Gerresheimer has developed plastic parenteral vials with improved barrier properties and increased impact resistance. The MultiShell vials are designed for the delivery of biopharmaceutical formulations. The resolution of human DNA has facilitated drugs with a highly selective action and increased potency. Growth due to the contribution from these biopharmaceutical drugs is in the double digit region and is predicted to increase further over the next decade. The production of biopharmaceuticals however includes challenges like reproducibility, easy scale-up and process robustness.
Plastic parenteral vials designed for the delivery of biopharmaceutical formulations (photos: Gerresheimer)
Although peptide and proteins have a limited shelf-life in solution, most biopharmaceutical drugs are launched as injectables because they cannot survive the oral administration route. Parenteral packaging components for biopharmaceuticals have a significant influence on the stability of the respective drug product formulation. They require more sophisticated glass and container closure systems, as the conventional material for vials sometimes reaches the limits of its capabilities.
Polymers for injectables
Plastic polymers such as polyethylene (PE) and polypropylene (PP) also are not ideal candidates for injectables due to their lack of transparency after sterilisation and their limited gas barrier properties. There are two examples of plastic polymers in the class of polyolefin (PO) compounds, which permit the long-term storage of a liquid drug product. One is cyclic olefin copolymer (COC), a copolymer of a six-member cyclic carbon hydride with polyethylene, and the other is cyclic olefin polymer (COP), a polymer based on a five-member cyclic carbon hydride. Superior properties compared to PE or PP are high transparency, low level of organic extractables and no extractable metal ions.
One reason for a still reluctant use is the limited experience in the pharmaceutical industry and long drug development times. Another is the cost pressure, because high quality polymers like COC and COP are rather expensive compared to glass. Finally, there is a difference in the processing of plastic vials on standard glass vial filling lines. The sensitivity of biopharmaceuticals anyhow has changed the picture and makes the use of high-end plastic polymers an interesting solution for the primary packaging of injectables.
Stability and adsorption of drugs
There are various degradation mechanisms which affect the stability and availability of biopharmaceutical drugs during storage in the final container. It has been observed that adsorption is proportional to surface area and depends on the type of protein, formulation and the container contact surface. Other publications claim that absorption is a very dynamic process occurring within 24h until equilibrium is reached and can reach up to 50% of the original concentrations, especially when the concentration is low and the contact surface area is high.
This means that the correct selection of the container material influences the stability of protein solutions and the efficiency. Comparative tests show a significantly reduced adsorption level of proteins on the inner surface of the COP multilayer vial compared to the glass vial. Based on this, it seems important to include COP vials in drug container compatibility screening tests for novel protein-based biopharmaceuticals parallel to glass vials.
In this study (by Gerresheimer) one 5ml multilayer plastic vial (COP/PA/COP; left) and one 5ml glass vial (tubular glass type 1; right) are filled with 5ml of 20% BSA solution in WFI. After a storage time of 24h at ambient temperature the solution is retracted. A subsequent dye treatment (Coomassie Violet R200) shows the most intense colouring and therefore the strongest protein adhesion in the glass vial. (photos: Gerresheimer)
As shown above, it is obvious that the use of COP-based plastic vials can improve drug potency by reduced adsorption on the container surface and could save overfill of typically expensive biopharmaceuticals which should more than compensate for the higher costs for the COP plastic vial.
Impacts on surface and shelf-life
Parenteral drug solutions with a pH value above seven attack the surface of glass. In severe cases the attack on the glass surface can even cause flaking. Under such conditions, the glass releases metal ions with potential adverse effect on the stability of sensitive biopharmaceuticals. COP-based vials are inert towards different pH values and an ideal solution for this problem.
Despite the superior compatibility properties, COP vials suffer from a weak gas barrier which can impact the shelf life of oxygen-sensitive biopharmaceuticals. Very recently, multilayer plastic vials have been introduced, that solve this problem. Measurements demonstrate a barrier level which is superior to any available plastic material in use for parenteral pharmaceutical packaging.
MultiShell vial (COP= cyclic olefin polymer, PA= polyamide)
Multilayer vials combine the advantages of COP with an increased oxygen barrier and an improved resistance against external or incidental impact. The drug contact surface area remains COP with its low adsorption tendency, no metal ion release, high transparency and high drainability.
MultiShell plastic vials show five to ten times higher impact resistance compared to glass. The right vial is intentionally treated with a tool to destroy the vial. No leakage was observed.
COP – combined characteristics
The enhanced barrier properties of COP-based multilayer plastic vial offer a new alternative to glass vials for sensitive biopharmaceuticals. The increased impact resistance of the multilayer design addresses concerns such as secure sterility of the filled injection solution during transport or storage or the protection of hospital staff and patients against contamination by toxic drug solutions through accidental breakage. Additionally, a higher break-resistance gives the biopharmaceutical production the opportunity to reduce production costs generated by breakage during filling and transportation. Gerresheimer expects that combined characteristics like stability throughout shelf-life, safety during filling, transportation and handling will change the niche role of multilayer plastic vials as parenteral containers for sensitive biopharmaceuticals.
MultiShell vials are available for 2, 5, 10, 15, 50 and 100ml
www.gerresheimer.com
Based on a specialist article by Wolfgang Dirk, Product Manager Parenteral and Business Development, Gerresheimer Plastic Packaging
