8 Factor Analysis and Drug Abuse Potential

As drug prices increase, the Hatch-Waxman Actopens in new window is increasingly being seen as a barrier to affordable access to prescription medications. To overcome this hurdle, the law supports the development of generic drugs that are identical to brand-name drugs but cost less. A critical component of the process is an 8-Factor Analysis.

Factor 1: Abuse Potential

Abuse potential is a critical aspect of the US 8 factor analysis required by FDA and DEA for new drug development. Generally, the assessment is conducted as part of the overall safety evaluation and includes testing for the ability to induce a state of physical dependence and tolerance.

The types of abuse-related studies vary between drugs, but include functional behavioural observational studies, clinical drug-related AEs and human physical dependence studies. Sponsors are advised to discuss their planned abuse-related studies with CSS early in the process.

Factor 2: Risk of Abuse

Although not specified in the CSA, abuse potential evaluations (often called 8-factor analyses or 8FAs) must be conducted by FDA and DEA prior to scheduling new drugs, rescheduling them from one schedule to another, or removal from the CSA. In general, these 8FAs must include preclinical and clinical studies of the drug’s effects in animals and humans, with particular emphasis on overlapping effects with other known drugs of abuse. Functional behavioural observation and drug self-administration (drug discrimination) studies are typically employed in these evaluations.

Factor 3: Dependence

The CSA requires FDA and DEA to develop 8 factor analyses for new drugs approved by FDA, for rescheduling from one schedule to another, or for descheduling from the Schedule I list. While the CSA does not specify what types of studies and evidence are required in each of the factors, there is considerable variation in how 8FAs are performed in practice. For example, functional behavioural observation studies are often conducted in factor 1. Table 1 provides examples of the kinds of research commonly considered for each of the factors.

Factor 5: Potential for Misuse

In addition to a sponsor’s own abuse potential evaluation, the CSA requires a comprehensive abuse-related safety assessment (known as an 8-factor analysis) by FDA and NIDA for all new drugs approved by FDA and rescheduling or descheduling of already-approved substances. The FDA 8-factor analysis will cover a broad range of research methodologies from preclinical to clinical, including functional behavioural observation in animals and epidemiological surveys of real-world drug use patterns by the public.

These studies typically include preclinical models that assess the extent to which a drug is reinforcing and/or self-administration and human abuse potential assessments in comparison to known drugs of abuse. Other lines of evidence include chemistry, nonclinical in vitro and animal studies, physiological dependence and withdrawal, and a review of clinical trial adverse event reports.

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