How To Get A Meeting With The Fda On The Drug Safety And Security Act

Transcription

1 April 7, 2014 Ms. Jane Axelrad, JD Associate Director for Policy Center for Drug Evaluation and Research U.S. Food and Drug Administration New Hampshire Avenue Silver Spring, Maryland Re: Drug Quality and Security Act Implementation Recommendations and Meeting Request. Dear Ms. Axelrad: The American Academy of Ophthalmology, American Society of Cataract and Refractive Surgeons, the American Society of Retina Specialists, the American Glaucoma Society, the Cornea Society, and the Macula Society, and the American Association for Pediatric Ophthalmology and Strabismus are writing to share their collective concerns and recommendations regarding implementation of the Drug Quality and Security Act (DQSA, P.L ), and to request a meeting on these issues. We applaud the U.S. Food and Drug Administration (FDA) for moving quickly to work with Congress to enhance the oversight of our nation s compounded drug supply and ensure these drugs are safe for administration to patients. We hope that FDA will take the same conscientious approach moving forward to ensure that access to important compounded drugs (which includes repackaged drugs) is not unduly restricted. Ophthalmologists, across all subspecialties, rely heavily on compounded drug products. Our organizations have therefore taken a significant interest in all iterations of legislation concerning the oversight of compounding pharmacies and compounded products, particularly how those bills affected safety of compounded drugs and access to compounded drugs by physicians and patients. That same interest now extends to the DQSA s implementation. Given the unique anatomy and physiology of the eye, many manufactured medications are not appropriate for use in treating conditions of the eye. Frequently, medications are not manufactured in dosage sizes appropriate for ophthalmic use and compounders repackage the product to meet physician and patient needs. In some cases, additional alterations are needed to compound a drug with the right composition for use in the eye, such as changes to the drug s concentration or removing the preservative from the drug. The lack of readily available, directfrom-manufacturer ophthalmic medications for many eye conditions has resulted in a significant number of ophthalmologists relying on compounding pharmacies to fill the gaps and provide critical, sight-saving drugs for physicians and patients. In many cases, access to these 1

2 compounded drugs is essential, as many drugs, such as ophthalmic anti-infectives used to treat urgent and emergent conditions in office settings are only available from a compounding facility. Other drugs, such as repackaged vascular endothelial growth factor (VEGF) inhibitors, are critical to the treatment of many patients with potentially-blinding conditions such as age-related macular degeneration (AMD), diabetic macular edema, and others. Maintaining access to these products is critical to the public health. Therefore, our organizations, and the patients our members serve, have a very strong interest in how FDA s implementation of the DQSA will affect access to these essential treatments. We are particularly interested in FDA s plans to address (1) drugs repackaged by outsourcing facilities for office use, and (2) access to office use drugs from traditional compounding pharmacies. Our concerns, and recommendations for assuring ready access to important medications, are outlined below. Drugs Repackaged by Outsourcing Facilities for Office Use Repackaged drugs for office use are a critical component of many ophthalmology practices. As discussed above, drugs are often repackaged for ophthalmic use because they are not manufactured in dosages appropriate for use in the eye. In some cases, if these drugs are not available for office use, it leaves ophthalmologists with no treatment options for patients. In others, should the repackaged drugs not be made available for office use, the only alternative treatments will be unaffordable for many patients, effectively leaving them with no treatment options. Therefore, as the DQSA is implemented, it is critical that FDA take any necessary steps to ensure access to safe repackaged drugs for office use. We are particularly concerned about maintaining access to repackaged bevacizumab biologic drug product (hereinafter bevacizumab ). Bevacizumab is a vascular endothelial growth factor (VEGF) inhibitor that is FDA-approved for use in treating various cancers, but is also frequently used to treat patients with neovascular age-related macular degeneration (AMD), the leading cause of uncorrectable vision loss among older adults. AMD is essentially a deterioration or breakdown of the macula, the part of the eye responsible for central vision and allowing patients to see fine details clearly. Patients with neovascular AMD are placed into a treatment regimen where their disease is monitored by an ophthalmologist on regular basis, usually monthly. At their regular monthly visit, the patient is examined by their ophthalmologist, the status of their condition is evaluated, and a determination is made as to whether the patient needs to be treated with an anti-vegf product at that time. If the patient needs the treatment, the ophthalmologist administers the anti- VEGF injection during that monthly examination. Because it is unknown whether a patient will need an anti-vegf injection until the time of examination, ophthalmologists order anti-vegf products in quantities sufficient to meet their possible needs prior to evaluating the affected patients. This allows for prompt treatment during 2

