In 2007, the Food and Drug Administration Amendments Act (FDAAA) was signed into law authorizing the Food and Drug Administration (FDA) to require a Risk Evaluation and Mitigation Strategy (REMS) from drug manufacturers, if deemed necessary to ensure that the potential benefits of a drug outweigh its risks. At the time of this writing, there have been 185 REMS approved by the FDA.

Sally Van Doren, PharmD, President & CEO, BioSoteria, Inc.

James Buchanan, PharmD, Senior Vice President, Pharmacovigilance & Risk Management, BioSoteria, Inc.

This published article helps drug safety professionals and study sponsors navigate through the complex rule on the new investigational new drug (IND) safety reporting requirements during clinical trials.  The FDA has announced changes to the US regulations on IND safety reporting, which go into effect on September 28, 2011.

Sally Van Doren, PharmD, President & CEO, BioSoteria, Inc.

 James Buchanan, PharmD, Senior Vice President, Pharmacovigilance & Risk Management, BioSoteria, Inc.

The New FDA Final Rule on IND Safety Reporting: Implications for Clinical Development Programs. ACRP Monitor April 2011:  17-21

The US Food and Drug Administration (FDA) Amendments Act was signed into law in 2007. It grants several additional authorities to the FDA, including requiring manufacturers in some situations to implement risk evaluation and mitigation strategies (REMS). In the vast majority of REMS, only a medication guide or a communication plan is required. A review of the published literature suggests that the traditional paper-based communication tools used over the decades by the FDA and drug industry, such as medication guides and Dear Doctor letters have not been shown to be effective or durable in changing prescriber or patient behaviors leading to risk reduction. Despite this, they currently serve as the primary tools used for risk mitigation. Paper-based communication tools need to be critically evaluated for future use and replaced with more effective risk communication strategies.

Sally Van Doren, PharmD, President & CEO, BioSoteria, Inc.

This final rule which codifies the FDA’s expectations for timely review, evaluation, and submission of relevant and useful safety information of drug and biologic products subject to an investigational new drug (IND) application. This final rule amends parts 312 and 320 of FDA regulations by revising the requirements for IND safety reporting and for bioavailability and bioequivalence studies, The IND regulation changes boil down to: clarification of several definitions, what to report and when (including additional safety information required for expedited reporting) and various other clarifications related to IND safety reporting. The effective date for the final rule is September 28, 2011.

 Sally Van Doren, PharmD, President & CEO, BioSoteria, Inc.

James Buchanan, PharmD, Senior Vice President, Pharmacovigilance & Risk Management, BioSoteria, Inc.

The 2007 Food and Drug Administration Amendments Act (FDAAA) grants FDA the authority to require Risk Evaluation and Mitigation Strategies (REMS) to be implemented post approval when deemed  necessary for a favorable risk/benefit balance for a product. The REMS elements cover three categories of risk mitigation activities described in the guidance: medication guide, communication plan and elements to assure safe use (ETASU). This paper discusses each category in detail as well as the required REMS assessment plans. The authors consider the future of REMS activities and how information coming out of REMS assessments will be used to best practices.

S. Sakai, S. Van Doren.  REMS in Practice: Recent Trends.  Regulatory Focus July 2010: 18-23

FDA issued a guidance document entitled “Adverse Reactions Section Labeling for Human Prescription Drug and Biological Products – Content and Format” in January 2006. This guidance is intended to assist both applicants and reviewers draft the Adverse Reactions section of the prescribing information in the new format specified by the new labeling rule. This BioSoteria White Paper examines the extent to which recent product labels follow this guidance. Recent examples of product labels under this new system indicate that many, but not all, of the concepts in the Rule are being applied. It is anticipated as both FDA reviewers and marketing applicants become more familiar with this new process, that the resulting labels will more closely match the intent of these guidance documents.

A poster presentation summarizing the findings described in the BioSoteria White Paper, "Evaluation of US Package Inserts Following the Physician Labeling Rule." 

In recent years, a greater emphasis has been placed on pharmacovigilance systems and risk management strategies to minimize product risk and maximize the benefits to the intended patient population. Although there have been efforts to eliminate unjustified differences and harmonize regulations between regions, a comparison of the EU and US risk management regulations and guidance's reveals similarities and differences that a sponsor must understand to meet the regulatory requirements in both regions.