`CENTER FOR DRUG EVALUATION AND RESEARCH
`
`Approval Package for:
`
`
`APPLICATION NUMBER:
`
`NDA 22-272
`
`Oxycontin, Tablets (Controlled Release)
`
`Trade Name:
`
`Generic Name:
`
`Sponsor:
`
`Approval Date:
`
`Indications:
`
`Oxycodone hydrochloride controlled-release
`
`Purdue Pharma
`
`4/5/10
` For the management of moderate to severe pain
`when a continuous, around-the-clock opioid
`analgesic is needed for an extended period of
`time
`
`

`

`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`APPLICATION NUMBER:
`22-272
`
`
`CONTENTS
`
`
`Reviews / Information Included in this NDA Review.
`
`
`
`Approval Letter
`Other Action Letters
`Labeling
`REMS
`Summary Review
`Officer/Employee List
`Office Director Memo
`Cross Discipline Team Leader Review
`Medical Review(s)
`Chemistry Review(s)
`Environmental Assessment
`Pharmacology Review(s)
`Statistical Review(s)
`Microbiology Review(s)
`Clinical Pharmacology/Biopharmaceutics Review(s)
`Other Reviews
`Risk Assessment and Risk Mitigation Review(s)
`Proprietary Name Review(s)
`Administrative/Correspondence Document(s)
`
`
`x
`x
`x
`x
`x
`x
`
`x
`x
`x
`
`x
`x
`
`x
`x
`x
`x
` x
`
`

`

`CENTER FOR DRUG EVALUATION AND
`
`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`RESEARCH
`
`
`
`
`
`APPLICATION NUMBER:
`22-272
`22-272
`
`
`APPLICA TION NUMBER:
`
`APPROVAL LETTER
`
`APPROVAL LETTER
`
`
`
`
`
`

`

`
`
`
`
`
`
`DEPARTMENT OF HEALTH AND HUMAN SERVICES
`
`
`
`
`
`
`
`
`Food and Drug Administration
`Silver Spring MD 20993
`
`NDA APPROVAL
`
`
`NDA 022272
`
`Purdue Pharma L.P.
`One Stamford Forum
`Stamford, CT 06901-3431
`
`Attention: Craig Landau, M.D.
`
`CMO & VP Clinical, Medical & Regulatory Affairs
`
`
`Dear Dr. Landau:
`
`Please refer to your new drug application (NDA) dated, received November 29, 2007, submitted
`under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for OxyContin
`(Oxycodone Hydrochloride Controlled-Release) Tablets.
`
`We acknowledge receipt of your submissions dated November 30, and December 19, 20 and 21,
`2007, January 14, February 8, 12, 14 (2), and 15 (2), March 7, 10, 14, 18, 25 (2), and 27, April
`11 (2) and 23, May 7, August 20, September 26, October 30, November 11 and 20, and
`December 5, 8, and 10, 2008, and March 30, May 18, June 2, 10, and 16, July 13 and 24, August
`7, September 18, October 6 and 9, and November 4, 6, 17, 19, and 23, December 16 and 22
`2009, and February 5, and 24, March 11, 25, 26, and 31, and April 2, 2010.
`
`The February 5, 2010, submission constituted a complete response to our December 30, 2009,
`action letter.
`
`This new drug application provides for the use of OxyContin (Oxycodone Hydrochloride
`Controlled-Release) Tablets, 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 60 mg, and 80 mg, for
`treatment of moderate-to-severe pain when a continuous, around-the-clock opioid analgesic is
`needed for an extended period of time.
`
`We have completed our review of this application, as amended. It is approved, effective on the
`date of this letter, for use as recommended in the content of labeling [21 CFR 314.50(1)] in
`structured product labeling (SPL) format submitted on March 31, 2010.
`
`We are waiving the requirements of 21 CFR 201.57(d)(8) regarding the length of Highlights of
`prescribing information. This waiver applies to all future supplements containing revised
`labeling unless we notify you otherwise.
`
`
`

