Glucagon (rDNA origin) for Injection - Glucagon Emergency Kit for Low Blood Sugar; Glucagon Diagnostic Kit
Status - approved; marketed
Organizations involved:
Lilly, Eli & Co. – Manuf.; R&D; Tech.; World mark.
Ben Venue Labs. – U.S. mark.
Boehringer Ingelheim GmbH – Parent
Cross ref.: See the Glucagon Products entry above, and the entry below for Glucagon from Novo Nordisk/Bedford Labs.
Description: Glucagon for Injection (rDNA origin) from Eli Lilly & Co. is a lyophilized (freeze-dried) formulation of recombinant non-glycosylated human glucagon (formulated as hydrochloride or HCl salt) expressed by Escherichia coli (E. coli). The same glucagon is used for both therapeutic and diagnostic indications:.
Glucagon from Lilly is marketed in two different packages (with different uses/indications:) – Glucagon Emergency Kit for Low Blood Sugar and the Glucagon Diagnostic Kit (available in the U.S. only). The content of both are identical – one 1 mg (1 unit) vial of glucagon HCl powder with 1 mL of diluent solution in a Hyporet (Lilly) disposable syringe. The vial solution also contains 49 mg of lactose. Hydrochloric acid may be added during manufacture to adjust the pH. Glucagon is stored at controlled room temperature (20-25°C; 68-77°F).
Glucagon Diagnostic Kit is also marketed by Bedford Labs. (a subsidiary of Ben Venue Labs., a subsidiary of Boehringer Ingelheim GmbH) as a generic equivalent of the product from Lilly.
Nomenclature: Glucagon, rDNA/Lilly [BIO]; Glucagon [CAS USAN INN BAN JAN]; Glucagon for Injection (rDNA origin) [FDA for active ingredient]; Glucagon Emergency Kit for Low Blood Sugar [FDA]; Glucagon Diagnostic Kit [FDA]; 16941-32-5[CAS RN]; 9007-92-5[CAS RN]; NDC 0002-8031-01; NDC 0002-8085-01 [NDC]
Companies.: Glucagon was developed and is manufactured and marketed by Eli Lilly & Co.
FDA class: Drug NDA 505(b)(2)
Approvals: Date = 19980911; first approval, NDA 20-928 granted under 505(b)(2)
Indications: [full text of "INDICATIONS AND USAGE” section for product insert/labeling]:
For the treatment of hypoglycemia: Glucagon is indicated as a treatment for severe hypoglycemia. Because patients with type 1 diabetes may have less of an increase in blood glucose levels compared with a stable type 2 patient, supplementary carbohydrate should be given as soon as possible, especially to a pediatric patient.
For use as a diagnostic aid: Glucagon is indicated as a diagnostic aid in the radiologic examination of the stomach, duodenum, small bowel, and colon when diminished intestinal motility would be advantageous. Glucagon is as effective for this examination as are the anticholinergic drugs. However, the addition of the anticholinergic agent may result in increased side effects.
Status: The original NDA was dated Dec. 11, 1997, filed on Dec. 12, 1997, and approved on Sept. 11, 1998 (approval time = ~.76 year). This product is presumed to be marketed in European and other countries worldwide.
Glucagon from Lilly received approval under 505(b)(2) regulations, allowing approval based on comparability with other previously-approved drug(s), and without the need for large-scale Phase III trials to prove safety and efficacy. In many respects, this might now be considered a generic biopharmaceutical (biogeneric, biosimilar, biocomparable, follow-on protein) approval.
