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U.S. Department of Health and Human Services


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FDA Opioid REMS Meeting with Industry (May 16, 2011)

May 16, 2011
Kirkland Conference Center, Nation Labor College
10000 New Hampshire Avenue
Silver Spring, MD 20993


FDA Leads:  Jane Axelrad; Gerald Dal Pan; Sharon Hertz; John K. Jenkins; Claudia Karwoski; Douglas Throckmorton; Mary Willy; Julie Zawisza

Other FDA Staff: Richardae Araojo; Katlin Backfield; Suzanne Barone; Lisa Basham; Carla Cartwright; Dominic Chiapperino; Randi Clark; Kimberly Compton; Kathleen Davies; Kristen Everett; Ellen Fields; LaShawn Griffiths; Mary Gross; Denise Hinton; Pamela Horn; Michie Hunt; Timothy Jiang; Mwango Kashoki; Carrie Lemley; Heidi Marchand; Kristen Miller; Megan Moncur; Frank Pucino; William Rickman; Robert Shibuya; Dale Slavin; Sara Stradley; Theresa Toigo; Elaine Vining

Industry Representatives:  Todd Baumgartner, Purdue Pharma, L.P.; Tara Chapman, Endo Pharmaceuticals, Inc.; Michael Clark, Endo Pharmaceuticals, Inc.; Paul Coplan, Purdue Pharma, L.P.; Eric Davis, Mylan Pharmaceuticals; Todd Delehant, Rhodes Pharmaceuticals, L.P.; Elizabeth Ernst, Roxane Laboratories; Cynthia Farner, Upsher-Smith Laboratories, Inc.;  Juliane Foley, Mylan Technologies; Kishore Gopu, Teva Pharmaceuticals; J. David Haddox, Purdue Pharma, L.P.;  Greg Hicks, Roxane Laboratories; Diana Hughes, Pfizer; Michael Kaufman, Johnson & Johnson; Marianne Kenny, Watson Laboratories; Stu Kim, Covidien; Linda Kitlinski, Endo Pharmaceuticals, Inc.; Gary Kozloski, Watson Laboratories; John Lay, VistaPharm, Inc.; Melissa Lofton, Rhodes Pharmaceuticals, L.P.; Lisa Malandro, Pfizer; Jean-Yves Maziere, Roxane Laboratories; Sherice Mills, Covidien; Terri Nataline, Actavis; Susan Nicholson, Johnson & Johnson; Joel Novendstern, Ranbaxy, Inc.; James Osborne, LaviPharm, Inc.; James Ottinger, Cephalon, Inc.; Janet Peterson, Johnson & Johnson; Eric Smith, Pfizer; Vince Suneja, Mylan Pharmaceuticals; Scott Tomsky, Ranbaxy, Inc.; Janet Vaughn, Watson Laboratories; Robert Vincent, Teva Pharmaceuticals; Joanna Waugh, Noven Pharmaceuticals; Greg Wedin, Upsher-Smith Laboratories, Inc.; Monique Weitz, Activis.


John Jenkins MD, Director, Office of New Drugs, FDA Center for Drug Evaluation and Research (CDER) opened the meeting, indicating the purpose of the meeting was to respond to industry questions concerning developing the required REMS for long-acting and extended release opioids.  On behalf of the IWG, Elizabeth Ernst thanked FDA for the opportunity to meet and expressed the hope that this meeting would be the beginning of a collaborative interaction.  She said that the IWG wished to maintain a dialogue with the FDA, and proposed that the IWG and FDA agree to a schedule for future meetings before the August 17, 2011 deadline for the REMS submission. 

Before the meeting, the IWG had submitted questions about the implementation of the REMS and the FDA had prepared responses in the areas of (1) prescriber training; (2) Medication Guides; (3) the REMS assessment plan; and (4) administration of the REMS.  The attached questions and responses were discussed.  In addition, during the meeting industry representatives posed the following additional questions and received these responses:

Prescriber Training

1.  Industry Question:  Which parts of the prescriber training should include product specific information? 

FDA Response:  FDA expects that some product specific information would be included in the general section, e.g., the special PK characteristics of some products, and that more detailed information would be provided in each of the follow-up modules for each specific product. 

For example, drug substance or product group toxicities should be introduced in the general section and then more specific information for each product might be included in the individual drug product sections, e.g., special considerations for patches, instructions to take some products with plenty of water, safe manipulation (such as sprinkling the drug on applesauce).  This should be done so that the health care provider will have a general understanding of the issues at the start and can then go to the drug-specific sections for more information about the product specific characteristics and safety issues.

2.  Industry Question:  Does FDA envision that prescribers would complete the training and receive certification for a period of time, based on this training?

FDA Response:  The REMS does not require prescribers to take the training or be certified to prescribe LA and ER opioids.  However, if Congress amends the Controlled Substances Act (CSA) to require prescribers to be trained in the use of opioids to be registered with the DEA to prescribe controlled substances, then it is possible that prescribers will be required to repeat their training every three years because they have to reregister every three years.

3.  Industry Question:  Would prescribers complete the general section of the training and then only do the product specific modules if they were prescribing those drugs?

FDA Response:  The training should be thought of as a package.  The intent is that the prescriber would acquire the basics for all of the products covered whether or not they prescribe the specific drugs. 

4.  Industry Question:  What further training will sponsors have to provide when new products are approved?

FDA Response:  The REMS will need to be updated periodically as new products are approved.  The new products will need to be added to the training package, perhaps as a new module.

