§ 442.270 21 CFR Ch. I (4–1–96 Edition)
Proceed as directed in § 442.60(b)(1), pre- (B) Cefpiramide content (milligrams of paring the sample solutions and cal- cefpiramide per vial). Calculate the culating the potency and content as cefpiramide content of the vial as fol- follows: lows: (i) Preparation of sample solutions. Use A× P × d separate containers for preparation of Milligrams of cefpiramide = u s each sample solution as described in per vial × paragraphs (b)(1)(i)(A) and (b)(1)(i)(B) As 1, 000 of this section. where: (A) Cefpiramide potency (micrograms of Au=Area of the cefpiramide peak in the cefpiramide per milligram). Dissolve an chromatogram of the sample (a ta retention time equal to that observed for the stand- accurately weighed sample with suffi- ards); cient mobile phase to obtain a solution As=Area of the cefpiramide peak in the containing approximately 0.25 milli- chromatogram of the cefpiramide working gram of cefpiramide per milliliter (es- standard; timated). Ps=Cefpiramide activity in the cefpiramide (B) Cefpiramide content (milligrams of working standard solution in micrograms cefpiramide per vial). Reconstitute the per milliliter; and d=Dilution factor of the sample. sample as directed in the labeling. Then, using a suitable hypodermic nee- (2) Sterility. Proceed as directed in dle and syringe, remove all of the § 436.20 of this chapter, using the meth- withdrawable contents if it is rep- od described in § 436.20(e)(1). resented as a single-dose container; or, (3) Pyrogens. Proceed as directed in if the labeling specifies the amount of § 436.32(b) of this chapter, using a solu- potency in a given volume of the re- tion containing 50 milligrams of sultant preparation, remove an accu- cefpiramide per milliliter. rately measured representative portion (4) Moisture. Proceed as directed in from each container. Dilute the solu- § 436.201 of this chapter. tion thus obtained with sufficient dis- (5) pH. Proceed as directed in § 436.202 tilled water to obtain a solution con- of this chapter, using an aqueous solu- taining 1.0 milligram of cefpiramide ac- tion containing 100 milligrams per mil- tivity per milliliter (estimated). Fur- liliter. ther dilute this solution with mobile (6) Identify. The high-performance phase to obtain a solution containing liquid chromatogram of the sample de- 0.25 milligram of cefpiramide activity termined as directed in paragraph per milliliter (estimated). (b)(1) of this section compares quali- (ii) Calculations—(A) Cefpiramide po- tatively to that of the cefpiramide tency (micrograms per milligram). Cal- working standard. culate the micrograms of cefpiramide [55 FR 14242, Apr. 17, 1990] per milligram as follows: § 442.270 Cefmetazole injectable dos- Micrograms of AP× ×100 age forms. cefpiramide = u s × × − § 442.270a Sterile cefmetazole sodium. per milligram As C u (100 m) The requirements for certification where: and the tests and methods of assay for Au=Area of the cefpiramide peak in the sterile cefmetazole sodium packaged chromatogram of the sample (at a retention time equal to that observed for the stand- for dispensing are described in § 442.70a. ard); [55 FR 6636, Feb. 26, 1990] As=Area of the cefpiramide peak in the chromatogram of the cefpiramide working § 442.270b Cefmetazole sodium injec- standard; tion. Ps=Cefpiramide activity in the cefpiramide working standard solution in micrograms (a) Requirements for certification—(1) per milliliter; Standards of identity, strength, quality, and purity. Cefmetazole sodium injec- Cu=Milligrams of the sample per milliliter of sample solution; tion is a frozen, aqueous, iso-osmotic m =Percent moisture content of the sam- solution of cefmetazole and sodium cit- ple. rate. It contains one or more suitable
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and harmless buffer substances and a sample solution just prior to its intro- tonicity adjusting agent. Each milli- duction into the chromatograph. liter contains cefmetazole sodium (ii) Calculation. Calculate the milli- equivalent to 20 milligrams or 40 milli- grams of cefmetazole per milliliter of grams of cefmetazole per milliliter. Its sample as follows: cefmetazole content is satisfactory if it is not less than 90 percent and not Milligrams of cefmetazole A× P × d more than 120 percent of the number of = U s milligrams of cefmetazole that it is per milliliter × As 1, 000 represented to contain. It is sterile. It contains not more than 0.2 endotoxin where:
units per milligram. Its pH is not less AU=Area of the cefmetazole peak in the chro- than 4.2 and not more than 6.2. It matogram of the – sample (at a retention passes the identity test. The time equal to that observed for the cefmetazole used conforms to the standard); standards prescribed by § 442.69(a)(1). AS=Area of the cefmetazole peak in the chro- matogram of the cefmetazole working (2) Labeling. It shall be labeled in ac- standard; cordance with the requirements of PS=Cefmetazole activity in the cefmetazole § 432.5 of this chapter. working standard solution in (3) Requests for certification; samples. micrograms per milliliter; and In addition to complying with the re- d = Dilution factor of the sample. quirements of § 431.1 of this chapter, (2) Sterility. Proceed as directed in each such request shall contain: § 436.20 of this chapter, using the meth- (i) Results of tests and assays on: od described in paragraph (e)(1) of that (A) The cefmetazole used in making section. the batch for potency, moisture, and (3) . Proceed as di- identity. Bacterial endotoxins rected in the United States Pharma- (B) The batch for potency, sterility, bacterial endotoxins, pH, and identity. copeia bacterial endotoxins test. (ii) Samples, if required by the Direc- (4) pH. Proceed as directed in § 436.202 tor, Center for Drug Evaluation and of this chapter, using the undiluted so- Research: lution. (A) The cefmetazole used in making (5) Identity. The high-performance the batch: 10 packages, each containing liquid chromatogram of the sample de- approximately 500 milligrams. termined as directed in paragraph (B) The batch: (b)(1) of this section compares quali- (1) For all tests except sterility: A tatively to that of the cefmetazole minimum of 12 immediate containers. working standard. (2) For sterility testing: 20 immediate [59 FR 12546, Mar. 17, 1994] containers, collected at regular inter- vals throughout each filling operation. PART 443—CARBACEPHEM (b) Tests and methods of assay. Thaw the sample as directed in the labeling. ANTIBIOTIC DRUGS The sample solution used for testing must be at room temperature. Subpart A—Bulk Drugs (1) Cefmetazole potency. Proceed as di- Sec. rected in § 442.70a(b)(1), except prepare 443.20 Loracarbef. the sample solution and calculate the cefmetazole content as follows: Subpart B—Oral Dosage Forms (i) Preparation of sample solution. Using a suitable hypodermic needle and 443.120 Loracarbef oral dosage forms. syringe, remove an accurately meas- 443.120a Loracarbef capsules. ured portion from each container im- 443.120b Loracarbef for oral suspension. mediately after thawing and reaching AUTHORITY: Sec. 507 of the Federal Food, room temperature and dilute with mo- Drug, and Cosmetic Act (21 U.S.C. 357). bile phase to obtain a solution contain- SOURCE: 58 FR 26667, May 4, 1993, unless ing 500 micrograms of cefmetazole per otherwise noted. milliliter (estimated). Prepare the
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