Postmarketing studies for approved human drug and licensed biological products; status reports. Food and Drug Administration, HHS. Final rule

The Food and Drug Administration (FDA) is revising the requirements for annual postmarketing status reports for approved human drug and biological products, and is requiring applicants to submit annual status reports for certain postmarketing studies of licensed biological products. This rule describes the types of postmarketing studies covered by these status reports, the information to be included in the reports, and the type of information that FDA would consider appropriate for public disclosure. This action will implement the Food and Drug Administration Modernization Act of 1997 (FDAMA).     

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.     

Medical devices; exemptions from premarket notification; class II devices--FDA, Final rule

The Food and Drug Administration (FDA) is codifying the exemption from premarket notification of all 62 class II (special controls) devices listed as exempt in a January 21, 1998, Federal Register notice, subject to the limitations on exemptions. FDA has determined that for these exempted devices, manufacturers' submissions of premarket notifications are unnecessary to provide a reasonable assurance of safety and effectiveness. These devices will remain subject to current good manufacturing practice (CGMP) regulations and other general controls. This rulemaking implements new authorities delegated to FDA under the Food and Drug Administration Modernization Act (FDAMA).     

Disqualification of a clinical investigator--FDA. Final rule

The Food and Drug Administration (FDA) is amending the investigational new drug regulation that provides for disqualification of clinical investigators who submit false information. The revision is intended to clarify the agency's authority to reach sponsor-investigators under the regulation.     

Orthopedic devices; classification for the resorbable calcium salt bone void filler device. Final rule

The Food and Drug Administration (FDA) is classifying the resorbable calcium salt bone void filler device intended to fill bony voids or gaps of the extremities, spine, and pelvis that are caused by trauma or surgery and are not intrinsic to the stability of the bony structure into class II (special controls). Elsewhere in this issue of the Federal Register, FDA is announcing the availability of a class II special controls guidance entitled "Class II Special Controls Guidance Document: Resorbable Calcium Salt Bone Void Filler Device; Guidance for Industry and FDA." This action is being undertaken based on new information submitted in a classification proposal from Wright Medical Technology under the Federal Food, Drug, and Cosmetic Act as amended by the Medical Device Amendments of 1976, the Safe Medical Devices Act of 1990, and the Food and Drug Administration Modernization Act of 1997.     

Medical devices; substantial equivalence; 510(K) summaries and 510(K) statements; class III summaries; confidentiality of information--FDA. Final rule

The Food and Drug Administration (FDA) is issuing this final rule to implement the provisions of the Safe Medical Devices Act of 1990 (the SMDA) that require all persons who submit a premarket notification (510(k)) to provide to FDA, as part of the submission, an adequate summary (510(k) summary) of any information respecting safety and effectiveness or a statement (510(k) statement) that such information will be made available upon request by any person. This rule also implements the requirement of the SMDA that 510(k) submitters claiming substantial equivalence to a class III preamendments device for which FDA has not yet called for premarket approval submit a class III summary and certify that they have conducted a search of safety and effectiveness data. In addition, this rule amends the device regulations governing the confidentiality of certain premarket notification submissions to conform to the SMDA. This rule also provides that persons who submit a premarket notification must certify that, to the best of their knowledge, all information is truthful and accurate and that no material fact has been omitted.     

Medical device reporting--FDA. Reproposal

The Food and Drug Administration (FDA) is issuing a revised proposal to require manufacturers and importers of medical devices to report to FDA whenever the manufacturer or importer has information that reasonably suggests, or a person alleges and the manufacturer or importer is aware of the allegation, that a device has caused or contributed to a death or serious injury or that a device has malfunctioned, if a recurrence of the malfunction is likely to cause or contribute to a death or serious injury. After FDA analyzes the results of its manufacturer complaint file inspection program, the agency will consider whether any reports in addition to those proposed in this rule are necessary and, if so, will propose additional reporting requirements.     

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.     

