New drugs for human use; clarification of requirements for patent holder notification--FDA. Proposed rule

The Food and Drug Administration (FDA) is proposing to amend its regulations on notice of certification of invalidity or noninfringement of a patent to provide additional methods for new drug and abbreviated new drug applicants to provide notice to patent owners and new drug application (NDA) holders, without removing the existing means. These proposed amendments reflect current business practices and are intended to ensure that notice is provided to patent owners and NDA holders in a timely manner. FDA is also proposing to require certain applicants to submit to FDA a copy of the notice of certification.     

Applications for Food and Drug Administration approval to market a new drug; postmarketing reports; reporting information about authorized generic drugs. Direct final rule

The Food and Drug Administration (FDA) is amending its regulations to require that the holder of a new drug application (NDA) submit certain information regarding authorized generic drugs in an annual report. We are taking this action as part of our implementation of the Food and Drug Administration Amendments Act of 2007 (FDAAA). FDAAA requires that FDA publish a list of all authorized generic drugs included in an annual report since 1999, and that the agency update the list quarterly. We are using direct final rulemaking for this action because the agency expects that there will be no significant adverse comment on the rule. In the proposed rule section of this issue of the Federal Register, we are concurrently proposing and soliciting comments on this rule. If significant adverse comments are received, we will withdraw this final rule and address the comments in a subsequent final rule. FDA will not provide additional opportunity for comment.     

Applications for FDA approval to market a dew drug: patent submission and listing requirements and application of 30-month stays on approval of abbreviated new drug applications certifying that a patent claiming a drug is invalid or will not be infringed. Final rule

The Food and Drug Administration (FDA) is amending its patent submission and listing requirements for new drug applications (NDAs). The final rule clarifies the types of patents that must and must not be submitted and revises the declaration that NDA applicants must provide regarding their patents to help ensure that NDA applicants submit only appropriate patents. The final rule also revises the regulations regarding the effective date of approval for certain abbreviated new drug applications (ANDAs) and certain other new drug applications, known as 505(b)(2) applications, submitted under the Federal Food, Drug, and Cosmetic Act (the act). In certain situations, Federal law bars FDA from making the approval of certain ANDA and 505(b)(2) applications effective for 30 months if the applicant has certified that the patent claiming a drug is invalid or will not be infringed, and the patent owner or NDA holder then brings suit for patent infringement. The final rule also states that there is only one opportunity for a 30-month stay in the approval date of each ANDA and 505(b)(2) application. The final rule will make the patent submission and listing process more efficient as well as enhance the ANDA and 505(b)(2) application approval processes.     

Supplemental applications proposing labeling changes for approved drugs, biologics, and medical devices. Final rule

The Food and Drug Administration (FDA) is amending its regulations regarding changes to an approved new drug application (NDA), biologics license application (BLA), or medical device premarket approval application (PMA). This final rule provides that a supplemental application submitted under certain FDA regulations is appropriate to amend the labeling for an approved product to reflect newly acquired information and to add or strengthen a contraindication, warning, precaution, or adverse reaction if there is sufficient evidence of a causal association with the drug, biologic, or device, as defined in other FDA regulations and guidance documents.     

Medical devices; various proposed rules for device classification; withdrawal of proposed rules. Food and Drug Administration. Withdrawal of proposed rules

The Food and Drug Administration (FDA) is withdrawing various proposed rules related to classification of general hospital and personal use devices, anesthesiology devices, and immunology and microbiology devices to eliminate unnecessary regulations.     

The battle over global drug markets: enforcement of pharmaceutical patents in the United States, Europe and Japan

Legal context: Pharmaceutical patent litigation is on the rise. The focal pointof this increasingly contentious area of litigation is the surgein pharmaceutical patent challenges mounted by generic drugmanufacturers. Pharmaceutical companies need to identify viableenforcement strategies that can survive these challenges andeffectively manage the life cycle of their pharmaceutical productsaround the world. Key points: The degree to which pharmaceutical companies can capitalizeupon the value of their second generation patents to extendthe protection given to existing drug products depends in parton the patent landscape, country by country, and also on theregulatory landscape for generic drug products and their entryinto the marketplace.This paper will examine the patent laws,drug approval regulations, and court decisions on the validityand enforceability of later stage or second generation patentsdirected to combination compounds, selection inventions, andnew indications, in three major jurisdictions: The United States,Europe/UK, and Japan. Practical significance: Successful pharmaceutical companies can maintain a competitiveadvantage in the global pharmaceutical industry by evaluatingand strengthening the way existing drug products are protectedand, in many cases, changing the nature of protection underthe patent laws by improving upon the pharmaceutical productitself.     

Investigational new drug application; exception from informed consent; technical amendment--FDA. Final rule

The Food and Drug Administration (FDA) is amending its investigational new drug application (IND) regulations to clarify that, within 30 days after the receipt of an IND for any clinical investigation involving an exception from informed consent, FDA will provide a written determination as to whether the investigation may begin. This action is intended to clarify a recent amendment to the IND regulations for clinical investigations involving an exception from informed consent that states that FDA will provide a written authorization within 30 days of receipt of the IND.     

