CFR - Code of Federal Regulations Title 21

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[Code of Federal Regulations]

[Title 21, Volume 1]

[CITE: 21CFR73]

TITLE 21--FOOD AND DRUGS
CHAPTER I--FOOD AND DRUG ADMINISTRATION
DEPARTMENT OF HEALTH AND HUMAN SERVICES
					
SUBCHAPTER A - GENERAL
					
							PART 73LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION

Subpart B - Drugs

Sec. 73.1001 Diluents in color additive mixtures for drug use exempt from certification.

The following diluents may be safely used in color additive mixtures that are exempt from certification and which are to be used for coloring drugs, subject to the condition that each straight color in the mixture has been exempted from certification or, if not so exempted, is from a batch that has previously been certified and has not changed in composition since certification. Such listing of diluents is not to be construed as superseding any of the other requirements of the Federal Food, Drug, and Cosmetic Act with respect to drugs, including new drugs. If a definition and specification for a particular diluent is not set forth in this subpart, the material shall be of a purity consistent with its intended use.

(a) Ingested drugs - (1) General use. Diluents listed in § 73.1(a) and the following:

Substances	Definitions and specifications	Restrictions
Alcohol, specially denatured	As set forth in 26 CFR, pt. 212	As set forth in 26 CFR, pt. 211.
Cetyl alcohol	As set forth in N.F. XI
Isopropyl alcohol		In color coatings for pharmaceutical forms, no residue.
Polyoxyethylene (20) sorbitan monostearate (Polysorbate 60)	As set forth in sec. 172.836 of this chapter
Polyoxyethylene (20) sorbitan tristearate (Polysorbate 65)	As set forth in sec. 172.838 of this chapter
Polysorbate 80	As set forth in sec. 172.840 of this chapter
Polyvinyl-pyrrolidone	As set forth in sec. 173.55 of this chapter
Sorbitan monooleate
Sorbitan monostearate	As set forth in sec. 172.842 of this chapter
Sorbitan trioleate

(2) Special use; inks for branding pharmaceutical forms. Items listed in paragraph (a)(1) of this section, § 73.1(b)(1)(i), and the following:

Ethyl lactate

Polyoxyethylene sorbitan monolaurate (20)

(b) Externally applied drugs. Diluents listed in paragraph (a)(1) of this section and the following:

Substances	Definitions and specifications
Benzyl alcohol	As set forth in N.F. XI.
Ethyl cellulose	As set forth in § 172.868 of this chapter.
Hydroxyethyl cellulose
Hydroxypropyl cellulose	As set forth in § 172.870 of this chapter.

Sec. 73.1010 Alumina (dried aluminum hydroxide).

(a) Identity. (1) The color additive alumina (dried aluminum hydroxide) is a white, odorless, tasteless, amorphous powder consisting essentially of aluminum hydroxide (Al2 O3- XH2 O).

(2) Color additive mixtures for drug use made with alumina (dried aluminum hydroxide) may contain only those diluents listed in this subpart as safe and suitable for use in color additive mixtures for coloring drugs.

(b) Specifications. Alumina (dried aluminum hydroxide) shall conform to the following specifications:

Acidity or alkalinity: Agitate 1 gram of the color additive with 25 milliliters of water and filter. The filtrate shall be neutral to litmus paper.

Matter insoluble in dilute hydrochloric acid, not more than 0.5 percent.

Lead (as Pb), not more than 10 parts per million.

Arsenic (as As), not more than 1 part per million.

Mercury (as Hg), not more than 1 part per million.

Aluminum oxide (Al2 O3), not less than 50 percent.

(c) Uses and restrictions. Alumina (dried aluminum hydroxide) may be safely used in amounts consistent with good manufacturing practice to color drugs generally.

(d) Labeling requirements. The label of the color additive and of any mixtures prepared therefrom intended solely or in part for coloring purposes shall conform to the requirements of § 70.25 of this chapter.

(e) Exemption from certification. Certification of this color additive is not necessary for the protection of the public health, and therefore batches thereof are exempt from the certification requirements of section 721(c) of the act.

Sec. 73.1015 Chromium-cobalt-aluminum oxide.

(a) Identity. The color additive chromium-cobalt-aluminum oxide is a blue-green pigment obtained by calcining a mixture of chromium oxide, cobalt carbonate, and aluminum oxide. It may contain small amounts (less than 1 percent each) of oxides of barium, boron, silicon, and nickel.

(b) Specifications. Chromium-cobalt-aluminum oxide shall conform to the following specifications:

Chromium, calculated as Cr2 O3, 34-37 percent.

Cobalt, calculated as CoO, 29-34 percent.

Aluminum, calculated as AL2 O3, 29-35 percent.

Lead (as Pb), not more than 30 parts per million.

Arsenic (as As), not more than 3 parts per million.

Total oxides of aluminum, chromium, and cobalt not less than 97 percent.

Lead and arsenic shall be determined in the solution obtained by boiling 10 grams of the chromium-cobalt-aluminum oxide for 15 minutes in 50 milliliters of 0.5 N hydrochloric acid.

(c) Uses and restrictions. The color additive chromium-cobalt-aluminum oxide may be safely used for coloring linear polyethylene surgical sutures, United States Pharmacopeia (U.S.P.), for use in general surgery, subject to the following restrictions:

(1) For coloring procedure, the color additive is blended with the polyethylene resin. The mixture is heated to a temperature of 500-550 deg.F. and extruded through a fixed orifice. The filaments are cooled, oriented by drawing, and set by annealing.

