S~~VICI;s
`
`( / ~ DEPARTMENT OF HEALTH & HUMAN SERVICES
`<<~-
`
`DEC 2 0 2006
`
`Anika Therapeutics, Inc.
`% Constance Garrison, MBA, RAC
`Vice President, Regulatory, Clinical and Quality Systems
`236 West Cummings Park
`Woburn, Massachusetts 01801
`
`Public Health Service
`
`Food and Drug Administration
`9200 Corporate Boulevard
`Rockville MD 20850
`
`Re
`
`P050033
`Cosmetic Tissue Augmentation Product
`Filed: September 2, 2005
`Amended: October 21 and December 12, 2005 and January 6, March 1, April20, May 11,
`June 9, August 31, September 15,22 and 27, October 11 and 18, and November 15,22
`and 29,2006
`Procode: LMH
`
`Dear Ms. Garrison:
`
`The Center for Devices and Radiological Health (CDRH) of the Food and Drug Administration
`(FDA) has completed its review of your premarket approval application (PMA) for the Cosmetic
`Tissue Augmentation Product. This device is indicated for injection into the mid to deep dermis
`for correction of moderate to severe facial wrinkles and folds (such as nasolabial folds). We are
`pleased to inform you that the PMA is approved. You may begin commercial distribution of the
`device in accordance with the conditions described below and in the "Conditions of Approval"
`(enclosed).
`
`The sale, distribution, and use of this device are restricted to prescription use in accordance with
`21 CFR 801.109 within the meaning of section 520(e) of the Federal Food, Drug, and Cosmetic
`Act (the act) under the authority of section 515( d)(! )(B)(ii) of the act. FDA has also determined
`that, to ensure the safe and effective use of the device, the device is further restricted within the
`meaning of section 520(e) under the authority of section 515(d)(1)(B)(ii) insofar as the sale,
`distribution, and use must not violate sections 502( q) and (r) of the act.
`
`In addition to the postapproval requirements outlined in the enclosure, this approval is subject to
`the following additional condition:
`
`Please submit a Post Approval study protocol for examining the safety of Cosmetic Tissue
`Augmentation Product (CTA) in persons of color. This post-approval protocol should describe
`an open-label, longitudinal, uncontrolled, study in a minimum of 100 patients with Fitzpatrick
`Skin Types 4, 5 or 6 at I 0 or more U.S. centers who have elected to undergo nasolabial fold
`treatment with intradermal (deep dermal) injection of CTA. Patients will be followed for a
`minimum of 24 weeks with visits assessment of pain, tenderness, redness, ecchymosis, swelling,
`itching, mass (nodule I cyst I abscess) formation, dermal pigmentation and keloid changes at the
`
`

`

`Page 2 - Constance Garrison, MBA, RAC
`
`site of injection at each follow-up point post-optimal cosmesis. The purpose of the study is to
`gain additional safety information, including the likelihood ofkeloid formation, in patients with
`Fitzpatrick Scale skin types 4, 5, and 6. Safety endpoint assessments of this study are: I) keloid
`formation at the site of injection at 12 and 24 weeks, 2) pigmentation changes at the site of
`injection compared to adjacent skin at 2 and 6 weeks, 3) adverse experience assessment, and 4) a
`patient diary symptom profile. The results from this study will be submitted to FDA on an
`annual basis in post approval study reports separately from your PMA annual reports. After the
`study has been evaluated by FDA, the labeling will be revised to include the study results via a
`PMA supplement.
`
`Expiration dating for this device has been established and approved at 15 months when stored at
`2-25°C.
`
`CDRH does not evaluate information related to contract liability warranties, however you should
`be aware that any such warranty statements must be truthful, accurate, and not misleading, and
`must be consistent with applicable Federal and State laws.
`
`CDRH will notify the public of its decision to approve your PMA by making available a
`summary of the safety and effectiveness data upon which the approval is based. The information
`can be found on the FDA CDRH Internet HomePage located at
`http://www.fda.gov/cdrh/pmapage.html. Written requests for this information can also be made
`to the Dockets Management Branch, (HF A-305), Food and Drug Administration, 5630 Fishers
`Lane, Rm. 1061, Rockville, MD 20852. The written request should include the PMA number or
`docket number. Within 30 days from the date that this information is placed on the Internet, any
`interested person may seek review of this decision by requesting an opportunity for
`administrative review, either through a hearing or review by an independent advisory committee,
`under section 515(g) of the Federal Food, Drug, and Cosmetic Act (the act).
`
`Failure to comply with any postapproval requirement constitutes a ground for withdrawal of
`approval of a PMA. Commercial distribution of a device that is not in compliance with these
`conditions is a violation of the act.
`
`You are reminded that, as soon as possible and before commercial distribution of your device,
`you must submit an amendment to this PMA submission with copies of all approved labeling in
`final printed form. The labeling will not routinely be reviewed by FDA staff when PMA
`applicants include with their submission of the final printed labeling a cover letter stating that the
`final printed labeling is identical to the labeling approved in draft form. If the final printed
`labeling is not identical, any changes from the final draft labeling should be highlighted and
`explained in the amendment.
`
`All required documents should be submitted in triplicate, unless otherwise specified, to the
`address below and should reference the above PMA number to facilitate processing.
`
`

