By Kurt R. Karst –
On May 29th, the U.S. House of Representatives Committee on Appropriations voted 31-18 during a mark-up session to send to the House floor its version of the Agriculture, Rural Development, Food and Drug Administration, and Related Agencies Appropriations Act, 2015, along with an accompanying report. The House Appropriations Committee vote follows a May 22nd mark-up session by the U.S. Senate Committee on Appropriations of its version of the Agriculture, Rural Development, Food and Drug Administration, and Related Agencies Appropriations Act, 2015 (S. 2389). The Senate Committee approved that measure by a 16-14 vote, along with an accompanying report, and they will go on to the full Senate for consideration. As is typical of FDA appropriations bills and reports, lawmakers heap on various recommendations and directives. We’ve gone ahead an extracted those items from each of the documents and added some links to background information. We’re not going to get into all of the appropriations funding numbers. Instead, we’ll leave that to the folks over at the Alliance for a Stronger FDA (see here).
House Fiscal Year 2015 FDA Appropriations Bill & Report
In what seems to be an effort to strongarm FDA into action on finalizing a guidance document on abuse deterrence opioid development (see our previous post here), Section 734 of the House bill provides:
Of the funds made available to the Food and Drug Administration, Salaries and Expenses, Office of the Commissioner, $20,000,000 shall not be available for obligation until the Food and Drug Administration finalizes the draft guidance of January 2013 entitled “Guidance for Industry: Abuse-Deterrent Opioids – Evaluation and Labeling”: Provided, That if the Food and Drug Administration fails to finalize such guidance by June 30, 2015, such funds shall be made available for obligation to the Food and Drug Administration’s Office of Criminal Investigation for the purpose of assisting Federal, state, and local agencies to combat the diversion and illegal sales of controlled substances.
The provision in the Senate report (below) uses much softer recommendation language.
FSMA Food Safety Preventative Controls for Human Food Rule.—FDA is directed not to implement an interim final or final rule regarding food safety plans under the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 301 et seq.) until regulatory requirements for supplier verification and testing programs are proposed for public review and comment as well as an economic analysis of the costs and benefits associated with the regulatory requirements pursuant to the Administrative Procedure Act.
Given the diversity in the food industry, FSMA was designed to be risk-based, flexible, and science-based. A one-size-fits-all approach will not work. Yet, the Committee is very concerned with the overly prescriptive regulatory approach that the agency is taking with many of the regulations including the monitoring of preventive controls and verification testing activities. Accordingly, FDA shall ensure all FSMA regulations are risk-based, flexible, and science-based, and embrace the well-established and recognized standards for food safety already employed through much of the industry.
Need to Manage Priorities.—The Committee is concerned that FDA is not taking necessary and required steps to provide agency stakeholders adequate input or economic consideration on an expanding list of highly technical regulatory proposals. In addition, the agency has provided questionable cost estimates on proposed rules, guidance documents, and notices of tentative determination. The food supply chain has been forced to provide comment on OMB Redline text on important FSMA proposed rules, not formally published in the Federal Register. Moreover, the agency’s dramatic shift in how it determines ingredient safety has tremendous potential to expose the Nation’s largest manufacturing sector and the agency to costly litigation that may unnecessarily lead to higher costs and taxpayer dollars with unknown benefits. At a time when the agency is requesting additional appropriations and revenue from user fees, the Committee recommends that the agency not overextend itself at the cost to consumer confidence and the Nation’s economic health.
FDA Partnerships Under FSMA.—The purpose of FSMA is to reform the nation’s food safety laws to ensure a safe public food supply. As FDA continues implementation of FSMA, the Committee encourages FDA to work in partnership with existing government food safety programs through Memorandum of Understandings to verify compliance with FSMA to rules once they are finalized as a way to eliminate duplication of activities under the law.
Pharmacy Compounding.—The Committee provides an increase of $12,000,000 for pharmacy compounding activities specified in the Drug Quality and Security Act (DQSA). The Committee urges FDA to complete inspections of compounding facilities that clearly fall within the agency’s jurisdiction and take all necessary enforcement actions needed to promote the safety of the drug supply chain. For those pharmacies unaffected by DQSA, state boards of pharmacy are the proper regulator of state licensed pharmacies and should remain so. The Committee will continue to monitor FDA spending and oversight over compounding pharmacies to ensure the intent of both funding and legislation approved by Congress is observed. (Additional information here.)
Menu Labeling.—The Committee remains concerned with FDA’s proposed rule to regulate Nutrition Labeling of Standard Menu Items at Chain Restaurants. The Committee is further concerned that FDA has not properly considered alternatives or appropriately measured their impact on affected entities. The Committee continues to urge FDA to adopt the proposed alternative Option 2 definition of similar retail food establishments, which only applies the rule to restaurants or retail establishments where the primary and majority of business is the selling of food for immediate consumption or the selling of food that is processed or prepared on the premises. The Committee directs FDA to complete and submit to the Committee a detailed cost-benefit analysis, to be used in the final rule’s review by the Office of Management and Budget, including an analysis of the agency’s proposed options for the defining of ‘‘similar retail food establishments’’ that fully incorporates the information provided by affected non-restaurant entities and determines which option is most compliant with Executive Orders 12866 (Regulatory Planning and Review) and 13563 (Improving Regulation and Regulatory Review).