(2) The quantity of the color additive does not exceed 2 percent by weight of the suture material.

(3) The dyed suture shall conform in all respects to the requirements of the U.S.P. XX (1980).

(4) When the sutures are used for the purpose specified in their labeling, there is no migration of the color additive to the surrounding tissue.

(5) If the suture is a new drug, an approved new drug application, pursuant to section 505 of the Federal Food, Drug, and Cosmetic Act, is in effect for it.

(d) Labeling. The label of the color additive shall conform to the requirements of § 70.25 of this chapter.

(e) Exemption from certification. Certification of this color additive is not necessary for the protection of the public health, and batches thereof are exempt from the certification requirements of section 721(c) of the act.

[42 FR 15643, Mar. 22, 1977, as amended at 49 FR 10089, Mar. 19, 1984]

Sec. 73.1025 Ferric ammonium citrate.

(a) Identity. The color additive ferric ammonium citrate consists of complex chelates prepared by the interaction of ferric hydroxide with citric acid in the presence of ammonia. The complex chelates occur in brown and green forms, are deliquescent in air, and are reducible by light.

(b) Specifications. Ferric ammonium citrate shall conform to the following specifications and shall be free from impurities other than those named to the extent that such impurities may be avoided by good manufacturing practice:

Iron (as Fe), not less than 14.5 percent and not more than 18.5 percent.

Lead (as Pb), not more than 20 p/m.

Arsenic (as As), not more than 3 p/m.

(c) Uses and restrictions. Ferric ammonium citrate may be safely used in combination with pyrogallol (as listed in § 73.1375), for coloring plain and chromic catgut sutures for use in general and ophthalmic surgery subject to the following conditions:

(1) The dyed suture shall conform in all respects to the requirements of the United States Pharmacopeia XX (1980).

(2) The level of the ferric ammonium citrate-pyrogallol complex shall not exceed 3 percent of the total weight of the suture material.

(3) When the sutures are used for the purposes specified in their labeling, there is no migration of the color additive to the surrounding tissue.

(4) If the suture is a new drug, an approved new drug application, pursuant to section 505 of the act, is in effect for it.

(d) Labeling. The labeling of the color-additive shall conform to the requirements of § 70.25 of this chapter.

(e) Exemption from certification. Certification of this color additive is not necessary for the protection of the public health and therefore batches thereof are exempt from the requirements of section 721(c) of the act.

[42 FR 15643, Mar. 22, 1977, as amended at 49 FR 10089, Mar. 19, 1984]

Sec. 73.1030 Annatto extract.

(a) Identity and specifications. (1) The color additive annatto extract shall conform in identity and specifications to the requirements of § 73.30(a)(1) and (b).

(2) Color additive mixtures for drug use made with annatto extract may contain only those diluents that are suitable and that are listed in this subpart as safe in color additive mixtures for coloring ingested drugs.

(b) Uses and restrictions. Annatto extract may be safely used for coloring drugs generally, including those intended for use in the area of the eye, in amounts consistent with good manufacturing practice.

(c) Labeling. The label of the color additive and any mixtures prepared therefrom and intended solely or in part for coloring purposes shall conform to the requirements of § 70.25 of this chapter. Labels shall bear information showing that the color is derived from annatto seed. The requirements of § 70.25(a) of this chapter that all ingredients shall be listed by name shall not be construed as requiring the declaration of residues of solvents listed in § 73.30(a)(1)(ii) of this chapter.

(d) Exemption from certification. Certification of this color additive is not necessary for the protection of the public health and therefore batches thereof are evempt from the certification requirements of section 721(c) of the act.

[42 FR 15643, Mar. 22, 1977, as amended at 42 FR 36994, July 19, 1977]

Sec. 73.1070 Calcium carbonate.

(a) Identity. (1) The color additive calcium carbonate is a fine, white, synthetically prepared powder consisting essentially of precipitated calcium carbonate (CaCO3).

(2) Color additive mixtures for drug use made with calcium carbonate may contain only those diluents listed in this subpart as safe and suitable for use in color additive mixtures for coloring drugs.

(b) Specifications. Calcium carbonate shall meet the specifications for precipitated calcium carbonate in the United States Pharmacopeia XX (1980).

(c) Uses and restrictions. Calcium carbonate may be safely used in amounts consistent with good manudacturing practice to color drugs generally.

[42 FR 15643, Mar. 22, 1977, as amended at 49 FR 10089, Mar. 19, 1984]

Sec. 73.1075 Canthaxanthin.

(a) Identity and specifications. (1) The color additive canthaxanthin shall conform in identity and specifications to the requirements of § 73.75(a)(1) and (b).

(2) Color additive mixtures for ingested drug use made with canthaxanthin may contain only those diluents that are suitable and that are listed in this subpart as safe in color additive mixtures for coloring ingested drugs.

(b) Uses and restrictions. Canthaxanthin may be safely used for coloring ingested drugs generally in amounts consistent with good manufacturing practice.

(c) Labeling requirements. The label of the color additive and of any mixtures prepared therefrom intended solely or in part for coloring purposes shall conform to the requirements of § 70.25 of this chapter.

