Heddie Martynowicz opened the session summarizing what will be discussed, and briefly addressed clinical and regulatory aspects of abuse liability potential assessment. She emphasized the importance to understand FDA guidance issued in 2010, which represents the most comprehensive guidance in the world at this point of time,

 

Mark A Amman informed the audience about the background of FDA Draft Guidance. In June of 2006, Cross Company Abuse Liability Consortium (CCALC) was founded. CCALC is a “Grass roots” Industry organization, consisted of approximately 80 people representing over 25 pharmaceutical companies. Different work-groups were formed, including regulatory, preclinical, clinical and risk management work-groups. The Objectives of CCALC are to collaborate to educate one another and to outreach for open scientific exchange with key stakeholders. Dr Amman outlined the key activities to date, which led

to Draft Guidance on Assessment of Abuse Potential of Drugs in January 2010 and presentation to the FDA in November 2011, where FDA provided a Draft Decision Tree for Assessment of Abuse Potential. Challenges in assessment of abuse liability were discussed among all relevant stakeholders.

 

The objective was to develop a preclinical and clinical methodology that was reliable, has clearly interpretable results and is predictive. Based on preclinical and clinical methodology, we should be able to determine whether there is a risk of abuse ands additionally qualify and quantify the risk. The overview of Draft Guideline was Issued January 2010.

 

Dr Michael Klein discussed FDA Guidance and Decision Tree on Assessing Abuse Potential of New Drugs. Abuse potential is a safety-related issue that must be addressed during NDA review. All safety assessments provide important information for the drug label , patient and public. The definitions of Abuse Potential and Abuse Liability were introduced, as well as requirements for Abuse Potential Assessment. Applicable Federal Laws were outlined.

 

Details of FDA published draft Guidance on Assessment of Abuse Potential of New Drugs were presented. The guidance addresses many questions, some of them being : 1. When to assess the abuse potential of a drug in relation to a drug development time frame? 2. Pre-IND Testing – what abuse potential data is needed at this stage? FDA is hoping that Draft Guidance will help companies manage the risk. It was suggested that by the end of Phase 2  may be the right time to do abuse potential. FDA also recommends that studies are to be repeated once therapeutic dose has been determined (Phase 3). FDA also accepts as valid Abuse Potential studies that use as negative control placebo as we do not know a lot about abuse potential of drugs already approved by FDA. Interesting comment was made by Dr Marta Sokolowska, who reviewed several case studies. While discussing the Abuse Potential Study conducted to assess abuse potential of Cymbalta. Dr Sokolowska noted that abuse potential of Cymbalta was compared to desipramine and methylphenidate. While scientific community was impressed by the study, FDA believed only needed is to compared Abuse potential of Cymbalta to Placebo.

 

Draft Decision Tree for the Assessment of Abuse Potential was presented by the FDA in November 2011 at a joint meeting by FDA, NIDA/NIH and the College on Problems of Drug Dependence. The authors are Katherine Binson PhD and Stephan Sun, MD-CSS. The objective of the Draft Decision Tree is to improve regulatory efficiency, consistency and transparency, align with real world development and allow for active dialog with feedback from stakeholders. The Draft Decision Tree aligns to Phases of drug development, from non-clinical studies to the NDA review. As drug development progresses, scientific questions related to abuse potential are answered through the outcomes of each study.

 

Use of the Decision Tree will allow a Sponsor to identify abuse potential early in the development process and manage the risk of the drug development. FDA welcomes feedback, based on real-life examples from pharmaceutical development.