The Committee believes that the agency should take into account the increased costs and logistical challenges chain restaurants will face in meeting the requirements of the proposed rule. To meet the requirements of the law, FDA should consider a clear, conspicuous statement of required nutritional information on a prominently displayed poster adjacent to the menu board and nutritional information to be provided in pamphlet form prominently displayed next to drive-through menu boards as meeting such requirements.
Consistent with the intent of Congress to enhance the provision of accurate and accessible nutritional information to consumers, the Committee urges FDA to modify the respective provisions in the proposed rule to permit restaurants and similar retail food establishments to: (1) label the number of calories in a multi-serving menu item that is typically divided before presentation to the consumer, by labeling the number of calories in the common unit division of that multi-serving menu item, or by labeling the number of servings and number of calories per serving; (2) determine and disclose nutrient content for variable standard menu items that come in different flavors, varieties, or combinations using methods that will enhance accuracy and accessibility to consumers, including ranges, averages, individual labeling of flavors or components, or labeling of one preset standard build; and (3) disclose nutrient content using a remote-access menu, such as one available on the Internet instead of an instore menu, in cases where the majority of orders are placed by customers who are off-premises. Furthermore, regarding the ‘‘reasonable basis’’ standard applied to restaurants and similar retail food establishments under Section 403(q)(5)(H)(iv) of the Federal Food, Drug, and Cosmetic Act, the Committee urges FDA to accept allowances for variation in nutrient content, such as brought about by variations in serving size, inadvertent human error in formulation of menu items, and variations in ingredients. FDA should not hold restaurants and similar retail food establishments liable for such variation in nutrient disclosure. If FDA’s proposed rule has been finalized prior to the issuance of this report, the Committee directs FDA to issue guidance within six months of the date of this report to inform regulated industry of the interpretations of the nutrition labeling requirements
set forth above.
Bioethics Committee.—The Committee directs the agency to utilize a bioethics committee within the Department of Health and Human Services to review novel cellular and gene therapy matters before the Office of Cellular, Tissue, and Gene Therapies. The bioethics committee should be tasked with reviewing scientific and bioethical considerations prior to the approval of clinical trials, especially those involving oocyte modifications. FDA is directed to report to the Committee at a minimum of 30 days prior to a final agency decision on such matters.
Imported Pet Food Product Transparency.—As of December 2013, FDA has received more than 4,600 complaints of illness related to consumption of chicken, duck, or sweet potato jerky treats, nearly all of which are imported from China. The reports involve more than 5,400 dogs, 23 cats, and include more than 900 canine deaths. These incidents date back to 2007. The Committee requests that FDA provide it with a summary of all activities, including discussion of noteworthy timeframes, associated with the investigation into the pet illnesses related to these products within 60 days of the enactment of this Act. In addition, the Committee requests that the agency provide it with an annual summary report on the status of the investigation into these illnesses beginning in April 2014 until the issue has been resolved.
Over-the-Counter (OTC) Cold Medicines for Children.—The Committee is concerned that FDA has not issued a proposed rule revising the monograph regulating the labeling of OTC cough and cold products for children. The Committee directs the agency to publish a proposed rule by June 30, 2014, based on scientific evidence for safety and efficacy in pediatric populations and consistent with the October 19, 2007, joint recommendations of its Pediatric Advisory Committee and Nonprescription Drugs Advisory Committee. While the Committee appreciates the agency’s effort to explore possible improvements to the OTC drug monograph process, these efforts should not impede the prompt publication of this proposed rule.
Drug Shortages.—The Committee is aware that shortages of critical drugs persist following the 2012 enactment of the Food and Drug Administration Safety and Innovation Act (FDASIA). Surveys conducted by the American Association of Nurse Anesthetists, the American Hospital Association, and the American Society of Health-System Pharmacists report persistent shortages of drugs used in anesthesia care, oncology, and other services, owing primarily to problems in manufacturing, which impair patient access to care and patient experiences in the healthcare system, delay surgical procedures, and possibly increase overall healthcare costs. Therefore, within the funding provided, the Committee directs the Commissioner to continue to prioritize the public reporting of manufacturing shortages, and to work with industry to prevent conditions that might lead to drug shortages.
Seafood Advisory.—The Committee is concerned that after many years, FDA has not published updated advice on seafood consumption for pregnant women, mothers, and children. Seafood is an important part of a healthy diet which contains critical vitamins and nutrients, such as Omega 3s, which are essential during pregnancy to ensure optimal fetal and child development. The Committee directs FDA to publish final advice to pregnant women on seafood consumption in conjunction with all applicable parties as directed in House Report 112–101 and Senate Report 112–73 by June 30, 2014. FDA shall issue its final seafood risk benefits assessment at the same time as the seafood advice. The seafood advice shall be consistent with the latest science and contain a clear and actionable advice that will enable the public, medical, and scientific communities to make informed dietary decisions and recommendations. Finally, FDA shall provide a progress report to the Committee 30 days after the enactment of this Act and every 30 days thereafter until the advisory and seafood risk benefits assessment are published.