(d) Exemption from certification. Certification of this color additive is not necessary for the protection of the public health, and therefore batches thereof are exempt from the certification requirements of section 721(c) of the act.

Sec. 73.1085 Caramel.

(a) Identity and specifications. (1) The color additive caramel shall conform in identity and specifications to the requirements of § 73.85(a) (1), (2), and (3) and (b).

(2) The diluents in color additive mixtures for drug use containing caramel shall be limited to those listed in this subpart as safe and suitable in color additive mixtures for coloring drugs.

(b) Uses and restrictions. Caramel may be used for coloring ingested and topically applied drugs generally in amounts consistent with good manufacturing practice.

(c) Exemption from certification. Certification of this color additive is not necessary for the protection of the public health and therefore batches thereof are exempt from the certification requirement of section 721(c) of the act.

Sec. 73.1095 [beta]-Carotene.

(a) Identity and specifications. (1) The color additive [beta]-carotene shall conform in identity and specifications to the requirements of § 73.95(a)(1) and (b).

(2) The diluents in color additive mixtures for drug use containing [beta]-carotene are limited to those listed in this subpart as safe and suitable in color additive mixtures for coloring ingested drugs.

(b) Uses and restrictions. The color additive [beta]-carotene may be safely used in coloring drugs generally, including those intended for use in the area of the eye, in amounts consistent with good manufacturing practice.

(c) Labeling requirements. The labeling of the color additive and any mixtures intended solely or in part for coloring purposes prepared therefrom shall conform to the requirements of § 70.25 of this chapter.

[42 FR 15643, Mar. 22, 1977, as amended at 42 FR 33722, July 1, 1977]

Sec. 73.1100 Cochineal extract; carmine.

(a) Identity and specifications. (1) The color additives cochineal extract and carmine shall conform in identity and specifications to the requirements of § 73.100(a) (1) and (2) and (b).

(2) Color additive mixtures for drug use made with carmine and cochineal extract may contain only those diluents that are suitable and that are listed in this subpart as safe in color additive mixtures for coloring drugs.

(b) Uses and restrictions. Cochineal extract and carmine may be safely used for coloring ingested and externally applied drugs in amounts consistent with good manufacturing practice.

(c) Labeling requirements. The label of the color additives and any mixtures intended solely or in part for coloring purposes prepared therefrom shall conform to the requirements of § 70.25 of this chapter.

(d) Exemption from certification. Certification of these color additives is not necessary for the protection of the public health, and therefore batches thereof are exempt from the certification requirements of section 721(c) of the act.

Sec. 73.1125 Potassium sodium copper chloropyhllin (chlorophyllin-copper complex).

(a) Identity. (1) The color additive potassium sodium copper chlorophyllin is a green to black powder obtained from chlorophyll by replacing the methyl and phytyl ester groups with alkali and replacing the magnesium with copper. The source of the chlorophyll is dehydrated alfalfa.

(2) Color additive mixtures for drug use made with potassium sodium copper chlorophyllin may contain only those diluents that are suitable and that are listed in this subpart as safe for use in color additive mixtures for coloring drugs.

(b) Specifications. Potassium sodium copper chlorophyllin shall conform to the following specifications and shall be free from impurities other than those named to the extent that such other impurities may be avoided by good manufacturing practice:

Moisture, not more than 5.0 percent.

Nitrogen, not more than 5.0 percent.

pH of 1 percent solution, 9 to 11.

Total copper, not less than 4 percent and not more than 6 percent.

Free copper, not more than 0.25 percent.

Iron, not more than 0.5 percent.

Lead (as Pb)), not more than 20 parts per million.

Arsenic (as As), not more than 5 parts per million.

Ratio, absorbance at 405 mÎ¼ to absorbance at 630 mÎ¼, not less than 3.4 and not more than 3.9.

Total color, not less than 75 percent.

(c) Uses and restrictions. Potassium sodium copper chlorophyllin may be safely used for coloring dentifrices that are drugs at a level not to exceed 0.1 percent. Authorization for this use shall not be construed as waiving any of the requirements of section 505 of the act with respect to the drug in which it is used.

(d) Labeling. The label of the color additive and any mixtures prepared therefrom intended solely or in part for coloring purposes shall conform to the requirements of § 70.25 of this chapter.

Sec. 73.1150 Dihydroxyacetone.

(a) Identity. (1) The color additive dihydroxyacetone is 1,3-dihydroxy-2-propanone.

(2) Color additive mixtures for drug use made with dihydroxyacetone may contain only those diluents that are listed in this subpart as safe and suitable in color additive mixtures for coloring externally applied drugs.

(b) Specifications. Dihydroxyacetone shall conform to the following specifications and shall be free from impurities other than those named to the extent that such impurities may be avoided by good manufacturing practice:

Volatile matter (at 34.6 deg.C. for 3 hours at a pressure of not more than 30 mm. mercury), not more than 0.5 percent.

Residue on ignition, not more than 0.4 percent.

Lead (as Pb), not more than 20 parts per million.

Arsenic (as As), not more than 3 parts per million.

Iron (as Fe), not more than 25 parts per million.

1,3-dihydroxy-2-propanone, not less than 98 percent.

(c) Uses and restrictions. Dihydroxyacetone may be safely used in amounts consistent with good manufacturing practice in externally applied drugs intended solely or in part to impart a color to the human body. Authorization for this use shall not be construed as waiving any of the requirements of section 505 of the act with respect to the drug in which it is used.

