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U.S. Department of Health and Human Services


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Questions and Answers about Onsolis (fentanyl buccal soluble film)




About Today's FDA Action

What action did FDA take today?

FDA approved Onsolis (fentanyl buccal soluble film), a new dosage form for fentanyl. Onsolis will be available under an approved Risk Evaluation and Mitigation Strategy or REMS.  The Food and Drug Administration Amendments Act of 2007 gave FDA the authority to require a REMS from manufacturers to ensure that the benefits of a drug or biological product outweigh its risks. Opioid medicines such as Onsolis have benefit when used properly and are a necessary component of pain management for certain patients. Opioid medicines also have serious risks when used improperly. The REMS for Onsolis is intended to help reduce these risks, while still ensuring that patients who need these drugs to treat pain will continue to have access to them.

What is a REMS?

A REMS is a tool to help ensure that the benefits of a drug continue to outweigh its risks. For background information on REMS go to http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm163655.htm

Why did FDA approve Onsolis before the finalization of a single-system REMS for extended-release (prolonged action) and high-potency opioids?

Onsolis is not an extended- release opioid and is only for opioid-tolerant patients.  Onsolis is an oral transmucosal fentanyl product, which is a highly potent opioid that is safe and effective in a much more limited patient population than extended-release and long-acting opioids.  Therefore FDA’s approval of Onsolis, including the Onsolis REMS, is independent of FDA’s effort to develop REMS for extended-release and high potency opioids. 

Is FDA still taking into consideration the recommendations that were made at the public meeting May 27th and 28th asking for input on the development of a REMS for certain extended-release opioids? 

Yes, all of the comments heard at the public meetings and received through submission to the public docket, number FDA-2009-N-0143 will be reviewed. This docket can be accessed at: http://www.regulations.gov/fdmspublic/component/main?main=DocketDetail&d=FDA-2009-N-0143 and is open for comments until June 30, 2009.   FDA believes this is valuable information that will lead to practical and effective solutions for development of a REMS and for appropriate use of opioid drug products.  The approval of Onsolis is independent of the larger extended-release and high potency opioid REMS effort.


About Onsolis

What is Onsolis?

Onsolis contains fentanyl, an opioid pain reliever, in a small film (about the size of a dime or nickel) that sticks to the inside of your cheek and eventually dissolves within 15 to 30 minutes after it is applied. Onsolis is used to manage breakthrough pain (flare-up of pain occurring in patients with otherwise stable, constant pain) in patients with cancer, 18 years of age and older, who are already using another opioid pain medicine around-the-clock and whose body is used to the medicine (opioid-tolerant). Onsolis comes in a foil package and is available in differing dosage strengths of 200 mcg, 400 mcg, 600 mcg, 800 mcg and 1200 mcg.

Is Onsolis a generic version of other transmucosal (delivered through the mucous membrane) fentanyl products?  Can it be substituted for other similar pain drugs?

NO. Onsolis is NOT a generic version of any other transmucosal fentanyl product. Onsolis cannot be substituted for any other fentanyl product. Substantial differences exist in how Onsolis is absorbed compared to other oral transmucosal fentanyl products. Substitution of Onsolis for any other oral transmucosal fentanyl product may result in fatal overdose.

How will Onsolis be supplied?

As part of the REMS for Onsolis, the drug will only be available through a restricted distribution program called the FOCUS Program.  The FOCUS Program prescription process includes the following steps:

  • Each patient, prescriber, distributor, and pharmacy completes the enrollment process to become enrolled in the FOCUS Program.
  • Prescriber faxes the initial prescription information for Onsolis to the FOCUS Program to start the verification process.
  • Prescriber sends the original, hardcopy prescription for Onsolis to a FOCUS pharmacy via courier using the supplied, shipping label for a FOCUS Program courier.
  • While the original, hardcopy prescription is in transit the FOCUS pharmacy confirms that the patient and prescriber are active in the FOCUS Program database,  the patient counseling call has been successfully completed, prepares the medication; and schedules Onsolis delivery to the patient.
  • Upon receipt of the original, hardcopy prescription, the FOCUS pharmacy dispenses Onsolis and delivers the medication directly to the patient via a secure, traceable courier (with adult signature required).

What should a patient do with unused Onsolis?

Patients are directed to dispose of unopened Onsolis films as soon as they are no longer needed:

  1. Remove the Onsolis film from its foil package.
  2. Drop the Onsolis film into the toilet.
  3. Repeat steps 1 and 2 for each Onsolis film. Flush the toilet after all unneeded films have been put into the toilet.

The Onsolis foil packages or cartons are not to be flushed down the toilet.



About the Onsolis REMS

What are the components of the Onsolis REMS?

