What’s New in Manufacturing: Upstream Technologies

December 6, 2019

The latest advances in upstream technologies include single-use equipment and a protein analyzer for titer monitoring, as well as new plasmid DNA manufacturing capability.

Various pieces of equipment to advance upstream bioprocess have been introduced within recent months. The following products showcase a select few of those advancements.

Single-use vessel for laboratory system

Sartorius Stedim Biotech introduced a new single-use vessel for the ambr 250, a modular, benchtop, automated mini-bioreactor system for biologics process optimization. The vessel was constructed for use with therapeutic cell lines for process development of cell and gene therapy applications. The vessel allows scale-up into cGMP single-use bioreactors and bags for clinical production of regenerative medicines.

The new unbaffled vessel design with a large, pitched-blade impeller has a working volume of 100–250 mL and the ability to handle gentle agitation and mixing without sedimentation for growth of single-cell suspensions, cell aggregates, and adherent cells on microcarriers. Compared to less predictive spinners and T-flask models, the new system enhances cell-culture performance for regenerative medicines, according to a company press release.

Additionally, the ambr 250 features a new 100–4500 rpm motor that allows lower stirrer speeds for therapeutic cell lines, including stem cells. Optional design of experiments software supports scale-up to the company’s stirred bioreactors and scale-out to the company’s rocking bags for production of autologous and allogeneic cell and gene therapies.

Large-scale single-use bioreactor

Custom Single Run (CSR) Bioreactors from ABEC are designed to work with volumes up to 6000 L, an increase from the company’s 4000-L single-use bioreactor size.

The new bioreactor is fully customizable and enhances cell culture capacity per unit of floorspace, which saves in capital, facility, and disposables cost. CSR bioreactors are designed to deliver equivalent power per volume while maintaining low shear mixing. CSR products use a non-proprietary material, instrument, and component supply chain.

“We understand that our customers cannot compromise on scalability and cost of goods when realizing other single-use benefits such as multi-product flexibility,” said Scott Pickering, ABEC president and CEO. “In applications where single-use is preferred, with 6000-L CSR bioreactors, customers can now achieve even greater economies of scale for cell culture production.”

Updated pilot bioreactors

INFORS HT’s updated Techfors pilot bioreactors for production-scale bioprocesses are equipped with workflow-oriented, touchscreen interfaces and a new version of the company’s eve bioprocess software to control, monitor, analyze, and document bioprocesses in a GMP-regulated environment. 

With all the capabilities of smaller bioreactors, Techfors give users the ability to start their projects right away, without the need for familiarization or new skill learning. The bioreactors can now also be custom-made to match the customer’s requirements.

“Besides the modern look with ergonomically arranged pumps and a tilting touch screen, we particularly focused on a consistently workflow-oriented user interface,” said Dr. Dirk Hebel, lead product manager, Bioreactors, INFORS HT.

Single-use assemblies

Watson-Marlow Fluid Technology Group expanded its range of puresu single-use assemblies for the manufacturing of biopharmaceuticals and personalized medicines. The components use an open-architecture design to allow creation of custom sterile fluid paths.

Three new product variants include sterile claim, gamma irradiated, and non-irradiated assemblies. Sterile puresu is used as a solution for fluid path bioprocesses for customers who require contamination risk mitigation, gamma irradiated is offered for customers who manage microbial control through bioburden reduction, and non-irradiated is designed for process development activities.

Assemblies are available with a sterility assurance level claim of 10-6 with a two-year shelf life. The company offers product traceability and documented quality systems compliant with ISO 9001.

Protein analyzer for titer monitoring

Tridex Protein Analyzer by IDEX Health & Science is a compact solution for real-time, at-line titer monitoring in a bioprocess environment. The device is the first protein analyzer designed specifically for bioprocess monitoring. It is designed to ensure that at-line results directly correlate to offline HPLC methodology.

It features a trap and elute technique to monitor the titer in a bioreactor and provides users with the option to connect to an automated sampling system so the system can integrate completely into a bioprocessing environment. Additionally, the sample path is enclosed, which enables single-use capabilities. The instrument measures over a dynamic range of 0.1–10 g/L, with minimal sample manipulation and results in under five minutes.

Plasmid DNA availability

Cytovance Biologics will add a single-use platform for the manufacturing of plasmid DNA (pDNA) to their facilities in Oklahoma City, OK. Critical Reagent Grades and CGMP-grades will be available in lot sizes from 1 g to 50 g, and one R&D grade will be available in lot sizes from 1 g to 5 g. 

“With this new platform, our teams will ensure high-quality, fast, and affordable plasmid development and delivery, which will be key to our clients and ultimately benefit the patients,” said Yan Wang, CEO of Cytovance Biologics.

“Whether our clients need pDNA for early pre-clinical work or for advanced commercial efforts, our team will ensure a cost-effective and robust supply of high-quality plasmids that align with the regulatory expectations across a product’s lifecycle,” added Jesse McCool, chief technology officer of Cytovance Biologics.

References

1. Sartorius Stedim Biotech, “New ambr 250 Modular Bioreactor Vessel Launched for Cell and Gene Therapy Applications,” Press Release, June 27, 2019.
2. ABEC, “ABEC Advances Single-Use Bioreactor Volumes to 6,000 Liters,” Press Release, Sept. 10, 2019.
3. INFORS HT, “INFORS HT launches new version of the Techfors pilot bioreactor,” Press Release, Oct. 3, 2019.
4. Watson-Marlow Fluid Technology Group, “Watson-Marlow Fluid Technology Group’s puresu single-use tube assemblies offer reliable, sterile, customisable solutions for bioprocessing,” Press Release, Oct. 31, 2019
5. IDEX Health & Science, “IDEX Health & Science, LLC Launches Dedicated Protein Analyzer for Bioprocessing: TRIDEX™,” Press Release, July 10, 2019.
6. Cytovance Biologics, “Cytovance Biologics Introduces An Integrated Single-Use Platform For Plasmid DNA (PDNA) Manufacture,” Press Release, Oct. 21, 2019.