(d) Labeling requirements. The label of the color additive and any mixtures prepared therefrom intended solely or in part for coloring purposes shall conform to the requirements of § 70.25 of this chapter.

Sec. 73.1162 Bismuth oxychloride.

(a) Identity. (1) The color additive bismuth oxychloride is a synthetically prepared white or nearly white amorphous or finely crystalline, odorless powder consisting principally of BiOCl.

(2) Color additive mixtures for drug use made with bismuth oxychloride may contain only those diluents that are suitable and that are listed in this subpart as safe in color additive mixtures for coloring externally applied drugs.

(b) Specifications. The color additive bismuth oxychloride shall conform to the following specifications and shall be free from impurities other than those named to the extent that such other impurities may be avoided by good manufacturing practice:

Volatile matter, not more than 0.5 percent.

Lead (as Pb), not more than 20 parts per million.

Arsenic (as As), not more than 3 parts per million.

Mercury (as Hg), not more than 1 part per million.

Bismuth oxychloride, not less than 98 percent.

(c) Uses and restrictions. The color additive bismuth oxychloride may be safely used in coloring externally applied drugs, including those intended for use in the area of the eye, in amounts consistent with good manufacturing practice.

(d) Labeling. The color additive and any mixture prepared therefrom intended solely or in part for coloring purposes shall bear, in addition to any information required by law, labeling in accordance with the provisions of § 70.25 of this chapter.

(e) Exemption from certification. Certification of this color additive is not necessary for the protection of the public health, and therefore batches thereof are exempt from certification pursuant to section 721(c) of the act.

[42 FR 52394, Sept. 30, 1977]

Sec. 73.1200 Synthetic iron oxide.

(a) Identity. (1) The color additive synthetic iron oxide consists of any one or any combination of synthetically prepared iron oxides, including the hydrated forms. It is free from admixture with other substances.

(2) Color additive mixtures for drug use made with synthetic iron oxide may contain only those diluents listed in this subpart as safe and suitable in color additive mixtures for coloring drugs.

(b) Specifications. Synthetic iron oxide shall conform to the following specifications, all on an "as is" basis:

Arsenic (as As), not more than 3 parts per million.

Lead (as Pb), not more than 10 parts per million.

Mercury (as Hg), not more than 3 parts per million.

(c) Uses and restrictions. The color additive synthetic iron oxide may be safely used to color ingested or topically applied drugs generally subject to the restriction that if the color additive is used in drugs ingested by man the amount consumed in accordance with labeled or prescribed dosages shall not exceed 5 milligrams, calculated as elemental iron, per day.

(d) Labeling requirements. The label of the color additive and any mixtures intended solely or in part for coloring purposes prepared therefrom shall conform to the requirements of § 70.25 of this chapter.

(e) Exemption from certification. Certification of this color additive is not necessary for the protection of the public health, and therefore batches thereof are exempt from certification requirements of section 721(c) of the act.

Sec. 73.1298 Ferric ammonium ferrocyanide.

(a) Identity. (1) The color additive ferric ammonium ferrocyanide is the blue pigment obtained by oxidizing under acidic conditions with sodium dichromate the acid digested precipitate resulting from mixing solutions of ferrous sulfate and sodium ferrocyanide in the presence of ammonium sulfate. The oxidized product is filtered, washed, and dried. The pigment consists principally of ferric ammonium ferrocyanide with smaller amounts of ferric ferrocyanide and ferric sodium ferrocyanide.

(2) Color additive mixtures for drug use made with ferric ammonium ferrocyanide may contain only those diluents listed in this subpart as safe and suitable for use in color additive mixtures for coloring drugs.

(b) Specifications. Ferric ammonium ferrocyanide shall conform to the following specifications and shall be free of impurities other than those named to the extent that the other impurities may be avoided by good manufacturing practice:

Oxalic acid or its salts, not more than 0.1 percent.

Water soluble matter, not more than 3 percent.

Water soluble cyanide, not more than 10 parts per million.

Volatile matter, not more than 4 percent.

Lead (as Pb), not more than 20 parts per million.

Arsenic (as As), not more than 3 parts per million.

Nickel (as Ni), not more than 200 parts per million.

Cobalt (as Co), not more than 200 parts per million.

Mercury (as Hg), not more than 1 part per million.

Total iron (as Fe corrected for volatile matter), not less than 33 percent and not more than 39 percent.

(c) Uses and restrictions. Ferric ammonium ferrocyanide may be safely used in amounts consistent with good manufacturing practice to color externally applied drugs, including those for use in the area of the eye.

(e) Exemption from certification. Certification of this color additive is not necessary for the protection of the public health, and therfore batches thereof are exempt from the certification requirements of section 721(c) of the act.

[42 FR 38562, July 29, 1977, as amended at 44 FR 28322, May 15, 1979]

Sec. 73.1299 Ferric ferrocyanide.

(a) Identity. (1) The color additive ferric ferrocyanide is a ferric hexacyanoferrate pigment characterized by the structual formula Fe4[Fe(CN)6]3-XH2O, which may contain small amounts of ferric sodium ferrocyanide and ferric potassium ferrocyanide.

(2) Color additive mixtures for drug use made with ferric ferrocyanide may contain only those diluents listed in this subpart as safe and suitable for use in color additive mixtures for coloring drugs.

