Panel Discussion: Generic Drug User Fee ACT (GDUFA)

Transcription

1 Panel Discussion: Generic Drug User Fee ACT (GDUFA) April 23, 2013

2 GDUFA: From the FDA s Website: ( accessed 4/16/13) The Generic Drug User Fee Amendments of 2012 (GDUFA) is designed to speed access to safe and effective generic drugs to the public and reduce costs to industry. The law requires industry to pay user fees to supplement the costs of reviewing generic drug applications and inspecting fees.

3 GDUFA Panel Members Jason R. Money Senior Director for Federal Government Affairs Generic Pharmaceutical Association (GPhA) Ed Price President PCI Synthesis Dr. Padam Bansal Vice President of Research and Development Amneal Pharmaceuticals April 23, 2013

4 What Is GDUFA and Why? Jason R. Money Senior Director for Federal Government Affairs Generic Pharmaceutical Association (GPhA)

5 GDUFA Program: Overview Fees additive to budget appropriation Fees do not replace current appropriations Provide FDA with additional resources Adequate to fund all necessary activities Predictable from year to year ANDA review goal of 10 months in year 5 Resources adjusted for inflation to provide $299 million annually Risk-based biennial facility surveillance inspection with foreign and domestic parity in year 5

6 Why Now? Office of Generic Drugs (OGD)/FDA has been significantly under resourced for more than a decade The pharmaceutical industry has globalized requiring FDA oversight of thousands of domestic and foreign facilities/supply chain entities Delays in foreign inspections Need for foreign and domestic inspectional parity Backlog of nearly 3000 unapproved ANDAs (and approving ~ 600 per year) ANDA approval times of ~ 30 months on average

7 Why Now?

8 Ex-US Inspections Original EER's by location - FDF profile group Original EER's by location - API profile group ANDA Domestic ANDA Foreign NDA Domestic NDA Foreign ANDA Domestic ANDA Foreign NDA Domestic NDA Foreign

9 Legislative Action Senate passed GDUFA as part of the Food and Drug Administration Safety and Innovation Act (FDASIA) on May 24, 2012 by a vote of 96-1 House passed their version of FDASIA on June 20, 2012 by voice vote Senate concurred with House language on June 26, 2012 by a vote of President Obama signed FDASIA into law (P.L ) on July 9, 2012

10 GDUFA Key Goals Critical Attributes of GDUFA Primary goal is to advance the public health Timely review and approval of generic drugs Safe and high quality generic medicine Increase FDA transparency Help FDA address challenges of globalization Advance regulatory science

11 Outline of the Legislation Funding level = inflation adjusted $299M/year Application Fees Applications in the backlog (year 1 only) Drug master file (DMF) fee ANDA and prior approval supplement (PAS) filing fee Includes PAS for labeling Facility Fees Involved in manufacture of generic drugs, whether API or FDF, domestic or foreign Individual fees calculated/published upon implementation

12 Outline of the Legislation (cont d) Segment split -80% from finished dosage form manufacturers, 20% from API manufacturers Type split -70% from facility fees (fixed), 30% from application fees (variable) 6% of overall revenue from DMF fees; 24% from ANDA/PAS fees; 56% from FDF facility fees; and 14% from API facility fees Individual fees have been published for ANDAs, PAS, DMFs and Facilities

13 Performance Metrics - ANDAs All Applications Grouped in Cohort Year Original ANDA Review (review and act on): 60% of submissions within 15 months for year 3 75% of submissions within 15 months for year 4 90% of submissions within 10 months for year 5 Expedite paragraph IV (Day 1 Submissions)

14 Performance Metrics PAS No Inspection Required 60% of submissions within 6 months for FY 2015 receipts 75% of submissions within 6 months for FY 2016 receipts 90% of submissions within 6 months for FY 2017 receipts Inspection Required 60% of submissions within 10 months for FY 2015 receipts 75% of submissions within 10 months for FY 2016 receipts 90% of submissions within 10 months for FY 2017 receipts

15 Performance Metrics Staffing Hire and Train 25% of Incremental Staff Hire and Train 50% of Incremental Staff Hire and Train 25% of Incremental Staff

16 Efficiency Enhancements Complete response letters for Agency comments Increased filing requirements to assure completeness of ANDA at the time of filing Develop and streamline intra-agency databases to facility communications among FDA Field, Compliance and Technical staff

17 Additional Program Metrics Inspection Metrics Risk Adjusted Facility Surveillance Inspection Achieve biennial inspection rate and parity of foreign and domestic frequency in FY2017 Pre-approval inspections continue in interim Pending ANDA Backlog Metrics Review and act on 90% of backlog applications pending on October 1, 2012, by end of FY 2017

18 GPhA Perspectives for 2013 Funding certainty is critical, GDUFA addresses this need Size and scope of program makes implementation especially challenging 1000 s of facilities impacted by program 100 s, if not thousands, of firms required to participate Pace of hiring is a concern/critical to achieve goals in coming years

19 GDUFA and Manufacturing Ed Price President, PCI Synthesis 3/8/13

20 Why GDUFA? Nearly 80% of API s from foreign facilities Only a fraction are inspected Nearly 2800 backlog of ANDA s 32 month average approval time Enhance safety of the supply chain by requiring sites to self identify Ultimately reduce risks within the supply chain

21 Who Decided? Bulk Pharmaceutical Task Force (BPHF) GPhA, FDA and other large trade groups Mostly US & European Manufacturers Watson, Teva, Mylan, DSM and others No involvement by small to midsized firms

