Cidofovir Injection Type of Posting Revision Bulletin Posting Date 27–Oct–2017 Official Date 01–Nov–2017 Expert Committee Chemical Medicines Monographs1 Reason for Revision Compliance In accordance with the Rules and Procedures of the 2015-2020 Council of Experts, the Chemical Medicines Monographs 1 Expert Committee has revised Cidofovir Injection monograph. The purpose for the revision is to widen the acceptance criteria for uracil analog impurity from NMT 5.0% to NMT 6.0% in the test for Organic impurities to accommodate the sponsor’s FDA approved specification. Additionally, the following changes have been made:

1. The calculations in the Assay and test for Organic impurities have been updated to delete the molecular weight correction based on label value of cidofovir on the USP Cidofovir RS certificate.

2. The calculation in the test for Organic impurities is updated to include the relative response factor needed for calculation of impurities.

The Cidofovir Injection Revision Bulletin supersedes the currently official monograph. The Revision Bulletin will be incorporated in the Second Supplement to USP 41–NF 36. Should you have any questions, please contact Shankari Shivaprasad, Ph.D. Senior Scientific Liaison (301-230-7426 or sns@usp.org).

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Revision BulletinOfficial November 1, 2017 Cidofovir 1

. Acceptance criteria: 95.0%–105.0% on the anhydrousbasisCidofovir Injection

IMPURITIESDEFINITIONCidofovir Injection is a sterile aqueous solution. It contains

Change to read:an amount of cidofovir equivalent to NLT 95.0% andNMT 105.0% of the labeled amount of anhydrous

• ORGANIC IMPURITIEScidofovir (C8H14N3O6P).Mobile phase and Chromatographic system: Proceed

IDENTIFICATION as directed in the Assay with a run time NLT 4.5 times• A. ULTRAVIOLET ABSORPTION ⟨197U⟩ the retention time of cidofovir.

Standard solution: 7.5 µg/mL of USP Cidofovir RS in Standard solution: 0.0015 mg/mL of USP Cidofovir RSwater. Adjust with 0.1 N sodium hydroxide to a pH of in water7.5. Sample solution: Nominally 1.5 mg/mL of anhydrous

Sample solution: Nominally 7.5 µg/mL of cidofovir cidofovir from Injection in waterfrom Injection in water System suitability

Acceptance criteria: Meets the requirements Sample: Standard solution• B. The retention time of the major peak of the Sample Suitability requirements

solution corresponds to that of the Standard solution, as Relative standard deviation: NMT 5.0%obtained in the Assay. Analysis

Samples: Standard solution and Sample solutionASSAY Calculate the percentage of each individual impurity in

the portion of Injection taken:Change to read:

Result = (rU/rS) × (CS/CU) × •.(1/F)• (RB 1-Nov-2017) × 100• PROCEDURE rU = peak response of each individual impuritySolution A: Acetonitrile and water (40:60) from the Sample solutionBuffer: Dissolve 1.2 g of dibasic ammonium phosphate rS = peak response of cidofovir from the Standardand 2.0 g of tetrabutylammonium phosphate in 1 L of solutionwater. Adjust with ammonium hydroxide to a pH of CS = concentration of USP Cidofovir RS in the9.2. Standard solution (mg/mL)Mobile phase: Solution A and Buffer (20:80) CU = nominal concentration of anhydrous cidofovirStandard solution: 0.17 mg/mL of USP Cidofovir RS in in the Sample solution (mg/mL)water. [NOTE—0.17 mg/mL of USP Cidofovir RS is •

.F = relative response factor (see Table 1)• (RB 1-Nov-equivalent to 0.15 mg/mL of cidofovir on the anhy-2017)drous basis.] Acceptance criteria: See Table 1.Sample solution: Nominally 0.15 mg/mL of cidofovir

from Injection in waterTable 1Chromatographic system

(See Chromatography ⟨621⟩, System Suitability.) Relative Relative AcceptanceMode: LC Retention Response Criteria,Detector: UV 274 nm Name Time Factor NMT (%)Column: 4.6-mm × 25-cm; 5-µm packing L1 Cidofovir diol

— —Temperatures analoga.

,.

b. 0.30Autosampler: 10°

Cidofovir relatedColumn: 30° — —compound Ab

. 0.54Flow rate: 1 mL/minCidofovir relatedInjection volume: 20 µL — —compound Bb

. 0.63System suitabilityCidofovir 1.0 — —Sample: Standard solution

Suitability requirements Cidofovir uracil •.6.0• (RB 1-Nov-

Tailing factor: NMT 1.5 analogc. 1.4 0.56 2017)

Relative standard deviation: NMT 2.0% Bromocidofovirb.

,.

d. 2.0 — —

Analysis Any individualSamples: Standard solution and Sample solution unspecified — —Calculate the percentage of the labeled amount of an- impurity 0.2hydrous cidofovir (C8H14N3O6P) in the portion of In-

Total impurities — — 6.0jection taken:a

. 1-[(S)-2,3-Dihydroxypropyl]cytosine.b

. These are included in the table for identification only. These are processResult = (rU/rS) × (CS/CU) •.• (RB 1-Nov-2017) × 100impurities controlled in the drug substance. They are not to be includedin the total impurities.rU = peak response of cidofovir from the Samplec

. 1-[(S)-3-Hydroxy-2-(phosphonomethoxy)propyl]uracil.solutiond

. 1-[(S)-3-Bromo-2-(phosphonomethoxy)propyl]cytosine. rS = peak response of cidofovir from the Standardsolution SPECIFIC TESTS

CS = concentration of USP Cidofovir RS in the • PH ⟨791⟩: 7.1–7.7Standard solution (mg/mL) • PARTICULATE MATTER IN INJECTIONS ⟨788⟩: Meets the

CU = nominal concentration of anhydrous cidofovir requirementsin the Sample solution (mg/mL)

•.• (RB 1-Nov-2017)

2017 The United States Pharmacopeial Convention All Rights Reserved.

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Revision Bulletin2 Cidofovir Official November 1, 2017

• BACTERIAL ENDOTOXINS TEST ⟨85⟩: NMT 1 USP Endotoxin • USP REFERENCE STANDARDS ⟨11⟩Unit/mg of anhydrous cidofovir USP Cidofovir RS

• STERILITY TESTS ⟨71⟩: Meets the requirements USP Endotoxin RS• OSMOLALITY AND OSMOLARITY ⟨785⟩, Osmolarity:

550–650 mOsmol/L• OTHER REQUIREMENTS: Meets the requirements in Injec-

tions and Implanted Drug Products ⟨1⟩

ADDITIONAL REQUIREMENTS• PACKAGING AND STORAGE: Preserve in single-dose con-

tainers. Store at controlled room temperature.

2017 The United States Pharmacopeial Convention All Rights Reserved.

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