The guidance, published March 16, 2023, is part of a larger effort to reduce the use of opioid pain relievers, according to the FDA. “Different local anesthetic products have different pharmacokinetic (PK) profiles, but their effects generally last for hours. However, there is interest in reducing or eliminating the use of opioid analgesic products. has led to the development of dosage forms for local anesthetic products, which extend the duration of action of drug products to days instead of hours,” wrote.
This guidance focuses on the development of local anesthetics that provide postoperative analgesia and require a New Drug Application (NDA) under Section 505(b) of Medicines. Federal Food, Drug, and Cosmetic Act.
development plan
FDA encourages sponsors to discuss development plans early with the Divisions of Anesthesiology, Addiction Medicine, and Pain Medicine at the FDA’s Center for Drug Evaluation and Research. The discussion should include planned comparative bioavailability studies and efficacy and safety studies.
Furthermore, development programs should be conducted sequentially, starting with in vitro studies to characterize drug release profiles. Sponsors should then conduct initial PK studies to identify doses and dosing regimens. Once initial work is completed, sponsors should conduct safety and efficacy studies designed to support the proposed indication. The number, type, and design of safety and efficacy studies show significant differences in whether the product is the first modified-release formulation of an existing immediate-release local anesthetic compared to listed agents. It depends on several factors, including whether there is
In some cases, clinical efficacy and safety studies may not be required to support approval, but sponsors are required to submit data characterizing local and systemic drug exposure. “Due to the unique product-specific characteristics of long-lived local anesthetic products, if the sponsor decides to conduct only relative bioavailability PK studies to support its local anesthetic product, or if available Sponsors considering exploring in vitro modeling approaches should discuss plans with departments early in the drug development program,” the agency wrote.
Efficacy and safety
For any new local anesthetic product, at least two relevant and well-controlled studies are required to support surgery-specific or anatomic site-specific indications. For modified release formulations of previously approved local anesthetic products, at least one adequate and well-controlled study is required for surgery-specific or anatomical site-specific indications.
The recommended primary efficacy endpoint for assessing postoperative analgesia is the area under the curve (AUC) of the pain score. The FDA noted that the clinical pain scores used should be validated in the patient population under study.
In its safety evaluation, the FDA considers the general safety implications of extending the duration of action of the product, the safety of novel inactive ingredients, the risk of administration site trauma and infection, the risk of systemic exposure, Risk of neuropathy, or sensory/motor impairment, safety of repeated doses, and compatibility with co-administration of other anesthetics.
Comments on the draft guidance can be submitted to regulations.gov and labeled with docket number FDA-2023-D-0608. The public comment period ends on June 14, 2023.
Product information for local anesthetics
