Development and Regulation of Abuse-Deterrent Formulations of Opioid Medications; Public Meeting
cder 2014-701 CDER2014175 Opioid
2015-01-27 2015-01-13 2015-01-13 2015-04-16 2015-01-27
FDA-2014-N-1359-0024 FDA-2014-N-1359-0013 FDA-2014-N-1359-0015 FDA-2014-N-1359-0033 FDA-2014-N-1359-0025
05:00:00 05:00:00 05:00:00 04:00:00 05:00:00
https://api.regulations.gov/v4/comments/FDA-2014-N-1359-0024 https://api.regulations.gov/v4/comments/FDA-2014-N-1359-0013 https://api.regulations.gov/v4/comments/FDA-2014-N-1359-0015 https://api.regulations.gov/v4/comments/FDA-2014-N-1359-0033 https://api.regulations.gov/v4/comments/FDA-2014-N-1359-0025
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Please find comments provided by Par Pharmaceutical, Inc., Spring Valley, NY.  This submission includes a cover letter and Appendix which contains Pars responses. With 100 million Americans experiencing chronic pain we need to find safer and more effective therapies.   Research has begun to suggest that abuse-deterrent opioids are safer than those without such properties.Therefore, I urge the FDA to require all extended-release opioid formulations on the market to have a minimum level of abuse-deterrent properties. This would not eliminate all abuse, addiction and overdose deaths related to opioids. It would, however, be a small but significant step forward.Industry and payers will need time to adjust to this required safety measure. Therefore, I urge the FDA to set a date  perhaps 2020  for this requirement to take effect.But the FDA must not stop there. Payers are reluctant to encourage use of these safer products because of added cost.  And as long as opioids without abuse-deterrent properties are available, industry has no incentive to create these safer analgesics. To eliminate these barriers, the FDA must remove all extended-release opioid formulations without abuse-deterrent properties from the market by a set date, perhaps 2020.    But there is another serious issue to consider. A move to more expensive abuse-deterrent formulations could lead to the less expensive methadone being prescribed for post-operative, cancer and chronic pain. Methadone represents less than 3% of all opioids prescribed for pain but is associated with 25-30 % of all unintentional overdose deaths. More methadone could lead to more overdose deaths. This would be a terrible unintended consequence. Research has shown that many of the deaths associated with methadone are due to physician errors in prescribing.  This is usually due to a knowledge deficit.  If payers wish to keep methadone available because it is inexpensive, those payers should have to demonstrate that providers are trained to prescribe it. Such payers would include Medicare, Medicaid and workers compensation. Since the FDA cannot require physician education I recommend that methadone be removed from the market for the treatment of pain until manufacturers or payers can demonstrate that prescribers have the minimum competency to prescribe it.  The rationale is that methadone must not remain the only low-cost option. The mechanism for demonstrating competency is not yet clear, and a process and criteria would need to be established. To be clear methadone should remain available for the treatment of addiction.  My suggestion applies only to methadone prescribed for the treatment of pain. To sum up, I urge the FDA to:Require abuse-deterrent properties in all extended-release opioid formulations on the market by 2020Remove extended-release opioid formulations without abuse-deterrent properties from the market, also by 2020Simultaneously, remove methadone for pain from the market until adequate training of prescribers can be demonstrated.Thank you.Lynn Webster MDVP Scientific AffairsPRA Health SciencesSalt Lake City, Utah801-892-5140WebsterLynn@PRAHS.com Statement by Alexander KrausFDA Public Meeting: Abuse-Deterrent (AD) FormulationOctober 30, 2014Good afternoon. My name is Alexander Kraus and I am VP Product Development  Technical Affairs at Grnenthal USA, Inc.  Grnenthal USAs German parent company has developed and licensed abuse deterrent technology and patents to opioid manufacturers in the United States.We believe that ADF technologies are a valuable tool to reduce prescription drug misuse, abuse and diversion and, when the necessary quality requirements are being met, can provide additional safety and benefit to prescribers, patients and society.In-vitro testing of products which are designed-to-be abuse deterrent is a critical element of ADF development. Results from scientifically rigorous, protocol-driven, in-vitro tests are key to understanding the properties of emerging ADF technologies and their applications. Although we support the concept of a standard in-vitro test battery, it will not be sufficient to assess the full potential or certain weaknesses of a product aiming to provide abuse deterrence.  And, depending on the approach and technology, new tests will always have to be conducted, in addition to the standard battery, that reflect specific circumstances relevant to the active ingredient or the formulation used.. This will ensure the most comprehensive insights into the strengths and weaknesses of a product and will inform manufacturers about the design of pharmacokinetic and abuse liability studies in order to assess whether a product may prove to show meaningful abuse deterrence in the community. However, in-vitro tests alone are not sufficient. The impact of a given technology on abuse deterrence is highly dependent on the subjective experience and sensation in individuals that seek euphoria and reward from abusing prescription drugs. To our knowledge, to date there is no established relationship between the parameters used in clinical abuse liability studies, like I am feeling high or I would take this drug again with the in-vitro properties of a formulation or even with the descriptive changes in systemic exposure to the drug after manipulation of the product. The unpleasant experience from insufflating a sample of course particles after manipulating a crush-resistant tablet or from an otherwise locally aversive agent cannot be predicted from in-vitro data or systemic blood concentrations alone as several factors add to the cumulative performance of the product. Therefore, we request that FDA will continue to base its pre-market assessment of products that apply for abuse deterrent labeling, be it NDAs or ANDAs, on an   integrated and rigorous in-vitro, pharmacokinetic and abuse liability testing. This approach is reflected in FDAs decisions on abuse deterrent products to date and is consistent with the concepts as laid out in existing FDA guidance documents. Grnenthal will be glad to assist FDA in advancing the science of abuse deterrence and to develop meaningful standards and concepts for in-vitro, pharmacokinetic, and abuse liability assessments. We believe that ADF technologies are an invaluable tool in the battle against prescription drug abuse and that these technologies can provide additional safety and benefit to prescribers, patients and society.Thank you for the opportunity to testify today! See Attacched Comments of the Generic Pharmaceutical Association for FDA-2014-N-1359-0001:  Development and Regulation of Abuse-Deterrent Formulations of Opioid Medications.