ANDA Review Prioritization.—In its Generic Drug User Fee Act commitment letter, FDA affirmed that in order to provide more certainty to the generic drug industry, it would expedite the review of Paragraph IV applications that become eligible for approval during the review period and other applications that have the potential to be the first generics to market. Within 45 days of enactment of this Act, the Committee directs FDA to report to the Committee how it has prioritized its abbreviated new drug application review process to ensure first generics are approved on the earliest possible date.
Mammography Quality Assurance Advisory Committee.—The Committee urges FDA to quickly follow up the November 2011 meeting of the National Mammography Quality Assurance Advisory Committee by promptly reviewing the evidence supporting including information related to an individual’s breast density in the mammogram lay report and physician report.
Accelerated Approval.—The Committee is concerned that FDA has underutilized the accelerated approval authority codified in FDASIA. Congress created this authority to facilitate review and approval of drugs to treat patients with rare, life-ending diseases that cannot reasonably be pursued through the standard FDA approval process. The committee directs FDA to report on the way it has used this authority since 2012, its plans to use it in the future, and a justification for using this authority for diseases that are not life-ending. (Additional information here and here.)
Duchenne Muscular Dystrophy.—The Committee commends the collaboration between FDA and the Duchenne Muscular Dystrophy community to advance useful regulatory tools for benefit-risk considerations in this disease population and drug development guidance. The Committee supports the agency’s engagement with the patient population for these purposes and to enable the appropriate use of regulatory flexibility as provided in FDASIA.
Special Protocol Assessment Agreements.—The Committee is concerned about questions that have arisen in connection with the rescission of a Special Protocol Assessment Agreement (SPA), including fundamental questions concerning FDA’s adherence to the statutory and regulatory guidelines that apply to the SPA process as well as to questions concerning fairness to the sponsors. The Committee would like to reiterate that FDA is expected to adhere to the established standard as informed by the Congressional Record and the 1997 PDUFA Goals Letter.
The Committee is aware of FDA’s ability to rescind a SPA agreement reached under section 505(b)(5)(C)(ii) of the Food, Drug, and Cosmetic Act only if it demonstrates that ‘‘a substantial scientific issue essential to determining the safety or efficacy of the product has been identified after the testing has begun.’’
This standard is informed by the Congressional Record and the 1997 PDUFA Goals Letter. The Congressional report explains that Congress intended ‘‘that such agreements should be binding on both parties’’ except when ‘‘a substantial scientific issue has come to light after an agreement has been reached and testing has begun, which has a direct bearing on the safety or effectiveness of the product.’’
The Committee also expects that, as a matter of public policy and fundamental fairness to the sponsor, FDA should be accountable for continued diligence in identifying issues that bear on the continued enforceability of a SPA agreement and in notifying the sponsor of such issues within a reasonable period of time after FDA becomes aware.
To ensure agreement over the standard to rescind a SPA, the Committee directs FDA to report to the Committees on Appropriations of the House and Senate within 60 days of enactment of this Act regarding the standard by which FDA would rescind a SPA. Lastly, to ensure agreement over the standard to rescind a SPA, the Committee directs FDA to revise and re-issue, after public comment, its existing guidance regarding SPA agreements to clarify the agency’s interpretation of the statutory standard regarding SPA agreements and the rescission of such agreements. (Additional background here.)
Blood Plasma Products.—The Committee notes that the FDA Circular of Information for the Use of Human Blood and Blood Components states that plasma from different sources has identical clinical indications. Plasma from manual donation may be transfused and if not needed for that indication, may be sent for further manufacture into biologics such as immunoglobulin, clotting factor concentrates, and albumin. However, plasma from automated donation may be transfused but cannot be shipped for further manufacture until approximately one year after the donation. At that point the plasma is too old to be manufactured into other biologics and is destroyed and wasted. This seems illogical since there is a shortage of these biologic products in the United States. The Committee directs FDA to report back within 60 days of enactment of this Act on the scientific or medical justification for the different post-donation manufacturing policies and under what circumstances those policies might be adjusted to allow for the more timely use of plasma from automated donations into other biologics.
Sunscreen Ingredient Review.—The Committee is extremely concerned that another year has passed without FDA completing its review of the pending Time and Extent Applications (TEAs) and the OTC Monograph rulemakings on sunscreens. Immediate action on sunscreens should be a priority since the need for sunscreens is evidenced by the nearly one million people that are currently living with skin cancer and the fact that melanoma is the fifth leading cause of cancer in the U.S. this year. FDA has listed actions related to sunscreen as a high priority in the Unified Agenda since 2008.