22 Who Pays GDUFA Fees? Any firm submitting an ANDA Holders of DMFs that are referenced in ANDAs Any firm submitting a PAS to an existing ANDA Facilities that manufacture, package or label generic drug FDF products Facilities that produce APIs for generic drugs

23 Generic Drug User Fees (Plan) All fees dependent on self-identifiers (denominator) GDUFA Fees (estimates based on $299 million) Facility Fees FDF facility: $70k $90k (2,239 facilities) API facility: $40k - $60k (861 facilities) Foreign facilities to have a surcharge to cover added costs of inspection ANDAs & PAS Original DMF $100k -$110k (750 per year) $50k - $60k (350 per year) ANDA Backlog Fee to be determined

24 How many self identified (SI)? Facilities/firms that make API/FDF must pay both fees 885 API facilities self identified (861 predicted) 122 domestic 763 foreign 758 FDF facilities self identified (2,239 predicted) 325 domestic 433 foreign

25 2013 Generic Drug User Fees GDUFA Fees (estimates based on $299 million) Domestic FDF facility: $175,389 Foreign FDF facility: $190,389 Domestic API facility: $26,458 Foreign API facility: $41,458 Original ANDA $51,520 PAS $25,760 Original DMF $21,340 ANDA Backlog Fee $17,434

26 Consequences of not Paying? Refusal to File ANDAs Publicly available arrears list FDFs and APIs will be deemed misbranded Violation of US Federal Law to ship in interstate commerce or import in to the US and as such would be seized Fees are an obligation of the US Government and failure to pay may result in collection activities by the US Government

27 Comparison to PDUFA? NDA establishment fee is $526,500 NDA application fee of just under $2M PDUFA targets innovative products, no guarantee of approval. Establishment fee after approval. ANDA should be approved eventually Designed for minimal impact (10 cents/script)

28 What to Expect for the Future 2013 User Fees included $50M in back log fees, which were one time fees contributing to the $300M raised by GDUFA (16.7% of the total budget) fees (paid in October 2013) may increase to make up the difference. As the impact of GDUFA is felt, new companies may self identify others may get out of the business (uncertainty).

29 Estimated 2014 User Fees GDUFA Fees (assuming no change to budgets $299 million) Domestic FDF facility: $204,679 Foreign FDF facility: $222,184 Domestic API facility: $30,877 Foreign API facility: $48,382 Original ANDA $60,124 PAS $30,062 Original DMF $24,904

30 GDUFA Pros/Cons and Generic Development Dr. Padam Bansal VP Research and Development Amneal Pharmaceuticals

31 Impact of GDUFA No positive impact planned for years 1 & 2 60% of submission within 15 months for year 3 75% of submission within 15 months for year 4 90% of submission within 10 months for year 5 Expedite PIV (Day 1 Submission) Submission for Year 1 and 2 cohort

32 Impact of GDUFA Application metrics Backlog metrics cgmp Inspection metrics-target risk based biennial cgmp surveillance inspections of generic API and FDF manufacturers, with the goal of achieving parity of inspection frequency between foreign and domestic firms in FY 2017 Efficiency enhancements

33 Positives Level the playing field (West vs. East) Low quality suppliers Consolidate the industry Should Speed approvals Might Improve safety Might Improve access and transparency Eliminate marketing applications

34 Negatives Written and designed by major players Creates new barriers to entry Regressive for smaller manufacturers Expected to take 5 years to implement. A facility could pay years until approval May stifle innovation May prevent API facilities from moving upstream to FDF

35 Impact of GDUFA As there are positive outcomes of GDUFA, it may create financial hardship to many small scale industry Some small business may not be able to pay such user fees. It may discourage small business enter in this field.

36 New Requirements in Jan 2014 Stability Expectations Long Term: 25 C ±2 C/ 60%RH ±5% -6 Months Intermediate: 30 C ±2 C/ 65%RH ±5% -6 Months Accelerated: 40 C ±2 C/ 75%RH ±5% -6 Months Stability data should be supplied on at least three batches of drug product made from two lots of API

37 New Requirements in Jan 2014 Same formulation, manufacturing process and specifications as those of market 2 of the 3 batches should be at least pilot scale (ANDA batch size or proposed scale up must be within 10 times of pilot scale up) One ANDA batch must be 100% packaged and other two 10% + Stability samples

38 You Decide The Generic Drug User Fee Amendments of 2012 (GDUFA) is designed to speed access to safe and effective generic drugs to the public and reduce costs to industry. The law requires industry to pay user fees to supplement the costs of reviewing generic drug applications and inspecting fees. Let s discuss what you think.

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40 Supporting Documents

41 Comparison to PDUFA and BSUFA? New User Fees for FY 2013 (PDUFA) (BsUFA) 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

42 Sponsors On FDA's Backlog Arrears List

43 GDUFA Facility Self-identification Total

44 GDUFA Facility Category Changes From Baseline

45 Regulatory Science Initiatives Bioequivalence of local acting orally inhaled drug products Bioequivalence of local acting topical dermatological drug products Bioequivalence of local acting gastro-intestinal drug products Quality by design of generic drug products Modeling and stimulation Pharmacokinetic studies and evaluation of anti-epileptic drugs Excipient effects on permeability and absorption of BCS Class 3 Drugs Product-and patient-related factors affecting switchabilityof drug-device combination products (e.g., orally inhaled and nasal drug products and injection drug products)

46 Regulatory Science Initiatives Postmarketingsurveillance of generic drug usage patterns and adverse events. Evaluation of drug product physical attributes on patient acceptability Postmarking assessment of generic drugs and their brand-name counterparts Physicochemical characterization of complex drug substances Develop a risk-based understanding of potential adverse impacts to drug product quality resulting from changes in API manufacturing and controls.