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Updated June 07, 2021

Bulk Substances Nominated for Use in Under Section 503B of the Federal , Drug, and Cosmetic Act

Three categories of bulk drug substances:

• Category 1: Bulk Drug Substances Under Evaluation • Category 2: Bulk Drug Substances that Raise Significant Safety Risks • Category 3: Bulk Drug Substances Nominated Without Adequate Support

Updates to Categories of Substances Nominated for the 503B Bulk Drug Substances List1

• Add the following entry to category 2 due to serious safety concerns of mutagenicity, cytotoxicity, and possible carcinogenicity when quinacrine hydrochloride is used for intrauterine administration for non- surgical female sterilization: 2,3 o Quinacrine Hydrochloride for intrauterine administration

• Revision to category 1 for clarity: o Modify the entry for “Quinacrine Hydrochloride” to “Quinacrine Hydrochloride (except for intrauterine administration).”

• Revision to category 1 to correct a substance name error: o Correct the error in the substance name “DHEA (dehydroepiandosterone)” to “DHEA ().”

1 For the purposes of the substance names in the categories, hydrated forms of the substance are included in the scope of the substance name. 2 Quinacrine HCl was previously reviewed in 2016 as part of FDA’s consideration of this bulk drug substance for inclusion on the 503A Bulks List. As part of this review, the Division of , Reproductive and Urologic Products (DBRUP), now the Division of Urology, Obstetrics and Gynecology (DUOG), evaluated the nomination of quinacrine for intrauterine administration for non-surgical female sterilization and recommended that quinacrine should not be included on the 503A Bulks List for this use. This recommendation was based on the lack of information on efficacy comparable to other available methods of female sterilization and serious safety concerns of mutagenicity, cytotoxicity and possible carcinogenicity in use of quinacrine for this indication and . See “FDA Briefing Document: Compounding Advisory Committee (PCAC) Meeting (March 8 and 9, 2016),” available at https://www.regulations.gov/document/FDA-2018-N-3240-0285. 3 See https://www.fda.gov/drugs/human-drug-compounding/safety-risks-associated-certain-bulk-drug-substances- nominated-use-compounding. 1

Updated June 07, 2021

503B Category 1: Bulk Drug Substances Under Evaluati on

** Designates bulk drug substances that are components of FDA approved drugs4

• 5-Methyltetrahydrofolate maleate, USP** • 17--Hydroxyprogesterone • ** • ** • ** • Acyclovir** • Hydrochloride** • ** • ** • ** • Calcipotriene** • ** • Alpha Lipoic ** • Alprostadil** • Cantharidin • Aluminum Chloride Hexahydrate • ** • Aluminum • Chlorpheniramine Maleate** • Hydrochloride** • Chloride • Hydrochloride** • Chromic Chloride** • ** • Chloride** • Anastrazole** • Olamine** • Hydrochloride/L-arginine • ** Hydrochloride** • Hydrochloride** • Ascorbic acid** • Anhydrous** • Ascorbyl Palmitate • /L-Citrulline • Phosphate** • ** • ** • sulfate** • Propionate** • ** • Hydrochloride** • ** • Hydrochloride** • Tar Hydrochloride • Hydrochloride** • ** • Gluconate • Betamethasone Dipropionate** • Cupric Sulfate** • Betamethasone Phosphate** • ** • ** • Hydrochloride** • Bismuth • Cyclosporine/Cyclosporine A** • Brilliant Blue • Hydrochloride** • ** • ** • sodium (for ophthalmic • ** only) ** • Acetate

4 A condition of section 503B of the FD&C Act is that the compounded drug product is not essentially a copy of one or more approved drug products. For more information about the “essentially a copy” provision in section 503B, see FDA’s guidance for industry “Compounded Drug Products That Are Essentially Copies of Approved Drug Products Under Section 503B of the Federal Food, Drug, and Cosmetic Act.” In addition, FDA does not intend to take action against an facility for failing to compound in accordance with section 503B(a)(5) if it fills orders for a compounded drug that is essentially a copy of an approved drug that has been discontinued and is no longer marketed. Bulk drug substances in Category 1 that are components of FDA-approved are designated with two asterisks (**) below. 2