Status of certain additional over-the-counter drug category II and III active ingredients--FDA. Final rule

The Food and Drug administration (FDA) is issuing a final rule stating that certain ingredients in over-the-counter (OTC) drug products are not generally recognized as safe and effective or are misbranded. FDA is issuing this final rule after considering the reports and recommendations of various OTC drug advisory review panels and public comments on proposed agency regulations, which were issued in the form of a tentative final monograph (proposed rule). Based on the absence of substantive comments in opposition to the agency's proposed nonmonograph status for these ingredients, as well as the failure of interested parties to submit new data or information to FDA under the regulation, the agency has determined that the presence of these ingredients in an OTC drug product would result in that drug product not being generally recognized as safe and effective or would result in misbranding. This final rule is part of the ongoing review of OTC drug products conducted by FDA.     

Revocation of Office of Generic Drug's interim policy statement on inactive ingredients. Food and Drug Administration, HHS. Notice

The Food and Drug Administration (FDA) is revoking an interim policy statement on inactive ingredients in parenteral, ophthalmic, otic, and topical generic drug products (Interim Inactive Ingredient Policy). These generic drug products are the subjects of abbreviated new drug applications (ANDA's). The Interim Inactive Ingredient Policy was issued as a memorandum from the Acting Director of the Center for Drug Evaluation and Research's (CDER's) Office of Generic Drugs, FDA, to CDER's Associate Director for Science and Medical Affairs, FDA. FDA is taking this action because the Interim Inactive Ingredient Policy no longer represents current agency policy.     

Current good manufacturing practice regulation and investigational new drugs. Direct final rule

The Food and Drug Administration (FDA) is amending its current good manufacturing practice (CGMP) regulations for human drugs, including biological products, to exempt most investigational "Phase 1" drugs from complying with the requirements in FDA's regulations. FDA will instead exercise oversight of production of these drugs under the agency's general statutory CGMP authority and investigational new drug application (IND) authority. In addition, FDA is making available simultaneously with the publication of this direct final rule, a guidance document setting forth recommendations on approaches to CGMP compliance for the exempted Phase 1 drugs. Elsewhere in this issue of the Federal Register, FDA is publishing a companion proposed rule, under FDA's usual procedure for notice-and-comment rulemaking, to provide a procedural framework to finalize the rule in the event the agency receives any significant adverse comments and withdraws this direct final rule. The companion proposed rule and direct final rule are substantively identical. Elsewhere in this issue of the Federal Register, FDA is announcing the availability of a draft guidance for industry entitled "INDs--Approaches to Complying With CGMP During Phase 1" to provide further guidance on the subject.     

Policy on 180-day marketing exclusivity for drugs marketed under abbreviated new drug applications; clarification--FDA. Clarification

The Center for Drug Evaluation and Research (CDER) of the Food and Drug Administration (FDA) is publishing this document to clarify the status of its practices governing 180 days of marketing exclusivity for generic drugs and the approval of abbreviated new drug applications (ANDA's) subject to patent litigation. This document is being published due to recent court decisions interpreting provisions of the Drug Price Competition and Patent Term Restoration Act of 1984 (Pub. L. 98-417) (the 1984 amendments).     

Regulations for in vivo radiopharmaceuticals used for diagnosis and monitoring; extension of comment period--FDA. Proposed rule; extension of comment period

The Food and Drug Administration (FDA) is extending to October 15, 1998, the comment period on a proposal rule that was published in the Federal Register of May 22, 1998 (63 FR 28301). The document proposed to amend the drug and biologics regulations by adding provisions that would clarify the evaluation and approval of in vivo radiopharmaceuticals used in the diagnosis or monitoring of diseases. The agency is taking this action to provide interested persons additional time to submit comments to FDA on the proposed rule.     

Financial disclosure by clinical investigators--FDA. Final rule

The food and Drug Administration (FDA) is issuing regulations requiring the sponsor of any drug, including a biological product, or device marketing application (applicant), to submit certain information concerning the compensation to, and financial interests of any clinical investigator conducting certain clinical studies. This requirement will apply to any covered clinical study of a drug or device submitted in a marketing application that the applicant or FDA relies on to establish that the product is effective, including studies that show equivalence to an effective product, or that make a significant contribution to the demonstration of safety. This final rule requires applicants to certify to the absence of certain financial interests of clinical investigators and/or disclose those financial interests, as required, when covered clinical studies are submitted to FDA in support of product marketing. This regulation is intended to ensure that financial interests and arrangements of clinical investigators that could affect reliability of data submitted to FDA in support of product marketing are identified and disclosed by the sponsor of any drug, biological product, or device marketing application. If the applicant does not include certification or disclosure, or both, if required, or does not certify that it was not possible to obtain the information, the agency may refuse to file the application. FDA intends to propose to extend these requirements to submissions for marketing approval related to human foods, animal foods, and animal drugs in a subsequent issue of the Federal Register.     

