Lapas attēli
PDF
ePub
[blocks in formation]

(ii) Calculate the percent of labeled amount of erythromycin released in 60 minutes as follows:

[blocks in formation]

Sec. 440.1a Sterile azlocillin sodium. 440.2a Sterile amdinocillin. 440.3 Amoxicillin trihydrate. 440.5 Ampicillin. 440.7 Ampicillin trihydrate. 440.7a Sterile ampicillin trihydrate. 440.8 Bacampicillin hydrochloride. 440.9a Sterile ampicillin sodium. 440.10 Benzylpenicilloyl-polylysine con

centrate. 440.11 Carbenicillin indanyl sodium. 440.13a Sterile carbenicillin disodium. 440.15 Cloxacillin sodium monohydrate. 440.17 Cyclacillin. 440.19 Dicloxacillin sodium monohydrate. 440.19a Sterile dicloxacillin sodium

monohydrate. 440.25 Hetacillin, 440.29 Hetacillin potassium. 440.29a Sterile hetacillin potassium. 440.36a Sterile methicillin sodium

monohydrate. 440.37a Sterile mezlocillin sodium

monohydrate. 440.41 Nafcillin sodium monohydrate. 440.412 Sterile

nafcillin

sodium monohydrate. 440.49 Oxacillin sodium monohydrate. 440.49a Sterile

oxacillin

sodium monohydrate. 440.55a Sterile penicillin G benzathine.

440.103 Amoxicillin oral dosage forms. 440.103a Amoxicillin trihydrate capsules. 440.103b Amoxicillin trihydrate for oral sus

pension. 440.103c Amoxicillin trihydrate chewable

tablets. 440.103d Amoxicillin trihydrate and

clavulanate potassium tablets. 440.103e Amoxicillin trihydrate and

clavulanate potassium for oral suspen

sion. 440.103f Amoxicillin trihydrate-clavulanate

potassium chewable tablets. 440.105 Ampicillin oral dosage forms. 440.105a Ampicillin tablets. 440.105b Ampicillin chewable tablets. 440.105C Ampicillin capsules. 440.105d Ampicillin for oral suspension. 440.107 Ampicillin trihydrate oral dosage

forms. 440.107a Ampicillin trihydrate chewable

tablets. 440.107b Ampicillin trihydrate capsules. 440.1070 Ampicillin trihydrate for oral sus

pension. 440.107d Ampicillin trihydrate-probenecid

for oral suspension.

Subpart C-Injectabie Dosage Forms

440.107e Ampicillin trihydrate-probenecid

capsules. 440.108 Bacampicillin hydrochloride dosage

forms. 440.108a Bacampicillin hydrochloride tab

lets. 440.108b Bacampicillin hydrochloride for

oral suspension. 440.111 Carbenicillin indanyl sodium tab

lets. 440.115 Cloxacillin sodium monohydrate

oral dosage forms. 440.115a Cloxacillin sodium monohydrate

capsules. 440.115b Cloxacillin sodium monohydrate

for oral solution. 440.117 Cyclacillin oral dosage forms. 440.117a Cyclacillin tablets. 440.1176 Cyclacillin for oral suspension. 440.119 Dicloxacillin sodium monohydrate

oral dosage forms. 440.119a Dicloxacillin sodium monohydrate

capsules. 440.119b Dicloxacillin sodium monohydrate

for oral suspension. 440.125 Hetacillin oral dosage forms. 440.125a Hetacillin chewable tablets. 440.125b Hetacillin for oral suspension. 440.129 Hetacillin potassium capsules. 440.141 Nafcillin sodium monohydrate oral

dosage forms. 440.141a Nafcillin sodium monohydrate tab

lets. 440.141b Nafcillin sodium monohydrate cap

sules. 440.1410 Nafcillin sodium monohydrate for

oral solution. 440.149 Oxacillin sodium monohydrate oral

dosage forms. 440.149a Oxacillin sodium monohydrate cap

sules. 440.149b Oxacillin sodium monohydrate for

oral solution.

