

• Increases Transparency

• Addresses Globalization

• Advances Regulatory Science

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Next Steps

Congress Acted – President signed July 9, 2012

Implementation program – devil in the details

Hiring and training staff

FR Notices and Guidance

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Contact Information

Gordon JohnstonSenior Associate

Lachman ConsultantsWestbury, NY 11590

516-222-6222 NY Office516-805-0379 Cell

Email: G.Johnston@LachmanConsultants.comwww.LachmanConsultants.com

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