The name of the Onsolis REMS is FOCUS (Full Ongoing Commitment to User Safety) Program. As part of the FOCUS program, Onsolis will only be available through a restricted distribution program with prescriber, pharmacy, distributor, and patient enrollment.  The FOCUS program will provide training and educational materials to prescribers and pharmacies, and patient education and counseling.  Orders will only be filled from participating pharmacies that courier the product directly to the patients’ homes. 

Why does Onsolis have a patient enrollment program?

Oral transmucosal fentanyl products are highly potent opioids that are highly effective in treating pain, but also have a very high risk of death when they are administered incorrectly, especially to patients who are not opioid tolerant. They are therefore safe and effective in a much more limited patient population than extended-release and long-acting opioids.  Experience with other transmucosal fentanyl products, Actiq and Fentora, has shown that ensuring the appropriate use of oral transmucosal fentanyl products cannot be accomplished by labeling and prescriber and patient education alone.  Therefore, FDA is requiring REMS that include restricted distribution programs for the class of transmucosal fentanyl products, which includes Onsolis, Actiq, and Fentora.  FDA is approving a REMS for Onsolis now and intends to approve REMS for Actiq and Fentora in the coming months.  Patient enrollment programs are a key element of these REMS because:

  • The indications for the transmucosal fentanyl products are unique.  Onsolis, Actiq and Fentora are indicated for breakthrough cancer pain in patients who are on around-the-clock opioids and are considered opioid-tolerant.  The misuse and abuse of these drugs in opioid nontolerant patients or patients who are not taking opioids daily has led to deaths. 
  • These products are not absorbed in the body the same way, and as a result, cannot be substituted for one another.  Medication errors have been reported with Fentora being substituted for Actiq, even though it is stated in a boxed warning not to do so.  This experience in light of a third oral transmucosal fentanyl coming onto the market warrants additional steps to reduce the likelihood of inappropriate substitution of these drugs. 
  • Fentanyl has become highly sought after by abusers.  There is concern that as more of these products reach the market, failure to anticipate and prevent misuse and abuse could result in a substantially large number of deaths.

Does this mean all opioids will be required to have a patient enrollment program?

Onsolis is not the same as the extended-release opioids and therefore, we do not see the specific items in the Onsolis REMS setting a precedent for other types of opioids.  The REMS for Onsolis is independent of the larger REMS efforts under discussion for extended-release and high potency opioids.

What is the goal of the FOCUS Program?

The goal of the FOCUS Program for Onsolis is to lessen the risk of fentanyl overdose, abuse, misuse, addiction, and serious complications due to medication errors by:

  • Helping to assure proper patient selection, including avoidance of the use of Onsolis in opioid non-tolerant patients;
  • Reducing the risk of exposure to Onsolis in persons for whom it was not prescribed, including accidental exposure in children; and
  • Training prescribers, pharmacists, and patients about proper dosing and administration.

How will FDA know if the FOCUS program is achieving its goal?

The company that makes Onsolis is required to submit a six month and one year assessment of the FOCUS Program as well as information from different data sources that monitor drug overdose, abuse, misuse, addiction and medication errors.

Will the elements of the Onsolis REMS create a precedent for elements to be included in the extended-release opioids REMS?

As noted above, Onsolis is not the same as the extended-release opioids and therefore, we do not see the specific items in the Onsolis REMS setting a precedent for other types of opioids. 

Will FDA evaluate the potential limitations of timely patient access? 

The Onsolis program is designed so that once a valid prescription is received in the pharmacy and there is confirmation that the physician and patient are properly enrolled, Onsolis will be delivered by courier to the patient’s home in most cases within 24 hours, but no longer than 5 business days for any patient.  Therefore, no undue delays are expected.  In some cases, this could result in availability of Onsolis sooner for patients compared to use of a community pharmacy which may not always have Onsolis in stock.  The FOCUS Program will distribute to all regions of the United States.

Will FDA evaluate the need for prescribers to substitute another opioid analgesic for Onsolis because of the Onsolis REMS?

This is a concern, particularly when the program is started because patients and prescribers will lack familiarity with the program.  However, once familiarity is gained, we do not expect that prescribers will refrain from prescribing Onsolis to appropriate patients.

Once the manufacturers of extended-release opioids establish their REMS, will the Onsolis REMS be included, or will it always remain separate?

As the programs are expected to be quite different, it is not expected that the Onsolis REMS will be modified to be equivalent to the REMS for the extended-release opioids.

What REMS elements does the FOCUS Program include?

