1. TAMPERABILITY/EXTRACTABILITY OF PRESCRIPTION DRUGS Robert P. Bianchi PDRC/NMS Labs Drug Delivery Partnership February 8, 2013 San Diego, CA

2. BACKGROUND Prescription drug abuse is the fastest rising category of drug abuse in the US, second only to cannabis and synthetic cannabinoids (ONDCP – Drug Control Strategy 2011). Emergency department visits resulting from non-medical use of prescription analgesics increased 98.4 percent between 2004 and 2009 (NIDA 2011). Seven of the ten substances most abused by high school seniors are legal drugs used non-medically. 2009, Monitoring the Future According to DEA, 17 of the top 25 drugs most often examined by forensic laboratories in 2011, are available as prescription drugs. (DEA, NFLIS, 2011 mid year report)

3. BACKGROUND An estimated (5%) 10.5 million Americans reported past year use of prescription drugs for non- medical purposes. (National Survey on Drug Use and Health, 2008). Nearly 7 percent of youth between the ages of 12 and 17 (1.7 million) have used such drugs which include pain relievers, sedatives, tranquilizers or stimulants, for non-medical purposes at some point. (National Survey on Drug Use and Health,2008)

4. BACKGROUND What caused this phenomenon ? Prescription drugs do not fall under the clandestine cloud of illegal drugs such as heroin, ecstasy or methamphetamine Prescription drugs are more available due to the development of new products and increased sales Drugs are FDA approved Friends and family use them Drugs are frequently obtained free of cost Doctors are over prescribing

5. Solutions Education - youth Treatment – limited success Enforcement – laws and regulations on mfg, dist, Dr., pharmacies, illicit traffickers Abuse Resistant Delivery Systems- Industry stepped up to the plate to do something

6. Unique Industry Resource The Prescription Drug Research Center (PDRC) National Medical Services (NMS) Laboratory Collaborated to create a “one stop shop” to provide assistance in preparing: Risk management programs In vitro studies Post marketing surveillance Rapid response investigations Advisory committee meetings

7. Draft FDA Guidance In January 2013 the FDA issued draft Industry Guidance Abuse-Deterrent Opioids — Evaluation and Labeling. Laboratory Manipulation and Extraction Studies should be utilized to evaluate the ease with which the potentially abuse-deterrent properties of a formulation can be defeated or compromised. FDA Previously recommended using outside consultants and laboratoriesto conduct in vitro studies

8. Prescription Drug Research Center Nationally known experts in regulatory drug control – Administrator of DEA, Director NIDA, Head of DEA Operations, Chief of DEA Laboratory Operations Section Developed in vitro studies to evaluate the ease with which abuse-deterrent formulations can be defeated or compromised Assisted in scheduling actions Facilitate advisory committee meetings Rapid response on diversion investigations Prepared post marketing studies

9. National Medical Medical Services Laboratories Forensic/clinical laboratory with over 200 employees Conducts “kitchen chemistry” experiments to challenge abuse deterrent delivery systems Provides comprehensive, objective, third- party opinions, conclusions and detailed confidential reports Compares study product to competitor products

10. DEFINITIONS Tampering – physical manipulation Crushing Physical separation components (beads, layers, gel) Heating, freezing, crisping, microwaving Extractability – chemical manipulation of a product to remove, concentrate and/or purify the active ingredient performed using commonly available equipment and chemicals

11. EXTRACTION EXPERIMENTS Standardized laboratory extractions must be developed for each type of dosage form, e.g. tablets, capsules, patches, liquids, implants, IR, SR using solvents & equipment commonly available. All experiments must be conducted at least in triplicate to provide statistical validity. Controls and a comparator must included.

12. IN-VITRO EXPERIMENTS aka KITCHEN CHEMISTRY NO STANDARD TESTS. Each delivery system requires a unique written protocol including controls and comparators' to assess tamperability. Sponsor knows product’s vulnerabilities and should develop experiments in concert with abuse experts based on product knowledge and current abuse methods of similar products using commonly available chemicals and equipment.

13. IN-VITRO EXPERIMENTS Develop written protocols that produce statistically valid, reproducible results. Include related comparator product Include controls Include quality assurance procedures Take photographs to illustrate results Use graphs and charts to illustrate data

14. Summary No objective measure exists to measure Tamperability/extractability Each product/system requires unique experiments designed to address vunerabilities Use independent laboratory & abuse experts Consider all modes of abuse & all strengths Include photographs, graphs & charts where appropriate No product has been proven to be tamper proof

15. Thank you Robert P. Bianchi Vice-President and Chief of Scientific and Technical affairs Prescription Drug Research Center 134 N. LaSalle Street Chicago, IL 60602 312-726-8620 - Office 571-233-4780 – Cell RBianchi@pdrcllc.com RBConsulting700@AOL.com