While the Committee is encouraged that FDA has issued two sunscreen final rules and feedback letters to some sunscreen TEA applicants, significantly more work remains to protect Americans from developing skin cancer. The Committee directs FDA to complete its review by December 2014 of the remaining safety and effectiveness submissions already submitted for sunscreen active ingredients that have been found eligible for potential inclusion in the sunscreen monograph via TEAs and to work expeditiously on completing the OTC monograph rulemakings. The Committee is also encouraged that FDA is seeking input from stakeholders on how to modernize the OTC Drug Review, including the TEA process, and directs FDA to continue to work with stakeholders through the process and explore ways to improve the OTC Drug Review more broadly. (See our previous post here.)
Import Clearance Process.—The Secretary, in consultation with the Secretary of Homeland Security acting through U.S. Customs and Border Protection, should consider reprioritizing existing funding to ensure sufficient FDA personnel are available to clear shipments expeditiously at the time of their arrival at the port of entry including outside normal working hours and on holidays. The Secretary, in consultation with the Secretary of Homeland Security acting through U.S. Customs and Border Protection, shall develop a Trusted Trader Program designed to allow shipments from highly compliant importers to be released with minimal documentation or additional information being provided. This program should be designed in a way as to not jeopardize the safety of food and medical products under the agency’s jurisdiction. Recognizing that FDA has a responsibility to ensure legitimate trade is cleared rapidly and that compliant shipments are not unduly detained, the agency will provide a report to relevant Committees of Congress on two statistics that measure the effectiveness of its targeting rules twice each year, beginning six months after the passage of this measure, and again after one year. This report will contain: (1) the number of shipments being identified for FDA examination as a percentage of all shipments subject to FDA regulatory review, and (2) the number of violative products detained as a percentage of those being held.
Deeming Regulations.—The Committee is encouraged that FDA has provided options for a way forward on distinguishing between premium cigars and other tobacco products in its recently proposed rule ‘‘Deeming Tobacco Products To Be Subject to the Federal Food, Drug, and Cosmetic Act, as Amended by the Family Smoking Prevention and Tobacco Control Act; Regulations on the Sale and Distribution of Tobacco Products and Required Warning Statements for Tobacco Products’’ (Docket No. FDA–2014–N–0189). In particular, the Committee notes that FDA is considering excluding premium cigars from the scope of this proposed rule through Option 2. The Committee believes this could be a viable solution, given that the Family Smoking Prevention and Tobacco Control Act makes little mention of cigars throughout the legislation, and there is even less evidence that Congress intended to focus on the unique subset of premium cigars. The Committee notes that premium cigars are shown to be distinct from other tobacco products in their effects on youth initiation, the frequency of their use by youth and young adults, and other such behavioral and economic factors. (See our previous post here.)
Artificial Pancreas.—The Committee commends FDA for taking critical steps in advancing artificial pancreas systems, including its recent approval of the threshold suspend system. The Committee encourages FDA to continue collaboration with key stakeholders to ensure that artificial pancreas systems are further developed, tested, and approved, ensuring timely access to safe and effective systems for patients with type 1 diabetes.
Natural Claims.—The Committee requests that the Commissioner submit to the Committees on Appropriations of both Houses of Congress a detailed document describing the agency’s current policy with respect to natural claims on food products within 90 days of enactment of this Act. (See our previous post here.)
Regulation of Tree Nuts.—The Committee urges FDA to consider the exemption of tree nut producers from regulation under section 419 of the Federal Food, Drug, and Cosmetic Act if such tree nuts meet the criteria for ‘‘rarely consumed raw’’ and the recipient of the produce performs commercial processing that adequately reduces pathogens as described in the proposed regulation ‘‘Standards for the Growing, Harvesting, Packing, and Holding of Produce for Human Consumption; Proposed Rule’’.
Generic drug labeling.—The Committee is deeply concerned with FDA’s proposed rule regarding ‘‘Supplemental Applications Proposing Labeling Changes for Approved Drugs and Biological Products’’ that would change longstanding policy and allow generics to alter their label without FDA’s prior approval. Ironically, FDA published this proposed rule after the agency’s recent success in launching the Sentinel Initiative. This initiative helps to electronically track the safety of drugs once they reach the market, especially in terms of identifying drug safety communications.
The Committee is unaware of evidence of a need to change existing regulations. The proposed rule has the potential to threaten public health by creating unprecedented patient and provider confusion by having multiple labels for the same product, therefore undermining the longstanding policy of sameness. The Committee urges FDA to maintain a system where prescription drug labels on the market are FDA-approved, grounded in scientific evidence, and present no opportunity for mismatched dispensing or use information between the name brand drug and the generic version drug.
Additionally, sufficient evidence is lacking on how FDA derived such a low cost estimate for this proposed rule. Under the proposed rule, generic and brand manufacturers could assume additional obligations and possible liability, which may drive smaller companies from the market, increase the cost of generic medications, and lead to additional drug shortages. FDA’s cost impact analysis has not accounted for or addressed these or other unintended consequences, and further the Committee is concerned about the resources necessary to carry out such a significant policy change.
FDA must clear up any potential confusion that will likely be created in going forward with the currently proposed regulation. The agency must also justify the cost of such a regulation that fails to provide a net health benefit to consumers and providers. The Committee directs the agency to complete a new economic analysis of the rule, paying particular attention to the cost of pharmaceutical products, before FDA finalizes the rule and report back to the Committee on Appropriations of both Houses of Congress within 90 days of enactment of this Act. (See our previous posts here and here.)
