Ask The Expert - Considerations in evaluating new plastic film for single-use technologies and film development

Published: February 8, 2016
Sponsored By: GE Healthcare Life Sciences
Session Closed
Session Expert: Susan Burke , GE Healthcare

The increase in adoption of single-use bioprocess technology for manufacturing biopharmaceuticals has been driven by the many advantages it offers, such as increased flexibility. However, the materials of construction can be more complex than conventional stainless steel vessels. Single-use containers are constructed from plastic films, which are often composed of several layers of polymers with additives for processing and performance.

The diversity of applications for single-use containers requires film that can achieve a wide variety of performance attributes such as mechanical strength, flexibility, biocompatibility, and suitable gas barrier properties to name but a few. The right balance of chemical composition and film architecture is critical for achieving desired performance across many applications. Also, in light of industry reports of a leachate, originating from bioprocess containers, that can negatively impact cell culture growth with certain sensitive cell lines, it has become imperative to understand the profile of extractable compounds resulting from the film chemistry. Over the past several years, GE Healthcare has worked closely with biopharmaceutical manufacturers to understand their applications and resulting requirements for bioprocess film performance. This investment in learning has led to the establishment of a scientifically driven film development process focused on the innovation of bioprocess films that are fit for purpose. The process is built on a strong foundation of knowledge in science, engineering, and bioprocess applications and incorporates key learnings about extractables and  leachables, as well as considerations for security of supply via supply chain management.

Questions and Answers

How has GE developed the capabilities to work with customers?

As the implementation of single-use technology continues to grow and expand into new applications, the industry will be presented with new challenges and requirements. In recent years, GE Healthcare has… Read More

We are a lab scaling up from benchtop glass bioreactors to disposable bags, but are still working at fairly small scale. What kind of film questions should we be asking as we make the transition?

Selecting a single-use assembly for an intended application requires consideration of a number of factors. For example, operating parameters such as temperature, humidity, working volume, and run time are key… Read More

We are a company just starting to work on risk assessment for extractables and leachables after moving from stainless steel, what do you see are the biggest challenges? Any advice on avoiding potential pitfalls?

Supplier may serve as a good source of information and to orient you to how other drug manufacturers manage the topic. A web or literature search will lead to articles… Read More

What film selection advice do you have for vaccine manufacturing and specifically virus production?

Standard principles related to understanding, managing, and mitigating risk apply to vaccine manufacturing. One might for example contend that virus adsorption to a plastic surface present a risk to be… Read More

How does your film interact with lipids, is there a film recommendation related to lipids?

The interactions between lipids and plastic film depend on the chemical structure of the lipids as well as the materials of construction of the film. If the polymers that make… Read More

Why doesn’t the industry move to standardized testing for single-use films and bags?

Although single-use technology is broadly accepted in pharmaceutical manufacturing, the industry continues to evolve with respect to the qualification requirements for these systems. Industry-wide discussions aimed at aligning on standardized… Read More

In your opinion do you think that there is another bDtBPP type compound that we haven’t identified yet or do you think the key leachables have been identified and are being addressed.

IIt is difficult to make predictions because there are many variable factors to consider, such as differences in the level of sensitivity of cell lines. In addition, the types of… Read More

Do you have recommendations for deciding how detailed the evaluation of extractables and leachables need to be? I know it is up to the company to decide but are there some guiding principals? Also, how is the work split between company and supplier when doing these evaluations. Is there some documentation that you will provide as part of the process?

A drug safety profile should be clinical-phase appropriate and based on patient risk. Considerations regarding extractables / leachables are an important part of the risk assessment. A number of factors… Read More

How do you match up the model solvents you use for testing with drug products?

The extraction studies conducted on single-use systems must try to account for as many extractable compounds as possible since the extraction efficiency of the fluids they are intended to contain… Read More

In your opinion when is the best time to evaluate extractables and leachables in your manufacturing process?

There is no one size fits all approach for determining the best time to evaluate extractables and leachables. A drug safety profile should be clinical-phase appropriate and based on patient… Read More

How concerned are you about leachables/extractables in single use connectors and tubing? Do you have plans in these areas?

One should be concerned about extractables and leachables coming from all components of a single-use assembly. As such, we have extractables data on connectors, tubing and all other components. This… Read More

Are bag decisions somewhat custom, I mean depending on the sensitivity of the cell line, drug product, etc. do you have recommendations about the make up of the bags that should be used?

GE Healthcare offers a variety of standard single-use assemblies; in addition, users can request custom solutions (film, ports, tubing configurations) designed to meet the needs of their specific process. Each… Read More

What about leak resistance? As you have made changes to reduce leachables how has this impacted the strength of the bags?

In order to ensure a film will have optimal strength for bioprocess applications, the polymer resins and additives must be carefully selected and optimized. A combination of chemistry, biology, and… Read More

How has GE applied its expertise in film development?

A good example of this is GE’s most recent film innovation, Bioclear 11. It is a low-antioxidant film developed as a response to the need in the industry for improved… Read More

Does the lower antioxidant level affect the shelf-life of Bioclear 11?

A shelf-life study was conducted with Bioclear 11 Cellbag bioreactors. They were found to have the same 2-year shelf-life as Bioclear 10 Cellbag bioreactors. Read More

What cell-line was used to evaluate cell culture performance with Bioclear™ 11 and how sensitive is it to the degradation product of TBPP?

The improved cell growth performance for Bioclear 11 Cellbag bioreactors was verified by using a CHO DG44 cell line. It showed sensitivity to the bDtBPP degradation product of TBPP at… Read More

What are the important factors to consider when evaluating film for single-use applications?

Defining the critical to quality attributes needed in single-use applications is the first important consideration. Once those are established, an in depth understanding of the materials of construction is needed… Read More