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

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Updated June 07, 2021 Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, 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 (dehydroepiandrosterone).” 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 Bone, 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 route of administration. See “FDA Briefing Document: Pharmacy 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 Calcium • Brompheniramine maleate, USP** • 17-alpha-Hydroxyprogesterone • Budesonide** • Acetylcysteine** • Bumetanide** • Acyclovir** • Bupivacaine Hydrochloride** • Adapalene** • Caffeine** • Adenosine** • Calcipotriene** • Allantoin • Calcium Chloride** • Alpha Lipoic Acid • Calcium Gluconate** • Alprostadil** • Cantharidin • Aluminum Chloride Hexahydrate • Chloroquine Phosphate** • Aluminum potassium sulfate • Chlorpheniramine Maleate** • Amantadine Hydrochloride** • Choline Chloride • Amitriptyline Hydrochloride** • Chromic Chloride** • Amphotericin B** • Chromium Chloride** • Anastrazole** • Ciclopirox Olamine** • Arginine Hydrochloride/L-arginine • Cimetidine** Hydrochloride** • Ciprofloxacin Hydrochloride** • Ascorbic acid** • Citric Acid Anhydrous** • Ascorbyl Palmitate • Citrulline/L-Citrulline • Aspartic Acid • Clindamycin Phosphate** • Atenolol** • Clioquinol** • Atropine sulfate** • Clobetasol Propionate** • Azelaic Acid** • Clomipramine Hydrochloride** • Baclofen** • Clonidine Hydrochloride** • Benzocaine • Coal Tar Solution • Betahistine Hydrochloride • Cocaine Hydrochloride** • Betamethasone Acetate** • Copper Gluconate • Betamethasone Dipropionate** • Cupric Sulfate** • Betamethasone Sodium Phosphate** • Cyanocobalamin** • Biotin** • Cyclobenzaprine Hydrochloride** • Bismuth Nitrate Oxide • Cyclosporine/Cyclosporine A** • Brilliant Blue • Dapiprazole Hydrochloride** • Brimonidine Tartrate** • Dapsone** • Bromfenac sodium (for ophthalmic • Desoximetasone** solutions only) ** • Dexamethasone 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 outsourcing 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 drugs are designated with two asterisks (**) below. 2 Updated June 07, 2021 • Dexamethasone Sodium Phosphate** • Glutamine** • Dexpanthenol** • Glutathione • DHEA (dehydroepiandrosterone) ** • Glycerin** • D-glucose** • Glycolic Acid • Diazepam** • Glycopyrrolate/ Glycopyrrolate • Dibucaine Hydrochloride** Bromide** • Diclofenac Sodium** • Haloperidol** • Diiodohyroxyquinolone • Heparin sodium** • Diltiazem Hydrochloride** • Hyaluronic acid sodium salt • Dimercapto-1-propanesulfonic acid • Hydralazine Hydrochloride** (DMPS)** • Hydrochloric Acid • Diphenhydramine Hydrochloride** • Hydrocortisone** • Diphenylcyclopropenone • Hydromorphone Hydrochloride** • Dipyridamole** • Hydroquinone** • Disulfiram** • Hydroxocobalamin Hydrochloride • Dobutamine Hydrochloride** • Hydroxychloroquine Sulfate** • Dopamine Hydrochloride** • Hydroxyzine Hydrochloride** • Droperidol** Ibuprofen** • Dyclonine Hydrochloride** • Ibutamoren Mesylate • Econazole Nitrate** • Imipramine Hydrochloride** • Edetate Calcium Disodium** • Imiquimod** • Edetate Disodium • Inositol • Ephedrine Hydrochloride • Iodoform • Ephedrine sulfate, USP** • Itraconazole** • Epinephrine** • Ivermectin** • Epinephrine Bitartrate** • Ketamine Hydrochloride** • Estradiol Cypionate** • Ketoconazole** • Estradiol** • Ketoprofen** • Estriol • Ketorolac Tromethamine** • Estrone** • Labetalol Hydrochloride** • Ethanol** • Lactic Acid** • Ethyl Aminobenzoate • Lansoprazole** • Etomidate** • Levocetirizine Dihydrochloride** • Famotidine** • Lidocaine Hydrochloride** • Fentanyl Citrate** • Lincomycin Hydrochloride** • Finasteride** • L-Lysine • Fluconazole** • L-lysine Hydrochloride/Lysine • Fluocinolone Acetonide** Hydrochloride • Fluocinonide** • Lorazepam** • Flurbiprofen** • L-Proline • Fluticasone Propionate** • Magnesium Chloride ** • Folic Acid** • Magnesium Sulfate ** • Formaldehyde • Malic Acid • Furosemide** • Manganese Chloride** • Gabapentin** • Manganese Sulfate ** • Gentamicin Sulfate** • Mannitol** • Glucosamine Sulfate Potassium Chloride • Medroxyprogesterone Acetate** • Glucosamine Sulfate Sodium Chloride • Meperidine Hydrochloride (a.k.a. • Glutamic acid** Pethidine Hydrochloride)** 3 Updated June 07, 2021 • Methacholine Chloride** • Precipitated Sulfur • Methionine/ Methionine (L) • Prednisolone** • Methylcobalamin/Methyl B12 • Prednisolone Acetate** • Methylprednisolone Acetate** • Prilocaine** • Methylsulfonylmethane (MSM) • Procainamide Hydrochloride** • Metoclopramide Hydrochloride ** • Procaine Hydrochloride** • Metronidazole** • Progesterone** • Midazolam Hydrochloride** • Promethazine Hydrochloride** • Mineral Oil** • Proparacaine Hydrochloride** • Minoxidil** • Propranolol hydrochloride** • Mitomycin** • Prostaglandin E1** • Mometasone Furoate** • Pyridoxal 5-Phosphate Monohydrate • Monosodium Glutamate • Pyridoxine Hydrochloride** • Morphine Sulfate ** • Quinacrine Hydrochloride (except for • Moxifloxacin hydrochloride** intrauterine administration) • Mupirocin** • Remifentanil Hydrochloride** • Nalbuphine Hydrochloride** • Riboflavin Sodium Phosphate ** • Naloxone Hydrochloride Dihydrate** • Rocuronium Bromide** • Nandrolone Decanoate** • Ropivacaine Hydrochloride** • Neomycin sulfate** • Salicylic Acid • Neostigmine Methylsulfate** • Scopolamine hydrobromide • Nepafenac** • Sermorelin Acetate** • Niacin** • Sincalide ** • Niacinamide** • Sodium Acetate Anhydrous** • Nifedipine** • Sodium Ascorbate** • Norepinephrine Bitartrate** • Sodium Benzoate** • Ondansetron Hydrochloride** • Sodium Bicarbonate** • Ornithine Hydrochloride • Sodium Chloride** • Oxymetazoline Hydrochloride** • Sodium Citrate** • Oxytocin** • Sodium L-Aspartate Monohydrate • Papaverine Hydrochloride • Sodium Molybdate • Pentoxifylline** • Sodium Nitroprusside ** • Phenol • Sodium phosphate/ Sodium Phosphate • Phenoxybenzamine Hydrochloride** Monobasic** • Phentolamine Mesylate** • Sodium Selenite • Phenylephrine Hydrochloride** • Sodium Tetradecyl Sulfate** • Phosphatidylcholine • Sodium thiosulfate** • Phytonadione** • Spironolactone** • Pitcher Plant • Squaric acid dibutyl ester • Podophyllum/Podophyllum Resin • Succinylcholine Chloride** • Polidocanol** • Sufentanil Citrate** • Polymyxin B Sulfate** • Sulfacetamide Sodium Monohydrate** • Potassium Acetate** • Sulfan Blue • Potassium chloride** • Tacrolimus** • Potassium Phosphate Monobasic • Taurine [KH2PO4]** • Tazarotene** • Potassium Phosphate Dibasic [K2HPO4]/ • Terbinafine Hydrochloride** Potassium Phosphate Dibasic • Testosterone** Anhydrous** • Testosterone Cypionate** 4 Updated June 07, 2021 • Testosterone Propionate** • Trypan Blue** • Tetracaine Hydrochloride** • Ubidecarenone (Coenzyme Q10) • Tetracycline Hydrochloride** • Urea** • Theophylline** • Vancomycin Hydrochloride** • Thiamine Hydrochloride
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    Hormonal Responses to Non-Nutritive Sweeteners in Water and Diet Soda Allison C

    Sylvetsky et al. Nutrition & Metabolism (2016) 13:71 DOI 10.1186/s12986-016-0129-3 RESEARCH Open Access Hormonal responses to non-nutritive sweeteners in water and diet soda Allison C. Sylvetsky1,2,3, Rebecca J. Brown1, Jenny E. Blau1, Mary Walter4 and Kristina I. Rother1* Abstract Background: Non-nutritive sweeteners (NNS), especially in form of diet soda, have been linked to metabolic derangements (e.g. obesity and diabetes) in epidemiologic studies. We aimed to test acute metabolic effects of NNS in isolation (water or seltzer) and in diet sodas. Methods: We conducted a four-period, cross-over study at the National Institutes of Health Clinical Center (Bethesda, Maryland). Thirty healthy adults consumed 355 mL water with 0 mg, 68 mg, 170 mg, and 250 mg sucralose, and 31 individuals consumed 355 mL caffeine-free Diet Rite Cola™, Diet Mountain Dew™ (18 mg sucralose, 18 mg acesulfame-potassium, 57 mg aspartame), and seltzer water with NNS (68 mg sucralose and 41 mg acesulfame-potassium, equivalent to Diet Rite Cola™) in randomized order, prior to oral glucose tolerance tests. Blood samples were collected serially for 130 min. Measures included GLP-1, GIP, glucose, insulin, C-peptide, glucose absorption, gastric emptying, and subjective hunger and satiety ratings. Results: Diet sodas augmented active GLP-1 (Diet Rite Cola™ vs. seltzer water, AUC, p =0.039;DietMountainDew™ vs. seltzer water, AUC, p = 0.07), but gastric emptying and satiety were unaffected. Insulin concentrations were nominally higher following all NNS conditions without altering glycemia. Sucralose alone (at any concentration) did not affect metabolic outcomes. Conclusions: Diet sodas but not NNS in water augmented GLP-1 responses to oral glucose.