440.201 Sterile azlocillin sodium. 440.202 Sterile amdinocillin. 440.207 Sterile ampicillin trihydrate for sus

pension. 440.209 Ampicillin sodium injectable dosage

forms. 440.209a Sterile ampicillin sodium. 440.209b Sterile ampicillin

ampicillin sodium and sulbactam sodium. 440.210 Benzylpenicilloyl-polylysine injec

tion. 440.213 Sterile carbenicillin disodium. 440.219 Dicloxacillin sodium monohydrate

injectable dosage forms. 440.219a Sterile dicloxacillin sodium

monohydrate. 440.219b Dicloxacillin sodium monohydrate

for injection. 440.229 Hetacillin potassium injectable dos

age forms. 440.229a Sterile hetacillin potassium. 440.229b Hetacillin potassium for injection. 440.236 Methicillin sodium monohydrate for

injection. 440.237 Sterile mezlocillin sodium

monohydrate. 440.241 Nafcillin sodium injectable dosage

forms. 440.241& Nafcillin sodium monohydrate for

injection. 440.241b Nafcillin sodium injection. 440.249 Oxacillin sodium injectable dosage

forms. 440.249a Oxacillin sodium monohydrate for

injection. 440.2496 Oxacillin sodium injection. 440.255 Penicillin G benzathine injectable

dosage forms. 440.255b Sterile penicillin G benzathine sus

pension. 440.255C Sterile penicillin G benzathine-pen

icillin G procaine suspension. 440.255d Sterile penicillin G benzathine for

suspension. 440.274 Penicillin G procaine injectable dos

age forms. 440.274a Sterile penicillin G procaine with

aluminum stearate suspension, 440.274b Sterile penicillin G procaine sus

pension. 440.274c Sterile penicillin G procaine for

suspension. 440.280 Penicillin G potassium injectable

dosage forms. 440.280a Sterile penicillin G potassium. 440.280b Penicillin G potassium for injec

tion. 440.280C Penicillin G potassium injection. 440.281 Penicillin G sodium injectable dos

age forms. 440.281a Sterile penicillin G sodium. 440.281b Penicillin G sodium for injection. 440.283 Sterile piperacillin sodium.

440.155 Penicillin G benzathine oral dosage

forms. 440.155a-440.155b (Reserved] 440.155C Penicillin G benzathine oral sus

pension. 440.155d Penicillin G benzathine tablets. 440.171 Penicillin V oral dosage forms. 440.171a Penicillin V capsuies. 440.171b Penicillin V for oral suspension. 440.1710 Penicillin V tablets. 440.173 Penicillin V potassium oral dosage

forms. 440.173a Penicillin V potassium capsules. 440.173b Penicillin V potassium chewable

tablets. 440.173c Penicillin V potassium tablets. 440.173d Penicillin V potassium for oral so

lution, 440.180 Penicillin G potassium oral dosage

forms. 440.180a Penicillin G potassium tablets. 440.180c Penicillin G potassium capsules. 440.180f Penicillin G potassium for oral so

lution. 440.180g Penicillin G potassium tablets for

solution.

440.290 Ticarcillin disodium injectable dos

age forms. 440.290a Sterile ticarcillin disodium. 440.290b Sterile ticarcillin disodium and

clavulanate potassium. 440.290c Ticarcillin

disodium

and clavulanate potassium injection.

Subparts D-J [Reserved]

Subpart K-Bulk Drug Formulations for Repacking or for Manufacturing Use

440.1080a Sterile penicillin G potassium

buffered. 440.1081a Sterile penicillin G sodium,

buffered.

AUTHORITY: 21 U.S.C. 357.

Subpart A-Bulk Drugs

$ 440.la Sterile azlocillin sodium.

(a) Requirements for certification—(1) Standards of identity, strength, quality, and purity. Sterile azlocillin sodium is the sodium salt of 4-thia-1azabicyclo[3.2.0]heptane-2-carboxylic acid, 3,3-dimethyl-7-oxo-6-[[[[(2-oxo-1imidazolidinyl)carbonyl] amino]phenylac-etyl)amino)-[2S[20,50,6B(S*)]]-. It is so purified and dried that:

(i) If the azlocillin sodium is not packaged for dispensing, its azlocillin content is not less than 859 micrograms and not more than 1,000 micrograms of azlocillin per milligram on an anhydrous basis. If the azlocillin sodium is packaged for dispensing, its azlocillin content is not less than 859 micrograms and not more than 1,000 micrograms of azlocillin per milligram on an anhydrous basis and also, each container contains not less than 90 percent and not more than 115 percent of the number of milligrams of azlocillin that it is represented to contain.

(ii) It is sterile.
(iii) It is nonpyrogenic.

(iv) Its moisture content is not more than 2.5 percent.

(v) Its pH in an aqueous solution containing 100 milligrams of azlocillin per milliliter is not less than 6.0 and not more than 8.0.

(vi) Its specific rotation in an aqueous solution containing 10 milligrams of azlocillin per milliliter is +170° to + 200°.

