Rx Name Risk Assessments Should Be Conducted By Manufacturers, FDA Says

Drug and biologic sponsors should conduct a risk assessment on the product's name, labeling and packaging to minimize medication errors, an FDA concept paper states.

"Ideally, a sponsor would conduct a risk assessment to ensure that a product's proprietary name, established name, container label, carton labeling, package insert, and/or packaging do not inadvertently contribute to medication errors," FDA's draft "Premarketing Risk Assessment" ¹ concept paper, released March 6, states.

The risk assessment, or "medication error prevention" analysis, should identify known and potential "medication error modalities" as well as potential and actual causes of each error, the paper states. It should also "prioritize the errors according to the expected outcomes" and "minimize the potential for an error through corrective action, including renaming, relabeling and repackaging."

"Although FDA currently undertakes such activities, it would help to minimize medication errors if sponsors also engaged in such risk assessments to support their proposed names, labeling and repackaging," the paper states, noting that "having such data from the sponsor could help speed FDA's review of these issues."

Sponsors should "obtain first-hand information from physicians, pharmacists, nurses, and consumers in inpatient and outpatient settings" through "questionnaires, on-duty observations, interviews, simulation testing, computer models, expert panels or focus tests."

The HHS Committee on Regulatory Reform recommended in September that FDA's drug name review should be based on data collected from sponsors, rather than internal agency tests (² 'The Pink Sheet' Sept. 16, 2002, In Brief).

The agency asked the public to comment on what the appropriate size of a sponsor's premarketing drug safety database should be, "because no guidance currently exists on determining the appropriate size of clinical safety databases for products intended only for acute use or for serious and life-threatening diseases."

Commenters should consider the International Conference on Harmonization E-1 guidance, which provides "a number of considerations that would suggest the need for a larger database."

FDA also listed "other reasons" a larger safety database might be needed, such as if the proposed treatment is for a healthy population; a very safe alternative to the investigational product is already available; or there is potential for rapid exposure to a large population.

"Time-to-event" analyses are appropriate for clinically important events that occur on a delayed basis and adverse events that occur at the initiation of treatment but diminish in frequency over time, FDA noted.

"Analyzing temporal associations between product exposure and adverse events is critical to risk assessment, because it can provide important clues for determining whether the event was product-related."

Sponsors also should "prospectively group adverse event terms and develop case definitions. A prospective approach is particularly important for syndromes that are not well characterized by a single term," such as serotonin syndrome or drug withdrawal.

Comparative safety data could be used in cases "when there is a need to characterize background rates of certain adverse events" as well as "when there is a well-established, well-characterized product with minimal toxicity to treat the condition of interest."

Sponsors also should consider submitting comparative safety trials "when there is a well-established related therapy." The trials "could show whether the toxicity profile for the established therapy holds for the novel therapy, or whether important differences exist."

In addition, comparative safety data could be useful "when there is a well-established treatment with an effect on survival or irreversible morbidity" and "when the sponsor hopes to claim superiority," the paper states.

FDA simultaneously released two other concept papers on risk management and pharmacovigilance (see ³ (Also see "Pharmacoepidemiologic Studies Should Estimate AE Background Rates – FDA" - Pink Sheet, 10 Mar, 2003.)). The agency is developing the concept papers to serve as precursors to guidances mandated by the prescription drug user fee reauthorization (⁴ (Also see "FDA Risk “Concept Papers” Expected In March; April Workshop Set" - Pink Sheet, 20 Jan, 2003.), p. 6).