On Monday, March 23, biologic products formerly evaluated for approval under section 505 of the Federal Food, Drug, and Cosmetic Act (FD&C Act) are now approvable only under section 351 of the Public Health Service Act (PHS Act). That means many categories of drugs will now be considered eligible for biosimilar competition.
The transition date was set under the Biologics Price Competition and Innovation Act. Under the European Medicines Agency (EMA), several of these drug categories, including insulin, were already subject to biosimilar approval (in fact, somatostatin was among the first biosimilars to be approved in Europe in 2006). The Table lists all agents affected by the transition. Insulins are the largest (and most significant category) affected by the transition.
According to a statement released by the FDA on March 23, “Today is a milestone for the future of insulin and other important treatments—potentially a new era of proposed biosimilar and interchangeable insulin products. We expect this regulatory transition to enable a vibrant competitive market for transitioning products, ultimately empowering patients by increasing choices and potentially lowering prices of safe, effective, high-quality medications.”
As reported previously in BR&R, the transition has been a long time in coming and had to address several hurdles. Whereas the FDA is hopeful that opening biologics like insulin to biosimilar competition will help lower prices and widen availability, few manufacturers have publicly stepped up to the plate and announced their plans to develop insulin biosimilars.
TABLE: DRUGS AFFECTED BY THE TRANSITION TO 351(K) BIOLOGIC STATUS
| Nonproprietary Name | Proprietary Name | NDA Holder | Initial Date(s) of Approval |
| aprotinin | Trasylol | Bayer HealthCare Pharmaceuticals Inc. | 12/29/1993 |
| beractant | Survanta | AbbVie Inc. | 07/01/1991 |
| calfactant | Infasurf | ONY INC | 07/01/1998 |
| choriogonadotropin alfa | (Multiple) | (Multiple) | Before 09/20/2000 |
| desirudin | Iprivask | Valeant Pharmaceuticals North America LLC | 04/04/2003 |
| fibrinolysin and desoxyribonuclease combined [bovine], with chloramphenicol | Lasechloromycetin | Pfizer, Inc. | 04/01/1964 |
| follitropin alfa | Gonal-F Gonal-F RFF Gonal-F RFF Redi-Ject | EMD Serono, Inc. | 09/29/1997, 03/25/2004, 05/25/2004 |
| follitropin beta and follicle-stimulating hormone | Follistim, Follistim AQ | Organon USA Inc, a subsidiary of Merck & Co | 09/29/1997 08/26/2005 |
| hyaluronidase | Amphadase | Amphastar Pharmaceuticals, Inc. | 10/26/2004 |
| hyaluronidase | Hydase | Akorn, Inc. | 10/25/2005 |
| hyaluronidase | Hylenex | Halozyme Therapeutics, Inc. | 12/02/2005 |
| hyaluronidase | Vitrase | Bausch & Lomb Incorporated | 05/05/2004 |
| imiglucerase | Cerezyme | Genzyme Corporation | 05/23/1994 |
| insulin aspart | Novolog, Fiasp | Novo Nordisk Inc. | 06/07/2000, 09/29/2017 |
| insulin aspart protamine and insulin aspart | Novolog Mix 50/50, Novolog Mix 70/30 | Novo Nordisk Inc. | 08/26/2008, 11/01/2001 |
| insulin degludec | Tresiba | Novo Nordisk Inc. | 09/25/2015 |
| insulin degludec and insulin aspart | Ryzodeg 70/30 | Novo Nordisk Inc. | 09/25/2015 |