(b) Specifications. Ferric ferrocyanide shall conform to the following specifications and shall be free from impurities other than those named to the extent that such impurities may be avoided by good manufacturing practice:

Water soluble cyanide, not more than 10 parts per million.

Lead (as Pb), not more than 20 parts per million.

Arsenic (as As), not more than 3 parts per million.

Nickel (as Ni), not more than 200 parts per million.

Cobalt (as Co), not more than 200 parts per million.

Mercury (as Hg), not more than 1 part per million.

Oxalic acid, not more than 0.1 percent.

Water soluble matter, not more than 3 percent.

Volatile matter, not more than 10 percent.

Total iron (as Fe corrected for volatile matter), not less than 37 percent and not more than 45 percent.

(c) Uses and restrictions. Ferric ferrocyanide may be safely used in amounts consistent with good manufacturing practice to color externally applied drugs including those intended for use in the area of the eye.

(e) Exemption from certification. Certification of this color additive is not necessary for the protection of the public health, and therefore batches thereof are exempt from certification requirements of section 721(c) of the act.

[43 FR 54235, Nov. 21, 1978]

Sec. 73.1326 Chromium hydroxide green.

(a) Identity. (1) The color additive chromium hydroxide green is principally hydrated chromic sesquioxide (Cr2O3-XH2O).

(2) Color additive mixtures for drug use made with chromium hydroxide green may contain only those diluents listed in this subpart as safe and suitable for use in color additive mixtures for coloring drugs.

(b) Specifications. Chromium hydroxide green shall conform to the following specifications and shall be free from impurities other than those named to the extent that such impurities may be avoided by good manufacturing practice:

Water soluble matter, not more than 2.5%.

Chromium in 2% NaOH extract, not more than 0.1% as Cr2O3 (based on sample weight).

Boron (as B2O3), not more than 8 percent.

Total volatile matter at 1000 deg.C, not more than 20%.

Cr2O3 not less than 75%.

Lead (as Pb), not more than 20 parts per million.

Arsenic (as As), not more than 3 parts per million.

Mercury (as Hg), not more than 1 part per million.

(c) Uses and restrictions. Chromium hydroxide green may be safely used in amounts consistent with good manufacturing practice to color externally applied drugs, including those for use in the area of the eye.

(d) Labeling requirements. The label of the color additive and of any mixtures prepared therefrom lintended solely or in part for coloring purposes shall conform to the requirements of § 70.25 of this chapter.

[42 FR 36451, July 15, 1977, as amended at 42 FR 59852, Nov. 22, 1977]

Sec. 73.1327 Chromium oxide greens.

(a) Identity. (1) The color additive chromium oxide greens is principally chromic sesquioxide (Cr2O3).

(2) Color additive mixtures for drug use made with chromium oxide greens may contain only those diluents listed in this subpart as safe and suitable for use in color additive mixtures for coloring drugs.

(b) Specifications. the color additive chormium oxide greens shall conform to the following specifications and shall be free from impurities other than those named to the extent that such impurities may be avoided by good manufacturing practice:

Chromium in 2% NaOH extract, not more than 0.075% as Cr2O3 (based on sample weight).

Arsenic (as As), not more than 3 parts per million.

Lead (as Pb), not more than 20 parts per million.

Mercury (as Hg), not more than 1 part per million.

Cr2O3, not less than 95%.

(c) Uses and restrictions. Chromium oxide greens is safe for use in coloring externally applied drugs, including those intended for use in the area of eye, in amounts consistent with good manufacturing practice.

(e) Exemption from certification. Certification of this color additive is not necessary for the protection of the public health, and therefore batches therof are exempt from certification pursuant to section 721(c) of the act.

[42 FR 36451, July 15, 1977]

Sec. 73.1329 Guanine.

(a) Identity. (1) The color additive guanine is the crystalline material obtained from fish scales and consists principally of the two purines, guanine and hypoxanthine. The guanine content will vary from 75 to 97 percent, and the hypoxanthine will vary from 3 to 25 percent, depending on the particular fish and tissue from which the crystals are derived.

(2) Color additive mixtures for drug use made with guanine may contain only those diluents listed in this subpart as safe and suitable for use in color additive mixtures for coloring externally applied drugs.

(b) Specifications. The color additive guanine shall conform to the following specifications and shall be free from impurities other than those named to the extent that such other impurities may be avoided by good manufacturing practice:

Guanine, not less than 75 percent.

Hypoxanthine, not more than 25 percent.

Ash (ignition at 800 deg.C), not more than 2 percent.

Lead (as Pb), not more than 20 parts per million.

Arsenic (as As), not more than 3 parts per million.

Assay, not less than 96 percent total purines.

Mercury (as Hg), not more than 1 part per million.

(c) Uses and restrictions. Guanine is safe for use in coloring externally applied drugs, including those intended for use in the area of the eye, in amounts consistent with good manufacturing practice.

[42 FR 37537, July 22, 1977]

Sec. 73.1350 Mica-based pearlescent pigments.

(a) Identity. (1) The color additive is formed by depositing titanium and/or iron salts onto mica, followed by heating to produce one of the following combinations: Titanium dioxide on mica; iron oxide on mica; titanium dioxide and iron oxide on mica. Mica used to manufacture the color additive shall conform in identity to the requirements of § 73.1496(a)(1).