Updated June 07, 2021

• Dexamethasone Sodium Phosphate** • ** • Dexpanthenol** • • DHEA (dehydroepiandrosterone) ** • Glycerin** • D-** • ** • Glycopyrrolate/ Glycopyrrolate • Dibucaine Hydrochloride** ** • Sodium** • ** • Diiodohyroxyquinolone • sodium** • Hydrochloride** • sodium • Dimercapto-1-propanesulfonic acid • Hydralazine Hydrochloride** (DMPS)** • Hydrochloride** • ** • Diphenylcyclopropenone • Hydrochloride** • ** • ** • ** • Hydrochloride • Hydrochloride** • Sulfate** • Hydrochloride** • Hydrochloride** • ** ** • Hydrochloride** • Mesylate • Nitrate** • Hydrochloride** • Edetate Calcium Disodium** • ** • Edetate Disodium • Hydrochloride • • Ephedrine sulfate, USP** • ** • Epinephrine** • ** • Epinephrine ** • Hydrochloride** • Cypionate** • ** • Estradiol** • ** • Tromethamine** • ** • Hydrochloride** • ** • Lactic Acid** • Ethyl Aminobenzoate • ** • ** • Dihydrochloride** • ** • Hydrochloride** • Citrate** • Lincomycin Hydrochloride** • ** • L-** • L-lysine Hydrochloride/Lysine • Acetonide** Hydrochloride • ** • ** • ** • L- Propionate** • Chloride ** • Folic Acid** • ** • • Malic Acid • ** • Chloride** • ** • Manganese Sulfate ** • Sulfate** • ** • Sulfate Acetate** • Glucosamine Sulfate • Meperidine Hydrochloride (a.k.a. • ** Hydrochloride)**

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Updated June 07, 2021

Chloride** • Precipitated / Methionine (L) • ** • /Methyl B12 • ** • Acetate** • ** • (MSM) • Hydrochloride** • Hydrochloride ** • Hydrochloride** • ** • ** • Hydrochloride** • Hydrochloride** • Oil** • Proparacaine Hydrochloride** • ** • hydrochloride** • Mitomycin** • E1** • Furoate** • Pyridoxal 5-Phosphate Monohydrate • Hydrochloride** • Sulfate ** • Quinacrine Hydrochloride (except for • hydrochloride** intrauterine administration) • ** • Hydrochloride** • Hydrochloride** • Sodium Phosphate ** • Hydrochloride Dihydrate** • ** • Decanoate** • Hydrochloride** • sulfate** • Methylsulfate** • hydrobromide • ** • Acetate** • ** • ** • Niacinamide** • Anhydrous** • ** • Sodium Ascorbate** • Bitartrate** • ** • Hydrochloride** • ** • Hydrochloride • Sodium Chloride** • Hydrochloride** • Sodium Citrate** • ** • Sodium L-Aspartate Monohydrate • Hydrochloride • Sodium ** • ** • • Sodium phosphate/ Sodium Phosphate • Hydrochloride** Monobasic** • Mesylate** • Hydrochloride** • Sodium Tetradecyl Sulfate** • • Sodium ** • Phytonadione** • ** • Pitcher • Squaric acid dibutyl • Podophyllum/Podophyllum • Succinylcholine Chloride** • ** • Citrate** • B Sulfate** • Sodium Monohydrate** • ** • Sulfan Blue • Potassium chloride** • ** • Potassium Phosphate Monobasic • [KH2PO4]** • ** • Potassium Phosphate Dibasic [K2HPO4]/ • Hydrochloride** Potassium Phosphate Dibasic • ** Anhydrous** • **

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Updated June 07, 2021

** • ** • Hydrochloride** • Ubidecarenone () • Hydrochloride** • ** • ** • Hydrochloride** • Hydrochloride ( B1) ** • Hydrochloride** • ** • ** • acetate • Hydrochloride** • Vitamin D3** • ** • ** • Acetonide** • Oxide** • ** • ** • Trichloroacetic Acid • Tromethamine** • **

