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.     

Investigational new drug applications and new drug applications--FDA. Final rule

The Food and Drug Administration (FDA) is amending its regulations pertaining to new drug applications (NDA's) to clearly define in the NDA format and content regulations the requirement to present effectiveness and safety data for important demographic subgroups, specifically gender, age, and racial subgroups. FDA also is amending its regulations pertaining to investigational new drug applications (IND's) to require sponsors to tabulate in their annual reports the numbers of subjects enrolled to date in clinical studies for drug and biological products according to age group, gender, and race. This action is intended to alert sponsors as early as possible to potential demographic deficiencies in enrollment that could lead to avoidable deficiencies later in the NDA submission. This rule does not address the requirements for the conduct of clinical studies and does not require sponsors to conduct additional studies or collect additional data. It also does not require the inclusion of a particular number of individuals from specific subgroups in any study or overall. The rule refers only to the presentation of data already collected.     

Current good manufacturing practice and investigational new drugs intended for use in clinical trials. Final rule

The Food and Drug Administration (FDA) is amending the current good manufacturing practice (CGMP) regulations for human drugs, including biological products, to exempt most phase 1 investigational drugs from complying with the regulatory CGMP requirements. FDA will continue to exercise oversight of the manufacture of these drugs under FDA's general statutory CGMP authority and through review of the investigational new drug applications (IND). In addition, elsewhere in this issue of the Federal Register, FDA is announcing the availability of a guidance document entitled "Guidance for Industry: CGMP for Phase 1 Investigational Drugs" dated November 2007 (the companion guidance). This guidance document sets forth recommendations on approaches to compliance with statutory CGMP for the exempted phase 1 investigational drugs. FDA is taking this action to focus a manufacturer's effort on applying CGMP that is appropriate and meaningful for the manufacture of the earliest stage investigational drug products intended for use in phase 1 clinical trials while ensuring safety and quality. This action will also streamline and promote the drug development process.     

Respiratory protection; correction--OSHA. Final rule; correction

OSHA is correcting errors in the regulatory text of the Respiratory Protection final rule that appeared in the Federal Register on January 8, 1998 (63 FR 1152).     

Medical devices; procedures for investigational device exemptions--Food and Drug Administration. Final rule

This rule sets forth the procedures and conditions under which investigations of medical devices involving human subjects may be exempt from certain requirements of the Federal Food, Drug, and Cosmetic Act, in accordance with the Medical Device Amendments of 1976. The rule sets out the procedures to obtain an investigational device exemption (IDE); it delineates the responsibilities of sponsors, institutional review boards, and clinical investigators with respect to clinical investigations of medical devices; and the rule also prescribes informed consent requirements and specifies recordkeeping and reporting requirements.     

New drug and biological drug products; evidence needed to demonstrate effectiveness of new drugs when human efficacy studies are not ethical or feasible. Final rule

The Food and Drug Administration (FDA) is amending its new drug and biological product regulations to allow appropriate studies in animals in certain cases to provide substantial evidence of the effectiveness of new drug and biological products used to reduce or prevent the toxicity of chemical, biological, radiological, or nuclear substances. This rule will apply when adequate and well-controlled clinical studies in humans cannot be ethically conducted and field efficacy studies are not feasible. In these situations, certain new drug and biological products that are intended to reduce or prevent serious or life-threatening conditions may be approved for marketing based on evidence of effectiveness derived from appropriate studies in animals and any additional supporting data.     

Investigational new drug, antibiotic, and biological product applications; clinical hold and termination--FDA. Final rule

The Food and Drug Administration (FDA) is issuing a final regulation that provides additional grounds for placing an investigation on "clinical hold" and for terminating an investigational new drug application (IND). Under this rule, FDA may require sponsors to cease distributing an experimental drug in an open, nonconcurrently controlled investigation if any of several specified conditions exist. This final rule is part of the Public Health Service's(PHS's) efforts to make promising drugs widely available to people with acquired immunodeficiency syndrome (AIDS) or human immunodeficiency virus (HIV)-related disease who lack satisfactory alternative therapies, while simultaneously ensuring that the adequate and well-controlled clinical trials essential to establishing a new drug's safety and effectiveness are expeditiously conducted.     