(2) Color additive mixtures for drug use made with mica-based pearlescent pigments may contain only those diluents listed in this subpart as safe and suitable for use in color additive mixtures for coloring ingested drugs.

(b) Specifications. Mica-based pearlescent pigments shall conform to the following specifications and shall be free from impurities other than those named to the extent that such other impurities may be avoided by good manufacturing practice:

(1) Lead (as Pb), not more than 4 parts per million (ppm).

(2) Arsenic (as As), not more than 3 ppm.

(3) Mercury (as Hg), not more than 1 ppm.

(c) Uses and restrictions. Mica-based pearlescent pigments may be safely used to color ingested drugs in amounts up to 3 percent, by weight, of the final drug product. The maximum amount of iron oxide to be used in producing said pigments is not to exceed 55 percent, by weight, in the finished pigment.

(d) Labeling. The label of the color additive and of any mixture prepared therefrom intended solely or in part for coloring purposes shall conform to the requirements of § 70.25 of this chapter.

[70 FR 42273, July 22, 2005. Redesignated at 72 FR 10357, Mar. 8, 2007]

Sec. 73.1375 Pyrogallol.

(a) Identity. The color additive pyrogallol is 1,2,3-trihydroxybenzene.

(b) Specifications. Pyrogallol shall conform to the following specifications and shall be free from impurities other than those named to the extent that such impurities may be avoided by good manufacturing practice:

Melting point, between 130deg. and 133 deg.C.

Residue on ignition, not more than 0.1 percent.

Lead (as Pb), not more than 20 p/m (parts per million).

Arsenic (as As), not more than 3 p/m.

(c) Uses and restrictions. Pyrogallol may be safely used in combination with ferric ammonium citrate (as listed in § 73.1025), for coloring plain and chromic catgut sutures for use in general and ophthalmic surgery, subject to the following restrictions:

(1) The dyed suture shall conform in all respects to the requirements of the United States Pharmacopeia XX (1980).

(2) The level of the ferric ammonium citrate-pyrogallol complex shall not exceed 3 percent of the total weight of the suture material.

(3) When the sutures are used for the purposes specified in their labeling, there is no migration of the color additive to the surrounding tissues.

(4) If the suture is a new drug, an approved new drug application, pursuant to section 505 of the act, is in effect for it.

(d) Labeling. The label of the color additive shall conform to the requirements of § 70.25 of this chapter.

[42 FR 15643, Mar. 22, 1977, as amended at 49 FR 10089, Mar. 19, 1984]

Sec. 73.1400 Pyrophyllite.

(a) Identity. (1) The color additive pyrophyllite is a naturally occurring mineral substance consisting predominantly of a hydrous aluminum silicate, Al2O3-4SiO2-H2 O, intimately mixed with lesser amounts of finely divided silica, SiO2. Small amounts, usually less than 3 percent, of other silicates, such as potassium aluminum silicate, may be present. Pyrophyllite may be identified and semiquantitatively determined by its characteristic X-ray powder diffraction pattern and by its optical properties.

(2) Color additive mixtures made with pyrophyllite are limited to those listed in this subpart as safe and suitable in color additive mixtures for coloring externally applied drugs.

(b) Specifications. Pyrophyllite shall conform to the following specifications:

Lead (as Pb), not more than 20 parts per million.

Arsenic (as As), not more than 3 parts per million.

Lead and arsenic shall be determined in the solution obtained by boiling 10 grams of the pyrophyllite for 15 minutes in 50 milliliters of 0.5N hydrochloric acid.

(c) Uses and restrictions. Pyrophyllite may be safely used in amounts consistent with good manufacturing practice to color drugs that are to be externally applied.

(d) Labeling requirements. The labeling of the color additive and any mixtures prepared therefrom intended solely or in part for coloring purposes shall conform to the requirements of § 70.25 of this chapter.

Sec. 73.1410 Logwood extract.

(a) Identity. The color additive logwood extract is a reddish brown-to-black solid material extracted from the heartwood of the leguminous tree Haematoxylon campechianum. The active colorant substance is principally hematein. The latent coloring material is the unoxidized or leuco form of hematein called hematoxylin. The leuco form is oxidized by air.

(b) Specifications. Logwood extract shall conform to the following specifications and shall be free from impurities other than those named to the extent that such imnurities may be avoided by good manufacturing practice:

Volatile matter (at 110 deg.C), not more than 15 percent.

Sulfated ash, not more than 20 percent.

Hematein, not less than 5 percent and not more than 20 percent.

Lead (as Pb), not more than 70 parts per million.

Arsenic (as As), not more than 4 parts per million.

Mercury (as Hg), not more than 3 parts per million.

(c) Use and restrictions. Logwood extract may be safely used to color nylon 66 (the copolymer of hexamethylenediamine and adipic acid), nylon 6 (the polymer of e -caprolactam), or silk non-absorable sutures for use in general and ophthalmic surgery subject to the following restrictions:

(1) The quantity of color additive does not exceed 1.0 percent by weight of the suture.

(2) When the sutures are used for the purposes specified in their labeling, there is no migration of the color additive to the surrounding tissue.

(3) If the suture is a new drug, an approved new drug application, pursuant to section 505 of the act, is in effect for it.

(d) Labeling. The label of the color additive shall conform to the requirements of § 70.25 of this chapter.

[42 FR 52393, Sept. 30, 1977; 43 FR 1490, Jan. 10, 1978]

Sec. 73.1496 Mica.

