Code of Federal Regulations: Containing a Codification of Documents of ...

polymyxin B, and 10 milligrams of hydrocortisone in a suitable and harmless vehicle. It may also contain one or more suitable and harmless buffers, dispersants, and solvents. Its neomycin sulfate content is satisfactory if it is not less than 90 percent and not more than 130 percent of the number of milligrams of neomycin that it is represented to contain. Its polymyxin B sulfate content is satisfactory if it is not less than 90 percent and not more than 130 percent of the number of units of polymyxin B that it is represented to contain. It is sterile. The pH is not less than 2.0 and not more than 4.5. The neomycin sulfate used conforms to the standards prescribed by §444.42(a)(1). The polymyxin B sulfate used conforms to the standards prescribed § 448.30(a)(1) of this chapter.

(2) `Labeling. It shall be labeled in accordance with the requirements of § 432.5 of this chapter.

(3) Requests for certification; samples. In addition to the requirements of § 431.1 of this chapter, each such request shall contain:

(i) Results of tests and assays on:

(a) The neomycin sulfate used in making the batch for potency, loss on drying, pH, and identity.

(b) The polymyxin B sulfate used in making the batch for potency, loss on drying, pH, and identity.

(a) The neomycin sulfate used in making the batch: 10 packages, each containing approximately 300 milligrams.

(b) The polymyxin B sulfate used in making the batch: 10 packages, each containing approximately 300 milligrams.

(1) For all tests except sterility: A minimum of six immediate containers.

(2) For sterility testing: 20 immediate containers, collected at regular intervals throughout each filling operation.

(b) Tests and methods of assay-(1) Potency—(1) Neomycin content. Proceed as directed in § 436.105 of this chapter, preparing the sample for assay as follows: Dilute an accurately measured representative portion of the sample with sufficient 0.1M potassium phosphate

buffer, pH 8.0 (solution 3), to the reference concentration of 1.0 microgram of neomycin per milliliter (estimated).

(ii) Polymyxin B content. Proceed as directed in § 436.105 of this chapter, except add to each concentration of polymyxin B standard response line a quantity of neomycin equal to the amount present when the sample is diluted to contain 10 units of polymyxin B per milliliter. Prepare the sample for assay as follows: Dilute an accurately measured representative portion of the sample with sufficient 10 percent potassium phosphate buffer, pH 6.0 (solution 6), to the reference concentration of 10 units of polymyxin B per milliliter (estimated).

(2) Sterility. Proceed as directed in § 436.20 of this chapter, using the method described in paragraph (e)(1) of that section.

(3) pH. Proceed as directed in §436.202 of this chapter, using the undiluted sample.

[41 FR 14186, Apr. 2, 1976; 46 FR 55091, Nov. 6, 1981, as amended at 50 FR 19919, May 13, 1985]

Subpart F-Dermatologic Dosage Forms

§ 444.520 Gentamicin sulfate dermatologic dosage forms.

$444.520a Gentamicin sulfate ointment.

(a) Requirements for certification—(1) Standards of identity, strength, quality, and purity. Gentamicin sulfate ointment is gentamicin sulfate with suitable preservatives in a white petrolatum base. Each gram contains gentamicin sulfate equivalent to 1.0 milligram of gentamicin. Its potency is satisfactory if it is not less than 90 percent and not more than 135 percent of the number of milligrams of gentamicin that it is represented to contain. Its moisture content is not more than 1.0 percent. The gentamicin sulfate used conforms to the standards prescribed therefor by § 444.20(a)(1).

(2) Packaging. In addition to the requirements of § 432.1 of this chapter, it may be dispensed from a pressurized container wherein it is maintained in a compartment separate from the gas used to supply the pressure.

(3) Labeling. It shall be labeled in accordance with the requirements of § 432.5 of this chapter.

(4) Requests for certification; samples. In addition to the requirements of § 431.1 of this chapter, each such request shall contain:

(i) Results of tests and assays on:

(a) The gentamicin sulfate used in making the batch for potency, loss on drying, pH, specific rotation, content of gentamicins C1, Cia, and C2, and identity.

(b) The batch for gentamicin potency and moisture.

(ii) Samples required:

(a) The gentamicin sulfate used in making the batch: 10 packages, each containing not less than 500 milligrams.

