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U.S. Department of Health and Human Services

Vaccines, Blood & Biologics

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Midcycle Memo, November 10, 2010 - Isoplate Solution

Mid-Cycle CMC Consult Review UPDATE Memo

Date:                10 November 2010
From:               Minerva Hughes, Ph.D,
                       CMC Reviewer,
Through:          Moo-Jhong Rhee, Ph.D
                       Chief, Branch IV
                         DNDQA II/ONDQA)
To:                  BN090067 Administrative Record

Application:      NDA BN090067
                       Sec. 505(b)(1)
                       Type 4,6 - Combination Product/New Indication
Product:           Isoplate Solution (multiple electrolyte injection type 1)
Applicant:        B. Braun Medical

 

CMC Consult Mid-Cycle Review Summary

  1. Information Summary

    B. Braun has submitted NDA BN090067 for the use of Isoplate Solution, a sterile, nonpyrogenic, multiple electrolyte solution, as a platelet additive solution for the storage of leukoreduced hyperconcentrated apheresis platelets collected on CaridianBCT’s Trima Accel System [510(k) pending] under standard blood banking conditions.  Isoplate Solution is the same product which B. Braun manufactures and markets under the proprietary name Isolyte S, pH 7.4 (ANDA 19696, approved in 1998) for use in adults and pediatric patients as a source of electrolytes and water for hydration, and as an alkalinizing agent.  The applicant purports that the only difference between Isolyte S, pH 7.4 and Isoplate Solution is the indication.

    CDER/ONDQA was consulted to perform a collaborative review of the chemistry, manufacturing, and controls (CMC) information submitted for the drug substance and drug product.  As Isoplate Solution is a sterile product, ONDQA’s consultative review focused primarily on the drug substance information, with CBER’s product quality reviewer serving as the primary reviewer for the validation of the drug product aseptic manufacturing process, product specifications, container closure systems, and manufacturing facility inspections.

    Drug Substance:There are seven drug substances in the drug product formulation:  sodium chloride USP, sodium acetate trihydrate USP, potassium chloride USP, magnesium chloride hexahydrate USP, sodium phosphate dibasic heptahydrate USP, potassium phosphate monobasic NF, and sodium gluconate USP.   Reference is made to DMF –b(4)- for details on sodium gluconate (DMF ------—b(4)-----) and to unspecified DMFs for sodium chloride USP and potassium chloride USP.   An information request was submitted in the Day-74 letter requesting a revised Letter of Authorization for the unspecified DMFs.  No responses have been received at the time of this memo.  All other drug substance information has been reviewed and found to be adequate with respect to the manufacture, characterization, controls, reference standards and stability of the material.  The drug substance suppliers and quality standards are the same as those approved for Isolyte S, pH 7.4, which has been verified where possible. Container closure system information, however, is incomplete.  Although the stability data do not suggest any compatibility issues with the selected container closure, details on the materials of construction should be included in the NDA.

    Drug Product:  Isoplate Solution is a sterile solution packaged in B. Braun’s EXCEL container.  Each 100 mL of Isoplate Solution contains sodium chloride USP 0.53 g, sodium gluconate USP 0.5 g, sodium acetate trihydrate USP 0.37 g, potassium chloride USP 0.037 g, magnesium chloride hexahydrate USP 0.03 g, water for injection USP qs.  NDA BN090067 contains sufficient information to assure the strength, identity, purity, and quality of the drug product from ONDQA’s perspective; however, labeling does not meet the requirements of 21 CFR 201 with respect to inclusion of the established name, multiple electrolytes injection type 1, which is the title of the USP monograph.  In addition, the label also does not reference the device product in the use statement, a comment which will be forwarded to the clinical and labeling team for consideration. 

     
  2. Review Comments To Be Communicated to applicant

    1. Provide complete details on the container closure system (i.e., materials of composition, suitability, and quality control) for the following drug substances: sodium chloride, sodium acetate trihydrate, potassium chloride, magnesium chloride, sodium phosphate dibasic heptahydrate, and monobasic potassium phosphate.  A statement of compliance with the appropriate indirect food contact regulations may be sufficient to establish the safety of the materials used.

       
    2. The draft labels and labeling do not comply with the established name requirements as per 21 CFR 201.10.  Submit revised labels and labeling that include the drug’s established name, multiple electrolytes injection type I, as defined by the USP monograph.