~ sERVICes
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`t.,-~ DEPARTMENT OF HEALTH & HUMAN SERVICES
`
`Public Health Service
`Food and Drug Administration
`Rockville, MD 20857
`
`NDA21-794
`
`QLT USA, Inc.
`Attention Cheri Jones, M.S., RAC
`Vice President, Regulatory Affairs
`2579 Midpoint Drive
`Fort Collins, CO 80525
`
`Dear Ms. Jones:
`
`Please refer to your new drug application (NDA) dated August 31, 2004, received September 7, 2004,
`submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act for ACZONE™
`( dapsone) Gel, 5%.
`
`We acknowledge receipt of your submissions dated September 10, 15 (2), October 20, November 12,
`and 15 (2), 2004 and January 3, 19 (2), February 2 (2), 9 (2), 16 (2), 22 (5), 24 (7), 25 (2), March 4 (2),
`7, April 7 (3), 8 (3), 19, 20, 21 (2), 22 (2), 27, June 3, 8, 20, 21, 22 (4), 27 (2), 28, and 30 (3,
`2-electronic mail), July 1 (2), 5 (2-electronic mail), 6 (electronic mail), and 7 (electronic), 2005.
`
`Your amendment 40 dated June 30, 2005, was not reviewed.
`
`This new drug application provides for the use of ACZONE™ ( dapsone) Gel, 5%, for the topical
`treatment of acne vulgaris. Glucose 6-phosphate dehydrogenase (G6PD) levels should be obtained
`prior to initiating therapy with ACZONE™ Gel, 5%. In patients with a history of anemia and
`predisposition to increased hemolytic effect with dapsone (e.g., glucose-6-phosphate dehydrogenase
`deficiency), closer follow-up for blood hemoglobin levels and reticulocyte counts should be
`implemented (see PRECAUTIONS). Alternatively, other therapies for acne than ACZONE™ Gel, 5%,
`may be considered.
`
`We completed our review of this application, as amended. It is approved, effective on the date of this
`letter, for use as recommended in the agreed-upon labeling text.
`
`We concur with your commitment to revise the 3 gram container label as per your amendment
`dated June 30, 2005. The final printed 3 gram container label must be identical to the enclosed
`labeling.
`
`The final printed labeling (FPL) must be identical to the enclosed labeling (text for the package insert,
`text for the patient package insert, immediate container and carton 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 an electronic version of the FPL according to the guidance for industry titled Providing
`(cid:17)(cid:3)
`Regulatory Submissions in Electronic Format - NDA
`
`1 of 4
`
`Almirall EXHIBIT 2045
`
`Amneal v. Almirall
`IPR2019-00207
`
`

`

`NDA21-794
`Page2
`
`Alternatively, you may submit 20 paper copies of the FPL as soon as it is available but no more than
`30 days after it is printed. Individually mount 15 of the copies on heavy-weight paper or similar
`material. For administrative purposes, designate this submission "FPL for approved NDA 21-794."
`(cid:36)(cid:83)(cid:83)(cid:85)(cid:82)(cid:89)(cid:68)(cid:79)(cid:3)(cid:82)(cid:73)(cid:3)(cid:87)(cid:75)(cid:76)(cid:86)(cid:3)(cid:86)(cid:88)(cid:69)(cid:80)(cid:76)(cid:86)(cid:86)(cid:76)(cid:82)(cid:81)(cid:3)(cid:69)(cid:92)(cid:3)(cid:41)(cid:39)(cid:36)(cid:3)(cid:76)(cid:86)(cid:3)(cid:81)(cid:82)(cid:87)
`required before the labeling is used.
`
`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. We are
`waiving the pediatric study requirement for pediatric patients below 12 years of age because there are
`too few children with acne vulgaris.
`
`We remind you of your postmarketing study commitment in your submission dated July 5, 2005. This
`commitment is listed below.
`
`1.
`
`Conduct a randomized, blinded, cross-over safety study with each acne patient treated with
`ACZONE Gel, 5%, for 12 weeks and vehicle for 12 weeks with at least a two week washout
`period in at least 50 evaluable G6PD deficient patients with acne vulgaris to further evaluate
`the risk of hematological adverse events with use of ACZONE Gel, 5%, in this population.
`Patients with rarer genetic abnormalities such as methemoglobin reductase or the congenital
`methemoglobinemias may also be studied. Obtain baseline, week 2, and end of each 12 week
`treatment period laboratory testing including complete blood count, reticulocyte counts,
`haptoglobin, and LDH levels. Plasma dapsone levels and N-acetyl dapsone levels should be
`obtained at baseline, week 2, and at the end of each 12 week treatment period. Additionally,
`plasma dapsone and its metabolite levels should be obtained in relation to adverse events which
`may be considered dapsone related.
`
`Study Protocol Submission:
`
`November 1, 2005
`
`Study Initiation:
`
`March 1, 2006
`
`Final Study Report Submission:
`
`January 1, 2008
`
`Submit clinical protocols to your IND for this product. Submit nonclinical and chemistry,
`manufacturing, and controls protocols and all study final reports to this NDA. In addition, under 21
`CFR 314.81(b)(2)(vii) and 314.81(b)(2)(viii), you should include a status summary of each
`commitment in your annual report to this NDA. The status summary should include expected
`summary completion and final report submission dates, any changes in plans since the last annual
`report, and, for clinical studies, number of patients entered into each study. All submissions, including
`supplements, relating to these postmarketing study commitments must be prominently labeled
`"Postmarketing Study Commitment Protocol", "Postmarketing Study Commitment Final Report", or
`"Postmarketing Study Commitment Correspondence."
`
`In addition, submit three copies of the introductory promotional materials that you propose to use for
`this product. Submit all proposed materials in draft or mock-up form, not final print. Send one copy to
`this division and two copies of both the promotional materials and the package insert directly to:
`
`2 of 4
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`

`

`NDA21-794
`Page 3
`
`Division of Drug Marketing, Advertising,
`and Communications, HFD-42
`Food and Drug Administration
`5600 Fishers Lane
`Rockville, MD 20857
`
`Please submit one market package of the drug product when it is available.
`
`We have not completed validation of the regulatory methods. However, we expect your continued
`cooperation to resolve any problems that may be identified.
`
`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, please call Frank H. Cross, Jr., M.A., MT (ASCP), CDR, Senior Regulatory
`Project Management Officer, at (301) 827-2020.
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Jonathan K. Wilkin, M.D.
`Director
`Division of Dermatologic & Dental Drug Products
`Office of Drug Evaluation III
`Center for Drug Evaluation and Research
`
`Enclosure
`
`3 of 4
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`

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` /s/
`---------------------
`Stanka Kukich
`7/7/05 03:11:06 PM
`sign off for Dr. Jonathan Wilkin
`
`4 of 4
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`