In “The FDA’s assessment of follow-on protein products: a historical perspective,” Nature Reviews Drug Discovery (published online April 13, 2007), FDA reported on and rationalized its prior approvals of biogeneric/follow-on products. FDA noted, “The FDA has approved two recombinant follow-on versions of glucagon. The approvals were based on data that bridged the recombinant versions to the clinical data supporting the determination of safety and effectiveness for the natural-source products; they were also based on the extensive clinical experience with those natural-source products. Data included structural characterization of the recombinant product, which demonstrated an amino-acid sequence identical to human and bovine pancreatic glucagons; pharmacokinetic and pharmacodynamic data, which demonstrated similarity to the natural-source products; immunogenicity and safety data, which showed no increase in antibody titres; and a safety profile comparable with the natural-source products.”
No centralized EU approval granted.
Tech. transfer: There are no unexpired patents for this product listed in the FDA Orange Book Database.
U.S. 4,033,941, "Process for purifying glucagon, was granted to Lilly in July 5, 1977, for animal-derived glucagon.
Trials: In a study of 25 volunteers, a subcutaneous dose of 1 mg glucagon resulted in a mean peak glucose concentration of 136 mg/dL 30 minutes after injection. Similarly, following intramuscular injection, the mean peak glucose level was 138 mg/dL, which occurred at 26 minutes after injection. No difference in maximum blood glucose concentration between animal-sourced and rDNA glucagon was observed after subcutaneous and intramuscular injection.
Market: The author’s rough guess for 2005 sales (with no information to work from) is in the range $10-40 million.
The 2007 Average Wholesale Price (AWP) the Glucagon Emergency Kit is $99.17, with a Direct Price (Manufacturer’s discount price) of $82.64 (Red Book, 2007). The AWP was $83.28 in 2005.
Companies involvement:
Full monograph
165 Glucagon, rDNA/Lilly
Nomenclature:
Glucagon for Injection (rDNA origin) [FDA for active ingredient]
Glucagon Diagnostic Kit [FDA]
Glucagon Emergency Kit for Low Blood Sugar [FDA]
Glucagon [CAS USAN INN BAN JAN]
16941-32-5 [CAS RN]
9007-92-5 [CAS RN]
N-methionyl glucagon, recombinant [SY]
NDC 0002-8031-01; NDC 0002-8085-01 [NDC]
molecular weight (kDa) = 3.5 [29 a.a. pollypeptide]
FDA Class: Drug NDA biogeneric follow-on protein 505(b)(2)
Year of approval (FDA) = 1998
Date of 1st FDA approval = 19980911
(in format YYYYMMDD)
Biosimilars/biobetters-related U.S. Patents: | no entries in Orange Book; approved through 505(b)(2) as a generic drug, so biomilars are not possible; 2010 is arbitraily used as the expiration date |
U.S. Patent Expiration Year: | 2011 |
U.S. Biosimilars Data Exclusivity Expiration: | |
U.S. Biosimilars Orphan Exclusivity Expiration: | |
U.S. Biosimilars Launchability Year: | |
U.S. Biobetters Launchability Year: | 2010 |
Biosimilars/biobetters-related EU Patents: | apparently long expired; 2010 is arbitraily used as the expiration date; no centralized EU approval, no biosimilars possible |
EU Patent Expiration Year: | 2011 |
EU Biosimilars Data Exclusivity Expiration: | |
EU Biosimilars Orphan Exclusivity Expiration: | |
EU Biosimilars Launchability Year: | 2011 |
EU Biobetters Launchability Year: | 2011 |
Index Terms:
biopharmaceutical products
Biorex-70 resin
exempt from CBER lot release requirements
hormones
recombinant DNA
bacterial culture <!-- bacterialculture -->
Escherichia coli (E. coli)
hydrochloric acid (HCl)
lactose
lyophilized (freeze-dried)
4D5 murine hybridoma cells
approval dates uncertain (FDA reports erroneous, conflicting, or simply has lost the original approval dates) (FDAapproved)
approval dates uncertain (FDA reports erroneous, conflicting, or simply has lost the original approval dates) (FDAapproved)
BHK-21 (C-13)
EU200 Currently Approved in EU
UM001 Marketed Product in US
US200 Currently Approved in US US777
EM001 Marketed Product in EU
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