One-way process solution

Disposable process solutions , also known as single-use technology , are used to manufacture biopharmaceutical products. This is understood to mean complete solutions consisting of one -way systems , which are also referred to as single-use systems , for an entire process line. This can include, for example: media and buffer production, bioreactors , cell harvesting, depth filtration , tangential flow filtration , chromatography and virus inactivation . Disposable process solutions are offered by companies such as Sartorius Stedim Biotech , Millipore , GE Healthcare , Pall or Thermo Scientific .

Disposable media and buffer manufacture

Various defined media are required for biotechnical processes, including nutrient solutions for the cells, buffers to stabilize the pH value , as well as acids and bases for setting and regulating the pH value during cultivation. All media used must be sterilized before use. In addition, two processes are essentially used in biotechnology, heat sterilization at 121 ° C at 1 bar pressure and sterile filtration . For media that contain heat-sensitive components such as vitamins , proteins and peptides , sterile filtration is the method of choice. The difference between the production of single-use media and buffers and conventional processes lies in the use of corresponding single-use products that have been specially developed for this purpose, for example special bags, single-use mixing systems and filters and corresponding pumps. In contrast to conventional filters, the filters used are pre-sterilized. In some cases, the bags, filters and pump heads are already connected to one another as a complete disposable system. The entire system is connected and delivered pre-sterilized to avoid contamination. The pore size of sterile filters is usually below 0.2 µm.

Disposable bioreactors

A single-use bioreactor is a bioreactor made of single-use material which is primarily used for animal cell culture technology for the production of biopharmaceutical products.

Disposable cell harvest

As part of a biotechnological manufacturing process, the cultivation is followed by the cell harvest. In general, the active ingredients are excreted by the cells and are in the culture medium after fermentation . As a first step in the processing of the product, cells and cell fragments are separated by means of depth filtration or centrifugation (with perfusion systems). Typically, a single-use cell harvest consists of a depth filter; H. a filter made of a material that is able to hold back the cells and cell debris. Depth filters often have a combination of different filter materials, e.g. B. glass fibers and polypropylene (fractionated depth filter membrane) ensures the retention of particles. They are ideally suited for clarification and pre-filtration prior to membrane filtration. Absorbent depth filters were developed for the removal of contaminants such as colloids, lipids, protein aggregates and particles from biopharmaceutical liquids. They are used to protect membrane filtration, chromatography and ultrafiltration systems in pharmaceutical and biotechnological production processes. The filtrate is collected in a 2 or 3-dimensional plastic bag (2D, 3D bag). The receptacle can either be the disposable bioreactor itself or another 2D or 3D bag. The liquid is transported by means of a pump with a pre-sterilized pump head, which is part of a system of pre-sterilized bags and tubes. There are pre-sterilized inserts for centrifuges that are integrated into the process via tubes. The centrifuges work continuously and return the concentrate to the storage tank.

Disposable purification

In the case of a single-use process solution, the solutions to be processed are usually stored temporarily in special bags and then, depending on the process step, pumped through or over the filter or chromatography membrane or a chromatography column. The purified solution is then collected in another disposable tank. A complete process step therefore consists of a disposable tank as a template, a pump head, the membrane (filter or chromatography) or column and a disposable tank or bag for holding the product. All components are connected with hoses. The system is self-contained and completely pre-sterilized. In order to be able to produce such systems, considerable developments had to be made, since all components must be sterilizable without losing their filtering and separating performance.

Special disposable developments

In addition to the above-mentioned one-way processes, each of which is based on a basic procedural operation, special methods and devices have been developed in the world of biopharmaceutical single-use production. B. sterile couplings and hose welding devices.

Sterile connections

The available one-way process solutions should each be viewed as a separate module. As part of a one-way production process, the basic procedural operations necessary for the production and purification of the target product are switched one after the other. The preconfigured single-use systems, which consist of hoses, single-use tanks, pump heads, and filtration or chromatography modules, are self-contained. To connect two successive process steps, sterile connection technologies, generally hose connections, are therefore required. On the one hand there are mechanical one-way couplings, on the other hand there are devices with which thermoplastic hoses can be welded together in a sterile manner or existing connections can be severed in a sterile manner and the ends of the hose welded. Special quick transfer systems have been developed for connections through a wall.

Modular one-way basic operations

There is a manageable number of basic procedural operations that are required in the context of biopharmaceutical production. As part of the single-use process solutions, the systems consisting of the single-use tank, hoses and pump head must be handled sensibly. This has resulted in the development of modular carriers on which a pump (suitable for the pump head), various connections for sensors and a process control are integrated. Furthermore, the filtration or chromatography modules can be attached to the carrier. The carrier is usually a mobile frame so that the entire modular unit can be moved in the biopharmaceutical production facility. Such solutions are now offered by all major manufacturers.

Complete one-way processes

Currently, most of the production processes that use single-use products are still so-called hybrid processes, in which single-use systems are combined with conventional systems made of stainless steel and glass. However, the first production plants that work exclusively with disposable systems are in the planning stage. A distinction is made between closed systems, in which the one-way systems are linked to one another in the order of the process steps, and station systems, in which the intermediate products are transported to the next process step by means of mobile containers.

literature

Status paper of the temporary DECHEMA working group for single-use technologies in biopharmaceutical production , September 2011 (updated: March 2012)

Individual evidence

^ T. Peuker, D. Eibl: Biopharmaceutical manufacturing facilities integrating single-use systems. In: R. Eibl, D. Eibl (Hrsg.): Single-use technology in biopharmaceutical manufacture. John Wiley & Sons, 2011, pp. 145-158.

[1] T. Peuker, D. Eibl: Biopharmaceutical manufacturing facilities integrating single-use systems. In: R. Eibl, D. Eibl (Hrsg.): Single-use technology in biopharmaceutical manufacture. John Wiley & Sons, 2011, pp. 145-158.