| insulin degludec and liraglutide | Xultophy100/3.6 | Novo Nordisk Inc. | 11/21/2016 |
| insulin detemir | Levemir | Novo Nordisk Inc. | 06/16/2005 and 10/19/2005 |
| insulin glargine | Basaglar | Eli Lilly and Company | 12/16/2015 |
| insulin glargine | Lantus, Toujeo | Sanofi-Aventis US LLC | 04/20/2000, 02/25/2015 |
| insulin glargine and lixisenatide | Soliqua | Sanofi-Aventis US LLC | 11/21/2016 |
| insulin glulisine | Apidra | Sanofi-Aventis US LLC | 04/16/2004 |
| insulin human | Afrezza | Mannkind Corporation | 06/27/2014 |
| insulin human | Humulin R U-500 and U-100 | Eli Lilly and Company | 10/28/1982 |
| insulin human | Myxredlin | Celerity Pharmaceuticals LLC | 06/20/2019 |
| human insulin isophane | Humulin N | Eli Lilly and Company | 10/28/1982 |
| human insulin isophane and human insulin | Humulin 70/30 | Eli Lilly and Company | 04/25/1989 |
| NPH, human insulin isophane | Novolin N | Novo Nordisk Inc. | 07/01/1991 |
| NPH, human insulin isophane and regular, human insulin | Novolin 70/30 | Novo Nordisk Inc. | 06/25/1991 |
| regular, human insulin | Novolin R | Novo Nordisk Inc. | 06/25/1991 |
| insulin lispro | Humalog | Eli Lilly and Company | 06/14/1996 and 05/26/2015 |
| insulin lispro | Admelog | Sanofi-Aventis US LLC | 12/11/2017 |
| insulin lispro protamine and insulin lispro | Humalog Mix 50/50, Humalog Mix 75/25 | Eli Lilly and Company | 12/22/1999 |
| iodinated 1-125 albumin | Jeanatope, Megatope | Iso Tex Diagnostics Inc | 02/23/1976 |
| albumin chromated CR-51 serum | Chromalbin | Iso Tex Diagnostics Inc | 02/23/1976 |
| kit for the preparation of technetium tc-99m albumin aggregated | (Multiple) | (Multiple) | Before 01/1/1988 |
| radiolabeled albumin technetium tc-99m albumin colloid kit | Microlite | Pharmalucence Inc | 03/25/1983 |
| lixisenatide | Adlyxin | Sanofi-Aventis US LLC | 07/27/2016 |
| mecasermin | Increlex | Ipsen Biopharmaceuticals, Inc. | 08/30/2005 |
| mecasermin rinfabate | Iplex | Insmed Incorporated | 12/12/2005 |
| menotropins | Humegon | Organon USA Inc, a subsidiary of Merck & Co | 09/01/1994 |
| menotropins | Repronex, Menopur | Ferring Pharmaceuticals Inc, | 08/27/1999, 10/29/2004 |
| menotropins | Pergonal | EMD Serono, Inc. | 08/22/1975 |
| pancrelipase | Creon | AbbVie Inc. | 04/30/2009 |
| pancrelipase | (multiple) | (multiple) | Before 05/18/2012 |
| pegademase bovine | Adagen | Leadiant Biosciences, Inc. | 03/21/1990 |
| pegvisomant | Somavert | Pharmacia & Upjohn Company | 03/25/2003 |
| poractant alfa | Curosurf | Chiesi USA, Inc. | 11/18/1999 |
| sacrosidase | Sucraid | QOL Medical, LLC | 04/09/1998 |
| somatropin | (multiple) | (multiple) | Before 01/24/2008 |
| taliglucerase alfa | Elelyso | Pfizer Inc. | 05/01/2012 |
| tesamorelin acetate | Egrifta SV | Theratechnologies Inc. | 11/10/2010 |
| thyrotropin alfa | Thyrogen | Genzyme Corporation | 11/30/1998 |
| urofollitropin | Bravelle | Ferring Pharmaceuticals Inc. | 05/06/2012 12/19/2002 |
| urokinase | Kinlytic | Microbix Biosystems Inc. | 01/16/1978 |
| velaglucerase alfa | VPRIV | Shire Human Genetic Therapies, Inc. | 02/26/2010 |
NDA = New drug approval. Source: Food and Drug Administration.
