Materials Science and Engineering Commons^™

Single-Use Bag Extractable Case Study: Lessons Learned, Jayanthi Grebin, Mike Johnson

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

A supplier's ability to furnish extractable data from single-use components and systems to end users is of extreme importance. The data allows an end user to effectively assess the risk these extractables have on process fluids and final drug products. The protocols followed to produce such data are currently a point of discussion between suppliers and end users. In this case study, single-use bags were subjected to a portion of the BioPhorum Operations Group (BPOG) extractable protocol. This poster documents the testing process and lessons learned when executing such an evaluation, along with suggestions to improve the uniformity of the …

Challenges Of Scale Down Model For Disposable Bioreactors: Case Studies On Growth & Product Quality Impacts, Jincai Li, Guangming Zhang, Huilin Zhu

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

Despite wide-spread use of disposable bioreactors, there is a lack of well-established scale-down model for larger scale SUBs. Here we report a case of NS0 cell culture process transfer from 2000L stainless steel bioreactor (SST) to 2000L disposable bioreactor (SUB). Initial attempts in trying to grow the NS0 cells in the small scale 2D bags yielded non-satisfactory results, as growth was impacted by bag material type as well as by suppliers of the same bag material type. However, 3D bags of 50L and above proved to be supportive of the NS0 cell line growth.

Even for cell lines that do …

Microbial Applications Of Single Use Bioreactor Systems, James Rutley, Gary Lye

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

This work describes the ongoing assessment of single use bioreactors (SUBs) and their suitability for culturing microbial expression systems. Microbial expression systems are responsible for significant revenues as part of the biotechnology industry, in fact, their projected value for 2016 is in excess of $250 billion [1]. This promotes further interest in the area, with novel expression systems and pathways constantly under construction for the generation of bulk and high value chemicals.

The advantages offered by single use bioreactor technology has lead to increased adoption in many areas of bioprocessing [2], and microbial fermentation is no different. Applications include simple …

What's In The Bag?, Rebecca Olsen, Diane Hahm, Jing Li

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

As the bioprocessing industry continues to shift towards single-use systems, there is an increasing need for polymers with improved functionality. This article includes a review of the chemistry and functionality of various polymeric families, and a description of various tools that can be useful. Polyethylene resins are largely used in a variety of single use applications. This paper describes polyethylene chemistry in more detail so that single use system manufacturers and biopharmaceuticals manufacturers can optimize the use of polyethylene polymers in a particular application. The process in which the families of polyethylene polymer resins are manufactured dictates the degree of …

Conversion Of Polymers – Properties And Processing, Phillip Jordan

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

The use of polymeric materials for manufacturing single-use disposable devices in biopharmaceutical processes to replace multi-use stainless steel systems is a steady trend.

A general overview on thermoplastic polymers is given: Commodity Materials, Engineering Plastics and High-Performance Plastics, with the focus on polymers frequently used in biotechnology applications.

This range of material covers rigid materials for components like connectors, filling needles, filters, etc., but also flexible materials for bags and tubing.

Thermoplastic Elastomeric materials (TPE) and Silicone are used for tubing applications. TPE materials can be seen as some kind of hybrid between thermoplastic and elastomeric polymers.

The characteristic conversion …

The Practical Application Of Bpog E&L Protocols To Viral Clearance Filters, Paul Killian, Thomas Stone, Jessica Shea

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

Regulatory guidance advocates virus control at various stages of the drug manufacturing process and directs that you test the capacity of the process to remove or inactivate virus. Patient safety concerns require you to determine what impurities may be added by the virus control steps you implement. While the application of a standardized approach to identifying and quantifying the extractables from these steps has benefits when making comparisons, choices have to be made when developing the protocol that take into account the characteristics of the clearance device and use conditions This presentation will illustrate the practical implementation of standardized extractables …

Static Vs. Dynamic Extraction – Comparing Best Practice For Single Use Technology, Paul Killian, Ven A. Raman, Jessica Shea, Mae Santos-Rosa

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

Which is the more discriminating method for single use technology– static or dynamic extraction? Discussion among industry groups and subject matter experts has been intense. However, very little data exist comparing the two techniques. This presentation will present the findings of a side-by-side study that compares the extractables generated from gamma irradiated 10” filters using each technique. The discussion will compare and contrast the profiles of the total organic carbon (TOC), volatile organic compounds (VOCs), semi-volatile organic compounds (SVOCs), pH, and metals extracted. The discussion will compare the profiles with time for each technique for each analysis, as well as …

