Transcript PRE0008 - PDRC | Prescription Drug Research Center

Bob Bianchi
Prescription Drug Research Center
Category 1 Focus Group Meeting
Washington DC November, 4 2015
Introduction
 The landscape in abuse deterrent product development and
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evaluation has changed since Purdue Pharma conducted in vitro
testing on their reformulated Oxycontin almost ten years ago.
More recently the approval of Inspirion’s ER morphine sulfate
product (MorphaBond) provides insight into FDA’s thinking.
Delivery platforms are different, and the most common forms of
abuse for each opioid formulation must be addressed
Of great interest is the development of in vitro testing protocols,
which is why we are here today.
No abuse proof product developed, YET
ADF formulations will only discourage the casual, recreational
abuser that makes up the majority of abusers.
Holy Grail in Pain Killers
FDA Thinking
 Adaptive approach
 The science of abuse deterrence is relatively new, and
both the formulation technologies and the analytical,
clinical, and statistical methods for evaluating those
technologies are rapidly evolving.
 FDA is taking a flexible, adaptive approach to the
evaluation and labeling of potentially abuse-deterrent
products.
 The development of an abuse-deterrent opioid product
should be guided by the need to reduce the abuse
known or expected to occur with similar products.
FDA Thinking
 Complete characterization
 First and foremost, any studies designed to evaluate the
abuse-deterrent characteristics of an opioid formulation
should be scientifically rigorous.
 Take into consideration the known routes of abuse for the
non-abuse-deterrent predecessor or similar products, as well
as anticipate the effect that deterring abuse by one route may
have on shifting abuse to other, possibly riskier route
 Testing should provide information sufficient to fully
characterize the product’s abuse-deterrent properties,
including the degree of effort required to bypass or defeat
those properties.
FDA Thinking
 Complete characterization (continued)
 The test product should be compared to appropriate
comparator products for ease of mechanical
manipulation
 The ability to crush, cut, grate, or grind the product
formulation using readily available tools such as spoons,
cutters, and coffee grinders should be assessed
 Particular attention should be given to particle size
distribution following each mode of physical
manipulation because particle size may influence the
rate of opioid extraction from manipulated product.
FDA Thinking
 Experiments must be reproducible and statistically valid
 Represent real world activities
 Explore the limits of abuse deterrent properties in heat &
cold
 Evaluate solubility in solvents of various polarity and pH
 Various time points and temperatures – 30
seconds- 12 hours or until 80% API extracted
 Evaluate dose dumping in alcohol of various
concentrations
 Evaluate liquid-liquid extraction with pH adjustment
Abuser Thinking
 Product selection
 Immediate release not as desirable as ER
 Not ADF
 Readily available
 Inexpensive
 Easy to access to API
 Method selection
 Fast, easy and requiring little technical
knowledge
 Few, inexpensive steps – no special equipment
Abuser Profile
 Most have little or no technical training
 Follows recipe from friend or Internet
 Limited resources
 Desperate – needs drug NOW
 Some hardened/experienced users have
chemistry training and accept the
intellectual challenge
Internet Resources
 http://www.rhodium.ws/chemistry/
 http://www.erowid.org/index.shtml
 http://www.drugs-forum.com/forum
 http://www.saferinjecting.net/safer-injectingdrugs.html
 http://groups.google.com/groups/dir?sel=usenet%3Dalt.
drugs http://forum.opiophile.org/
 http://www.bluelight.ru/vb/home.php
Scientist’s Thinking
 This is not traditional analytical chemistry - Alza
 What would an abuser do?
 Extraction/manipulation method selection
 Search Internet
 Consult expert
 Determine most prevalent mode of abuse
 Must be reliable, reproducible and efficient
 Must be safe for lab & staff
 Determine resource requirements – equipment, solvents
 Determine ease of manipulations – subjective assessment
 Draw conclusion about ease & efficiency of method
 Take Pictures
 Every formulation is different
Don’t Be Fooled by Appearance
Conclusion
 Each formulation has its own unique
properties requiring unique approaches.
 Experiments must be comprehensive
 Satisfy FDA recommendations
 Engage an independent laboratory
 Think like an abuser
 Provide regular feedback to sponsor
Thank You
Bob Bianchi
Prescription Drug Research Center
134 N LaSalle Street Suite 2200
Chicago, IL 60602
www.PDRCLLC.Com
RBianchi @PDRCLLC.com
571-233-4780