The FOCUS Program includes the following elements:

  • Medication Guide
  • Communication Plan
  • Elements to Assure Safe Use
  • Implementation System
  • Timetable for Submission of Assessments


Brief Summaries of REMS Elements 

Medication Guide:

What is a Medication Guide?
A Medication Guide is a paper handout that is provided to patients with many prescription medicines, for example anti-depressants and NSAIDs (non-steroidal anti-inflammatory drugs). The guide addresses safety concerns that are specific to a particular drugor drug class.  The purpose of a Medication Guide is to provide FDA-approved information to patients when FDA determines that it is necessary to patients’ safe and effective use of drug products.  FDA will require the distribution of a Medication Guide for a drug if FDA determines that it could help prevent serious adverse events, or if the drug has serious risks relative to benefits that patients should be made aware of because it could affect patients’ decision to use or continue to use the drug, or if the drug is important to health and patient adherence to directions for use is crucial to the drug’s effectiveness.

Communication Plan:

What is the Onsolis Communication Plan?
The company that makes Onsolis, BioDelivery Sciences International, Inc. (BDSI), will execute a communication plan to healthcare providers.  This includes letters to prescribers telling them about Onsolis and about the FOCUS Program.  

Elements to Assure Safe Use:

The FOCUS Program includes safe use conditions described below to manage the risks of Onsolis.  The program is directed to prescribers, patients, distributors, and pharmacies. The FOCUS Program database maintains an enrollment list and the status of enrollees (i.e., active or inactive).

Prescriber enrollment will include mandatory review of  the educational material and enrollment renewal on a periodic basis. Prescribers are required to review the information in the prescribing information and to:

  • Ensure appropriate patient selection, including that the patient is opioid tolerant
  • Provide the Medication Guide for patient review
  • Complete the FOCUS Program prescriber enrollment form (including prescriber knowledge assessment); sign and fax the form to the FOCUS Program
  • Obtain the patient’s signature on the patient enrollment form; sign and fax the form to the FOCUS Program
  • Follow FOCUS Program-specific procedures for prescribing Onsolis

Patients are counseled by their prescriber on the Medication Guide.

  • The prescriber and patient complete and sign the Patient Enrollment Form and the prescriber faxes it to the FOCUS Program. 
  • The patient receives a FOCUS counseling call with the initial prescription to review the safe use conditions.

Focus Pharmacies - Pharmacies will be enrolled in FOCUS, and Onsolis will be dispensed only by the enrolled pharmacies via courier to the patient.  Onsolis will not be available in other health care settings, such as retail outlet pharmacies or hospitals.  Pharmacy enrollment must be renewed every 2 years or when there have been substantial changes to the program.  The enrolled pharmacies will have a Call Center for all pharmacist-patient interactions.  FOCUS Pharmacies that dispense Onsolis must:

  • Review the educational materials (Website Educational Materials or Printed Educational Materials).
  • Document that all pharmacy staff dispensing Onsolis have been trained on the FOCUS Program procedures and have reviewed the program educational materials.
  • Complete and sign the Pharmacy Enrollment Form and fax it to the FOCUS Program.

Implementation System:

In order to keep the FOCUS program running, BDSI is required to develop an implementation system to:

  • Ensure that wholesalers/distributors who distribute Onsolis are specially certified.  To become certified, wholesalers/distributors will be enrolled in the FOCUS Program.  Wholesaler/distributor renewal will occur every 2 years or when there have been substantial changes to the program.  Wholesalers/distributors that ship Onsolis to the specialty pharmacies must review the REMS document and complete and sign the Distributor Enrollment Form and fax it to the FOCUS Program.
  • Maintain a database of all enrolled entities (including patients, pharmacies and prescribers) to monitor and evaluate implementation of the elements of the program regarding patient and pharmacy enrollment in the FOCUS Program.
  • Monitor the distribution of Onsolis to ensure that the drug is only shipped to active FOCUS pharmacies, and that only active patients are receiving Onsolis and only active prescribers are prescribing Onsolis. 
  • Monitor, audit, and evaluate all active FOCUS pharmacies, distributors, and the FOCUS Program vendor at the initiation of the program to ensure they implement the program as directed.
  • Monitor and evaluate the elements to assure safe use regarding patient and pharmacy enrollment in the FOCUS Program in the manner described in the REMS Supporting Document, and take reasonable steps to work to improve implementation of these elements.

Timetable for Submission of Assessments:

BDSI will be required by FDA to submit an assessment of the FOCUS Program for review 6 months and 1 year after the approval date for Onsolis and once a year thereafter.  There will be a number of areas assessed as part of a program to monitor the effectiveness of the FOCUS program.  The FDA will be interested in measuring the FOCUS Program’s ability to ensure safe use conditions such as controlling drug overdose, abuse, misuse, addiction and medication errors. Other areas of interest will be evaluating the timeliness of patient access.