New drug applications; drug master files. Food and Drug Administration, HHS. Final rule

The Food and Drug Administration (FDA) is revising its regulation governing drug master files (DMF's). FDA is removing the provision for submitting Type I DMF's and will no longer permit information submitted in a Type I DMF to be incorporated by reference in investigational new drug applications (IND's), new drug applications (NDA's), abbreviated new drug applications (ANDA's), or amendments or supplements to any of these. This rule is intended to eliminate submissions of information that are not necessary either to conduct inspections of manufacturing facilities or to review the chemistry, manufacturing, and controls sections of IND's, NDA's, and abbreviated applications.     

Order for transitional class III devices; submission of safety and effectiveness information under section 520(1)(5)(A) of the Federal Food, Drug, and Cosmetic Act--FDA. Notice

The Food and Drug Administration (FDA) is issuing an order requiring manufacturers of transitional class III devices to submit to FDA a summary of, and a citation to, any information known or otherwise available to the manufacturers respecting the devices, including adverse safety or effectiveness information which has not been submitted under section 519 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360i). This is the first step in the process of determining the appropriate classification of transitional devices under the Safe Medical Devices Act of 1990.     

Medical devices; reclassification of the cutaneous carbon dioxide and the cutaneous oxygen monitor. Final rule

The Food and Drug Administration (FDA) is reclassifying the cutaneous carbon dioxide (PcCO2) monitor from class II (performance standards) into class II (special controls). FDA is also reclassifying the cutaneous oxygen (PcO2) monitor for an infant patient who is not under gas anesthesia from class II (performance standards) into class II (special controls) and is reclassifying the cutaneous oxygen (PcO2) monitor for all other uses from class III (premarket approval) into class II (special controls). Elsewhere in this issue of the Federal Register, FDA is announcing the availability of the guidance document entitled "Class II [[Page 76679]] Special Controls Guidance Document: Cutaneous Carbon Dioxide (PcCO2) and Oxygen (PcO2) Monitors; Guidance for Industry and FDA" that will serve as the special control for the devices. These reclassifications are taken on the agency's own initiative based on new information. These actions are being taken under the Federal Food, Drug, and Cosmetic Act (the act), as amended by the Medical Device Amendments of 1976 (the 1976 amendments), the Safe Medical Devices Act of 1990 (the SMDA), the Food and Drug Administration Modernization Act of 1997 (FDAMA), and the Medical Device User Fee and Modernization Act.     

Medical devices containing materials derived from animal sources (except for in vitro diagnostic devices), guidance for FDA reviewers and industry; availability--FDA. Notice

The Food and Drug Administration (FDA) is announcing the availability of the guidance entitled "Medical Devices Containing Materials Derived From Animal Sources (Except for In Vitro Diagnostic Devices), Guidance for FDA Reviewers and Industry." This guidance is intended to provide recommendations for information that is to be included in premarket submissions--investigational device exemption (IDE), premarket approval application (PMA), and 510(k) submissions for medical devices that either contain or are exposed to animal-derived materials during manufacturing.     

Food labeling: nutrient content claims, expansion of the nutrient content claim "lean". Final rule

The Food and Drug Administration (FDA) is amending its food labeling regulations for the expanded use of the nutrient content claim "lean" on the labels of foods categorized as "mixed dishes not measurable with a cup" that meet certain criteria for total fat, saturated fat, and cholesterol content. This final rule responds to a nutrient content claim petition submitted by Nestlé Prepared Foods Co. (Nestlé) under the Federal Food, Drug, and Cosmetic Act (the act). This action is also being taken to provide reliable information that would assist consumers in maintaining healthy dietary practices.     

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.     

Biological products regulated under Section 351 of the Public Health Services Act; implementation of biologics license; elimination of establishment license and product license--FDA. Proposed rule

The Food and Drug Administration (FDA) is proposing to amend the biologics regulations to eliminate references to establishment licenses and product licenses for all products regulated under the Public Health Service Act (PHS Act). In lieu of filing an establishment license application (ELA) and product license application (PLA) in order to market a biological product in interstate commerce, a manufacturer would file a single biologics license application (BLA) with the agency. Upon approval of the BLA, a manufacturer would receive a biologics license to market the product in interstate commerce. This action is part of FDA's continuing effort to achieve the objectives of the President's "Reinventing Government" initiatives and is intended to reduce unnecessary burdens for industry without diminishing public health protection. This action also proposes regulations to implement certain sections of the Food and Drug Administration Modernization Act of 1997 (FDAMA).     