3 the monthly visit, and avoids the patient having to schedule a second follow-up visit to get treatment. Follow-up visits are much more than an inconvenience for AMD patients; they represent a significant barrier to essential treatment. AMD patients are typically seniors and are usually experiencing varying degrees of vision loss, so they frequently rely on caregivers to assist them in driving to appointments. Return appointments, in a few days once the drug is received, are disruptive, difficult, and frequently costly for older patients and their caregivers and do not represent a practical way to offer treatment for AMD patients. Return appointments also pose a substantial barrier to treatment for those patients living in rural areas. For patients living long distances from treating clinics, return appointments are not always a viable option. This is especially true for seniors that rely on caregivers for transportation. Requiring a return appointment for a patient-specific product would place a significant number of at-risk and underserved patients at a disproportionate risk for preventable vision loss. Additionally, return appointments place strain on a busy ophthalmology practice that would have to find time to schedule a significant number of return visits every month for AMD patients. Bevacizumab is an anti-vegf product with a long history of safe and effective use in treating AMD. With well over one million intravitreal bevacizumab injections given safely to ophthalmology patients in the United States each year, it represents a vital component to the treatment of many potentially-blinding eye conditions. Extensive comparative effectiveness studies performed by the National Eye Institute which showed that bevacizumab and ranibizumab, an FDA-approved AMD treatment, had equivalent effects on visual acuity. 1 However, bevacizumab is only sold by its manufacturer in 100 and 400 mg formats, the dosages necessary for its FDA-approved cancer-fighting uses. 2 To treat AMD, approximately 1.25 mg is generally needed, 3 so a single manufactured vial of bevacizumab contains approximately 80 or 320 AMD doses. This leaves physicians with three options: using a single vial of a drug 80 or 320 times; using a vial once and discarding the remainder; or relying on products that are repackaged specifically for ophthalmic use. It is generally unsafe to repeatedly use a vial of bevacizumab in an office setting to administer multiple injections due to the potential for loss of sterility and stability over time. Also, depending on the number of neovascular AMD patients treated, a large volume of a drug in a manufacturer s vial may go unused prior to expiration. Using a single vial once, then discarding the remainder, would provide reimbursement for only a single dose and leave the 1 Comparison of Age-related Macular Degeneration Treatments Trials (CATT) Research Group, Martin DF, Maguire MG, Fine SL, Ying GS, Jaffe GJ, Grunwald JE, Toth C, Redford M, Ferris FL 3rd. Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: two-year results. Ophthalmology Jul;119(7): Epub 2012 May 1. 2 Avastin (bevacizumab) Prescribing Information, Section 16: How Supplied/Storage and Handling (2013). 3 Id. 3

4 ophthalmologists to cover 79 or 319 discarded doses out of pocket, which is an unsustainable practice. The third option is really the only option using bevacizumab that has been repackaged in a safe and sterile facility into appropriate dosages for treatment of AMD. Therefore, limiting access to repackaged office use bevacizumab by interpreting the DQSA in a way that eliminates access to the product, or requires an individual identified patient requirement for orders, will keep ophthalmologists from getting many AMD patients the safe and effective treatment they need. If repackaged bevacizumab was made unavailable, many patients would be left without treatment options. Although there are FDA-approved anti-vegf treatments on the market, the price differential between the marketed products and repackaged bevacizumab makes them unavailable to many patients. While the average Medicare beneficiary pays an average cost of $11 (co-payment) for one treatment with repackaged bevacizumab, the same beneficiary would pay approximately $400 (co-payment) per dose of the FDA-approved alternatives. For patients who are on monthly treatment regimens for neovascular AMD, the annual cost of treatment using one of the alternative marketed products is approximately $4800 (versus $132 for a year of treatments with repackaged bevacizumab). If the patient needs treatment in both eyes, this cost doubles to almost $10,000 annually. 4 If a patient-specific order was placed for that patient prior to their regular monthly examination, the ophthalmologist would be responsible for the product cost if the patient didn t need treatment or didn t show up for their appointment. In addition, in a busy retina practice, juggling hundreds of patient specific vials a week would be a significant administrative burden. Our organizations recognize the importance of ensuring product safety and sterility during the repackaging process. Given that this drug would be used for injection into the eye, it must meet high quality standards. The same would hold true for other, similarly administered ophthalmic drug products. The right balance between access and sterility/safety issues can be achieved by allowing 503B outsourcing facilities to repackage sterile products, such as bevacizumab, and make these drugs available to physicians and patients for office use without undue limitations. Outsourcing facilities are required to meet the highest possible drug safety and sterility standards current 4 The cost to the Medicare system as a whole is also substantial. A wholesale switch to the marketed products alone will result an increase cost to the Medicare system of over $1 billion per year, a number which is likely to increase as the senior population increases and more Americans need treatment for AMD. These added healthcare costs could reduce availability of treatments for other conditions. 4

