Anatomy of Films Used in Bioprocessing
In the early days of disposable medical devices, the biopharmaceutical industry manufactured single-use films made with "off-the-shelf" materials borrowed from other industries, such as food. Over the years, various experiences and research into the safety of medical grade materials have taught manufacturers that using materials not specifically designed and intended for use with pharmaceuticals was not the wisest choice.
Currently, the industry is focusing on developing single-use films that are appropriate and better suited to fit the exacting needs of the biomanufacturing industry. Let's look at the anatomy of bioprocessing films, including the various layers, the manufacturing process, and the outlook for the future.
Film Structure and Construction Materials
An example of GE's 10-layer (33um) film structure is composed of the following:
- Outer layer: nylon
- Tie layers (4): modified polyethylene
- Dual EVOH gas barrier layers
- Film interior (2): polyethylene blend
- Contact layer: blend of polyethylene and cyclic olefin copolymer
The Function of Each Layer
The outer layer: nylon was selected on its excellent performance under the humid conditions the film would undergo in the bioprocess applications. It is designed to resist abrasion, puncture, and flexural fatigue.
The tie layers: modified polyethylene blend provides robustness and flexibility over a wide temperature range.
Dual EVOH gas barrier layers help achieve optimum gas barrier properties, such as biologic and product stability to support applications in both dry and wet conditions.
Film interior is composed of less flexible resin layers that provide a neutral plane where compressive and tensile stresses are minimized.
The contact layer: a blend of polyethylene and cyclic olefin copolymer creates a clean, inert surface. A significant advantage is that it does not require small molecule slip agents, which are potential leachables. Cyclic olefin copolymers are specifically used due to their potential benefit of low protein adsorption.
Challenges in Manufacturing Bioprocessing Films
In the case of GE, their researchers and testers applied rigorous criteria to develop their new Fortem film. During this process, they sought to answer questions such as:
- Will it maintain its integrity when exposed to freezing conditions?
- Can it support large volumes while also maintaining its integrity?
- Is it strong enough for bulk liquid transport?
- Will it be able to endure long-term storage and high temperatures?
- Can it resist flexural fatigue during wave rocking motion in bioreactors?
The overall goal was to design a film for bioprocessing applications that can keep pace with industry needs and ultimately be the basis and cornerstone to guide future developments.
The Coextrusion Process
Coextrusion is the solution to the scenario where a single polymer cannot meet all the demands of a given application. This process retains each separate material as distinct layers while allowing for the appropriate placement of materials with differing properties. In this way, all the most desirable qualities can be combined, such as strength, flexibility, oxygen permeability, and wear resistance.
Single-use medical devices have gained rapid acceptance in biopharmaceutical manufacturing worldwide, due in large part to being a cost-effective alternative to traditional glass or stainless steel reusable equipment.
However, one of the most commonly cited risk factors is the potential release of toxic or inhibitory substances know as leachables. The chemical compounds that originate from the plastic materials used in the manufacture of the films are generated during storage and when undergoing gamma-irradiation.
Very few polymers can be processed or used without additives. In films designed for single-use bioprocessing, the two types of additives typically used are slipping (or slip) agents and antioxidants. In the case of GE's Fortem film, one key advantage of the contact layer is that it does not require or contain slip agents, which can potentially become leachables.
In this study, Verification of a New Biocompatible Single-Use Film Formulation with Optimized Additive Content for Multiple Bioprocess Applications, researchers investigated the concern that plastic materials might release potentially toxic substances and under what circumstances.
The Future of Bioprocessing Films
The demand and range of applications for flexible containers and single-use medical devices continue to increase globally. In addition to meeting the need of the marketplace, manufacturers must also focus on safety, biocompatibility, and sustainability for long-term success.