Food and Drug Administration, HHS Pt. 436
from the requirements of section 502(l) (e) The quantity shipped is limited to and from the certification require- an amount reasonable for the purpose ments of section 512(n) of the act if of patch testing in the normal course shipped or sold to, or in the possession of the practice of medicine and is used of, persons regularly and lawfully en- solely for such patch testing. gaged in instruction in pharmacy, (f) The manufacturer or distributor chemistry, or medicine not involving maintains records of all shipments for clinical use; or in law enforcement; or this purpose for a period of 2 years in research not involving clinical use; after shipment and will make them or in chemical analysis or physical available to the Food and Drug Admin- testing, provided they are to be used istration upon request. only for such instruction, law enforce- ment, research, analysis, or testing, [43 FR 11151, Mar. 17, 1978] and provided further that their labels bear the statement ‘‘Not for drug use.’’ Subpart D—Records and Reports
§ 433.25 [Reserved] § 433.30 Records retention. § 433.26 Neomycin sulfate ointment in- At the option of the person having tended for hypersensitivity testing. control of records required to be kept Neomycin sulfate ointment subject by any regulation in this part 433, pho- to sections 502(l) and 507 of the act and tostatic or other permannnt reproduc- packaged for use as an allergen for skin tions may be substituted for such patch testing of hypersensitivity shall records after the first 2 years of the be exempt from the certification re- holding period. quirements of section 502(l) and 507 of the act if it complies with all the fol- PART 436—TESTS AND METHODS OF lowing conditions: ASSAY OF ANTIBIOTIC AND AN- (a) It contains neomycin sulfate equivalent to 200 milligrams of neomy- TIBIOTIC-CONTAINING DRUGS cin per gram in petrolatum. (b) The neomycin sulfate used in pre- Sec. paring the neomycin sulfate ointment Subpart A—Definitions; Interpretations; conforms to the standards prescribed Requirements by § 444.42(a)(1) of this chapter except § 444.42(a)(1)(ii). 436.1 Sterility requirements of items (c) The shipment of neomycin sulfate packaged with sterile antibiotic drugs. is made as a result of a specific request 436.2 Alternative assay methods. made to the manufacturer or distribu- tor by a practitioner licensed by law to Subpart B—Sterility Test Methods administer such drug, and the use of 436.20 Sterility test methods and proce- neomycin sulfate ointment for patch dures. testing is not promoted by the manu- facturer or distributor. Subpart C—Biological Test Methods (d) Each package shall bear on its outside wrapper or container and on 436.31 Equipment and diluents for use in bi- the immediate container, in addition ological testing. to other labeling information required 436.32 Pyrogen test. by the act and regulations, the follow- 436.35 Depressor substances test. ing statements in lieu of adequate di- rections for use: Subpart D—Microbiological Assay (1) The statement, ‘‘Caution: Federal Methods law prohibits dispensing without pre- 436.100 Laboratory equipment. scription’’. 436.101 Solutions. (2) The statement, ‘‘For use only in 436.102 Culture media. patch testing’’. 436.103 Test organisms. (3) The potency of the ointment. 436.104 Penicillin activity. (4) The expiration date as prescribed 436.105 Microbiological agar diffusion assay. by § 432.5(a)(3) of this chapter. 436.106 Microbiological turbidimetric assay.
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Subpart E—General Chemical Tests for 436.322 High–pressure liquid Antibiotics chromatographic assay for anthracycline antibiotics. 436.200 Loss on drying. 436.323 Continuous flow thin layer chroma- 436.201 Moisture determination. tography identity test for cefamandole 436.202 pH. nafate. 436.203 Crystallinity. 436.324 Polarographic analysis of 436.204 Iodometric assay. cefamandole. 436.205 Hydroxylamine colorimetric assay. 436.325 High pressure liquid chroma- 436.206 Test for metal particles in ophthal- tography assay for vidarabine. mic ointments. 436.326 Thin layer chromatographic identity 436.207 Residue on ignition. test for cefoxitin sodium. 436.208 Heavy metals determination. 436.327 Thin layer chromatographic identity 436.209 Melting range or temperature. test for cyclacillin. 436.210 Specific rotation. 436.328 High pressure liquid 436.211 Identity tests by infrared chromatographic assay for sulfisoxazole spectrophotometry. acetyl content. 436.212 Disintegration test. 436.329 High-pressure liquid 436.213 Nonaqueous titrations. chromatographic assay for meclocycline. 436.214 Heat stability. 436.330 Thin layer chromatographic identity 436.215 Dissolution test. test for bacampicillin. 436.216 High–performance liquid 436.331 High-pressure liquid chromatographic assay. chromatographic assay for 436.217 Film-coat rupture test. dactinomycin. 436.332 High-pressure liquid Subpart F—Chemical Tests for Specific chromatographic assay for moxalactam. Antibiotics 436.333 Thin layer chromatographic identity test for moxalactam. 436.300 Polarimetric assay of carbenicillin 436.334 High-pressure liquid indanyl sodium. chromatographic assay for piperacillin. 436.301 Thin layer chromatography identity 436.335 High-pressure liquid test for carbenicillin indanyl. chromatographic assay for chlor- 436.302 Clindamycin vapor phase chroma- amphenicol palmitate. tography. 436.336 Thin layer chromatographic identity 436.303 Clindamycin content of clindamycin test for azlocillin. palmitate hydrochloride by vapor phase 436.337 High-pressure liquid chromatography. chromatographic assay for cephradine. 436.304 Clindamycin phosphate vapor phase 436.338 High-pressure liquid chromatography. chromatographic assay for cefoperazone. 