`

`NDA 022272
`Page 2
`
`
`CONTENT OF LABELING
`
`As soon as possible, but no later than 14 days from the date of this letter, please resubmit the
`content of labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format, as described
`at http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm, that is
`identical to the enclosed labeling text for the package insert and Medication Guide. For
`administrative purposes, please designate this submission, “SPL for approved NDA 022272.”
`
`
`CARTON AND IMMEDIATE CONTAINER LABELS
`
`We acknowledge your March 31, 2010, submission containing final printed carton and container
`labels.
`
`Marketing the product with FPL that is not identical to the approved labeling text may render the
`product misbranded and an unapproved new drug.
`
`
`POSTMARKETING REQUIREMENTS UNDER 505(o)
`
`As you were informed in our December 30, 2009, Complete Response Letter, FDA has
`determined that you are required to conduct postmarketing studies of OxyContin (Oxycodone
`Hydrochloride Controlled-Release) Tablets to assess the known serious risks of OxyContin
`(Oxycodone Hydrochloride Controlled-Release) Tablets, in particular, whether the changes made
`to the OxyContin (Oxycodone Hydrochloride Controlled-Release) Tablets formulation that are
`the subject of this application and which are intended to deter misuse and abuse actually result in
`a decrease in the risks of misuse and abuse, and their consequences.
`
`Specifically, we have determined that you are required, pursuant to section 505(o)(3) of the
`FDCA, to conduct epidemiological studies to address whether the changes made to the
`OxyContin (Oxycodone Hydrochloride Controlled-Release) Tablets formulation that are the
`subject of this application result in a decrease in misuse and abuse, and their consequences:
`addiction, overdose, and death.
`
`We acknowledge receipt of your proposal, included in your February 5, 2010, resubmission to
`this application, that contains brief descriptions of possible postmarketing studies to fulfill this
`requirement. Because of design and methodology challenges, we continue to be concerned that
`the proposed studies will not successfully capture the necessary information that will allow us to
`assess the impact, if any, attributable to the change in the OxyContin (Oxycodone Hydrochloride
`Controlled-Release) Tablets formulation. Therefore, we will continue discussion of your
`postmarketing study proposals at an advisory committee meeting in the fall of 2010 on the
`design and methodology of the proposed studies.
`
`For the study to be conducted first, you must submit the final protocol and the timetable for
`completion of the study by January 31, 2011. Likewise, for the study to be conducted last, you
`must submit the final protocol and timetable for completion of the study by March 1, 2011.
`
`
`

`

`NDA 022272
`Page 3
`
`
`Submit future correspondences regarding your proposal(s) to address this requirement to your
`IND, with a cross-reference letter to this NDA. Prominently identify the submission(s) with the
`following wording in bold capital letters at the top of the first page of the submission:
`
`
`• REQUIRED POSTMARKETING CORRESPONDENCE UNDER 505(o)
`
`
`
`RISK EVALUATION AND MITIGATION STRATEGY REQUIREMENTS
`
`Section 505-1 of the FDCA authorizes FDA to require the submission of a Risk Evaluation and
`Mitigation Strategy (REMS) if FDA determines that such a strategy is necessary to ensure that
`the benefits of the drug outweigh the risks (section 505-1(a)).
`
`Pursuant to 505-1(f)(1), we have determined that OxyContin (Oxycodone Hydrochloride
`Controlled-Release) Tablets can be approved only if elements necessary to assure safe use are
`required as part of a REMS to mitigate the risks of abuse, misuse, and overdose, and addiction,
`as well as the risk of use of doses greater than 60 mg of OxyContin (Oxycodone Hydrochloride
`Controlled-Release) Tablets in non-opioid tolerant individuals, listed in the labeling. The
`elements to assure safe use will ensure that OxyContin (Oxycodone Hydrochloride Controlled-
`Release) Tablets will only be prescribed by healthcare providers who have particular training
`under 505-1(f)(3)(A) and will mitigate the aforementioned risks through informing and training
`healthcare providers about the potential risks and the safe use of OxyContin (Oxycodone
`Hydrochloride Controlled-Release) Tablets.
`
`Your proposed REMS, submitted on April 2, 2010, and appended to this letter, is approved. The
`REMS consists of a Medication Guide, elements to assure safe use, and a timetable for
`submission of assessments of the REMS.
`
`As you know, we are considering what REMS elements should be implemented for a number of
`opioid products, including modified-release opioids to address the risks of: 1) use in non-opioid-
`tolerant individuals and 2) abuse, misuse, overdose, and addiction. As discussed, once that
`determination is made, we will notify you in writing and you will be required to submit a
`modified REMS incorporating those elements.
`
`The REMS assessment plan should include but is not limited to the following:
`
`
`
`
`1. An evaluation of patients’ understanding of the serious risks of OxyContin (Oxycodone
`Hydrochloride Controlled-Release) Tablets.
`
`
`2. A report on periodic assessments of the distribution and dispensing of the Medication
`Guide in accordance with 21 CFR 208.24.
`
`
`3. A report on failures to adhere to distribution and dispensing requirements, and corrective
`actions taken to address noncompliance.
`
`4. A report on the status of the training program for healthcare providers including the
`number of Dear Healthcare Professional letters mailed to each specialty identified in the
`REMS, when the letters were mailed, and what information was included in the mailings.
`
`

