GDUFA Policy Development Hearing

Transcription

1 GDUFA Policy Development Hearing David R. Gaugh, R.Ph. Senior Vice President for Sciences and Regulatory Affairs Generic Pharmaceutical Association September 17, 2014

2 About GPhA GPhA represents the manufacturers and distributors of finished generic pharmaceutical products, manufacturers and distributors of bulk active pharmaceutical chemicals, and suppliers of other goods and services to the generic pharmaceutical industry. Our members manufacture more than 90% of all generic pharmaceuticals dispensed in the U.S., and their products are used in more than three billion prescriptions every year. Generics represent greater than 84% of all prescriptions dispensed in the U.S 2

3 GPhA Members Alvogen In.c Amneal Pharmaceuticals, LLC Apotex Corporation Baxter Healthcare Corporation BD Rx, Inc. Bedford Laboratories Dr. Reddy's Laboratories, Inc. Fresenius Kabi USA LLC G & W Laboratories, Inc. Heritage Pharmaceuticals Inc. Hospira Inc. Impax Laboratories, Inc. InnoPharma, Inc. JHP Pharmaceuticals LLC Kremers-Urban Pharmaceuticals Inc. Lupin Pharmaceuticals Inc. Mallinckrodt Pharmaceuticals Momenta Pharmaceuticals Inc. Mylan Inc. Novel Laboratories-Gavis Pharma Par Pharmaceuticals Companies, Inc. Perrigo PLC Ranbaxy Inc. Roxane Laboratories, Inc. Sagent Pharmaceuticals, Inc. Sandoz Inc. Taro Pharmaceuticals USA Inc. Teva Pharmaceuticals USA Zydus Pharmaceuticals USA 3

4 Commitment GDUFA represents significant changes in many ways that generic drug product and active pharmaceutical ingredient manufacturers must operate To speed and enhance the approval process, we must equip FDA with the resources it needs Working together, we can ensure that millions of Americans and patients around the world, continue to receive the timely access to safe, effective and affordable generic drugs that they rely on See Slide 18 of the Appendix 4

5 ANDA Submissions Content and Format of ANDAs While each applicant is responsible for the best possible submission, there have been some historical barriers to fully address all expectations, especially for more complex products Interaction and advice from FDA regarding specific ANDA issues typically have been too limited (i.e. lack of pre-anda consultations), limited transparency has reduced predictability for applicants. In many cases it is one way communication Inconsistencies among reviewers produce challenges for industry Retrospective application of new criteria that have come into place since the date of the original submission, in some cases years after the product was developed and the ANDA submitted Since the implementation of GDUFA, all informal contact between reviewers and applicant has ceased and has not been replaced with any meaningful alternative. Result major reduction in transparency 5

6 Controlled Correspondence Related to Generic Drug Development GPhA has significant concerns regarding certain aspects of the Draft Guidance To meet our shared aim of reducing review cycles, FDA should encourage early engagement and feedback in advance of submission in order to minimize FDA review timeframe and expedite patient access to generics What is the Agency's plan for reviewing and providing a response to Controlled Correspondences pending an Agency response prior to FY2015? 6

7 ANDA Submissions Amendments and Easily Correctable Deficiencies Under GDUFA GPhA believes a significant portion of the issues identified during the technical reviews can be classified as easily correctable deficiencies (ECD) and communicated to applicants during the review process Industry is able to respond to ECDs in a short period of time (on the average less than 5 days upon receipt of the ECD) which can facilitate the review process and enhance efficiencies for both the Agency and industry In the spirit of the goals letter we request more opportunities to resolve questions via phone or 7

8 ANDA Submissions Prior Approval Supplements Under GDUFA The draft guidance helps outline the agency's implementation of GDUFA, allowing greater predictability for industry and more timely review of supplements Clarification requested on changes in GDUFA metrics when addition of amendments to PAS Provides valuable clarification on GMP inspection cycles and risk based approach 8

9 Completeness of the IID The Inactive Ingredient Database (IID) is an important area in need of updating The IID is a critical tool for the generic industry and needs updating The IID supports ANDAs, and should be complete, accurate and transparent Industry should have access to the MDI for all routes of administration 9

10 Additional Policy Priorities Communications and/or communication with applicants ANDA priorities based on public health needs, target action dates, and other related actions for ANDAs are not included in the cohort metric A realistic plan based upon dedicated resources, to address the enormous backlog of ANDA and PAS submissions Continued meaningful interaction with industry while planning new guidance, before enforcing draft guidance as final Pre ANDA consultation meetings and communications Central repository or bulletin board announcements to industry, to post current thinking on ANDA data requirements, webinars etc. Provide specific timeframes (e.g., 60 days or similar to Controlled Correspondence) to answer Suitability Petitions See Slide 24 of the Appendix More detail will be provided in our written comments following the workshop 10

