PECVD-Coated Primary Drug Containers for Protein Stability
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Solution Overview
Problem
Biologic drugs stored in traditional primary containers made of Type 1 borosilicate glass are prone to protein denaturation and aggregation due to air/liquid interfaces, container walls, and silicone oil lubricants, leading to particle contamination and potential adverse immune responses in patients.
Innovation Solution
A primary drug container with an injection-molded thermoplastic wall and a PECVD drug-contact coating composed of SiOxCyHz, which reduces particle formation and immune response by minimizing protein denaturation and aggregation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional Type 1 borosilicate glass primary containers are used, then chemical inertness and heat resistance are improved, but protein stability deteriorates due to denaturation at air/liquid interface and container walls
Solution Approach 1:
A coating layer comprising a first layer of amorphous silica and a second layer of fluorinated alkyl silane is applied to the inner surface of the glass container. This coating acts as an intermediary between the glass wall and the protein drug, preventing direct contact and denaturation while maintaining the chemical inertness of the glass container.
Solution Approach 2:
The invention changes the surface properties of the glass container by applying a coating with different chemical composition and surface energy characteristics. The fluorinated alkyl silane layer specifically modifies the surface parameters to reduce protein adsorption and denaturation, while the amorphous silica layer provides a stable base coat.
2Ease of operation
If silicone oil lubricant is used in pre-filled syringes, then ease of operation is improved, but protein stability deteriorates due to unfolding and aggregation caused by silicone oil droplets
Solution Approach 1:
The fluorinated alkyl silane coating layer serves as an intermediary barrier between the silicone oil lubricant and the protein drug. This coating prevents silicone oil droplets from detaching and interacting with the protein, thereby maintaining protein stability while allowing the silicone oil to remain in place for lubrication during injection.
Solution Approach 2:
The coating provides localized protection at the critical interface where silicone oil contacts the drug solution. The fluorinated alkyl silane layer specifically addresses the protein-silicone oil interaction zone, creating a protective boundary that maintains different properties in different regions of the container.
3Ease of operation
If large air headspace is provided in vials, then ease of operation is improved, but protein stability deteriorates due to aggregation at air/liquid interface
Solution Approach 1:
The amorphous silica and fluorinated alkyl silane coating layers act as an intermediary barrier at the air/liquid interface. This coating reduces protein aggregation at the interface while allowing the vial to maintain its headspace volume for ease of operation and dispensing.
4Reliability
If glass container walls are used, then chemical resistance is improved, but particle contamination increases due to glass breakdown producing small particles
Solution Approach 1:
The coating layers serve as a protective intermediary between the glass wall and the drug solution. This coating prevents direct interaction that could lead to glass breakdown and particle generation, while the glass wall maintains its chemical resistance properties.
Solution Approach 2:
The harmful surface properties of the glass wall that lead to particle generation are effectively removed by applying the coating. The coating extracts or eliminates the problematic interaction between glass and protein, separating the beneficial chemical resistance of glass from its harmful particle-generating surface properties.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The solution significantly decreases particle contamination and immune response risks, maintaining drug efficacy and safety by stabilizing proteins during storage.
Implementation Method 1
a PECVD (plasma-enhanced chemical vapor deposition) drug-contact coating... The PECVD coating is supported on or adjacent to the internal surface
Data Source
AI summary
A primary drug container is described having an injection-molded thermoplastic wall having an internal surface defining a lumen, a PECVD (plasma-enhanced chemical vapor deposition) drug-contact coating, and a polypeptide composition contained in the lumen. The drug-contact coating is on or adjacent to the internal surface, positioned to contact a fluid in the lumen, and consists essentially of SiOxCyHz. The primary drug container contains between a lower limit of 1,000 and an upper limit of 100,000 particles having effective spherical diameters greater than 2 and no more than 10 micrometers (μm) per mL of solution.