(a) Identity. (1) The color additive mica is a white powder obtained from the naturally occurring mineral, muscovite mica, consisting predominantly of a potassium aluminum silicate, K2Al4(Al2Si6O20)(OH)4 or, alternatively, H2KAl3 (SiO4)3. Mica may be identified and semiquantitatively determined by its characteristic X-ray diffraction pattern and by its optical properties.

(2) Color additive mixtures for drug use made with mica may contain only those diluents listed in this subpart as safe and suitable for use in color additive mixtures for coloring drugs.

(b) Specifications. Mica shall conform to the following specifications and shall be free from impurities other than those named to the extent that such other impurities may be avoided by good manufacturing practice:

Fineness, 100 percent shall pass through a 100-mesh sieve.

Loss on ignition at 600-650 deg.C, not more than 2 percent.

Lead (as Pb), not more than 20 parts per million.

Arsenic (as As), not more than 3 parts per million.

Mercury (as Hg), not more than 1 part per million.

(c) Uses and restrictions. Mica may be safely used in amounts consistent with good manufacturing practice to color dentifrices and externally applied drugs, including those for use in the area of the eye.

(d) Labeling requirements. The label of the color additive and of any mixture prepared therefrom intended solely or in part for coloring purposes shall conform to the requirements of § 70.25 of this chapter.

(e) Exemption from certification. Certification of this color additive is not necessary for the protection of the public health, and therefore batches therof are exempt from the certification requirements of section 721(c) of the act.

[42 FR 38561, July 29, 1977, as amended at 52 FR 29665, Aug. 11, 1987]

Sec. 73.1530 Spirulina extract.

(a) Identity. (1) The color additive spirulina extract is prepared by the filtered aqueous extraction of the dried biomass of Arthrospira platensis. The color additive contains phycocyanins as the principal coloring components.

(2) Color additive mixtures for drug use made with spirulina extract may contain only those diluents that are suitable and are listed in this subpart as safe for use in color additive mixtures for coloring ingested drugs.

(b) Specifications. Spirulina extract must conform to the following specifications and must be free from impurities, other than those named, to the extent that such other impurities may be avoided by good manufacturing practice:

(1) Lead, not more than 2 milligrams per kilogram (mg/kg) (2 parts per million (ppm));

(2) Arsenic, not more than 2 mg/kg (2 ppm);

(3) Mercury, not more than 1 mg/kg (1 ppm); and

(4) Negative for microcystin toxin.

(c) Uses and restrictions. Spirulina extract may be safely used for coloring coating formulations applied to drug tablets and capsules, at levels consistent with good manufacturing practice.

(d) Labeling requirements. The label of the color additive and any mixture prepared therefrom intended solely or in part for coloring purposes shall conform to the requirements of § 70.25 of this chapter.

[80 FR 50765, Aug. 21, 2015]

Sec. 73.1550 Talc.

(a) Identity. (1) The color additive talc is a finely powdered, native, hydrous magnesium silicate sometimes containing a small proportion of aluminum silicate.

(2) Color additive mixtures for drug use made with talc may contain only those diluents listed in this subpart as safe and suitable for use in color additive mixtures for coloring drugs.

(b) Specifications. Talc shall meet the specifications for talc in the United States Pharmacopeia XX (1980) and the following:

Lead (as Pb), not more than 20 parts per million.

Arsenic (as As), not more than 3 parts per million.

Lead and arsenic shall be determined in the solution obtained by boiling 10 grams of the talc for 15 minutes in 50 milliliters of 0.5N hydrochloric acid.

(c) Uses and restrictions. Talc may be safely used in amounts consistent with good manufacturing practice to color drugs generally.

[42 FR 15643, Mar. 22, 1977, as amended at 49 FR 10089, Mar. 19, 1984]

Sec. 73.1575 Titanium dioxide.

(a) Identity and specifications. (1) The color additive titanium dioxide shall conform in identity and specifications to the requirements of § 73.575(a)(1) and (b).

(2) Color additive mixtures for drug use made with titanium dioxide may contain only those diluents that are suitable and that are listed in this subpart as safe in color additive mixtures for coloring drugs, and the following: Silicon dioxide, SiO2, and/or aluminum oxide, Al2O3, as dispersing aids - not more than 2 percent total.

(b) Uses and restrictions. The color additive titanium dioxide may be used for coloring ingested and externally applied drugs generally, in amounts consistent with good manufacturing practice. External application includes use in the area of the eye.

(c) Labeling. The label of the color additive and any mixtures prepared therefrom and intended solely or in part for coloring purposes shall conform to the requirements of § 70.25 of the chapter.

(d) Exemption from certification. Certification of this color additive is not necessary for the protection of the public health and therefore batches thereof are exempt from the certification requirements of section 721(c) of the act.

Sec. 73.1645 Aluminum powder.

(a) Identity. (1) The color additive aluminum powder shall be composed of finely divided particles of aluminum prepared from virgin aluminum. It is free from admixture with other substances.

(2) Color additive mixtures for external drug use made with aluminum powder may contain only those diluents listed in this subpart as safe and suitable in color additive mixtures for coloring externally applied drugs.

(b) Specifications. Aluminum powder shall conform to the following specifications and shall be free from impurities other than those named to the extent that such impurities may be avoided by good manufacturing practice:

Fineness, 100 percent shall pass through a 200-mesh screen and 95 percent shall pass through a 325-mesh screen.

