NDA 20-965
`
`
`Guidelines, Incorporated
`Attention: Mr. Samuel D. Swetland
`Vice President, Regulatory Affairs and Compliance
`10320 USA Today Way
`Miramar, Florida 33025
`
`Dear Mr. Swetland:
`
`Please refer to your new drug application (NDA) dated June 29, 1998, received July 1, 1998,
`submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act for LEVULAN®
`KERASTICK (aminolevulinic acid HCl) for Topical Solution, 20%, for use in photodynamic therapy
`™
`with blue light irradiation using the BLU-U Illuminator.
`™
`
`We acknowledge receipt of your submissions dated June 21, July 7 and 28, October 1, 8 and 11,
`November 11, and December 2 and 3, 1999 (facsimiles). Your submission of October 1, 1999,
`constituted a complete response to our June 27, 1999, action letter.
`
`This new drug application provides for the use of LEVULAN KERASTICK (aminolevulinic acid
`®
`™
`HCl) for Topical Solution, 20%, when used with blue light irradiation using the BLU-U™ Illuminator
`for the photodynamic therapy of actinic keratoses of the face and scalp.
`
`We have completed the review of this application, as amended, and have concluded that adequate
`information has been presented to demonstrate that the drug product is safe and effective for use as
`recommended in the agreed upon enclosed labeling text. Accordingly, the application is approved
`effective on the date of this letter.
`
`The final printed labeling (FPL) must be identical to the enclosed labeling (text for the package insert,
`text for the patient package insert, carton and applicator 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.
`
`Please submit 20 copies of the FPL as soon as it is available, in no case more than 30 days after it is
`printed. Please individually mount ten of the copies on heavy-weight paper or similar material. For
`administrative purposes, this submission should be designated "FPL for approved NDA 20-965."
`Approval of this submission by FDA is not required before the labeling is used.
`
`

`

`NDA 20-965
`Page 2
`
`We remind you of your Phase 4 commitments specified in your submissions dated October 1, and
`December 2, 1999. These commitments, along with any completion dates agreed upon, are listed
`below:
`
`1. A commitment to characterize the potential for dermal allergenicity of LEVULAN®
`KERASTICK (aminolevulinic acid HCl) for Topical Solution, 20%, within 24 months of
`™
`approval.
`
`2. A commitment to characterize the safety and efficacy of LEVULAN KERASTICK
`®
`™
`(aminolevulinic acid HCl) for Topical Solution, 20%, plus blue light photodynamic therapy to assess
`the long-term recurrence rate of actinic keratosis lesions over a 12-month follow-up period. As
`part of this study, the histopathology of treated actinic keratosis lesions (including lesions that recur
`in long-term follow-up) should be characterized. Patients with Fitzpatrick skin types IV-VI should
`be included in this study. This study would be completed within 4 years of approval.
`
`3. A commitment to re-evaluate the drug substance and drug product specification limits for [ ]
`once adequate data are available.
`
`Protocols, data, and final reports should be submitted to your IND for this product and a copy of the
`cover letter sent to this NDA. If an IND is not required to meet your Phase 4 commitments, please
`submit protocols, data and final reports to this NDA as correspondence. In addition, under 21 CFR
`314.82(b)(2)(vii), we request that you include a status summary of each commitment in your annual
`report to this NDA. The status summary should include the number of patients entered in each study,
`expected completion and submission dates, and any changes in plans since the last annual report. For
`administrative purposes, all submissions, including labeling supplements, relating to these Phase 4
`commitments must be clearly designated "Phase 4 Commitments."
`
`Validation of the regulatory methods has not been completed. At the present time, it is the policy of the
`Center not to withhold approval because the methods are being validated. Nevertheless, we expect
`your continued cooperation to resolve any problems that may be identified.
`
`Be advised that, as of April 1, 1999, all applications for new active ingredients, new dosage forms, new
`indications, new routes of administration, and new dosing regimens are required to contain an
`assessment of the safety and effectiveness of the product in pediatric patients unless this requirement is
`waived or deferred (63 FR 66632). We note that you have not fulfilled the requirements of 21 CFR
`314.55 (or 601.27). We are deferring submission of your pediatric studies until December 2, 2000.
`However, in the interim, please submit your pediatric drug development plans within 120 days from the
`date of this letter unless you believe a waiver is appropriate.
`
`

`

`NDA 20-965
`Page 3
`
`If you believe that this drug qualifies for a waiver of the pediatric study requirement, you should submit
`a request for a waiver with supporting information and documentation in accordance with the provisions
`of 21 CFR 314.55 within 60 days from the date of this letter. We will notify you within 120 days of
`receipt of your response whether a waiver is granted. If a waiver is not granted, we will ask you to
`submit your pediatric drug development plans within 120 days from the date of denial of the waiver.
`
`Pediatric studies conducted under the terms of section 505A of the Federal Food, Drug, and
` Cosmetic Act may result in additional marketing exclusivity for certain products (pediatric exclusivity).
`You should refer to the Guidance for Industry on Qualifying for Pediatric Exclusivity (available on
`our web site at www.fda.gov.cder/pediatric) for details. If you wish to qualify for pediatric exclusivity
`you should submit a "Proposed Pediatric Study Request" (PPSR) in addition to your plans for pediatric
`drug development described above. We recommend that you submit a Proposed Pediatric Study
`Request within 120 days from the date of this letter. If you are unable to meet this time frame but are
`interested in pediatric exclusivity, please notify the division in writing. FDA generally will not accept
`studies submitted to an NDA before issuance of a Written Request as responsive to a Written Request.
`Sponsors should obtain a Written Request before submitting pediatric studies to an NDA. If you do
`not submit a PPSR or indicate that you are interested in pediatric exclusivity, we will proceed with the
`pediatric drug development plan that you submit and notify you of the pediatric studies that are required
`under section 21 CFR 314.55. Please note that satisfaction of the requirements in 21 CFR 314.55
`alone may not qualify you for pediatric exclusivity. FDA does not necessarily ask a sponsor to
`complete the same scope of studies to qualify for pediatric exclusivity as it does to fulfill the
`requirements of the pediatric rule.
`
`In addition, please submit three copies of the introductory promotional materials that you propose to
`use for this product. All proposed materials should be submitted in draft or mock-up form, not final
`print. Please send one copy to the Division of Dermatologic and Dental Drug Products and two copies
`of both the promotional materials and the package insert directly to:
`
`Division of Drug Marketing, Advertising, and Communications, HFD-40
`Food and Drug Administration
`5600 Fishers Lane
`Rockville, Maryland 20857
`
`Please submit one market package of the drug product when it is available.
`
`We remind you that you must comply with the requirements for an approved NDA set forth under
`21 CFR 314.80 and 314.81.
`
`

`

`NDA 20-965
`Page 4
`
`If you have any questions, contact Olga Cintron, Project Manager, at (301) 827-2020.
`
`Sincerely,
`
`Robert J. DeLap, M.D., Ph.D.
`Director
`Office of Drug Evaluation V
`Center for Drug Evaluation and Research
`
`

`

`NDA 20-965
`NDA 20—965
`Page 5
`Page 5
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