National Antimicrobial Response Monitoring System (NARMS).—The Committee expects FDA to provide funding for the National Antimicrobial Response Monitoring System at $7,800,000 and urges FDA to consider providing additional funding for this program if warranted. The Committee encourages FDA to utilize NARMS as part of the strategy to preserve the effectiveness of antibiotics. The agency should continue to use the NARMS data for evaluating new food animal antibiotics, guiding policy and regulations on the use of antibiotics, conducting risk assessments, and tracking changes in resistance to identify potential human and animal health problems.
FDA User Fee Collections/Obligations.—The Committee continues to be concerned about the financial management of FDA’s user fee programs. The Committee directs that not later than November 1, 2014, and each month thereafter through the months covered by this Act, the Commissioner to submit to the Committees on Appropriations of the House and the Senate a report on user fees collected for each user fee program included in the Act. The report shall also include monthly obligations incurred against such fee collections. The first report shall include a distinct categorization of the user fee balances that are being carried forward into fiscal year 2015 for each user fee account as well as a detailed explanation of what accounts for the balance and what the balance will be used for.
Finalization of the Veterinary Feed Directive.—The Committee directs the Secretary of Health and Human Services to require FDA to finalize the Veterinary Feed Directive regulation by December 2014. (See our previous post here.)
Food Safety Monitoring.—The Committee notes that the National Agriculture and Food Defense Strategy Plan is being finalized as required by Section 108 of Public Law 111–353. As research needs are identified to carry out this section, the Committee encourages FDA to consider funding research that would provide portable and technologically advanced testing platforms needed to effectively monitor and protect against intentional adulteration of the food supply.
Cosmetics and Colors.—The Committee directs the Office of Cosmetics and Colors (OCAC) to respond by March 15, 2015, to a citizen petition setting safety levels for trace amounts of lead in cosmetics. The Committee notes that every year since FY 2012, it has repeatedly requested that OCAC respond to this petition. The Committee urges OCAC to make this a priority.
Food and Veterinary Medicine.—The Committee is aware of the important support provided to FDA’s food and veterinary medicine programs and through its research and program relations with their centers of excellence. The Committee encourages FDA to maintain an appropriate funding level for both FSMA-related activities and the base work performed by these centers.
Concerns with Opioid Application Approvals.—The Committee is alarmed by a growing trend of prescription drug and opioid abuse. The Committee notes that FDA has taken a number of positive steps in recent years to address this complex challenge. However, the Committee is discouraged by FDA’s 2013 approval of a New Drug Application for Zohydro, a high-dose undiluted painkiller containing hydrocodone. While the United States makes up only 4.6 percent of the world’s population, its residents consume 99 percent of the world’s supply of hydrocodone. These drugs are now the most widely prescribed painkillers in the U.S., and emergency room visits involving hydrocodone rose from 38,000 in 2004 to more than 115,000 in 2010.
Approving this powerful narcotic without any abuse deterrent formulation, despite the strong opposition of the relevant FDA expert Advisory Panel, seems counter to the assertion that ‘‘the prevention of prescription opioid abuse is of the highest priority for the FDA.’’ The DEA Administrator indicated to the Committee that the agency is spending considerable resources to educating agents, diversion investigators, and tactical diversion squads about the approval of this medication that ‘‘frightens us all.’’ In addition to strong concerns that the drug is ripe for misuse and addiction, the Committee is concerned that approving new applications without abuse deterrent properties will stifle innovation in this newly emerging field of scientific research.
The Committee therefore requests that FDA provide a report within 60 days of enactment, including a detailed accounting of FDA’s methodology for post-market tracking of Zohydro and findings to date. In addition, the Committee encourages FDA to continue its outreach to the medical community and provide data about the utilization of REMS-compliant training programs by prescribers. Lastly, the Committee includes bill language that prevents FDA from obligating $20,000,000 of its discretionary funding for the Office of the Commissioner unless the agency finalizes the draft guidance entitled ‘‘Industry Guidance: Abuse-Deterrent Opioids—Evaluation and Labeling’’. If by June 30, 2015, FDA does not complete this guidance, the $20,000,000 will be used by the Office of Criminal Investigation to assist in the prevention of opioid drug abuse. (See our previoous posts here and here.)
Tobacco Product Smuggling.—The Committee understands that nearly one in four packs of cigarettes consumed in Texas is smuggled in from Mexico and more than half of the cigarettes consumed in New York are the result of interstate smuggling operations. In addition, an average of one out of every five packs of cigarettes consumed in California, Arizona, and New Mexico are the result of smuggling operations. FDA’s regulation over tobacco products provides the agency with unique expertise and intelligence in the area of tobacco sales and market dynamics. The Committee recommends FDA’s Office of Criminal Investigations assist Federal, state, and local agencies in targeting the highest-level criminal tobacco trafficking organizations by gathering intelligence and disseminating leads with their partner organizations to help address this illicit activity.