11 What Other GDUFA Implementation Topics Need The Development Of Guidance? Guidance clarifying QbD/QOS requirements and expectations. Industry needs a consistent approach and predictability To date guidance documents have focused on process rather than what is quality for an ANDA submission from the Agency s perspective GPhA recommends that FDA collaborate with industry to develop a guidance to address common quality issues for ANDA submissions 11

12 First Generics Prioritization of applications must focus on the public health impact Consistent with the purposes of the Hatch Waxman Act to approve generics on the earliest possible date upon which no legal barriers to approval exists, FDA should aim to approve applications immediately upon patent expiration, exclusivity expiration, expiration of a 30 month stay, commencement of a patent license date or the earliest date that no other legal barrier to approval exists At least 19 first applicants have forfeited the 180 day exclusivity after enactment of GDUFA on Oct. 1, 2012 for failing to obtain a timely tentative approval 1 See Slides of the Appendix 12

13 Conclusion We appreciate the opportunity to continue our dialogue and pursuit of a successful Generic Drug Review Program Continued transparency, meaningful and frequent consultation with industry during both the guidance and application process will benefit all participants 13

14 Thank You! Thank You GPhA will provide further comments in our formal docket submission following today's workshop 14

15 Thank You! Appendix 15

16 Why FDA and Industry Created GDUFA Since the passage of the Hatch Waxman Act in 1984, which created the framework to get safe, affordable, high quality generics into patient hands as quickly as possible, the generic drug industry has played an increasingly vital role in the nation's public health. FDA has approved more than 8,000 generic equivalents to brand name drugs, resulting in generics representing more than 85% of all prescriptions in the U.S. and saving U.S. consumers and the healthcare system $1.5 trillion in the past decade alone. Thank You! Due to the globalization of drug manufacturing and the increase in FDA regulated drug products, the time to get a new generic approved doubled over the last decade as FDA's resources have not kept up with its generic workload. Additionally, ensuring a safe and effective drug supply is much more challenging than in the past. Prior to passage of the FDA Safety and Innovation Act, U.S. and foreign manufacturers were held to two different quality standards as FDA was able to inspect only 11% of the foreign establishments in its database, compared to 40% of domestic sites. Because FDA expects a satisfactory inspection evaluation before approval, generic drug approval times have increasingly suffered as a result of the inspection disparity. To help hold all participants in the U.S. generic drug system to the same quality standards, and to increase the likelihood that American consumers get more timely access to low cost, high quality generic drugs, FDA and industry jointly negotiated a user fee program focused on three key public health aims - improved Safety, Access and Transparency. GDUFA was passed into law in 2012 and began as a five year program starting Oct. 1, 2012, with industry paying annual inflation adjusted fees of $299 million through Sept. 30,

17 Why FDA and Industry Created GDUFA "We are at something of a tipping point Looking ahead, it is clear that FDA will not be able to make ends meet with current resourcing, and more approvals will be Thank You! delayed because of a lack of inspectional resources. That is why it is so important... to constructively address the Generic Drug User Fee. No one benefits from a pendingapplication queue of 2,000-plus products. Uncertainty and delays are costly to consumers, costly to industry and hurtful to the public." -Margaret Hamburg, MD, FDA Commissioner GPhA Annual Meeting, Feb "Currently, more than 2,700 generic applications are awaiting approval from the FDA and the average approval time for an application is now stretching beyond 30 months, five times longer than the statutory six-month review time called for by Hatch- Waxman Act. Unfortunately, this backlog keeps safe, low-cost generic drugs off the market and reduces competition... GDUFA will help alleviate the backlog and expedite consumer access to generic drugs, while also enhancing drug quality and safety by ensuring inspection parity among both foreign and domestic manufacturing sites." -David Gaugh, GPhA, House Energy and Commerce Subcommittee on Health, Apr. 18,

18 3 Key Goals of GDUFA: Improved Safety, Access and Transparency GDUFA GOALS LETTER FDA and industry jointly agreed to a user fee program focused on three key public health aims: Thank You! SAFETY: Ensuring that both foreign and domestic industry participants in the U.S. generic drug system are held to consistent high quality standards and are inspected by FDA biennially using a risk-based approach. ACCESS: Expediting the availability of low cost, high quality generic drugs by bringing greater predictability to review times for ANDAs and increasing timeliness in the review process. TRANSPARENCY: Enhancing FDA's ability to protect Americans in the complex global supply environment by requiring the identification of facilities involved in the manufacture of generic drugs and associated active pharmaceutical ingredients and improving FDA's communications and feedback with industry in order to expedite product access and enhance FDA s ability to protect Americans. "GDUFA is aimed at putting FDA's generic drugs program on a firm financial footing to ensure timely access to safe, high-quality, affordable generic drugs." -Janet Woodcock, MD, FDA House Subcommittee on Health, Feb. 9,