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Updated June 07, 2021

503B Category 2: Bulk Drug Substances that Raise Significant Safety Risks

• Germanium Sesquioxide • Quinacrine Hydrochloride for intrauterine administration

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Updated June 07, 2021

503B Category 3: Bulk Drug Substances Nominated Without Adequate Support

• 4-Aminopyridine • Attapulgite • 7-Keto Dehydroepiandrosterone, Micronized • Barosma • Acacia Gum, Spray-Dried • Basic Fuchsin • Acacia • Beachwood • Betamechlomathasone • • Beta- Dinucleotide • Acetone • Acetyl Hexapeptide-3 • Bichloroacetic Acid • Acidophilus • Bipeptide Biocosmetic • Adenosine-5-triphosphate disodium salt • Bronopol • Agar • Buffer Solution, pH Buffer Acid • Alcloxa • • Aldioxa • Butylene Glycol • • Calcium Alginate • • Calcium Folinate • Alfalfa leaves • Calcium glycinate • • Capsules, Empty • Aliphatic Polyesters • Carbamide • Almadrate sulfate • Carbazochrome • Aloin • • Alpha Ketoglutaric acid • Carbolic Acid • Alumina Powder, hydrated • Carbomer 940 • Aluminum acetate • Caustic Potash • Aluminum chloride • Caustic Soda () • Aluminum phosphate • Cedarwood Essential Oil • Aluminum sulfate • Ceratonia • Aminacrine Hydrochloride • Ceresin • Aminoacetic acid • solution, strong • Diacetate Hydrate • Alginate • Choline Bitartrate • • Choline magnesium trisalicylate • • Ammonium hydroxide • Chromium glycinate • oil • Cidofovir • Anise • Argentyn • Oil Edible • Arginine • Coenzyme Q50 • Aromatic powder • • Asafetida • Colophony • Ascelepias tuberosa • Copper • Asefetida Tincture • Copper Bisglycinate • • Copper Hydrosol • • Corn Oil • Aspergillus oryza • Corn Starch 7

Updated June 07, 2021

• Corn Starch and Pregelatinized Starch • Gloconic acid calcium salt • Cottonseed Oil • solution • , Monohydrate • Formal • Cucumber Melon Fragrance • Glyceryl Monostearate • • Glyceryl Palmitostearate • Decyl Oleate • Glycofurol • Decylmethylsulfoxide • Glydiazinamide • Deoxy-DGlucose • Grape seed oil • • Diaminopyridine (3,4-) • Hectorite • Dichloroacetic Acid • Heptafluoropropane • Difluoroethane • • Diindolymethane • Hyaluronidase, salt free • sulfate • Dimethyl (aka Methoxymethane) • Hydroxyethylpiperazine Sulfonic Acid • Dimethyl • Hydroxymethylmethyl • Dimethyl • Ichthammol • Dimethylacetamide • ICU Bottom Paste (Maalox) • Dimethylaminoethanol Bitartrate • • Dimethylaminoethanol Complex • -3-carbinol • Hydrochloride • Inositol Hexanicotinate • Dinitrochlorobenzene • Iodochlorhydroxyquin • Diphenhydramine • Iopanoic Acid • Dipropylene Glycol • Glycinate Chelate • Disodium Phosphate • Isopropyl Isostearate • • Kaolin, Colloidal Powder • Disodium Salt Trihydrate • Karaya Gum • DL- • Ketoifen Fumarate • Docosanol • • Dodecyl Gallate • Monohydrate • • Lactose, Monohydrate and Corn Starch • Edetate tetrasodium tetrahydrate • Lactose, Monohydrate and Microcrystalline • Mesylates Cellulose • Tartrate • Lactose, Monohydrate and Powdered Cellulose • Lactose, Spray-Dried • Ethyl Lactate • Lanolin, Hydrous • Vinyl Acetate • L-Aspartic Acid Sodium Salt • Ferric subsulfate • Lavender Oil • Ferric sulfate solution • L- calcium salt • L- Fumarate Dihydrate • L- and Pregelatinized Starch • Soya Granular • Gamma Aminobutyric Acid • Lecithin Organogel • GHRP-2 • Levomenthol • GHRP-6 • Levulose • powder • L- Monohydrochloride, Monohydrate • Ginko Biloba Standardized Extract • Lidocaine, Epinephrine, and Tetracaine