Adopting A Fully Single-Use Process To Improve Speed To Clinic: A Leachables Case Study, Jessica Shea, Elizabeth Goodrich, Ross Acucena, Paul Killian, Janmeet Anant

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

The implementation of single-use technologies for pharmaceutical product development continues to gain momentum; this trend is due to the advantages of increased flexibility, speed of implementation and lower capital investment In particular, they are seen as a means to accelerate the production of material for clinical trials. However, a primary concern regarding the use of such technologies is the impact leachables on patient safety in the final drug substance. Typically this concern is addressed through a patient safety evaluation utilizing extractable substances data based on model solvent extractions and from individual components and devices.

However, little if any data has …

Interchangeability Of Sus - Functional Specification And Materials Of Construction, Chris Smalley

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

Functionally equivalent substitution of an alternate supplier of a Single Use Component for an existing Single Use design provides a business contingency, or a process improvement, with equivalent performance and product quality. As an end-user, we are responsible for assessing the quality requirements to assure that the specifications are being met. This presentation will discuss the need for standards for designs and points to consider when implementing a Single Use Strategy that incorporates the potential for interchangeability

Large Scale Freeze-Thaw Bag System For Protein Bulk Storage: Prototypes Development, Phillippe Lam

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

Freezing of large quantities of protein bulk has generally been handled using “freeze-thaw vessels”, which are essentially jacketed metal tanks with additional cooling surface provided by internal coil and fin assemblies. With the recent industry push towards using disposables, it is desirable to explore disposable technology alternatives to costly freeze-thaw vessels. In this presentation we discuss our approach at designing and testing of first and second generation prototypes for a large bag freezing system developed in-house. The system, which is compatible with our existing and commercially available freeze-thaw skids, can handle 300 L of bulk at a time. Our approach …

Particulates Reduction Efforts In Single Use Technologies: A Case Study, Klaus Wormuth, Royce Brockett, Mathieu Labedan

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

Single use technologies require a close collaboration between supplier and end-user with regards to cleanliness issues, primarily focused on particulate contamination. Since a large percentage of drug recalls relate to particulate contamination, and detection of a single visible particle in a dose of injectable drug is considered a critical issue and thus causes significant time and money to remedy, reduction of risk related to particulate contamination is of highest priority. Particulate detection is challenging in single use systems due to the complexity of the devices. As this presentation will show, concerted efforts to reduce particulate generation at all steps of …

Appraisal Of The Mixing Performance Of Single-Use Shaken Bioreactors, Gregorio Rodriguez, Tibor Anderlei, Andrea Ducci, Martina Micheleti

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

The pharmaceutical industry is at the forefront of the production of antibodies using mammalian cell-based cultures, with single-use technologies gaining prominence in the manufacturing process. At laboratory scale mammalian cells are usually grown in low shear devices, with disposable shaken bioreactors being largely employed in the early stages of bioprocess development. It has been a recent industry trend to use shaken bioreactors at large scale in the upstream process, performing cell culture in single-use bags which eliminate the need for cleaning in place, offer flexibility and lower production down-times. Single-use Orbitally Shaken Bioreactors (OSRs) consist of a shaker, a structural …

Integration Considerations For Replacing Stainless Steel Tanks With Single-Use Mixers, Hana Sheikh

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

There is an increased interest in single use technology in the biotechnology industry. The first integration of single use technology in traditional facilities may come with many growing pains during implementation. There are challenges in meeting the demands of end users and the changes to standard operating procedures and processes. By replacing stainless steel tanks with single use mixers, there can be a significant change to operations such as: sampling, pool hold, mixing, additions, and pool transfer. Through thoughtful design of the single-use mixers many of these changes to operations can be managed and integrated seamlessly into the processes. In …

An Approach To Evaluate New Single-Use Film Types, Katharina Blasckczok, Lidija Lisica, Regine Eibl

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

During the last decade, single-use bioreactors or storage vessels made of flexible bags have been well-established in biopharmaceutical production. However, some developers and producers of biopharmaceuticals refuse their usage because of potential interactions of the plastic material with cells and proteins. Most dreaded apart from extractables are leachables (such as bDtBPP [1]), that derive from additives and are formed during the bag manufacturing process or gamma sterilization. Leachables can migrate from the film contact layer into the process fluid under process conditions and can inhibit cell growth or impair product quality. A further reason for cell growth limitations can be …