Senate Fiscal Year 2015 FDA Appropriations Bill & Report
The Senate bill includes a provision stating that of the finds appropriated to FDA, “not less than $150,000 shall be used to implement a requirement that the labeling of genetically engineered salmon offered for sale to consumers indicate that such salmon is genetically engineered. . . . ”
Abuse Deterrent Drug Development– The Committee urges FDA to make faster progress on setting and applying appropriate regulatory incentives and expectations regarding abuse-deterrent opioids. This includes finalizing the January 2013 draft guidance on evaluation and labeling of abuse-deterrent opioids and publishing draft guidance on the assessment of generic versions of such products. The draft guidance on generics should include a discussion of whether and in what circumstances human abuse liability studies will be needed, and if so, how applicants can ensure that such studies are acceptable for review by FDA. The Committee further urges FDA to include, where appropriate, descriptions of studies of a product's abuse-deterrent properties when a sponsor has not yet established a claim of abuse deterrence.
Antibiotics– The Commissioner is urged to devise a strategy to help ensure the use of medically important antibiotics in food animals for disease prevention, as defined in guidance for Industry No. 213, that is judicious and appropriate. Additionally, the Commissioner is directed to finalize a Veterinary Feed Directive rule prior to April 1, 2015, and is encouraged to include provisions that provide adequate assurance that licensed veterinarians will be familiar with the animals and premises where they are kept when prescribing medically important antibiotics for use in food animals.
Artificial Pancreas– The Committee commends the FDA for taking critical steps in advancing artificial pancreas systems, including its recent approval of the threshold suspend system. The Committee encourages the FDA to continue collaboration with key stakeholders to ensure that artificial pancreas systems are further developed, tested and approved, ensuring timely access to safe and effective systems for patients with type I diabetes.
Compounding Guidance Documents– The Committee notes that the Food and Drug Administration has begun implementing the Compounding Quality Act by releasing guidances and working to appoint members to the Pharmacy Compounding Advisory Committee. The Committee is concerned that the Food and Drug Administration is not meeting with any stakeholders before publicly releasing further guidance for public comment. The Committee directs the Food and Drug Administration to meet with stakeholders to help inform the implementation of the Compounding Quality Act to ensure continued access to safe compounded drugs for which there is a clinical need.
Comprehensive Device Review Assessment– FDA is directed to participate in a comprehensive assessment of the process for the review of device applications conducted by an independent entity capable of performing technical analysis, management assessment, and program evaluation for the device review program. In consultation with FDA and industry, the assessment should include, but is not limited to, an identification of process improvements and best practices for conducting predictable, efficient, and consistent premarket reviews that meet regulatory review standards; analysis of elements of the review process to facilitate a more efficient process; assessment of FDA methods and controls for collecting and reporting information on premarket review process resource use and performance; assessment of the effectiveness of FDA's Reviewer Training Program implementation; and recommendations for ongoing periodic assessments and any additional, more detailed or focused program assessments. Following this assessment, FDA is directed to report to the Committee, within 120 days of the enactment of this act, on the findings of the assessment and the agency's plan to incorporate those findings and recommendations, as appropriate, into its management of the premarket review program.
Counterfeit Products– The Committee recommendation includes an increase of $4,820,000 to provide FDA with additional resources to investigate counterfeit drugs both within the United States and internationally. These funds will be used to complete undercover purchases of suspected counterfeit products for testing; to remove counterfeit products from the market; and to prosecute criminal actors. The Committee believes that the growing marketplace for counterfeit drugs available on the Internet is particularly concerning, and these funds will allow FDA to enhance its cybercrime program, which will ultimately allow FDA to seek appropriate criminal fines and forfeitures, and to protect the public health.
Fixed Dose Combination Drugs– The Committee applauds the agency's issuance of draft guidance to promote the development of fixed combination drug products for critical diseases like cancer, HIV, global diseases like malaria and tuberculosis, and against health threats like drug-resistant infections. The Committee encourages the FDA to finalize the guidance by the end of this calendar year to facilitate development of new treatments against serious and life-threatening diseases. (See our previous post here.)
Food Safety Modernization Act– The Committee notes that FDA has stated its intent to re-propose certain sections of the Food Safety Modernization Act proposed rules for produce safety and preventive controls for human food and animal food because significant changes are warranted. The Committee is concerned that the agency only intends to address discrete portions of these proposed rules. FDA is reminded that the activities covered by the proposed rules are complex and interrelated and that the concerns raised by the rules are broader than the handful of items FDA has announced that it will address. The agency shall ensure that all Food Safety Modernization Act regulations are science-based, risk-based, and flexible, taking into account the different risks posed by different commodities. For example, the secondary market for spent grains and byproduct from human food manufacturing and agricultural practices is an important part of the supply chain for agricultural producers that reduces waste and produces safe, cost effective animal feed. FDA should reconsider how its proposed preventive controls for animal food rule will affect this relationship and the environment. Additionally, FDA should take into account the diversity of many integrated livestock and poultry feeding arrangements, and aquaculture feeding arrangements, when promulgating the final rule.