(b) The batch: A minimum of five immediate containers.

(b) Tests and methods of assay—(1) Potency. Proceed as directed in § 436.105 of this chapter, preparing the sample for assay as follows: Place an accurately weighed representative portion of the ointment into a separatory funnel containing 50 milliliters of peroxide-free ether. Shake the sample and ether until homogeneous, add 20-25 milliliters of 0.1 M potassium phosphate buffer, pH 8.0 (solution 3), and shake well. Allow the layers to separate. Remove the buffer layer and repeat the extraction with new portions of the buffer and repeat any additional times necessary to insure complete extraction of the antibiotic. Combine the extractives and adjust to an appropriate volume to give a stock solution of convenient concentration. Further dilute with solution 3 to the reference concentration of 0.1 microgram of gentamicin per milliliter (estimated).

(2) Moisture. Proceed as directed in § 436.201 of this chapter.

[39 FR 19046, May 30, 1974, as amended at 50 FR 19919, May 13, 1985]

§ 444.520b Gentamicin sulfate cream.

(a) Requirements for certification—(1) Standards of identity, strength, quality, and purity. Gentamicin sulfate cream is gentamicin sulfate with one or more suitable emollients, dispersants, and preservatives in a suitable and harmless cream base. Each gram contains gentamicin sulfate equivalent to 1.0

milligram of gentamicin. Its potency is satisfactory if it is not less than 90 percent and not more than 135 percent of the number of milligrams of gentamicin that it is represented to contain. The gentamicin sulfate used conforms to the standards prescribed therefor by § 444.20(a)(1).

(3) Labeling. It shall be labeled in accordance with the requirements of § 432.5 of this chapter.

(4) Requests for certification; samples. In addition to the requirements of § 431.1 of this chapter, each such request shall contain:

(i) Results of tests and assays on:

(a) The gentamicin sulfate used in making the batch for potency, loss on drying, pH, specific rotation, gentamicins C1, Cia, and C2, and identity.

(b) The batch for gentamicin potency. (ii) Samples required:

(a) The gentamicin sulfate used in making the batch: 10 packages, each containing not less than 500 milligrams.

(b) The batch: A minimum of five immediate containers.

(b) Tests and methods of assay; potency. Proceed as directed in § 436.105 of this chapter, preparing the sample for assay as follows: Place an accurately weighed representative portion of the cream into a separatory funnel containing approximately 50 milliliters of peroxide-free ether. Shake the sample and ether until homogeneous. Add 20 to 25 milliliters of 0.1M potassium phosphate buffer, ph 8.0 (solution 3), and shake gently to avoid gel formation. Allow the layers to separate. Remove the buffer layer and repeat the extraction procedure with each of three more 20 to 25 milliliter quantities of solution 3. Combine the buffer extractives and adjust to an appropriate volume to obtain a stock solution of convenient concentration. Further dilute with solution 3 to the reference concentration

of 0.1 microgram of gentamicin per milliliter (estimated).

[39 FR 19046, May 30, 1974, as amended at 46 FR 45332, Sept. 11, 1981; 50 FR 19919, May 13, 1985]

§ 444.540 Neomycin palmitate dermatologic dosage forms.

§ 444.542 Neomycin sulfate dermatologic dosage forms.

§ 444.542a Neomycin sulfate ointment; neomycin sulfateointment (the blank being filled in with the established name(s) of the other active ingredient(s) present in accordance with paragraph (a)(1) of this section).

(a) Requirements for certification—(1) Standards of identity, strength, quality, and purity. Neomycin sulfate ointment contains, in each gram, 3.5 milligrams of neomycin in a suitable and harmless water-soluble or oleaginous ointment base, with or without one or more suitable and harmless dispersants, emollients, and preservatives. The following other drugs may be combined with neomycin sulfate ointment in the indicated amounts, per gram:

2.5 milligrams or 5.0 milligrams of prednisolone acetate; or

(g) 15.0 milligrans of cortisone acetate.

If it is an oleaginous base, its moisture content is not more than 1.0 percent. If it is intended for ophthalmic use, it is sterile. The neomycin sulfate used conforms to the standards prescribed by § 444.42a(a)(1)(i), (vi), and (vii). Each other substance used, if its name is recognized in the U.S.P. or N.F., conforms to the standards prescribed therefor by such official compendium.