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Updated June 07, 2021

• Methoxypolyoxyethyleneglycol • L-Ornithin Hydrochloride 350 laurate • Loxasperse • Methyl nicotinate • L- Sodium • • Lysine • Methylbenzethoniuim chloride • • Methylcellulose • Magnesium • Methylparaben • Magnesium aluminum silicate • Methypyrilene Hydrochloride • Magnesium ascorbate • nitrate • Magnesium bisglycinate • Microcrystalline Cellulose • Magnesium and • Milk of sulfur • • Milk , dried • and Lanolin • Molasses • • Glycinate e • Magnesium trisilicate • Mono- and di-glycerides • Malt • Monosodium L-Aspartate • Malt soup extract • • Maltodextrin • Mullein • Manganese Bisglycinate • oil (alltlishthiocyanate) • Manganese citrate • Mycozyme • Mannitol and • MBK • Myrrh gum tincture • m- • Myrrh tincture • Hydrochloride • N-Acetyl-D-Glucosamine • Medium Cream • Hydrochloride • Menfegol • Natural estrogenic • Neohesperidine Dihydrochalcone • Menthol/ oil • Nettle • Meradimate (menthyl anthranilate) • -pectin • Meralein sodium • Nicotinamide • • Nicotinic Acid • Mercufenol chloride • • Mercuric chloride • Non- Dry Milk • Mercuric oxide • Nonylphenoxypoly (ethyleneoxy) ethanol • Mercuric salicylate iodin • Mercuric sulfide • Nonylphenxypoly nonoxynol 9 • • Mercury oleate • Noscapine Hydrochloride • oil • Mercury, ammoniated • Nux vomica extract • Metaproterenol sulfate • • Methenamine • Obtundia • Hydrochloride • Octinoxate • Octisalate

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Updated June 07, 2021

• Octocrylene • Phenoxyacetic acid • Octoxynol 9 • • Octyl Gallate • Phenylalanine • Octyl triazone • Phenylephrine bitratrate • Oil of erigeron • Phenylmercuric powder • Phenylmercuric cetate • Opium tincture • • Organic bitartrate • Orthophosphoric acid • Phenylpropanolamine Hydrochloride • Ox bile • Phenylpropanolamine maleate • Ox bile extract • citrate • Oxitriptan • Phenyltoloxamine dihydrogen citrate • Oxybenzone • Phenyltoloxamine Hydrochloride • Oxyquinoline • Phosphate fluoride • Hydrochloride • Phosphorated • Padimate a • • Padimate o • • Pambron • Phytolacca • Pancreatin • Nitrate • • Papaverine • Pineapple enzymes • enzymes • citrate • Papaya, natural • Hydrochloride • Para-chloromercuriphenol • Piperonyl butoxide • Paraffin • Pipsissewa • • Parethoxycaine Hydrochloride • Piracetam dihydrogen citrate • • Piscidia erythrina • Passion flower extract • Plantago ovata husks • Patchouli Essential Oil • Plantago seed • Pectin • Poloxamer • Pennyroyal Oil • Poloxamer- complex • Pentylenetetrazole • Poly (DL-Lactic Acid) • Peppermint • Poly(methyl vinyl ether/maleic anhydride) • Peppermint Oil • Polycarbophil • Peppermint Spirit • Polydimethylsiloxane and poloxamer • 1450 • Peruvian Balsam • Polyethylene Glycol 300 • Petrolatum • Polyethylene Glycol 400 • Hydrochloride • Polyethylene Glycol 6000 • Tartrate • Polyols, liquid • Maleate • Polyoxeythylene laurate • • Polysorbate 20 • Phenolate sodium • Polysorbate 80 • • Polyvinyl

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Updated June 07, 2021

• Potash • Raffinose • • Red petrolatum • • Reosote (Creosote?) • • Resorcinol monoacetate • Potassium chlorate • • Retinoic Acid-All Trans • fluid extract • Potassium • Rhubarb, Chinese • • Rice polishings • • Romohydrate • Potassium nitrate • Sabadilla,

