The FDA this week issued a direct final rule, to become effective Sept. 16, to update its requirements for standard preparations, potency limits and dating period limitations for biologics. The rule will remove obsolete or duplicative requirements to accommodate new and evolving technology and testing capabilities, the agency said in a notice published in Wednesday's Federal Register. If it receives "significant adverse comments" by July 18, the FDA said it will withdraw the direct rule and continue the rule-making process with a companion proposed rule that also was published Wednesday.

The FDA also revised a 14-year-old draft guidance on special protocol assessments (SPAs) in hopes of improving the quality of submission materials and requests for the assessments, as well as its subsequent interaction with sponsors. Major changes from the 2002 guidance include clarification about which protocols are eligible for an SPA, the addition of animal rule efficacy protocols intended to support approval of certain drugs and biologics, the addition of protocols to support approval of a biosimilar, more detail about the content of an SPA submission and clarification about the process to rescind an SPA agreement. Comments on the draft are due by July 5.

And, reflecting advances in interferon (IFN)-free regimens, the FDA released a revision of its 2013 draft guidance addressing all phases of development of direct-acting antivirals to treat hepatitis C. The new draft discusses the noninferiority margin for active-controlled phase III trials to evaluate IFN-free regimens, and trial design options and safety evaluation for specific patient populations. The FDA modified several sections to focus on IFN-free regimens and provided additional details on phase II and III trial design options to evaluate the regimens in treatment-naïve and -experienced patients. The guidance recommends that each marketing application include at least one active-controlled comparative trial. The comment deadline is July 5.

JUMPING THE GUN

Oeyama-Moto Medical Group Foundation, of West Covina, Calif., received an FDA warning letter citing it for beginning a phase II cancer trial a few days before the agency lifted a clinical hold. The FDA had placed the investigational new drug application for the study on a full clinical hold at the end of 2012, pointing to problems with the protocol and investigator brochure. It also had said the study posed unreasonable, significant risk of illness or injury to the subjects and the sponsor had provided insufficient information to assess those risks. To address the problems, Oeyama-Moto submitted a new protocol March 24, 2014, to evaluate the efficacy of a low dose vs. a high dose of bromelain in patients with advanced late-stage cancers. In its response to the FDA, the sponsor said agency officials had communicated that if it didn't receive a rejection within 30 days, it could proceed with the trial in early May 2014. As a result, an investigator administered the drug to two patients May 3 and to four patients May 7. The FDA issued the official letter lifting the hold May 9.

SECOND-HAND DRUGS

Robin Deleonrosa, of New York, was arrested in connection with a nationwide black market ring that sold second-hand HIV drugs to patients and pharmacies. The group purchased the drugs from patients, removed the labels using hazardous substances and then distributed them as new drugs, according to the U.S. Department of Justice (DoJ). Deleonrosa personally obtained and sold more than $1.9 million worth of the drugs, DoJ said. When he was arrested, investigators seized more than 1,000 bottles of second-hand HIV prescription pills from his apartment. Deleonrosa has been charged with one count of conspiracy to commit health care fraud.

RARE DISEASE GRANTS

Applications for the next round of the FDA's Orphan Products Development Natural History Grants Program are due Oct. 14. The grants support studies that advance the development of treatments for rare diseases through characterization of the natural history of the disease, identification of genotypic and phenotypic subpopulations, and development or validation of clinical outcome measures, biomarkers or companion diagnostics. Details about the applications and the program are available in an FDA notice published in Wednesday's Federal Register.