436.305 Thin layer chromatographic identity 436.339 High-pressure liquid test for hetacillin. chromatographic assay for bleomycin 436.306 Lincomycin gas liquid chroma- fractions. tography. 436.340 High-pressure liquid 436.307 Spectinomycin vapor phase chroma- chromatographic assay for tetracycline tography. hydrochloride content and 4– 436.308 Paper chromatography identity test epitetracycline hydrochloride content. for tetracyclines. 436.341 High-pressure liquid 436.309 Anhydrotetracyclines and 4-epian- chromatographic assay for plicamycin. hydrotetracycline. 436.342 High-pressure liquid 436.310 Thin layer chromatography identity chromatographic assay for cefazolin. test for mitomycin. 436.343 High-pressure liquid 436.311 Thin layer chromatography identity chromatographic assay for cefuroxime. test for amoxicillin. 436.344 Thin layer chromatographic identity 436.312 Atomic absorption method for deter- test for cefuroxime. mining the zinc content of zinc baci- 436.345 High-pressure liquid tracin. chromatographic assay for ceftizoxime. 436.316 Determination of penicillin G con- 436.346 High-pressure liquid tent. chromatographic assay for cyclosporine. 436.317 Solubility characteristic test for 436.347 High-pressure liquid griseofulvin (ultramicrosize) tablets. chromatographic assay for cefoxitin. 436.318 Continuous flow thin layer chroma- 436.348 High-pressure liquid tography identity test. chromatographic assay for ceforanide. 436.319 Thin layer chromatography identity 436.349 High-pressure liquid test for bacitracin and bacitracin zinc. chromatographic assay for L-lysine in 436.320 Ferric chloride colorimetric assay. ceforanide for injection. 436.321 Griseofulvin gas liquid chroma- 436.350 High-performance liquid tography. chromatographic assay for cefonicid.
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436.351 High-performance liquid 436.505 Penicillin-streptomycin-bacitracin chromatographic assay for amoxicillin ointment; penicillin-dihydrostrepto- and clavulanic acid. mycin-bacitracin ointment; penicillin- 436.352 High-performance liquid streptomycin-bacitracin methylene disa- chromatographic assay for determining licylate ointment; penicillin-dihydro- clavam-2-carboxylate content in streptomycin-bacitracin methylene disa- clavulanate potassium. licylate ointment. 436.353 High-performance liquid 436.506 Benzathine penicillin G and buffered chromatographic assay for amdinocillin. crystalline penicillin for aqueous injec- 436.354 High-performance liquid tion. chromatographic assay for ceftriaxone. 436.507 Benzathine-procaine-buffered crys- 436.355 High–performance liquid talline penicillins for aqueous injection. chromatographic assay for ticarcillin– 436.508 Penicillin - bacitracin - neomycin clavulanic acid. ointment; penicillin-bacitracin-neomycin 436.356 High–performance liquid in oil. chromatographic assay for ceftazidime. 436.509 Procaine penicillin-streptomycin- 436.357 Atomic absorption test for sodium polymyxin in oil; procaine penicillin-di- carbonate content. hydrostreptomycin-polymyxin in oil; 436.358 High–performance liquid procaine penicillin-streptomycin- chromatographic assay for pyridine. polymyxin ointment; procaine penicillin- dihydrostreptomycin-polymyxin oint- 436.360 Gel permeation chromatographic ment. assay for high molecular weight polymer. 436.510 Penicillin - streptomycin - erythro- 436.361 High–performance liquid mycin ointment; penicillin-dihydro- chromatographic assay for aztreonam. streptomycin - erythromycin ointment. 436.362 Thin-layer chromatographic test for 436.511 Penicillin-streptomycin-bacitracin free erythromycin content in erythro- methylene disalicylate-neomycin oint- mycin estolate bulk. ment; penicillin-dihydrostreptomycin- 436.363 High-performance liquid bacitracin methylene disalicylate-neo- chromatographic assay for cefmenoxime. mycin ointment. 436.364 Atomic absorption test for sodium 436.512 Procaine penicillin G-novobiocin-ne- carbonate content of cefmenoxime hy- omycin-dihydrostreptomycin in oil. drochloride for injection. 436.513 Chlortetracycline troches; tetra- 436.365 Thin layer chromatographic identity cycline hydrochloride troches. test for rifampin. 436.514 Chlortetracycline hydrochloride 436.366 High-performance liquid chroma- powder topical; tetracycline hydro- tography assay for determining chloride powder topical. chromatographic purity of vancomycin. 436.515 Capsules tetracycline and 436.367 Thin-layer chromatographic identity oleandomycin phosphate; capsules tetra- test for cephalexin hydrochloride. cycline and troleandomycin; capsules 436.368 Thin layer chromatographic identity tetracycline hydrochloride and test for cefprozil. oleandomycin phosphate; capsules tetra- 436.369 Thin layer chromatography test for cycline hydrochloride and free N-isobutylpiperidone content in troleandomycin. rifabutin. 436.516 Tetracycline-neomycin complex 436.370 Spectrophotometric identity test for powder topical; tetracycline hydro- rifabutin capsules. chloride-neomycin sulfate powder topi- cal. Subpart G—Chemical Tests for 436.517 Bacitracin-neomycin tablets; zinc Nonantibiotic Active Ingredients bacitracin-neomycin tablets; bacitracin methylene disalicylate-neomycin tab- 436.400 Thin layer chromatographic identity lets. test for iodochlorhydroxyquin. 436.542 Acid resistance/dissolution test for enteric-coated erythromycin pellets. Subpart H—Tests for Specific Antibiotic 436.543 Acid resistance test for pellet-filled Dosage Forms doxycycline hyclate capsules. 436.544 Dissolution test for pellet-filled 436.500 Penicillin in oil and wax. doxycycline hyclate capsules. 436.503 Procaine penicillin and buffered 436.545 Acid resistance test for erythro- crystalline penicillin for aqueous injec- mycin particles in tablets. tion. 436.504 Penicillin-bacitracin ointment. AUTHORITY: Sec. 507 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 357).
