Edition 1 / March 2020
At CordenPharma, we believe that our vertically-integrated supply chain model provides development and manufacturing expertise spanning the complete GMP supply chain. Our extensive infrastructure expands the supply chain with cGMP starting materials, API manufacturing, commercial-scale Drug Products (including Finished Dosage Formulation), and Pharma Packaging & Logistics. This model benefits customers in terms of reduced development and manufacturing time and cost. As a demonstration of our fully-integrated supply chain expertise, we would like to highlight a recent case study developed in our CordenPharma Caponago facility on the Injectable Drug-Device Combination Product Liraglutide.
Liraglutide, sold under the brand name Victoza® among others, is a medication used to treat diabetes mellitus type 2 and obesity. It is a fragment (see Figure 1) of the naturally occurring human glucagon-like peptide-1 sequence position 7-37, with 97% homology and a lipophilic substituent for the prolongation of half-life. It is a modified polypeptide of 31 amino acid residues with a covalent linkage at the γ-position of N-palmitoylglutamic acid to the ε-amino group of Lys.
Liraglutide reduces meal-related hyperglycemia (for 24 hours after administration) by increasing insulin secretion (only) when required by the increase of glucose levels, thus delaying gastric emptying, and suppressing prandial glucagon secretion. It is a multi-dose parenteral drug-device combination product, filled in a 3 mL glass cartridge, and assembled into an Auto-Injector.
Specifically, Liraglutide makes for an excellent example of our capabilities to provide an integrated supply solution, where the API is manufactured under our Peptides, Lipids & Carbohydrates Platform (CordenPharma Brussels & CordenPharma Colorado), while the Drug Product is ideally suited for our Injectables Platform (CordenPharma Caponago).
CordenPharma Caponago’s Injectable manufacturing capacity covers both Terminal Sterilization and Aseptic Filling Technologies for Pre-filled Syringes (PFS), vials, ampoules and lyophilized vials, with a wide range of filling volumes (Aseptic from 0.5 to 10 ml fill volume; Terminally Sterilized from 5 to 100 ml). With multiple process and filling lines, and an overall annual capacity of ~100 million units, the Injectable Platform offers the flexibility to support multiple programs and customers (> 100 markets) in parallel, at any scale and stage of drug development & commercialization.
In this case study, we will focus on the Drug Product component of the project and in particular, the CMC development of this drug.
The drug product development project started with an initial risk assessment to identify all the development-associated risk factors, along with potential mitigation strategies. In the laboratory, initial work began on the development of appropriate stability, indicating analytical methods that would enable the assessment of the formulation trials. As would be expected, these drug product methods used the API methods as a starting point, but were then further refined and developed to engineer appropriate robust drug product methods. The final stage of the development scoping activities was to obtain the Reference Listed Drug (RLD) of Victoza® and conduct a de-formulation exercise to create the target profile for the development studies.
The formulation strategy was based on the evaluation of the formulation robustness. According to the International Conference on Harmonization Q8 (R2), critical formulation attributes and process parameters are generally identified through an assessment of the extent to which their variation can impact the quality of the drug product, which can then inform the need to assess the robustness of a formulation. A multivariate formulation robustness study was performed to demonstrate acceptable quality at the target composition, as well as at the edges of the allowable composition ranges.
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