19 Improved SAFETY Status Check on GDUFA's 3 Public Health Aims: Improved Safety, Access and Transparency Pre-GDUFA: Due to a lack of resources and outdated legal authority, on average FDA inspected U.S. manufacturers every 2.5 years and foreign sites every nine years, causing an unleveled playing field as well as delays in new generic approvals as applications lacked a recent inspection history for approval. 2 In 2010, GAO reported that FDA inspected only 11% of the foreign sites in its database, compared to 40% of domestic sites inspected the same year. Thank You! 3 FDA made around 400 annual acceptable compliance recommendations in 2011, less than half of annual generic applications received. Today: In fiscal year 2013, FDA reported that it had inspected 65% of all foreign facilities within the last two years and 82% of domestic facilities, making progress toward GDUFA's goal to achieve inspection parity using a risk based approach by fiscal year FDA has also made approximately 1,300 acceptable compliance recommendations for generic applications in Industry continues to report approval delays as a result of outstanding inspection administrative close out with FDA's Office of Compliance despite a successful FDA inspection as FDA works to finalize the IT infrastructure. 19

20 Improved SAFETY GPhA urges FDA to dedicate resources to addressing the enormous and growing backlog of ANDA and PAS submissions Thank You! Status Check on GDUFA's 3 Public Health Aims: Improved Safety, Access and Transparency Do not flag a site s compliance status as pending unless a particular GMP issue has been identified. It is contrary to GDUFA goals and the principle of Access to prohibit approval of a new generic product simply because an EIR has not yet been signed off by headquarters, for an inspection of a site with a good compliance history, that had ZERO 483 observations. Yet this has occurred many times over the past two years. Allow a site s acceptable compliance status to benefit from the full compliance reevaluation period (i.e. 2 years for FDF sites; 3 years for API sites or testing labs). Currently, if an inspection is scheduled a few months before the 2 year compliance window is up, the compliance status is flipped to pending so applications can t be approved. Even if the inspection results in no 483 observations, the compliance status is not reverted to acceptable until after the EIR is issued and approved, generally many months later (up to 5-7 months). Thus, the site really only has an acceptable compliance status for months, and when multiple sites are involved, it s unlikely to get their compliance statuses to line up at the same time. 20

21 Status Check on GDUFA's 3 Public Health Aims: Improved Safety, Access and Transparency Improved TRANSPARENCY Pre-GDUFA: Until GDUFA, FDA's facilities database lacked accurate information on facilities Thank involved You! in the manufacture of drugs due to the growth in facilities abroad and significant industry consolidation. Additionally, communication and feedback with industry waned as FDA lacked the resources to keep up with the growing generic workload, making it more difficult for industry to predict FDA's timing and to make informed business decisions to be ready for launch immediately upon approval given the hyper-competitive Hatch Waxman dynamics. Today: Over 3,900 facilities supporting generic drug applications have annually selfidentified improving FDA's visibility into the global drug supply chain. 6 FDA implemented internal procedures contrary to the key GDUFA aim of Transparency as the Office of Generic Drugs MAPP has precluded agency project management staff from discussing any specific deficiencies or providing projected time lines for action to an applicant. This lack of visibility and interaction has caused significant uncertainty and unpredictability for industry, hampering earliest access to generic drugs. 21

22 Status Check on GDUFA's 3 Public Health Aims: Improved Safety, Access and Transparency Improved TRANSPARENCY GPhA applauds FDA for developing the Target Action Date initiative for Thank You! applications in the backlog, and year 1 & 2 submissions. GPhA urges FDA to assign and meet target action dates that provide patient access to generics on the earliest date upon which no legal barriers block approval. Provide more transparency into the true status of reviews. In particular increase communication between the agency and applicants. GPhA wishes to continue collaboration with the agency on potential transparency opportunities. 22

23 Improved ACCESS Status Check on GDUFA's 3 Public Health Aims: Improved Safety, Access and Transparency Pre-GDUFA: In 2011, median time for generic approval had increased to 31 months, significantly slowing patient access to more affordable medicine. Thank You! 7 These delays caused applicants to inadvertently forfeit 180 day exclusivity which was intended by Congress to incentivize applicants to take on the legal risk with challenging patents (when the provision finding forfeiture for failing to gain 30 month tentative approval was enacted in 2003, the median approval time was 16 months). 8 Today: In 2013, the median time for generic drug approval jumped to 36 months 9 and is projected at 43 months for In the last year, the U.S. healthcare system has lost at least $1.25 billion in savings due to first generic approval delays with a median time for approval at 55 months. 11 Additionally, it appears at least 19 first applicants have forfeited 180 day exclusivity after enactment of GDUFA on Oct. 1, 2012 for failing to obtain a timely tentative approval. 12 FDA has experienced an anticipated record number of new applications in 2014 with more than 600 applications submitted in the month of June alone just before FDA's revised stability requirements took effect

