Considerations For Development And Approval Of Analgesic Products

By David Shoemaker, Senior Vice President, Research and Development, Rho

The regulatory landscape for the development and approval of analgesic products has a well-documented history in the literature and the regulatory annals for these extremely important therapeutic compounds. Current products range from the frequently administered non-steroidal anti-inflammatory drugs (NSAIDs) for treatment of acute pain, osteoarthritis and other sensory/nociceptive pain to the controlled opioids, Selective Serotonin Reuptake Inhibitors/Serotonin and Norepinephrine Reuptake Inhibitors (SSRIs/SNRIs), and gamma-Aminobutyric acid (GABA) analogues that relieve pain of a more chronic and neuropathic nature. Both of these drug classes have accompanying side effects ranging from gastrointestinal, renal, and cardiac effects of the NSAIDs to constipation, respiratory depression, and potential for abuse of the opioids. Consequently, a significant clinical need exists for the development of novel pain medications.

Recent years have seen a dearth of novel product approvals for analgesics, with only one analgesic new chemical entity licensed for marketing in the United States since 2005. Industry has chosen instead to combine well-established, marketed pain products with other established products to address untoward effects (e.g. opioids combined with anti-constipation products and anti-abuse products) or to repurpose products marketed for other indications (e.g., SSRIs/SNRIs for depression and GABA analogues for epilepsy).

Industry has adopted the current strategy for two reasons. First, there is a definite need for improvement in the existing marketed products and the regulatory development pathway is complex and more expeditiously navigated by products whose absorption, distribution, metabolism, excretion, safety, and efficacy characteristics and mechanism of action are well established. Second, there are many physiologic types of pain, each requiring a tailored pharmacotherapy; analgesia is therefore a varied and extremely complex pharmacologic phenomenon. Therefore, the development pathway to approval for a novel analgesic is extremely difficult to plan and execute without a clearly defined intended patient population and a sound scientific understanding of the novel investigational product’s mechanism of action and potential pharmacological effects for that population’s pain type(s). This leads to a development program that is extremely expensive if not planned comprehensively and executed efficiently to navigate the regulatory requirements.