Medical devices; clinical chemistry and clinical toxicology devices; drug metabolizing enzyme genotyping system. Final rule

The Food and Drug Administration (FDA) is classifying drug metabolizing enzyme (DME) genotyping test systems into class II (special controls). The special control that will apply to the device is the guidance document entitled "Class II Special Controls Guidance Document: Drug Metabolizing Enzyme Genotyping System." The agency is classifying the device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of the device. Elsewhere in this issue of the Federal Register, FDA is publishing a notice of availability of a guidance document that is the special control for this device.     

Medicaid program; multiple source drug definition. Final rule

This final rule revises the definition of "multiple source drug" to better conform the regulatory definition to the provisions of section 1927(k)(7) of the Social Security Act. It also responds to public comments received on the March 14, 2008 interim final rule with comment period.     

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.     

Delegations of authority and organization; new drug applications--Food and Drug Administration. Final rule

The Food and Drug Administration (FDA) is amending the regulations for delegations of authority regarding approval of new drug applications (NDA's) by redelegating to the Directors of Divisions conducting new drug evaluations authority to approve an additional class of NDA's to expedite the approval process. Published elsewhere in this issue of the Federal Register is a notice reorganizing the Bureau of Drugs and Bureau of Biologics into the National Center for Drugs and Biologics. This document also updates organizational references in accordance with the reorganization.     

Investigational new drugs: export requirements for unapproved new drug products. Final rule

The Food and Drug Administration (FDA) is amending its regulations on the exportation of investigational new drugs, including biological products. The final rule describes four different mechanisms for exporting an investigational new drug product. These provisions implement changes in FDA's export authority resulting from the FDA Export Reform and Enhancement Act of 1996 and also simplify the existing requirements for exports of investigational new drugs.     

Health and Human Services policy for protection of human subjects research--HHS. Final rule

The Department of Health and Human Services (HHS) is amending its Human Subjects Protection regulations to rescind the provision requiring prior review and advice from an Ethical Advisory Board for research applications and proposals involving in vitro fertilization (IVF) of human ova as a prerequisite to funding by HHS and its components. The provision was nullified by the National Institutes of Health Revitalization Act of 1993. The regulations are being amended to reflect this statutory nullification. Institutional Review Board (IRB) review and approval of applications and proposals involving in vitro fertilization (IVF) of human ova continues to be required in accordance with other provisions of the Human Subjects Protection regulations. Furthermore, the Secretary may still exercise the option of seeking advice from an Ethical Advisory Board on ethical issues, including IVF, raised by research applications and proposals.     

Medicaid program; time limitation on recordkeeping requirements under the drug rebate program. Final rule

This final rule finalizes 10-year recordkeeping requirements for drug manufacturers under the Medicaid drug rebate program. Manufacturers must retain records for 10 years from the date the manufacturer reports data to us for a rebate period. This final rule also finalizes the requirement that manufacturers must retain records beyond the 10-year period if the records are known by the manufacturer to be the subject of an audit or a government investigation. Furthermore, this final rule responds to public comments on the January 6, 2004 interim final rule with comment period and the proposed rule pertaining to the 10-year recordkeeping requirements, respectively.     

Supplements and other changes to an approved application. Final rule

The Food and Drug Administration (FDA) is amending its regulations on supplements and other changes to an approved application to implement the manufacturing changes provision of the Food and Drug Administration Modernization Act of 1997 (the Modernization Act). The final rule requires manufacturers to assess the effects of manufacturing changes on the identity, strength, quality, purity, and potency of a drug or biological product as those factors relate to the safety or effectiveness of the product. The final rule sets forth requirements for changes requiring supplement submission and approval before the distribution of the product made using the change, changes requiring supplement submission at least 30 days prior to the distribution of the product, changes requiring supplement submission at the time of distribution, and changes to be described in an annual report.     

Financial disclosure by clinical investigators; correction--FDA. Final rule; correction

The Food and Drug Administration (FDA) is correcting a final rule that appeared in the Federal Register of February 2, 1998 (63 FR 5233). The document issued regulations requiring the sponsor of any drug, including a biological product, or device marketing application (applicant), to submit certain information covering the compensation to, and financial interests of, any clinical investigator conducting certain clinical studies. The document was published with an error. This document corrects that error.     

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.