Further, FDA is directed to ensure that the public has an opportunity to review and comment on all preventive controls for human food requirements, accompanied by an economic analysis, including such elements as supplier verification, environmental monitoring, and verification testing of products in the form of a proposed rule, not an interim final or final rule. FDA should allow flexibility in the location and frequency of verification testing. The Committee strongly encourages the agency to re-propose the produce safety and preventive controls for human and animal food rules in their entirety so stakeholders may comment on the agency's proposals as a whole. (See our previous posts here and here.)
Food Safety Outreach and Technical Assistance– As FDA implements the requirements of the Food Safety Modernization Act [FSMA], it is critical that the agency work with USDA to perform outreach and technical assistance to farmers and small businesses to help them understand FSMA requirements and resources available to help with FSMA compliance as rules are developed and implemented. The Committee recommendation includes $2,500,000 for the National Institute of Food and Agriculture to conduct extension activities related to FSMA, as requested in the budget.
Global Drug Supply Chain– FDA is directed to ensure that adequate resources are dedicated to the Office Global Regulatory Operations and Policy and the Center for Drug Evaluation and Research to advance the agency's strategic priority of strengthening the safety and integrity of the global drug supply chain. In order to advance this initiative, resources should be dedicated to FDA's international leadership to combat threats to global health and the global drug supply chain from counterfeit medicines; promote regulatory convergence and the harmonization of international standards that will strengthen global drug supply chain security; and build upon and achieve key goals as articulated in FDA's reports on Global Engagement and the Pathway to Global Product Safety and Quality. As part of this effort, funding and personnel should be dedicated to advance the success of key efforts, including the FDA-championed Global Road Map on Medical Product Quality and Supply Chain Integrity under the Asia Pacific Economic Cooperation Regulatory Harmonization Steering Committee which will require FDA's continued leadership to ensure its success and tangible outcomes. In addition, adequate resources should be dedicated to FDA's work to improve policy, international cooperation, and enforcement collaboration related to the Internet and the unprecedented growth in illegal drug sales via the Internet, including the online trade of counterfeit, adulterated, misbranded, and unapproved drugs.
Import Shipments– The Commissioner is encouraged to ensure that sufficient FDA personnel are available to clear shipments expeditiously at the time of their arrival at the port of entry, including outside normal working hours and on holidays. The Commissioner is further encouraged to work to develop a process by which shipments from highly compliant importers may be released with minimal administrative disruption. Recognizing that FDA has a responsibility to ensure legitimate trade is cleared rapidly and that compliant shipments are not unduly detained, FDA is directed to provide two reports to the Committees on Appropriations, the first 6 months after the enactment of this act, and the second in 6 additional months. These reports shall provide information on the number of shipments being identified for FDA examination as a percentage of all shipments subject to FDA regulatory review and the number of violative products detained as a percentage of those being held.
Inclusion in Clinical Trials– Research has shown that gender differences, as well as differences based on age, race, or other factors, may contribute to differences in the safety and efficacy of drugs, biologics, and devices. The Committee directs FDA to encourages diverse participation, including women, racial and ethnic minorities, and the elderly, to help assure that clinical trials are representative of those individuals who ultimately will use these medical products, and that the products will be safe and effective for people in these demographic subgroups. The Committee urges the FDA to issue the Action Plan required by section 907 of the Food and Drug Administration Safety and Innovation Act and provide a timeline for implementation of the actions FDA will take, in cooperation with industry stakeholders, to ensure that women, minorities, and others are appropriately represented in clinical research, that meaningful subgroup analyses of clinical trials are conducted, and that subgroup specific clinical trial results are made publically available in an accessible and timely manner. (Additional information here and here.)
Mammography Quality Standards Act– The Committee recommendation includes full funding as requested for implementation of the Mammography Quality Standards Act. This program sets national quality standards for mammography facilities, equipment, personnel and operating procedures, and has improved the quality of mammography and made mammograms a more reliable tool to detect breast cancers.
Nanotechnology– The Committee recognizes the increased capabilities that FDA has developed to study environment, health, and safety of nanomaterials within FDA's Jefferson Laboratory Campus, including the National Center for Toxicological Research, and its consolidated headquarters at White Oak, Maryland. The Committee expects FDA to continue to support collaborative research with universities and industry on the toxicology of nanotechnology products and processes in accordance with the National Nanotechnology Initiative Environment, Health, and Safety Research Strategy as updated in October 2011.
Office of Cosmetics and Colors– The Committee recommendation includes not less than $11,700,000 for cosmetics activities, including not less than $7,200,000 for the Office of Colors and Cosmetics [OCAC]. Funding provided for OCAC is for direct support of the operation, staffing, compliance, research and international activities performed by this office. The Committee notes that every year since fiscal year 2012, it has requested that OCAC respond to a citizen petition setting safety levels for trace amount of lead in cosmetics. The Committee is disappointed that OCAC has not responded to these requests and urges OCAC to make this a priority. Therefore, the Committee directs the Office of Colors and Cosmetics to respond to the petition by March 15, 2015. Additionally, in light of China's importance to U.S.-based manufacturers and consumers, the Committee directs FDA establish a bilateral technical dialogue with Chinese regulators. The Committee directs FDA to promote international regulatory harmonization and trade in cosmetic products by supporting international trade negotiations on cosmetics in bilateral and multilateral trade agreements.