Mercury, not more than 1 part per million.

Arsenic, not more than 3 parts per million.

Lead, not more than 20 parts per million.

Aluminum, not less than 99 percent.

(c) Uses and restrictions. Aluminum powder is safe for use in externally applied drugs, including those intended for use in the area of the eye, in amounts consistent with good manufacturing practice.

[42 FR 38563, July 29, 1977]

Sec. 73.1646 Bronze powder.

(a) Identity. (1) The color additive bronze powder is a very fine metallic powder prepared from alloys consisting principally of virgin electrolytic copper and zinc with small amounts of the virgin metals aluminum and tin. It contains small amounts of stearic or oleic acid as lubricants.

(2) Color additive mixtures for drug use made with bronze powder may contain only those diluents listed in this subpart as safe and suitable for use in color additive mixtures for coloring externally applied drugs.

(b) Specifications. Bronze powder shall conform to the following specifications and shall be free from impurities other than those named to the extent that such impurities may be avoided by good manufacturing practice:

Stearic or oleic acid, not more than 5 percent.

Cadmium (as Cd), not more than 15 parts per million.

Lead (as Pb), not more than 20 parts per million.

Arsenic (as As), not more than 3 parts per million.

Mercury (as Hg), not more than 1 part per million

Aluminum (as Al), not more than 0.5 percent.

Tin (as Sn), not more than 0.5 percent.

Copper (as Cu), not more than 95 percent and not less than 70 percent.

Zinc (as Zn), not more than 30 percent.

Maximum particle size 45[micro] (95 percent minimum).

Aluminum, zinc, tin, and copper content shall be based on the weight of the dried powder after being thoroughly washed with ether.

(c) Uses and restrictions. Bronze powder may be safely used in color externally applied drugs, including those intended for use in the area of the eye, in amounts consistent with good manufacturing practice.

(d) Labeling. The color additive and any mixture prepared therefrom intended solely or in part for coloring purposes shall conform to the requirements of § 70.25 of this chapter.

(e) Exemption from certification. Certification of the color additive is not necessary for the protection of the public health, and therefore batches thereof are exempt from the certification requirements of section 721(c) of the act.

[42 FR 33723, July 1, 1977]

Sec. 73.1647 Copper powder.

(a) Identity. (1) The color additive copper powder is a very fine free-flowing metallic powder prepared from virgin electrolytic copper. It contains small amounts of stearic or oleic acid as lubricants.

(2) Color additive mixtures for drug use made with copper powder may contain only those diluents listed in this subpart as safe and suitable for use in color additive mixtures for coloring externally applied drugs.

(b) Specifications. Copper powder shall conform to the following specifications and shall be free from impurities other than those named to the extent that such impurities may be avoided by good manufacturing practice:

Stearic or oleic acid, not more than 5 percent.

Cadmium (as Cd), not more than 15 parts per million.

Lead (as Pb), not more than 20 parts per million.

Arsenic (as As), not more than 3 parts per million.

Mercury (as Hg), not more than 1 part per million.

Copper (as Cu), not less than 95 percent.

Maximum particle size 45[micro] (95 percent minimum).

(c) Uses and restrictions. Copper powder may be safely used in coloring externally applied drugs, including those intended for use in the area of the eye, in amounts consistent with good manufacturing practice.

(d) Labeling. The color additive and any mixture prepared therefrom intended solely or in part for coloring purposes shall conform to the requirements of § 70.25 of this chapter.

[42 FR 33723, July 1, 1977]

Sec. 73.1991 Zinc oxide.

(a) Identity. (1) The color additive zinc oxide is a white or yellow-white amorphous powder manufactured by the French process (described as the indirect process whereby zinc metal isolated from the zinc-containing ore is vaporized and then oxidized). It is principally composed of Zn.

(2) Color additive mixtures for drug use made with zinc oxide may contain only those diluents listed in this subpart as safe and suitable in color additive mixtures for coloring externally applied drugs.

(b) Specifications. Zinc oxide shall conform to the following specifications and shall be free from impurities other than those named to the extent that such impurities may be avoided by good manufacturing practice:

Zinc oxide (as ZnO), not less than 99 percent.

Loss on ignition at 800 deg.C, not more than 1 percent.

Cadmium (as Cd), not more than 15 parts per million.

Mercury (as Hg), not more than 1 part per million.

Arsenic (as As), not more than 3 parts per million.

Lead (as Pb), not more than 20 parts per million.

(c) Uses and restrictions. The color additive zinc oxide may be safely used for coloring externally applied drugs, including those used in the area of the eye, in amounts consistent with good manufacturing practice.

(d) Labeling. The color additive and any mixtues prepared therefrom intended solely or in part for coloring purposes shall bear, in addition to any information required by law, labeling in accordance with the provisions of § 70.25 of this chapter.

(e) Exemption from certification. Certification of this color additive is not necessary for the protection of the public health, and therefore batches therof are exempt from the certifiation pursuant to section 721(c) of the act.

[42 FR 37537, July 22, 1977]

Authority: 21 U.S.C. 321, 341, 342, 343, 348, 351, 352, 355, 361, 362, 371, 379e.
Source: 42 FR 15643, Mar. 22, 1977, unless otherwise noted.

CFR - Code of Federal Regulations Title 21

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