(vii) It gives a positive identity test for azlocillin.

(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 complying with the requirements of $ 431.1 of this chapter, each such request shall contain

(1) Results of tests and assays on the batch for potency, sterility, pyrogens, moisture, pH, specific rotation, and identity.

(ii) Samples, if required by the Director, Center for Drug Evaluation and Research:

(a) If it is packaged for repacking or for use in the manufacture of another drug:

(1) For all tests except sterility: 10 packages, each containing approximately 300 milligrams; and 5 packages, each containing approximately 1 gram.

(2) For sterility testing: 20 packages, each containing approximately 300 milligrams.

(6) If it is packaged for dispensing:

(1) For all tests except sterility: A minimum of 15 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. Proceed as directed in $ 442.40(b)(1)(ii) of this chapter, except:

(i) Dilute Brij 35 solution. In lieu of the hydroxylamine hydrochloride solution described in $ 442.40(b)(1)(ii)(b)(1) of this chapter, use dilute Brij 35 solution in the reference channel. Prepare dilute Brij 35 solution as follows: Place 1 milliliter of Brij 35, 30 percent solution, into a 1-liter volumetric flask containing 900 milliliters of distilled water. Swirl gently and dilute to volume slowly with distilled water. Mix well.

(ii) Buffer. In lieu of the buffer described in $442.40(b)(1)(ii)(b)(2) of this chapter, use the buffer prepared as follows: Dissolve 200 grams of primary standard tris (hydroxymethyl) aminomethane in sufficient distilled water to make 1 liter. Filter before use.

(iii) Preparation of working standard solution. Dissolve and dilute an accurately weighed portion of the azlocillin working standard with sufficient distilled water to obtain a concentration of 1.0 milligram of azlocillin per milliliter.

[blocks in formation]

(iv) Preparation of sample solutions (a) Product not packaged for dispensing (micrograms of azlocillin per milligram). Dissolve and dilute an accurately weighed portion of the sample with sufficient distilled water to obtain a stock solution of 1.0 milligram of azlocillin per milliliter (estimated).

(6) Product packaged for dispensing. Determine both micrograms of azlocillin per milligram of the sample and milligrams of azlocillin per container. Use separate containers for preparation of each sample solution as described in paragraphs (b)(1)(iv)(6)(1) and (2) of this section.

(1) Micrograms of azlocillin per milligram. Dissolve and dilute an accurately weighed portion of the sample with sufficient distilled water to obtain a stock solution of 1.0 milligram of azlocillin per milliliter (estimated).

(2) Milligrams of azlocillin per container. Reconstitute as directed in the labeling using distilled water in lieu of the reconstituting fluid. Then, using a suitable hypodermic needle and syringe, remove all of the withdrawable contents if it is represented as a singledose container; or, if the labeling specifies the amount of potency in a given volume of the resultant preparation, remove an accurately measured representative portion from each container. Dilute with distilled water to obtain a stock solution of convenient concentration. Further dilute an aliquot of the stock solution with distilled water to a concentration of 1.0 milligram of azlocillin per milliliter (estimated).

(v) Calculations-(a) Calculate the micrograms of azlocillin per milligram of sample as follows:

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

(3) Pyrogens. Proceed as directed in $ 436.32(b) of this chapter, using a solution containing 100 milligrams of azlocillin per milliliter.

(4) Moisture. Proceed as directed in $ 436.201 of this chapter, using the titration procedure and calculations described in paragraph (e)(2) of that section and preparing the sample as follows: Weigh the vial. Rapidly transfer a portion of the powder into the titration vessel, add the Karl Fischer reagent and restopper the vial immediately. Reweigh the vial to obtain the sample weight. A nitrogen purged glove bag or glove box should be used for preparing the sample.

(5) PH. Proceed as directed in $436.202 of this chapter, using an aqueous solution containing 100 milligrams of azlocillin per milliliter.

(6) Specific rotation. Proceed as directed in $436.210 of this chapter, using an aqueous solution containing 10 milligrams of azlocillin per milliliter and a 1.0-decimeter polarimeter tube. Calculate the specific rotation on an anhydrous basis.

(7) Identity. Proceed as directed in $ 436.336 of this chapter.

(47 FR 53348, Nov. 26, 1982, as amended at 50 FR 1504, Jan. 11, 1985; 55 FR 11582, Mar. 29, 1990]

$ 440.2a Sterile amdinocillin.