• Potassium Phosphate Tribasic [K3PO4] • • Sage Oil • Povidone • • Povidone-iodine • • Povidone-vinylacetate copolymers • • Powdered Cellulose • Sanguinaria extract • Pracasil Plus • Saponite • Pramoxine Hydrochloride • Saw palmetto • micronized • mineral • Prolase • , human 99% • • Propylene glycol • Selenium sulfide • • Senecio aureus • Propylparaben • Senna • • Senna fluid extract • hydrolysate • Senna pod concentrate • Protirelin • Senna syrup • Prune concentrate dehydrate • Sennosides a and b • Prune powder • Hydrochloride • Hydrochloride • Oil • Pseudoephedrine Sulfate • Sesame Seed • Psyllium • Shark oil • Psyllium hydrophilic mucilloid • , Organic • Psyllium seed • Short Chain • P-T-butyl-m-cresol • Bulk Drug Substance • pamoate • extract • Silver protein mild • Pyridoxine • Silver, colloidal • Pyrilamine maleate • Silver[1] (Canadian_License_Sovereign_) • Pyrithione zinc • Simethicone • Pyrrolidone • Simplgel 30 • Pyruvic 40% protectant • Quinine • Sodium • Racemethionine • Sodium 3, 4-dimethylphenyl-glyoxylate • Racephpedrine Hydrochloride • Sodium acetylsalicylate

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Updated June 07, 2021

• Sodium aluminum chlorohydroxy lactate • Sulfobutylether B-Cyclodextrin • Sodium aspartate • Sulfur • Sodium biphosphate • Sulisobenzone • • Supposibase-F • Sodium borate • T3 Sodium Dilution • • Sodium caprylate • Tannic acid • • Tannic acid glycerite • Sodium carboxymethylcellulose • Taraxacum officinale • Sodium caseinate • • Sodium diacetate • Tartrate • Oil • Sodium dihydrogen phosphate • Teaberry Oil • hydrate preparations • Sodium monofluoro phosphate • Tetrafluoroethane • • Tetrahydrochloride • Sodium octanoate • • Sodium oleate • Hydrochloride • Sodium para-amino benzoate • • Theophylline calcium salicylate • Sodium phosphate dibasic • Theophylline sodium glycinate • Sodium phosphate monobasic • Theophylline, anhydrous • Sodium • Theophyllline compound with • Sodium priopionate • Sodium salicylate • Thiamine mononitrate (vitamin B1) • • Thimerosal • Soft Paraffin • Thioctic • Sols, secondary • Thiocyanoacetate • Sorbitol • Hydrochloride • Soy meal • oil • Thylene blue • Soybean protein • Thymol • Splenda • dioxide • Squill preparations • Tolindate • Stannous fluoride • Toltrazuril • Stannous pyrophosphate • Tolu balsam • • Tommy gel • Stem • Topical starch • Powder Extract • Tranilast • • Triacetin • chloride • Tricalcium phosphate • • Tricaprylin • Sublimed sulfur • • Triethanolamine • Sulfacetamide sodium • Triglycerides • Sulferated oils of • Trillium

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Updated June 07, 2021

germ • Triolein • White ointment • Hydrochloride • White petrolatum • Triple • Witch hazel (hamamelis ) • Hydrochloride • Witch hazel skin • Triticum • Woodruff • (triethanolamine • Xanthan gum salicylate) • Hydrochloride • • Turpantine Oil • Yeast derivative • Turpantine, Venice • mercuric oxide • • Zinc • Uinolinium bromide • • Ulose • Zinc caprylate • Undecoylium chlorideiodine complex • Zinc carbonate • • Zinc chloride • Uva ursi, extract of • Zinc citrate • Valic acid • Zinc phenol sulfonate • • Zinc picolinate • Vitamin A palmitate • Zinc propionate • • Vitromersol • Zinc stearate • Water and additives • Zinc sulfide • Water, purified • Zinc undecylenate • , Anionic Emulsifying • oxide • Wax, white • Zyloxin • Wax, yellow

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