5.  Industry Question:  What does FDA envision as the number of hours of training that the sponsors will need to provide?

FDA Response:  FDA expects the training to take at least a couple of hours, but the length of time will depend on how the CME and CE providers develop it.  These providers may also link the training in LA and ER opioids required under the REMS to general training in pain management. 

6.  Industry Question:  During the December 2009 meeting on the REMS, the IWG had proposed that, under ETASU, a provider already certified under pain management would be exempt from the training.  Would FDA comment?

FDA Response:  The REMS will not require individual health care provider training to prescribe LA and ER opioid drugs.  FDA wants an assessment of the number of unique providers taking the training, and will not be collecting information on whether individual practitioners have been trained.   Therefore, a specific exemption is not required.  If and when Congress passes legislation that would make training mandatory as a condition of DEA registration, Congress could consider whether such an exemption should be provided.

7.  Industry Question:  Does the proposed legislation to amend the CSA to require prescribers to be trained cover only opioids or all controlled substances?

FDA Response:  The Office of National Drug Control Policy (ONDCP) document, Epidemic:  Responding to America’s Prescription Drug Abuse Crisis, published on April 19, 2011, announced the administration’s intent to seek legislation, and that document addressed only opioids.

8.  Industry Question:  How will the funding of grants for training be shared, and how will generics be involved?

FDA Response:  Cost sharing is a matter for the sponsors to work out among themselves.  In other REMS with single shared systems, one of the first things the sponsors do is work out cost and governance issues.  

Discussion of FDA’s “Blueprint” Approach

The IWG reported that on April 22, 2011 their representatives had met with Dr. Murray Kopelow, Chief Executive Officer of the Accreditation Council for Continuing Medical Education (ACCME) to discuss the Opioid REMS.  At this time, Dr.  Kopelow was unsure that the blueprint approach of the REMS would work.  FDA responded that on May 6, 2011 the Agency had held its own teleconference with Dr. Kopelow to discuss the REMS.  In this conversation, FDA had explored the “blueprint” concept with Dr. Kopelow, and he had indicated that he thought that this approach would work.

FDA clarified that the Agency expects the blueprint to contain key messages and concepts, but not to “be a book.”  FDA expects CME providers would consult the blueprint and then develop the content in their own way.

FDA Comment:  Regarding the patient information sheet to assist the prescriber in counseling the patient, the Agency wants one patient education sheet for the class REMS.   This is intended to be a common sheet for the shared system with common information and a space for the provider to write in product-specific information.  This format complements the training that the provider would have received. 

Medication Guides

1. Industry Question:  What is the time frame for the FDA to make model Medication Guide available to sponsors?

FDA Response:  FDA cannot provide a specific time frame, but staff is actively working on the format of the Medication Guide to make it shorter, less redundant, and more user friendly.  The final work by the individual companies should be limited because the Agency will be drafting the content.  Changes can be proposed during the REMS review. 

2.  Industry Comment:  Patients have difficulty in understanding the differences between dependence, tolerance, and addiction.  The Agency may wish to consider this problem in creating the model Medication Guide. 

REMS Assessment Plan

1. Industry Question:  If a provider takes some of the modular training but does not complete all the modules, would he be considered to have completed the training?

FDA Response:  The modular format is intended to organize the information logically.  The provider would get credit only after completing the entire training (all modules).  FDA would also like for the REMS assessment to count unique providers rather than episodes of training that the same provider might take multiple times.

Industry Comment:  Gathering data on unique providers would require a unique identifier for a data base operated by a third party and capable of storing personal information securely.

2. Industry Question:  With what frequency does FDA expect industry sponsors to audit the training?

 FDA Response:  Industry can propose a plan for auditing the training as part of the REMS assessment submission, which FDA will review.  This plan would include the frequency.  The audit would need to be performed by a third party and the main purpose of the audit is to determine how well the blueprint messages are being conveyed and whether the training is free of promotional content. 

3. Industry Question:  The product specific information required for the REMS assessment is current up to 60 days prior to the assessment report.  If we want to build in an independent assessment, 60 days would be tight.  Would FDA comment?

FDA Response:  Industry should submit a proposal.  FDA does need timely information to assess the REMS.

4. Industry Comment:  Companies have concerns about providing comparative data on competing products and would prefer to perform general surveillance, looking at the changes in adverse events for the class or at the level of active drug substance, rather than for specific products. 

FDA Response.  The Agency would like to see as much product specific information as possible. 

5. Industry Question:  Does FDA expect the REMS assessment to include separate data for the innovator (brand) and generic versions of each product, or only for the overall product?

FDA Response:  Separate data for the brand and generic versions should be provided where they are available, although FDA recognizes that often they will not be.

II. Next Steps

A. Future Discussions Between FDA and Industry

  1. FDA is open to additional discussions with industry before August 17, the REMS due date.  However, the IWG’s proposal of a bi-weekly meeting is too frequent.  FDA suggests that a teleconference be held in early to mid-June.
  2. The IWG will formulate questions for the FDA at its next meeting on June 2, and forward them to FDA soon afterward in anticipation of this teleconference. 
  3. The IWG invited companies that are not already members to contact them.

B. Future Meetings with Accrediting Bodies

  1. The IWG reported that it would like to schedule a meeting with ACCME and other accrediting organizations and invite FDA.
  2. FDA plans to have further discussions with the ACCME and other accrediting bodies.  These will be coordinated through Theresa Toigo.  However, the Agency is willing to meet jointly with the IWG and these groups as well.