24 Improving ACCESS Prioritization of applications that provide the most public health impact FDA's recent Prioritization MAPP provides a good foundation to address the current challenges of delayed approvals. GPhA proposes the following refinements to ensure the public health goal of earliest access to more affordable medicine is met. Thank You! To provide patients with earliest access to more affordable medicine, FDA should prioritize the following applications in addition to those involving PEPFAR and Drug Shortage, regardless of when such applications were submitted: First generics Day 181 Improving Access to Generic Drugs Criteria: Generally, first generics include those applications for which no other generic version of the same reference listed drug has yet been brought to the market under an approved ANDA. Consistent with the purposes of the Hatch Waxman Act to approve generics on the earliest possible date upon which no legal barriers to approval exists, FDA should aim to approve applications immediately upon patent expiration, exclusivity expiration, expiration of a 30 month stay, commencement of a patent license date or the earliest date that no other legal barrier to approval exists. Criteria: Applications that are first eligible for approval upon expiration or forfeiture of a first applicant's 180- day exclusivity period Any other application for which the applicant can sufficiently demonstrate a significant public health need Criteria: The following factors should be taken into consideration such as whether the product will alleviate a drug shortage and/or fulfills an unmet public health need and/or satisfies an undue economic hardship as demonstrated by supporting data provided by the applicant in a general correspondence to the application. 24

25 Improving ACCESS Target Action Dates for prioritized applications FDA has indicated it will issue Target Action Dates ("TAD") for applications that are prioritized and communicate these to applicants. These dates should reflect the date that best facilitates issuance of approval on the earliest Thank You! Improving Access to Generic Drugs possible date, based on patent and exclusivity considerations if any, under the Hatch-Waxman framework E.g., for a first generic that is first eligible for approval on Dec. 16, 2014 upon expiration of the 30 month stay, the TAD should be a date well in advance of Dec. 16 th that would allow enough time for approval letter to be issued on Dec. 16 th Pending first generic applications that have passed their earliest entry date (e.g., a patent license date of Feb. 1, 2014 has already passed without a final approval on the ANDA), should be given the highest priority with aggressive Target Action Dates aimed at concluding any remaining activity necessary for approval as quickly as possible to avoid further delay. For second or subsequent entry generics, the target action date should be as soon as possible following approval or forfeiture of the first generic or on day 181 where exclusivity has been granted. Once a TAD has been identified, target action dates should have the ability to change to an earlier date based on a change in facts that impact the public health, the dynamic nature of the generic drug industry, and the associated Hatch Waxman framework All divisions within FDA that can impact the approvability of an application should be held accountable to the Target Action Date (ie, Office of compliance, legal review, consults, etc) 25

26 Endnotes 1. See 180 Day Exclusivity Tracker available at summarizing forfeitures (FDA punted on 9 of the 19 ANDAs which failed to obtain a tentative approval but the agency is waiting for a subsequent applicant to necessitate a formal determination). 2. U.S. Government Accountability Office. Drug Safety (Publication No. GAO ) at 15 (Sep. 2010). 3. Id. Thank You! 4. FDA. FY 2013 Annual GDUFA Performance Report to the President and Congress at 14 (Nov. 2013). 5. FDA/GPhA Quarterly Board Meeting on GDUFA Implementation, presentation by Frances Godwin, Office of Compliance (Aug. 24, 2014). 6. A. Gaffney, RAC. "Time for Generic Pharma Companies to Re-Identify Themselves" (Apr. 30, 2014). 7. FDA. FY 2013 Annual GDUFA Performance Report to the President and Congress at 2 (Nov. 2013). 8. GPhA. Correspondence to Congress (Jun. 4, 2012). 9. FDA. FY 2015 FDA Justification of Estimates for Appropriations Committee at 48 (2014). 10. FDA has not made public the median approval time for 2014 but a sample size of 89 approvals shows a median approval time of 43 Months while the median approval time of 10 first generics is 55 months. Industry data on file. 11. Industry data on file for known delays of first generic applications that have missed approval on the earliest date in which no further legal barriers exist to approval using NACDS and IMS estimated average retail price and brand and generic utilization. 12. See 180 Day Exclusivity Tracker available at summarizing forfeitures (FDA punted on 9 of the 19 ANDAs which failed to obtain a tentative approval but the agency is waiting for a subsequent applicant to necessitate a formal determination). 13. B. Pollack. "June ANDA Submissions Ran Industry Dry for July!" (Aug. 15, 2014). 26