(2) Labeling. If it contains a steroid or if it is intended for ophthalmic use, it shall be labeled in accordance with the requirements prescribed by § 432.5 of this chapter, and its expiration date is 12 months. If it does not contain a steroid or it is not intended for ophthalmic use each package shall bear on its label or labeling, as hereinafter indicated, the following:

(i) On the label of the immediate container and on the outside wrapper or container, if any:

(a) The batch mark.

(b) The name and quantity of each active ingredient contained in the drug.

(ii) On the label of the immediate container or other labeling attached to or within the package, adequate directions under which the layman can use the drug safely and efficaciously.

(3) Requests for certification; samples. In addition to the requirements of § 431.1 of this chapter, each such request shall contain:

(i) Results of tests and assays on:

(a) The neomycin sulfate used in making the batch for potency, pH, and identity.

(b) The batch for potency and for moisture if the ointment base is oleaginous and for sterility if the ointment is intended for ophthalmic use.

(ii) Samples required:

(a) The neomycin sulfate used in making the batch: 10 packages each containing approximately 300 milligrams.

(b) The batch:

(1) For all tests except sterility: A minimum of five immediate contain

ers.

(2) For sterility testing: Twenty immediate containers, collected at regular intervals throughout each filling operation.

(c) In the case of an initial request for certification, each other ingredient used in making the batch: One package of each containing approximately 5 grams.

(b) Tests and methods of assay—(1) Poditency-(i) Extraction. Proceed as rected in §444.42a(b)(1) of this chapter, except prepare the sample by placing an accurately weighed representative portion of the ointment into a separatory funnel containing 50 milliliters of peroxide-free ether. Shake the sample and ether until homogeneous. Add 25 milliliters of 0.1M potassium phosphate buffer, pH 8.0, and shake well. Allow the layers to separate. Remove the buffer layer and repeat the extraction with new portions of the buffer at least three times and any additional times necessary to insure complete extraction of the antibiotic. Combine the extractives and adjust to an appropriate volume to give a stock solution of convenient concentration. Further dilute with 0.1M potassium phosphate buffer, pH 8.0, to the proper prescribed reference concentration.

(ii) Blending. Proceed as directed in § 444.42a(b)(1), except prepare the sample for assay as follows: Transfer an accurately weighed sample into a highspeed glass blender, add 1.0 milliliter of polysorbate 80 and sufficient 0.1M potassium phosphate buffer, pH 8.0, to give a stock solution of convenient concentration. Blend 3 to 5 minutes. Further dilute with 0.1M potassium phosphate buffer, pH 8.0, to the proper prescribed reference concentration. The content of neomycin is satisfactory if it is not less than 90 percent and not more than 135 percent of the number of milligrams of neomycin that it is represented to contain.

(2) Sterility. If the ointment is intended for ophthalmic use, proceed as directed in §436.20 of this chapter, using the method as described in paragraph (e)(3) of that section.

(3) Moisture. If the ointment has an oleaginous base, proceed as directed in § 436.201 of this chapter.

[39 FR 19045, May 30, 1974, as amended at 39 FR 33666, Sept. 19, 1974; 47 FR 23442, May 28, 1982; 49 FR 34351, Aug. 30, 1984; 50 FR 19919, May 13, 1985; 50 FR 47213, Nov. 15, 1985]

§ 444.542b Neomycin sulfate cream; neomycin sulfate cream (the

blank being filled in with the established name(s) of the other active ingredient(s) present in accordance with paragraph (a)(1) of this section).

(a) Requirements for certification—(1) Standards of identity, strength, quality, and purity. Neomycin sulfate cream contains, in each gram, 3.5 milligrams of neomycin in a suitable cream base, with or without one or more suitable and harmless emollients, perfumes, dispersants, and preservatives. The following other drugs may be combined with neomycin sulfate cream in the indicated amounts per gram:

(i) 2 milligrams of betamethasone; or (ii) Dexamethasone sodium phosphate equivalent to 1.0 milligram of dexamethasone phosphate; or

(iii) 1 milligram of sodium dexamethasone phosphate; or

(iv) 2.5 milligrams of dichlorisone acetate; or

(v) 0.25 milligram of fluocinolone acetonide; or

(vi) 2.5 milligrams, 5 milligrams, or 10 milligrams of methylprednisolone acetate; or