SOURCE: 39 FR 18944, May 30, 1974, unless otherwise noted.
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Subpart A—Definitions; ter area per minute with a differential Interpretations; Requirements pressure of 70 centimeters of mercury at 25° C. § 436.1 Sterility requirements of items (2) Penicillinase solutions. When the packaged with sterile antibiotic amount of penicillinase to be used is drugs. specified in terms of Levy units, use a (a) Diluents packaged in combination penicillinase solution standardized in with sterile antibiotic drugs. If a sterile terms of Levy units. One Levy unit of antibiotic drug is packaged in com- penicillinase inactivates 59.3 units of bination with an immediate container penicillin G in 1 hour at 25° C. and at a of a diluent, the immediate container pH of 7.0 in a phosphate buffered solu- of diluent shall be sterile when tested tion of a pure alkali salt of penicillin G by the method prescribed in when the substrate is in sufficient con- § 436.20(e)(1). centration to maintain a zero order re- (b) Dispensers packaged in combination action. with sterile antibiotic drugs. If a sterile (c) Culture media. Use ingredients antibiotic drug is packaged in com- that conform to the standards pre- bination with a dispenser, such dis- scribed by the U.S.P. or N.F. In lieu of penser shall be sterile when tested by preparing the media from the individ- the method prescribed in § 436.20(e)(1). ual ingredients, they may be made from dehydrated mixtures which, when [39 FR 18944, May 30, 1974, as amended at 41 reconstituted with distilled water, FR 46852, Oct. 26, 1976] have the same or equivalent composi- § 436.2 Alternative assay methods. tion as such media and have growth- promoting buffering, and oxygen ten- Alternative assay methods (including sion-controlling properties equal to or automated procedures) employing the better than such media. The pH of each same basic chemistry or microbiology medium should be adjusted with 2N hy- as the official methods described in drochloric acid or sodium hydroxide this part and in the individual mono- before sterilization, so that after steri- graphs of this chapter may be used, lization and the addition of the penicil- provided the results obtained are of linase, if necessary, the pH will fall equivalent accuracy. However, only the within the specified range. Dispense results obtained from the official 90±10 milliliter quantities of the liquid methods designated in the individual media into individual test tubes (38 monographs are conclusive. millimeters x 200 millimeters). Close the tubes with suitable closures, and Subpart B—Sterility Test Methods sterilize in an autoclave at 121° C. for 20 minutes. The autoclave temperature § 436.20 Sterility test methods and pro- should be reached within 10 minutes. cedures. After sterilization, cool the medium at (a) Laboratory facilities. The test must once to approximately 25° C. and store be performed using aseptic techniques at 20° C. to 30° C. The sterility of each in an area as free from contamination lot of tubes of liquid medium may be as is possible to achieve. Testing confirmed by incubating an adequate should not be conducted under direct number of tubes as described in the exposure to ultraviolet light or in test procedures in paragraph (e) of this areas under aerosol treatment. Envi- section. ronmental tests to assess the suit- (1) Medium A. Use U.S.P. fluid ability of testing conditions should be thioglycolate medium I. made frequently enough to assure the (2) Medium B. Use U.S.P. fluid validity of test results. thioglycolate medium I, with sufficient (b) Equipment and reagents—(1) Bac- sterile penicillinase added to inac- terial membrane filter. The filter has a tivate the penicillin activity in the nominal porosity of 0.45 micron±0.02 sample under test. The penicillinase micron, a diameter of approximately 47 must be added to individual tubes of millimeters, and a flowrate of 55 milli- sterile medium A, using aseptic tech- liters to 75 milliliters of distilled water nique. Prior to use, or at the time of passing each square centimeter of fil- the test, a representative number of
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