The webinar will be divided into three parts:
1) Introduction and Background: Abuse liability of a drug refers to its potential use in a non-medical situation for the positive psychoactive effects it produces through its Central Nervous System (CNS) activity. The assessment of the abuse liability/potential of a drug encompasses all properties of the drug (chemical, pharmacological, pharmacokinetics, usage and diversion history), and is part of the overall assessment of drug safety under the evaluation of a New Drug Application (NDA) in the U.S. or a Market Authorization Application (MAA) ex-U.S.
2) Regulatory Environment: In the U.S., the Comprehensive Drug Abuse Prevention and Control Act, referred to as the Controlled Substance Act of 1970 (CSA), provides the legal basis for the government to control drugs and other substances that have potential for abuse (21CFR801). The CSA refers to “potential for abuse” and “addiction-forming or addiction-sustaining liability” but does not define these terms, which are frequently used interchangeably. The Drug Enforcement Administration (DEA), under the CSA, is responsible for the scheduling of drugs considered to have potential for abuse. All individuals and firms authorized to handle controlled substances are required to be registered by the DEA, to maintain complete and accurate inventories and records of all transactions involving controlled substances, and to comply with security requirements for the storage of controlled substances.
Until 2006, assessment of the abuse potential of New Molecular Entities (NMEs) was required for specific pharmacological classes (i.e., psychostimulants, sedatives, opioids, cannabinoids), but since then, as regulatory guidance became available in the U.S., EU and Canada, assessment of abuse potential is required to be completed before NDA/MAA filing for all brain-penetrant compounds and metabolites regardless of the indication. Finalized and Draft guidances for industry in the U.S. make recommendations for the overall nonclinical and clinical assessment of abuse potential (2017 guidance), and the development of abuse-deterrent formulations (ADF) for new and generic opioids analgesics (2015 guidance and 2016 draft guidance, respectively). Taken together these guidances are part of the “FDA Opioid Action Plan” announced in 2016 in response to the alarming increase in the number of opioid related overdoses and deaths (Califf et al., 2016). In regards to the scheduling process of new approved medicines, on November 25, 2015, President Obama signed the Improving Regulatory Transparency for New Medical Therapies Act to amend the CSA with respect to drug scheduling recommendations by the FDA and the Secretary of Health and Human Services. The Act determines the time frame for the DEA to issue an interim scheduling determination of drugs with potential for abuse, and redefines the calculation of exclusivity and patent terms.
3) Regulatory Challenges and Strategy for assessing abuse potential of CNS active compounds in development: While developers have the burden to identify the risk of abuse and frequently are called to prove the null hypothesis, regulators are challenged to evaluate the probability that such risk (i.e., the exposure to the chance of abuse) could extrapolate from the confined clinical trial environment to the real world. Integrating the assessment of abuse potential in drug development is a critical exercise that sponsors and regulators are called to face, and the earlier the collaboration is established between the parties, the better the outcome.
Beatriz de A. Rocha
Covance Executive Director, Head of Clinical Regulatory Strategy
Dr Beatriz Rocha has more than 30 years of professional experience that spans from academia and government to industry. It includes clinical practice in anesthesia and pain management, clinical research, basic research, and regulatory affairs during the last 14 years. As a board certified anaesthesiologist and behavioral pharmacologist, Dr. Rocha spent 20 years in clinical and laboratory practice and in 2001 she joined Merck Research Laboratories in Rahway, NJ.
Dr. Rocha has extensive experience interacting with Board(s) of Health (BoH), including FDA (US), European Medicines Agency (EMA), Health Canada (HC), and Ministry of Health, Labor and Welfare (MHLW/PMDA) in Japan, in several therapeutic areas of oncology, immunology, urology, dermatology, respiratory and CNS.
Dr. Rocha is a worldwide recognized expert in the area of addiction and abuse liability. She serves in the College on Problems of Drug Dependence (CPDD) Board of Directors, and has been recently elected as the chief operating officer of the Cross Company Abuse Liability Council (CCALC). At Covance, Dr. Rocha currently heads the Global Regulatory Affairs Clinical Strategy group that provides strategic regulatory input for internal and external customers, including working with clients and global Regulatory Agencies in the organization and preparation of clinical development plans and agency interactions.
Silvia N. Calderon-Gutkind, Ph.D.
Senior Scientist, Controlled Substance Staff, CDER, FDA
Dr. Calderon is a Senior Scientist in the Food and Drug Administration (FDA), Center for Drug Evaluation and Research (CDER). She provides leadership to pharmacologists on policy and review issues related to the abuse liability assessment of new drug products and formulations. Since joining the FDA in 1996, she has reviewed numerous Investigational New Drug Applications (INDs) and New Drug Applications (NDAs) for drugs active in the central nervous system.
Dr. Calderon has represented the FDA as a leader and expert in the area of abuse liability assessment of drugs, and she has actively participated in the development of the recently published guidance, Guidance for Industry: Assessment of Abuse Potential of Drugs, and Guidance for Industry: Abuse-Deterrent Opioids-Evaluation and Labeling. Dr. Calderon-Gutkind received her Ph.D. in Medicinal Chemistry from the University of Buenos Aires, Argentina. Her training and expertise are concentrated in the fields of medicinal chemistry and pharmacology of drugs of abuse. She began post-doctoral training as a National Research Council Fellow in the Department of Neuropsychiatry at Walter Reed Army Institute of Research (WRAIR), where she actively worked on the synthesis and development of novel anticonvulsant agents as new medications for the treatment of epilepsy and other seizure-provoking disorders. Training continued at the Addiction Research Center, National Institute of Drug Abuse, National Institutes of Health (NIH), where she specialized in chemical and biochemical aspects of drugs of abuse. She subsequently worked on the synthesis and design of potent and extremely selective novel non-peptidic delta opioid ligands at the Laboratory of Medicinal Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, NIH.
Dr. Calderon has numerous publications in the areas of medicinal chemistry and abuse liability assessment, holds several patents on the synthesis and pharmacological properties of novel anticonvulsants and neuroprotective agents, and review scientific-research publications for well-known journals in the field of medicinal chemistry and addiction.
- Understand the regulatory environment and legal framework of the evaluation of abuse potential of CNS active compounds under development.
- Recognize the critical steps defining the regulatory strategy of the assessment of abuse potential of CNS active compounds in general, and in particular of analgesics.
- Identify abuse potential critical data for discussion with Regulators and when best to engage with Regulators.
- Recognize regulatory expectations and challenges for the development of opioid and non-opioid analgesics.
- Regulatory
- Clinical Operations
- Clinical Pharmacology
- Neuroscience
- Toxicology