Investigational new drug applications; clinical holds--FDA. Direct final rule

The Food and Drug Administration (FDA) is amending its regulations governing investigational new drug applications (IND's) for human drug and biological products. This action amends the IND clinical hold requirements to state that the agency will respond in writing to a sponsor's request that a clinical hold be removed from an investigation within 30-calendar days of the agency's receipt of the request and the sponsor's complete response to the issue(s) that led to the clinical hold. FDA is taking this action in accordance with provisions of the Food and Drug Administration Modernization Act of 1997 (the Modernization Act). Elsewhere in this issue of the Federal Register, FDA is publishing a companion proposed rule under FDA's usual procedure for notice-and-comment rulemaking to provide a procedural framework to finalize the rule in the event the agency receives significant adverse comments and withdraws this direct final rule.     

Investigational new drug applications; clinical holds; companion document to direct final rule--FDA. Proposed rule

The Food and Drug Administration (FDA) is proposing to amend its regulations governing investigational new drug applications (IND's) for human drug and biological products. This proposed action would amend the IND clinical hold requirements to state that the agency will respond in writing to a sponsor's request that a clinical hold be removed from an investigation within 30-calendar days of the agency's receipt of the request and the sponsor's complete response to the issue(s) that led to the clinical hold. This proposed action is being taken in accordance with provisions of the Food and Drug Administration Modernization Act of 1997 (the Modernization Act). This proposed rule is a companion document to a direct final rule published elsewhere in this issue of the Federal Register. If FDA receives any significant adverse comment, the direct final rule will be withdrawn, and the comments will be considered in the development of a final rule using usual notice-and-comment rulemaking based on this proposed rule.     

Regulations for in vivo radiopharmaceuticals used for diagnosis and monitoring--FDA. Proposed rule

The Food and Drug Administration (FDA), in response to the requirements of the Food and Drug Administration Modernization Act of 1997 (FDAMA), is proposing to amend the drug and biologics regulations by adding provisions that would clarify the evaluation and approval of in vivo radiopharmaceuticals used in the diagnosis or monitoring of diseases. The proposed regulations would describe certain types of indications for which FDA may approve diagnostic radiopharmaceuticals. The proposed rule also would include criteria that the agency would use to evaluate the safety and effectiveness of a diagnostic radiopharmaceutical under the Federal Food, Drug, and Cosmetic Act (the act) and the Public Health Service Act (the PHS Act.     

Dissemination of information on unapproved/new uses for marketed drugs, biologics, and devices--FDA. Proposed rule

The Food and Drug Administration (FDA) is proposing to issue new regulations pertaining to the dissemination of information on unapproved uses (also referred to as "new uses" and "off-label uses") for marketed drug, including biologics, and devices. The proposal, which would implement the dissemination provisions of the Food and Drug Administration Modernization Act of 1997 (FDAMA), would describe the content of and establish procedures for a manufacturer's submissions to FDA before it may begin disseminating information on the new use. The proposal also would describe how manufacturers seeking to disseminate new use information must agree to submit a supplement for that use within a specified period of time, unless a supplemental application already has been submitted or FDA has exempted the manufacturer from the requirement to submit a supplement. The proposal also would provide for requests to extend the time period for submitting a supplement for a new use, and it would describe how a manufacturer can seek an exemption from the requirement to submit a supplement. Additionally, the proposal would discuss FDA actions in response to manufacturer's submissions, corrective actions that FDA may take, and recordkeeping and reporting requirements.     

General administrative rulings and decisions; amendment to the examination and investigation sample requirements; companion document to direct final rule--FDA. Proposed rule

The Food and Drug Administration (FDA) is proposing to amend its regulations regarding the collection of twice the quantity of food, drug, or cosmetic estimated to be sufficient for analysis. This action increases the dollar amount that FDA will consider to determine whether to routinely collect a reserve sample of a food, drug, or cosmetic product in addition to the quantity sufficient for analysis. Experience has demonstrated that the current dollar amount does not adequately cover the cost of most quantities sufficient for analysis plus reserve samples. This proposed rule is a companion to the direct final rule published elsewhere in this issue of the Federal Register. This action is part of FDA's continuing effort to achieve the objectives of the President's "Reinventing Government" initiative, and it is intended to reduce the burden of unnecessary regulations on food, drugs, and cosmetics without diminishing the protection of the public health.     

Amendment to examination and investigation sample requirements--FDA. Direct final rule

The Food and Drug Administration (FDA) is amending its regulations regarding the collection of twice the quantity of food, drug, or cosmetic estimated to be sufficient for analysis. This action increases the dollar amount that FDA will consider to determine whether to routinely collect a reserve sample of a food, drug, or cosmetic product in addition to the quantity sufficient for analysis. Experience has demonstrated that the current dollar amount does not adequately cover the cost of most quantities sufficient for analysis plus reserve samples. This direct final rule is part of FDA's continuing effort to achieve the objectives of the President's "Reinventing Government" initiative, and is intended to reduce the burden of unnecessary regulations on food, drugs, and cosmetics without diminishing the protection of the public health. Elsewhere in this issue of the Federal Register, FDA is publishing a companion proposed rule under FDA's usual procedures for notice and comment to provide a procedural framework to finalize the rule in the event the agency receives any significant adverse comment and withdraws this direct final rule.