Micrograms of
azlocillin per

Ą,XP,x100 milligram of sample A, C,x(100cm) where: :

Au-Absorbance of sample solution;

Ps-Potency of working standard solution in micrograms per milliliter;

As=Absorbance of working standard solution;

Cu=Milligrams of sample per milliliter of sample solution; and

m=Percent moisture in sample.

(a) Requirements for certification-(1) Standards of identity, strength, quality, and purity. Sterile amdinocillin is 4thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, 6-[[(hexahydro-1H-azepin1-yl)-methylene)amino]-3,3-dimethyl-7OXO-, [2S-24,5a,61))-. It is so purified and dried that:

(6) Calculate the azlocillin content of the single-dose vial as follows:

(i) If the amdinocillin is not pack- (b) Tests and methods of assay-(1) aged for dispensing, its amdinocillin Amdinocillin potency and container conpotency is

not less than 950 tent. Proceed as directed in $ 436.353 of micrograms and not more than 1,050 this chapter, using ambient temperamicrograms of amdinocillin per milli- ture, an ultraviolet detection system gram on an anhydrous basis. If the

operating at a wavelength of 220 amdinocillin is packaged for dispens- nanometers, a column packed with ing, its amdinocillin potency is not less microparticulate (3 to 10 micrometers than 950 micrograms and not more in diameter) reversed phase packing than 1,050 micrograms of amdinocillin material such as octadecyl hydroper milligram on an anhydrous basis carbon bonded silicas, e.g., a Whatman and also, each container contains not ODS-3 column (25-centimeter column less than 90 percent and not more than having an inside diameter of 4.6 milli120 percent of the number of milli- meters and 5 micrometer particle size grams of amdinocillin that it is rep- or equivalent), a flow rate of 1.0 milliresented to contain.

liter per minute, and an injection vol(ii) It is sterile.

ume of 20 microliters. Reagents, work(iii) It is nonpyrogenic.

ing standard and sample solutions, sys(iv) Its moisture content is not more

tem suitability requirements, and calthan 0.5 percent.

culations are as follows: (v) Its pH in an aqueous solution con

(i) Reagents-(a) Buffer solution 0.01M

5.0. Transfer PH

1.36 taining 100 milligrams of amdinocillin

grams of per milliliter is not less than 4.0 and monobasic potassium phosphate in sufnot more than 6.2.

ficient water to make 1,000 milliliters (vi) It is crystalline.

of solution. Adjust the pH to 5.0 + 0.1 (vii) It gives a positive identity test

with 18N phosphoric acid or 10N sodium for amdinocillin.

hydroxide.

(6) Mobile phase. Mix acetonitrile (2) Labeling. It shall be labeled in ac

(high-pressure liquid chromatography cordance with the requirements of

grade): 0.01M pH 5.0 phosphate buffer $ 432.5 of this chapter.

(15:85). (3) Requests for certification; samples. In addition to complying with the re

(ii) Working standard and sample solu

tions-(a) Preparation of working standquirements of $ 431.1 of this chapter,

ard solution. Prepare the working each such request shall contain:

standard solution fresh before injection (i) Results of tests and assays on the

by dissolving an accurately weighed batch for amdinocillin potency, and if

portion of the amdinocillin working packaged for dispensing, amdinocillin

standard with sufficient distilled water potency and container content, steril

to obtain a stock solution containing ity, pyrogens, moisture, pH, crystallin

approximately 100 micrograms of ity, and identity

amdinocillin per milliliter. (ii) Samples, if required by the Direc

(6) Preparation of sampie solutions-(1) tor, Center for Drug Evaluation and

Product not packaged for dispensing Research:

(micrograms of amdinocillin per milli(a) If it is packaged for repacking or

gram). Dissolve an accurately weighed for use in the manufacture of another

portion of the sample with sufficient drug:

distilled water to obtain a solution (1) For all tests except sterility: 10

containing 100 micrograms of packages, each containing approxi- amdinocillin per milliliter (estimated). mately 300 milligrams.

(2) Product packaged for dispensing. (2) For sterility testing: 20 packages, Determine both micrograms of each containing approximately 300 mil- amdinocillin per milligram of the samligrams.

ple and milligrams of amdinocillin per (6) If it is packaged for dispensing: container. Use separate containers for

(1) For all tests except sterility: A preparation of each sample solution as minimum of 15 immediate containers. described in paragraphs (b)(1)(ii)(b)(2)

(2) For sterility testing: 25 immediate (i) and (ii) of this section. containers, collected at regular inter- (i) Micrograms of amdinocillin per millivals throughout each filling operation. gram. Dissolve an accurately weighed

« iepriekšējāTurpināt »