Oversight Activities– The Committee notes that over the past 5 years FDA's responsibilities have grown significantly and resources available to the agency have increased more than 60 percent. The Committee is concerned that oversight of FDA has not kept pace with the growth in the agency's regulatory authority or funding. Therefore, the Committee recommendation includes $1,500,000 for the HHS Office of Inspector General specifically for oversight of FDA activities. The funding provided under this appropriation is in addition to FDA oversight activities supported within the Inspector General's regular appropriation. The Committee instructs the Inspector General to submit a plan, within 60 days of the enactment of this act, on the additional oversight activities planned with this funding.
Pediatric Device Consortia Grants– The Committee is pleased that the nine FDA-funded Pediatric Device Consortia have assisted in advancing the development of 324 proposed pediatric medical devices since its inception in 2009, as well as promoting job-growth in the healthcare sector, and as such, continues to support this critical effort. The program funds consortia to assist innovators in developing medical and surgical devices designed for the unique needs of children, needs that often go unmet by devices currently available on the market. However, the Committee remains concerned that children's medical devices continue to lag behind those manufactured for adults and directs the FDA to fund the program at the levels authorized by the Food and Drug Safety and Innovation Act of 2012 (Public Law 112-144).
Prescription Drug Inserts– The Committee is aware that FDA is considering regulatory changes that could eliminate printed professional inserts for prescription drugs. A July 2013 GAO report on the topic concluded that while there were potential public health benefits associated with electronic drug labeling, relying exclusively on electronic labeling could disadvantage physicians, pharmacists, other healthcare providers, and ultimately patients, potentially adversely impacting public health. Therefore, the Committee directs FDA to ensure that any proposed regulation regarding electronic inserts of drug labeling does not come in lieu of paper inserts.
Seafood Advisory– The Committee is concerned that after many years, the FDA has not published an updated advice on seafood consumption for pregnant women, mothers and children. The Committee directs the FDA to publish final advice to pregnant women on seafood consumption in conjunction with all applicable parties as directed in House Report 112-101 and Senate Report 112-73 by June 30, 2014.
Seafood Economic Integrity– The Committee recognizes the importance of seafood to a healthy diet, but is concerned that the FDA does not focus sufficient attention on economic integrity issues, particularly with respect to mislabeling of species, weights, and treatment. The Committee encourages the FDA to work with States and the Department of Commerce to more aggressively combat fraud in parts of the seafood industry.
Shellfish Embargo– As a result of a dispute over sanitation protocols, the European Union imposed a retaliatory ban on U.S. shellfish in July 2010, depriving U.S. shellfish growers of a lucrative market. The Committee is concerned that, in nearly 4 years, a resolution has not been achieved. The Committee recommends that the FDA continue its ongoing consultation with the U.S. Trade Representative [USTR] to address the issue as expeditiously as possible. The FDA is also directed to provide a report to the Committee on this issue within 100 days.
Special Protocol Assessment– The Committee is aware that questions have arisen in connection with the rescission of a Special Protocol Assessment [SPA] Agreement. While FDA can rescind a SPA agreement reached under section 505(b)(5)(C) of the Food, Drug, and Cosmetic Act if certain requirements are met, the Committee expects that FDA should be accountable for continued diligence in in identifying issues that bear on a SPA agreement and in notifying the sponsor of such issues within a reasonable period of time after FDA becomes aware. To ensure clarity over the standard to rescind a SPA agreement, the Committee encourages FDA to revise and re-issue, after public comment, its existing guidance regarding SPA agreements, including the statutory standards associated with the rescission of such agreements.
Sunscreen Labeling Regulations– The Committee is pleased that FDA finalized regulations establishing significant new labeling and testing requirements for products marketed under FDA's monograph for over-the-counter sunscreen drug products. The Committee directs the FDA to finalize its proposed rule limiting the maximum Sun Protection Factor [SPF] to `50' or `50+' and issue a proposed rule to establish testing and labeling standards for sunscreen sprays.
User Fees– The Committee notes that the restoration in fiscal year 2014 of user fees sequestered in fiscal year 2013 was to be used by FDA to mitigate the impact of the sequester on the user fee programs. This includes the hiring of new staff, and FDA initiatives supported by PDUFA user fees, including the regulatory science activities as outlined in sections IX, X, and XI of the PDUFA Reauthorization Performance Goals and Procedures Fiscal Years 2013 Through 2017. The Committee requests that FDA provide a detailed financial summary for the restored fiscal year 2013 PDUFA user fees; identify funding spent to date; and a detailed plan for the allocation of the remaining funds. Specifically, the Committee requests that FDA identify and report to the Committee an itemized accounting of any and all funds expended for each of the regulatory science activities as outlined in sections IX, X, and XI of the PDUFA V Performance Goals and provide a plan for how the PDUFA user fees will be allocated for each such activity through fiscal year 2017.