`

`NDA 022272
`Page 4
`
`
`
`
`5. An evaluation of healthcare providers’ awareness and understanding of the serious risks
`associated with OxyContin (Oxycodone Hydrochloride Controlled-Release) Tablets (for
`example, through surveys of healthcare providers).
`
`6. Specification of measures that would be taken to increase awareness if surveys of
`healthcare providers indicate that healthcare provider awareness is not adequate.
`
`7. An analysis and summary of surveillance and monitoring activities for abuse, misuse,
`overdose, and addiction and any intervention taken resulting from signals of abuse,
`misuse, overdose, and addiction.
`
`8. An analysis to evaluate OxyContin (Oxycodone Hydrochloride Controlled-Release)
`Tablets utilization patterns including use in non-opioid tolerant patients.
`
`
`
`
`
`
`
`
`
`9. With respect to REMS goals, an assessment of the extent to which the elements to assure
`safe use are meeting the goals or whether the goals or such elements should be modified.
`
`
`The requirements for assessments of an approved REMS under section 505-1(g)(3) include, in
`section 505-1(g)(3)(A), an assessment of the extent to which the elements to assure safe use are
`meeting the goal or goals to mitigate a specific serious risk listed in the labeling of the drug, or
`whether the goal or goals or such elements should be modified.
`
`
`Assessments of an approved REMS must also include, under section 505-1(g)(3)(B) and (C),
`information on the status of any postapproval study or clinical trial required under section 505(o)
`or otherwise undertaken to investigate a safety issue. You can satisfy these requirements in your
`REMS assessments by referring to relevant information included in the most recent annual report
`required under section 506B and 21 CFR 314.81(b)(2)(vii) and including any updates to the
`status information since the annual report was prepared. Failure to comply with the REMS
`assessments provisions in 505-1(g) could result in enforcement action.
`
`We remind you that in addition to the assessments submitted according to the timetable included
`in the approved REMS, you must submit a REMS assessment and may propose a modification to
`the approved REMS when you submit a supplemental application for a new indication for use as
`described in Section 505-1(g)(2)(A) of FDCA.
`
`Prominently identify any submission containing the REMS assessment or proposed
`modifications with the following wording in bold capital letters at the top of the first page of the
`submission:
`
`
`N 022272 REMS ASSESSMENT
`
`NEW SUPPLEMENT FOR N 022272
`PROPOSED REMS MODIFICATION
`REMS ASSESSMENT
`
`NEW SUPPLEMENT (NEW INDICATION FOR USE)
`FOR N 022272
`
`

`

`NDA 022272
`Page 5
`
`
`
`REMS ASSESSMENT
`PROPOSED REMS MODIFICATION (if included)
`
`
`If you do not submit electronically, please send 5 copies of REMS-related submissions.
`
`PROMOTIONAL MATERIALS
`
`You may request advisory comments on proposed introductory advertising and promotional
`labeling. To do so, submit, in triplicate, a cover letter requesting advisory comments, the
`proposed materials in draft or mock-up form with annotated references, and the package insert
`to:
`
`
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Division of Drug Marketing, Advertising, and Communications
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
`
`
`As required under 21 CFR 314.81(b)(3)(i), you must submit final promotional materials, and the
`package insert, at the time of initial dissemination or publication, accompanied by a Form FDA
`2253. For instruction on completing the Form FDA 2253, see page 2 of the Form. For more
`information about submission of promotional materials to the Division of Drug Marketing,
`Advertising, and Communications (DDMAC), see
`http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
`
`EXPIRATION DATING PERIOD
`
`An expiration dating period of 24 months is granted to the 10, 15, 20, 30, 40, 60, and 80 mg
`OxyContin tablets in HDPE bottle packaging configurations, stored at 25°C (77°F); excursions
`permitted between 15°-30°C (59°-86°F).
`
`LETTERS TO HEALTH CARE PROFESSIONALS
`
`If you decide to issue a letter communicating important safety-related information about this
`drug product (i.e., a “Dear Health Care Professional” letter), we request that you submit, at least
`24 hours prior to issuing the letter, an electronic copy of the letter to this NDA, to
`CDERMedWatchSafetyAlerts@fda.hhs.gov, and to the following address:
`
`
`MedWatch
`Food and Drug Administration
`Suite 12B-05
`5600 Fishers Lane
`Rockville, MD 20857
`
`

`

`NDA 022272
`Page 6
`
`
`
`REPORTING REQUIREMENTS
`
`We remind you that you must comply with reporting requirements for an approved NDA (21
`CFR 314.80 and 314.81).
`
`If you have any questions, call Lisa Basham, Senior Regulatory Health Project Manager, at (301)
`796-1175.
`
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Bob A. Rappaport, MD
`Director
`Division of Anesthesia and Analgesia
`Products
`Office of Drug Evaluation II
`Center for Drug Evaluation and Research
`
`
`
`Enclosures:
`
`Package Insert
`Medication Guide
`Container Labels
`REMS
`REMS Materials
`
`

`

`Application
`Type/Number
`--------------------
`NDA-22272
`
`Submission
`Type/Number
`--------------------
`ORIG-1
`
`Submitter Name
`
`Product Name
`
`--------------------
`PURDUE PHARMA
`INC
`
`------------------------------------------
`OXYCONTIN
`
`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`BOB A RAPPAPORT
`04/05/2010
`
`