Current good manufacturing practice in manufacturing, packaging, labeling, or holding operations for dietary supplements. Final rule

The Food and Drug Administration (FDA) is issuing a final rule regarding current good manufacturing practice (CGMP) for dietary supplements. The final rule establishes the minimum CGMPs necessary for activities related to manufacturing, packaging, labeling, or holding dietary supplements to ensure the quality of the dietary supplement. The final rule is one of many actions related to dietary supplements that we are taking to promote and protect the public health.     

Orthopedic devices: reclassification of the hip joint metal/polymer constrained cemented or uncemented prosthesis. Final Rule

The Food and Drug Administration (FDA) is reclassifying the hip joint metal/polymer constrained cemented or uncemented prosthesis intended to replace a hip joint from class III (premarket approval) to class II (special controls). FDA is also [[Page 21172]] identifying the guidance document entitled "Class II Special Controls Guidance Document: Hip Joint Metal/Polymer Constrained Cemented or Uncemented Prosthesis" as the special control that the agency believes will reasonably ensure the safety and effectiveness of the device. This reclassification is being undertaken based on new information regarding the device contained in a reclassification petition submitted by the Orthopedic Surgical Manufacturers Association (OSMA), under the Federal Food, Drug, and Cosmetic Act (the act), as amended by the Medical Device Amendments of 1976 (the 1976 Amendments), the Safe Medical Devices Act of 1990 (SMDA), and the Food and Drug Administration Moderization Act of 1997 (FDAMA). FDA is also revising the device identification to accurately describe the device.     

Toll-free number for reporting adverse events on labeling for human drug products. Interim final rule

The Food and Drug Administration (FDA) is issuing an interim final rule to codify the provisions of the proposed rule entitled "Toll-Free Number for Reporting Adverse Events on Labeling for Human Drug Products" (69 FR 21778, April 22, 2004) (the toll-free number proposed rule or proposed rule) that, under the Food and Drug Administration Amendments Act of 2007 (FDAAA), became effective by operation of law on January 1, 2008. This interim final rule requires the addition of a statement on the labeling of certain human drug products for which an application is approved under the Federal Food, Drug, and Cosmetic Act (the act). The added statement includes a toll-free number and advises that the number is to be used only for reporting side effects and is not intended for medical advice (the side effects statement). As mandated by FDAAA, this interim final rule does not apply to over-the-counter drug products approved as new drugs under the act if the product packaging includes a manufacturer's or distributor's toll-free number for reporting complaints.     

Applications for Food and Drug Administration application approval to market a new drug; revision of postmarketing reporting requirements. Final rule

The Food and Drug Administration (FDA) is amending its regulations describing postmarketing reporting requirements to implement certain provisions of the Food and Drug Administration Modernization Act of 1997 (the Modernization Act). The changes apply to drug products that are life supporting, life sustaining, or intended for use in the prevention of a serious disease or condition and that were not originally derived from human tissue and replaced by a recombinant product. The final rule implements provisions of the Modernization Act by requiring an applicant who is the sole manufacturer of one of these products to notify FDA at least 6 months before discontinuing manufacture of the drug product.     

Public information; communications with state and foreign government officials--FDA. Proposed rule

The Food and Drug Administration (FDA) is proposing to amend its regulations governing communications with State and foreign government officials. The proposed rule would permit FDA to disclose confidential commercial information to international organizations having responsibility to facilitate global or regional harmonization of standards and requirements. These disclosures would, in almost all instances, occur only with the consent of the person providing the confidential commercial information to FDA. The proposed rule would also streamline the process for FDA officials to disclose certain nonpublic, predecisional documents (such as draft rules and guidance documents) to State and foreign government officials. The proposal does not alter current procedures for sharing documents that contain confidential commercial information. These changes are intended to facilitate information exchanges with State and foreign governments and certain international organizations.