Building an Effective Global Risk Management and Drug Safety Program

By Jim Mittler, PhD

Since 2007, the FDA has had the authority to require pharmaceutical companies to develop a risk evaluation and management strategy (REMS) for marketed products to ensure that the benefits of a medicine outweigh the potential risks. This applies to novel compounds needing FDA approval as well as currently approved products if the FDA determines there is a potential risk for unsafe use. REMS programs have multiple components that include planning, implementation, and assessment; all of which make achieving a successful REMS programquite challenging, albeit critical to ensuring patient safety.

This week, FDAnews hosts their 2nd-annual Risk Management and Drug Safety Summit, entitled Building an Effective Global Risk Management and Drug Safety Program, to help pharma companies (and their respective agency partners) navigate the current regulatory landscape of risk mitigation. This event is very timely because this week the FDA released the draft “Guidance for Industry document for the content and format for REMS programs. [Editorial note: the sponsors joked that it was, in fact, their intention to have the meeting coincide with this release!]

The biggest take-away from the first day of the summit was REMS programs are not about ultraconservatism on the part of the FDA nor an additional regulatory hurdle placed upon pharmaceutical companies; rather, REMS programs are meant to ensure that the therapeutic benefit of a medicine outweighs the potential risk in the “real world. Clearly, during development of a new therapeutic compound the sponsor studies the clinical efficacy and safety by performing clinical trials and the FDA evaluates the data to approve, or not approve, a medicine for wide-spread clinical use. Evaluation of safety cant stop at the point of FDA approval because the dosing of a medicine, study population, study endpoints, etc, are well defined and controlled in clinical trials. In the “real world there are numerous “condition-of-use factors that can affect drug safety, which are out of the realm of a clinical trial; including, inappropriate prescribing to a certain patient population who may be predisposed to a known adverse event, poor patient adhere to medication (or concomitant medications), medication errors, and abuse or diversion of a medication. The goal of REMS programs are to clearly communicate the known risks (and benefits) of medication to physicians and patients so they can make better prescribing and personal healthcare decisions, respectively; but also to minimize the chance of inappropriate use of a medication by requiring certain constraints that ensure the right patient, is getting the right drug, in the right way, and is appropriately monitored, so that they can receive the benefit of the medicine in the safest possible way.

REMS programs are multifactorial and different medications can require various tactical components. Tactics can include professional and patient communication tools that describe the risk/benefit of a medication, educational tools describing appropriate use of a medication, and regulated prescribing and dispensing protocols. Common to all REMS programs is that each tactic must be evaluated to determine if the REMS program is successful. Clearly, a decrease in the incidence of adverse events is the ultimate goal but this is not always clinically possible; therefore, the FDA requires that certain performance metrics be monitored with regard to healthcare practitioner, pharmacy, and patient education; prescription and dispensing practices; and documented patient monitoring.

While the FDA Amendment Act of 2007 has been law for nearly 2 years, FDA guidance on REMS has just been released. Representatives from the FDA admit that the REMS program is still a work in progress. The new guidance recommends a certain format, content, and assessment for a REMS program; however, the measurement of success has yet to be defined. The FDA is committed to working with pharmaceutical companies to aid in the development and approval of REMS programs, and to open dialog that can help expedite an approved REMS program. Representatives from several pharmaceutical companies (Biogen Idec, Roche, and sanofi-aventis) who spoke at the summit, and have successfully implemented REMS programs, also indicated that early and proactive planning with the FDA can minimize some of the regulatory challenges that are required to a get a new medication, and the respective REMS program, approved for use.