Flexural Fatigue Behavior Of Rocking Bioreactor Films, Donald Buckley, K. Amanda Misner, Terry Saunders, Andrew Burns, Hongyi Zhou, Eugene Boden, Susan Burke, Ross Acucena, Mark Roberts

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

The fields of biopharmaceutical processing and cell therapy are adopting single-use, closed systems throughout their workflows to enhance sterility, minimize waste wash effluent and enable manufacturing flexibility compared to traditional stainless steel bioreactors. One of the key single-use technologies in use is the rocking bioreactor, comprising a polymer film bag (outfitted with ports and sensors) mounted to a tray capable of mixing the contents of the bag and a control system (controlling temperature, agitation, and potentially media perfusion).

One of the challenges encountered in rocking bioreactor bags is the fact that upon inflation/filling with media, the originally flat bioreactor bags …

Preventing Leaks In A Single Use System, Trishna Ray-Chaudhuri

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

Assurance of the integrity of a single use system is important to ensure process fluids are contained and to limit the potential for a sterility breach. This discussion will describe an approach for the technical assessment of single use systems (SUS) for a specific biopharmaceutical process step. The presentation considers the key properties that need to be evaluated to ensure the integral components of a single use assembly are able to meet the performance attributes for the process step.

Understanding the polymer properties associated with the plastic materials used in single use system (SUS) ensures that the system will be …

Monitoring Clearance Of Extractables And Leachables From Single-Use Technologies By Nmr, Nicholas Margarian, Kate Lee, Kunal Nagpal, Ken Skidmore

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

Process validation at Genentech requires NMR methods capable of detecting and reliably quantifying trace levels of process impurities and leachables. Measurements must be done in solutions which are far from ideal for NMR. Depending on the application, high protein and buffer concentrations, along with the presence of water, necessitate an approach to NMR measurements and data interpretation which differs greatly from traditional NMR methods. Here, we show how we deal with these complications, and how our methods may be applied to measuring the concentrations of leachables from single-use products.

Hazard And Risk Assessments For Impurities, Residual Solvents, Extractables, And Leachables., Jan Oberdoerster

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

During their life-cycle (i.e., manufacture to end-use), single-use products in the biotechnology industry come in contact with processing equipment, packaging components, and delivery systems. Small amounts of chemicals that may transfer to the single-use product at any step in the life-cycle may subsequently leach into the pharmaceutical drug product and be delivered to the patient along with the dose. It is important that this chemical transfer does not occur in quantities that alter the safety, identity, strength or quality of the drug product. The assessment of potential leachable chemicals begins with a detailed analysis of compounds released from the single-use …

Container Closure Integrity (Cci) For Single-Use Systems (Sus): Regulatory Trends, Challenges And Technology Transfer Of Test Methods, Carole Langlois, Marc Horeve

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

Single-use fluid management solutions are being applied in critical downstream and final filling applications including applications requiring container closure integrity testing. Single-use bags are increasingly used for the storage, mixing, shipping, freezing of drug substances and drug products. Since single use bags are migrating towards more critical process steps and applications, there is a growing regulatory scrutiny and industry requirement for testing the containers in order to guarantee their integrity and their sterility before their use in commercial production processes.

This presentation will consider the regulatory trends for Container Closure Integrity of single-use systems with a focus on the proposed …

Evaluation Of Single-Use Bioreactors For The Production Of A Hepatitis C Vaccine Candidate, Ricardo Silva, Joao Clemente, Rute Castro, Lenaig Savary, Alex Xenopoulos, Cristina Peixoto, Manuel Carrondo, Paula Alves

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

During the last decade, the usage of single-use bioreactors has been increasing in the biopharmaceutical industry. This technology offers some appealing advantages over their conventional counterparts made of glass or stainless steel, such as operational flexibility, faster batch-to-batch turnaround times and the reduction of clean-up and validation characteristic of single-use materials.

The present work examines a stirred single-use bioreactor for its suitability for the production of a Hepatitis C Virus-Like Particles (VLPs) vaccine candidate using the baculovirus expression system with Sf9 cells.

In this sense a 2L glass stirred tank and a Mobius^® 3L Bioreactor are compared in terms …