5 Good Manufacturing Practices comparable to drug manufacturing facilities so the sterility/safety concerns which prompted FDA and Congressional action will be properly addressed. Suggested Guidance: For FDA s consideration, we are proposing guidance (attached) regarding interpretation and implementation of 503B outsourcing facility requirements. If adopted, the guidance would ensure that physicians and patients maintain access to critical repackaged products, including bevacizumab, while ensuring these products are produced in facilities that meet the highest safety and sterility standards. Our organizations feel the guidance furthers the public health and the intent of the DQSA. Many members of Congress, both on the House and Senate floor submitted for the Congressional Record speaking to this issue. During floor debate on the DQSA, statements by several members of Congress who were instrumental to the creation and passage of the legislation, reflected that the quest for safer compounded drugs should not unduly limit physician and patient access to important drugs. Whatever policies or regulations FDA ultimately adopts should further this intent. Office Use Drugs from Traditional Compounding Pharmacies Our recommendation regarding use of outsourcing facilities will work well, provided that a sufficient number of outsourcing facilities register with FDA. However, if outsourcing facilities do not register in sufficient numbers, ophthalmologists must turn to traditional compounding pharmacies authorized under Section 503A of the Food, Drug, and Cosmetic Act. This poses significant problems under FDA s current interpretation of Section 503A. Our organizations have been contacted by several member ophthalmologists over the past year who have had difficulties in accessing necessary medications for office use. Recent FDA warning letters to compounding pharmacies that have a long history of supplying a large number of ophthalmologists with safe and sterile drugs are amplifying concerns that FDA s implementation of the DQSA will drive compounders out of the sterile compounding business or out of business altogether, resulting in significant drug access issues for ophthalmologists and other providers. The nature of our members practices and patients requires our members to have certain sterile and non-sterile compounded medications on site to prevent potentially disastrous situations, such as permanent blindness. Office use compounding has become essential to many ophthalmology practices, where our members frequently need to have medications on hand, ranging from compounded antibiotics for use in emergency cases of potentially blinding eye infections and special combination dilating eye drops for diagnostic use in children, to drugs used in surgery on a non-patient-specific basis. It is absolutely critical to the practice of ophthalmology that these products be available to physicians without prescriptions. 5

6 On its face, section 503A permits office-use compounding pharmacists and physicians may compound limited quantities of drug in anticipation of prescriptions based on a history of receiving prescriptions. 5 However, FDA has been applying a very narrow reading of this provision that may make office-use compounding under Section 503A virtually non-existent. The Academy recommends that until an adequate number of outsourcing facilities are available to provide essential ophthalmic products for office use under the DQSA, the Agency should allow Section 503A traditional pharmacies to compound drugs, as needed, to meet the needs of patients and with the understanding that they will be under significant State and FDA scrutiny to ensure drug safety. * * * * * The below signed organizations welcome the opportunity to further discuss these issues with FDA in hopes that we can work together to find an implementation strategy that both ensures the safety of compounded and repackaged drugs while allowing physicians and patients access to the critical, sight-saving treatments they need. We would like to request a meeting to further discuss these issues with yourself and other relevant FDA staff. Please let us know when you may have time to meet. The Academy looks forward to continuing a dialogue with FDA on these important issues. Please do not hesitate to contact Shannon Curtis in the American Academy of Ophthalmology s Washington, D.C. office (scurtis@aaodc.org, ) to determine an appropriate time to meet and if we can be of further assistance on this matter. Sincerely, Gregory L. Skuta, MD American Academy of Ophthalmology Sharon Freedman, MD American Association for Pediatric Ophthalmology and Strabismus 5 Food, Drug, and Cosmetic Act 503A(a)(2). 6

7 This image cannot currently be displayed. Kuldev Singh, MD, MPH American Glaucoma Society Eric D. Donnenfeld, MD American Society of Cataract and Refractive Surgeons John T. Thompson, MD American Society of Retina Specialists Christopher J. Rapuano, MD The Cornea Society Paul Sternberg, MD The Macula Society 7