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.     

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.     

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 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.     

Assignment of agency component for review of premarket applications--FDA. Final rule

The Food and Drug Administration (FDA) is promulgating a new regulation to describe how the agency will determine which component within FDA will have primary jurisdiction for the premarket review and regulation of: (1) A combination drug, device, or biologic product or (2) any drug, device, or biologic product where the center with primary jurisdiction is unclear or in dispute. This rule describes how to identify the agency's assigned review component which will, in most cases, eliminate the need for a sponsor to obtain approval from more than one FDA component for a combination product.     

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.     

Investigational new drug applications; amendment to clinical hold regulations for products intended for life-threatening diseases and conditions. Food and Drug Administration, HHS. Final rule

The Food and Drug Administration (FDA) is amending the regulations governing investigational new drug applications (IND's) to permit FDA to place a clinical hold on one or more studies under an IND involving a drug that is intended to treat a life-threatening disease or condition affecting both genders. The amendments permit the agency to place a clinical hold on such studies if men or women with reproductive potential who have the disease or condition are otherwise eligible but are categorically excluded from participation solely because of a perceived risk or potential risk of reproductive or developmental toxicity from use of the investigational drug. This rule was developed in response to the past practice of excluding women with reproductive potential from early clinical trials because of a perceived risk or potential risk of reproductive or developmental toxicity. The final rule does not impose requirements to enroll or recruit a specific number of men or women with reproductive potential.     

Investigational new drug safety reporting requirements for human drug and biological products and safety reporting requirements for bioavailability and bioequivalence studies in humans. Final rule

The Food and Drug Administration (FDA) is amending its regulations governing safety reporting requirements for human drug and biological products subject to an investigational new drug application (IND). The final rule codifies the agency's expectations for timely review, evaluation, and submission of relevant and useful safety information and implements internationally harmonized definitions and reporting standards. The revisions will improve the utility of IND safety reports, reduce the number of reports that do not contribute in a meaningful way to the developing safety profile of the drug, expedite FDA's review of critical safety information, better protect human subjects enrolled in clinical trials, subject bioavailability and bioequivalence studies to safety reporting requirements, promote a consistent approach to safety reporting internationally, and enable the agency to better protect and promote public health.     

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.     

Sanofi Pharmaceuticals, Inc., et al.; withdrawal of approval of 21 new drug applications and 62 abbreviated new drug applications--FDA. Notice

The Food and Drug Administration (FDA) is withdrawing approval of 21 new drug applications (NDA's) and 62 abbreviated new drug applications (ANDA's). The holders of the applications notified the agency in writing that the drug products were no longer marketed and requested that the approval of the applications be withdrawn.     

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.     

Anorectal drug products for over-the-counter human use. Final rule

The Food and Drug Administration (FDA) is issuing a final rule establishing that any over-the-counter (OTC) drug product containing a combination of hydrocortisone and pramoxine hydrochloride (HCl) for anorectal use is not generally recognized as safe and effective and is misbranded. This combination product is not currently marketed OTC. This final rule discusses data on the combination of hydrocortisone and pramoxine HCl that were still under review when an earlier final rule on OTC anorectal drug products was issued. This rule is part of FDA's ongoing review of OTC drug products.     

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.     

Procedures for transportation workplace drug and alcohol testing programs. Final rule

The Department of Transportation is amending certain provisions of its drug and alcohol testing procedures to change instructions to collectors, laboratories, medical review officers, and employers regarding adulterated, substituted, diluted, and invalid urine specimen results. These changes are intended to create consistency with specimen validity requirements established by the U.S. Department of Health and Human Services and to clarify and integrate some measures taken in two of our own Interim Final Rules. This Final Rule makes specimen validity testing mandatory within the regulated transportation industries.     

Filing of applications and requirements for widow's and widower's benefits. Final rule

We are revising one of our regulations to clarify that we will protect a title II claimant's filing date as of the date the claimant or other proper applicant on the claimant's behalf completes and transmits to the Social Security Administration (SSA) the Personal Information Identification data on the Internet Social Security Benefit Application (ISBA). This revision addresses an aspect of implementing the ISBA to provide certain rights to Internet filers that we afford to other filers. In addition, we are correcting one word in a different title II regulation. The revision is necessary to correctly reflect the circumstances under which a claimant for widow's or widower's benefits as the insured person's surviving divorced spouse would be considered "unmarried."     

Tamper-evident packaging requirements for over-the-counter human drug products--FDA. Final rule

The Food and Drug Administration (FDA) is amending its regulations on tamper-resistant packaging to require that all over-the-counter (OTC) human drug products marketed in two-piece, hard gelatin capsules be sealed using a tamper-evident technology; to change the term "tamper-resistant" in the labeling of all OTC drug products to "tamper-evident;" and to specify that the required OTC drug product labeling statement must refer to all packaging features used to comply with the tamper-evident packaging requirements, including those on the secondary package, the immediate container or closure, and any capsule sealing technologies used. FDA is taking this action as a result of its continuing review of the potential public health threat posed by product tampering and to improve consumer protection by addressing specific vulnerabilities in the OTC drug market.