`

`Page 3 - Constance Garrison, MBA, RAC
`
`PMA Document Mail Center (HFZ-401)
`
`Center for Devices and Radiological Health
`
`Food and Drug Administration
`
`9200 Corporate Blvd.
`
`Rockville, Maryland 20850
`
`
`If you have any questions concerning this approval order, please contact Charles N. Durfor,
`Ph.D. at (240) 276-3555.
`
`1t('~
`
`Mark N. Melkerson
`Director
`Division of General, Restorative
`and Neurological Devices
`Office of Device Evaluation
`Center for Devices and
`Radiological Health
`
`Enclosure
`
`

`

`Last Modified: 10-18-06
`
`CONDITIONS OF APPROVAL
`
`PREMARKET APPROVAL APPLICATION (PMA) SUPPLEMENT. Before making any
`change affecting the safety or effectiveness of the device, submit a PMA supplement for review
`and approval by FDA unless the change is of a type for which a "Special PMA
`Supplement-Changes Being Effected" is permitted under 21 CFR 814.39(d) or an alternate
`submission is permitted in accordance with 21 CFR 814.39(e) or (f). A PMA supplement or
`alternate submission shall comply with applicable requirements under 21 CFR 814.39 of the final
`rule for Premarket Approval of Medical Devices.
`
`All situations that require a PMA supplement cannot be briefly summarized; therefore, please
`consult the PMA regulation for further guidance. The guidance provided below is only for
`several key instances.
`
`A PMA supplement must be submitted when unanticipated adverse effects, increases in the
`incidence of anticipated adverse effects, or device failures necessitate a labeling, manufacturing,
`or device modification.
`
`A PMA supplement must be submitted if the device is to be modified and the modified device
`should be subjected to animal or laboratory or clinical testing designed to determine if the
`modified device remains safe and effective.
`
`A "Special PMA Supplement- Changes Being Effected" is limited to the labeling, quality control
`and manufacturing process changes specified under 21 CFR 814.39( d)(2). It allows for the
`addition of, but not the replacement of previously approved, quality control specifications and
`test methods. These changes may be implemented before FDA approval upon acknowledgment
`by FDA that the submission is being processed as a "Special PMA Supplement - Changes Being
`Effected." This procedure is not applicable to changes in device design, composition,
`specifications, circuitry, software or energy source.
`
`Alternate submissions permitted under 21 CF'R 814.39( e) apply to changes that otherwise require
`approval of a PMA supplement before implementation of the change and include the use of a
`30-day PMA supplement or annual postapproval report (see below). FDA must have previously
`indicated in an advisory opinion to the affected industry or in correspondence with the applicant
`that the alternate submission is permitted for the change. Before such can occur, FDA and the
`PMA applicant(s) involved must agree upon any needed testing protocol, test results, reporting
`format, information to be reported, and the alternate submission to be used.
`
`Alternate submissions permitted under 21 CFR 814.39(±) for manufacturing process changes
`indude the use of a 30-day Notice. The manufacturer may distribute the device 30 days after the
`date on which the FDA receives the 30-day Notice, unless the FDA notifies the applicant within
`30 days from receipt of the notice that the notice is not adequate.
`
`page I
`
`