(vii) 1 milligram of triamcinolone acetonide; or

(viii) 2.5 milligrams, 5.0 milligrams, or 10.0 milligrams of hydrocortisone; or (ix) 10.0 milligrams or 25.0 milligrams of hydrocortisone acetate; or

(x) 0.5 milligram of flurandrenolide. The neomycin sulfate used conforms to the standards prescribed by § 444.42a(a)(1) (i), (vi), and (vii). Each other substance used, if its name is recognized in the U.S.P. or N.F., conforms to the standards prescribed therefor by such official compendium.

(2) Labeling. If it contains corticosteroid, it shall be labeled in accordance with the requirements prescribed by § 432.5 of this chapter, and its expiration date is 12 months. If it does not contain a corticosteriod, each

package shall bear on its label or labeling, as hereinafter indicated, the following:

(i) On the label of the immediate container and on the outside wrapper or container, if any:

(a) The batch mark.

(b) The name and quantity of each active ingredient contained in the drug.

(ii) On the label of the immediate container or other labeling attached to or within the package, adequate directions under which the layman can use the drug safely and efficaciously.

(3) Requests for certification; samples. In addition to the requirements of § 431.1 of this chapter, each such request shall contain:

(i) Results of tests and assays on:

(a) The neomycin sulfate used in making the batch for potency, pH, and identity.

(b) The batch for potency. (ii) Samples required:

(a) The neomycin sulfate used in making the batch: 10 packages, each containing approximately 300 milligrams.

(b) The batch: A minimum of five immediate containers.

(c) In case of an initial request for certification, each other ingredient used in making the batch: One package of each containing approximately 5 grams.

(b) Tests and methods of assay; potency. Proceed as directed in § 444.42a(b)(1), except prepare the sample for assay as follows: Transfer an accurately weighed representative portion into a high-speed glass blender. Add 1.0 milliliter of polysorbate 80 and sufficient 0.1M potassium phosphate buffer, pH 8.0, to give a stock solution of convenient concentration and blend 3 to 5 minutes. Further dilute with 0.1M potassium phosphate buffer, pH 8.0, to the proper prescribed reference concentration. Its neomycin content is satisfactory if it is not less than 90 percent nor more than 135 percent of the

number of milligrams of neomycin that it is represented to contain.

[39 FR 19046, May 30, 1974, as amended at 49 FR 34351, Aug. 30, 1984; 53 FR 18838, May 25, 1988]

§ 444.542c Neomycin

sulfate

lotion (the blank being filled in with the established name(s) of the other active ingredient(s) present in accordance with paragraph (a)(1) of this section).

(a) Requirements for certification—(1) Standards of identity, strength, quality, and purity. The drug is a suspension containing, in each milliliter, 3.5 milligrams of neomycin and the following other active ingredients in a suitable and harmless vehicle:

(i) 10 milligrams of diperodon hydrochloride and 7.5 milligrams of aluminum dihydroxy allantoinate; or (ii) 5 milligrams or 10 milligrams of hydrocortisone acetate; or

(iii) 5 milligrams, 10 milligrams, or 20 milligrams of hydrocortisone; or

(iv) 1 milligram, 2.5 milligrams, or 5 milligrams of prednisolone acetate; or

(v) Prednisolone sodium phosphate equivalent to 5.0 milligrams of prednisolone phosphate; or

(vi) 0.5 milligram of flurandrenolide. It may also contain one or more suitable and harmless dispersants, emollients, and preservatives. The neomycin sulfate used conforms to the standards prescribed by §444.42a(a)(1) (i), (vi), and (vii). Each other substance used, if its name is recognized in the U.S.P. or N.F., conforms to the standards prescribed therefor by such official compendium.

(2) Labeling. If it contains a corticosteroid, it shall be labeled in accordance with the requirements prescribed by § 432.5 of this chapter and its expiration date is 12 months. If it does not contain a corticosteroid, each package shall bear, on its label or labeling, as hereinafter indicated, the following:

(i) On the label of the immediate container and on the outside wrapper or container, if any:

(a) The batch mark.

(b) The name and quantity of each active ingredient contained in the drug.

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