`

`POST APPROVAL REPORTS. Continued approval of this PMA is contingent upon the
`submission ofpostapproval reports required under 21 CFR 814.84 at intervals of I year from the
`date of approval of the original PMA. Postapproval reports for supplements approved under the
`original PMA. if applicable, are to be included in the next and subsequent annual reports for the
`original PMA unless specified otherwise in the approval order for the PMA supplement. Two
`copies identified as "Annual Report" and bearing the applicable PMA reference number are to be
`submitted to the PMA Document Mail Center (HFZ-40 I), Center for Devices and Radiological
`Health, Food and Drug Administration, 9200 Corporate Blvd., Rockville, Maryland 20850. The
`postapproval report shall indicate the beginning and ending date of the period covered by the
`report and shall include the following information required by 21 CFR 814.84:
`
`1.
`
`2.
`
`Identification of changes described in 21 CFR 814.39(a) and changes required to be
`reported to FDA under 21 CFR 814.39(b ).
`
`Bibliography and summary of the following information not previously submitted
`as part of the PMA and that is known to or reasonably should be known to the
`applicant:
`
`a. unpublished reports of data from any clinical investigations or nonclinical
`laboratory studies involving the device or related devices ("related" devices
`include devices which are the same or substantially similar to the applicant's
`device); and
`
`b. reports in the scientific literature concerning the device.
`
`If, after reviewing the bibliography and summary, FDA concludes that.agency review of one or
`more of the above reports is required, the applicant shall submit two copies of each identified
`report when so notified by FDA.
`
`ADVERSE REACTION AND DEVICE DEFECT REPORTING. As provided by 21 CFR
`8!4.82(a)(9), FDA has determined that in order to provide continued reasonable assurance of the
`safety and effectiveness of the device, the applicant shall submit 3 copies of a written report
`identified, as applicable, as an "Adverse Reaction Report" or "Device Defect Report" to the PMA
`Document Mail Center (HFZ-401), Center for Devices and Radiological Health, Food and Drug
`Administration, 9200 Corporate Blvd., Rockville, Maryland 20850 within I 0 days after the
`applicant receives or has knowledge of information concerning:
`
`1. A mix-up of the device or its labeling with another article.
`
`2. Any adverse reaction, side effect, injury, toxicity, or sensitivity reaction that is
`
`attributable to the device and:
`
`
`a.
`
`has not been addressed by the device's labeling; or
`
`b. has been addressed by the device's labeling but is occurring with unexpected
`severity or frequency.
`
`page 2
`
`

`

`3. Any significant chemical, physical or other change or deterioration in the device, or any
`failure of the device to meet the specifications established in the approved PMA that
`could not cause or contribute to death or serious injury but are not correctable by
`adjustments or other maintenance procedures described in the approved labeling. The
`report shall include a discussion of the applicant's assessment of the change,
`deterioration or failure and any proposed or implemented corrective action by the
`applicant. When such events are correctable by adjustments or other maintenance
`procedures described in the approved labeling, all such events known to the applicant
`shall be included in the Annual Report described under "Postapproval Reports" above
`unless specified otherwise in the conditions of approval to this PMA. This postapproval
`report shall appropriately categorize these events and include the number of reported
`and otherwise known instances of each category during the reporting period. Additional
`information regarding the events discussed above shall be submitted by the applicant
`when determined by FDA to be necessary to provide continued reasonable assurance of
`the safety and effectiveness of the device for its intended use.
`
`ru;PORTING UNDER THE MEDICAL DEVICE REPORTING (MDR) REGULATION.
`The Medical Device Reporting (MDR) Regulation became effective on December 13, 1984.
`This regulation was replaced by the reporting requirements of the Safe Medical Devices Act of
`1990 which became effective July 31, 1996 and requires that all manufacturers and importers of
`medical devices, including in vitro diagnostic devices, report to the FDA whenever they receive
`or otherwise become aware of information, from any source, that reasonably suggests thata
`device marketed by the manufacturer or importer:
`
`1. May have caused or contributed to a death or serious injury; or
`
`2.
`
`Has malfunctioned and such device or similar device marketed by the
`manufacturer or importer would be likely to cause or contribute to a death or
`serious injury ifthe malfunction were to recur.
`
`The same events subject to reporting under the MDR Regulation may also be subject to the
`above "Adverse Reaction and Device Defect Reporting" requirements in the "Conditions of
`Approval" for this PMA. FDA has determined that such duplicative reporting is unnecessary.
`Whenever an event involving a device is subject to reporting under both the MDR Regulation
`and the "Conditions of Approval" for a PMA, the manufacturer shall submit the appropriate
`reports required by the MDR Regulation within the time frames as identified in 21 CFR
`803.10(c) using FDA Form 3500A, i.e., 30 days after becoming aware of a reportable death,
`serious injury, or malfunction as described in 21 CFR 803.50 and 21 CFR 803.52 and 5 days
`after becoming aware that a reportable MDR event requires remedial action to prevent an
`unreasonable risk of substantial harm to the public health. The manufacturer is responsible for
`submitting a baseline report on FDA Form 3417 for a device when the device model is first
`reported under 21 CFR 803.50. This baseline report is to include the PMA reference number.
`Any written report and its envelope is to be specifically identified, e.g., "Manufacturer Report,"
`"5--Day Report," "Baseline Report," etc.
`
`page 3
`
`

`

`Any written report is to be submitted to:
`
`Food and Drug Administration
`
`Center for Devices and Radiological Health
`
`Medical Device Reporting
`
`PO Box 3002
`
`Rockville, Maryland 20847-3002
`
`
`Additional information on MDR is available at http://www.fda.gov/cdrh/devadvice/35J.html
`
`page 4
`
`
`