The biopharmaceutical industry is making increasing use of disposable single-use systems for the development and manufacture of many vaccines, therapeutic proteins and monoclonal antibodies (Mab's). What devices are available on the market? What advantages do they offer? For what applications? Pemflow provides an update.
Innovative systems that are easy to install
Biopharmaceutical processes are complex and involve numerous stages, including filtration. In these industries
, the constraints in terms of purity, quality and compliance with standards are very high. In this demanding context, single-use systems (SUS) offer a number of advantages, including reduced capital expenditure and shorter changeover times for equipment on production lines. They also bring flexibility to processes.
In processing industries (pharmaceuticals, but also food) requiring frequent and regular cleaning of equipment, SUS eliminates the need for time-consuming and costly clean-in-place (CIP) and sterilization-in-place (SIP) procedures.
The validation steps that are essential when using reusable stainless steel systems also become obsolete when using SUS.
In research and R&D, SUS enable researchers and process engineers to work with different molecules - antibodies, proteins, vaccines, etc. - in the same facility. A definite advantage for the transition from the laboratory to the market for new drugs.
Ready to use, economical and flexible, single-use systems avoid the purchase, maintenance and cleaning costs inherent in stainless steel filter housings and dispense with CIP/SIP procedures.
Controlling extractables
As with any device that comes into contact with a biopharmaceutical product, SUS can potentially release compounds into the latter, or interact chemically with it, altering its purity, composition and potentially its efficacy, or even rendering it unfit for marketing. Controlling the nature, quantity and fate of substances extractable from SUS, which are composed of polymers, is therefore a major concern.
It is therefore up to the manufacturer who uses them to quantify these elements and their subsequent impact on the purity of the drug. To do this, it is essential that the SUS supplier provides detailed information on extractable substances, useful for leaching studies.
Using, for example, gas chromatography-mass spectrometry (GCMS) or liquid chromatography-mass spectrometry (LCMS) analyses, the supplier can accurately characterise the various components of the SUS for volatile, semi-volatile and non-volatile extractables, with several extraction media and under different time and temperature conditions.
SUS devices in practice: bags, filters and sampling systems
SUSs can therefore be used to meet a variety of requirements and needs: microbial retention, sterility, endotoxin filtration, biosafety, etc. Existing devices are also designed to operate in a wide range of applications in terms of flow rate, burst strength, temperature, pressure, pressure drop, etc.
In practice, disposable single-use devices come in a wide variety of forms. They may be sterile bags, sampling systems, filtering devices (filter capsules in particular), tubes, connectors, etc.
2D & 3D sterile bags are used to store and transfer sterile media, intermediates, sterile buffers with a wide pH range, sterile medicinal substances and formulations.
The storage and transfer of these fluids during and between process steps, and between different process zones, is particularly critical. Disposable, pre-sterilised storage and transfer systems meet regulatory requirements while preserving the nature, strength, quality and purity of the fluids.
Single-use, γ-irradiated aseptic sampling systems, meanwhile, are used for the aseptic sampling of fluids at various stages of pharmaceutical and biopharmaceutical processing. They can cover the following needs:
sterile bulk and sterile transfers, vaccine formulation at various stages of maturation, fermentation cycles, cell culture from bioreactors.
Multiple tubing options in thermoplastic elastomers (TPE) and platinum-cured silicone are available, in a wide range of internal and external diameters to suit all needs.
Finally, filters, and in particular filter capsules, are particularly well suited to pre-filtration, microbial load reduction and sterilising filtration applications.
Focus on single-use sterilising capsules
Filter capsules, also known as monobloc filters, are available in different formats and media types, in sterilised or non-sterilised gamma versions. Ready to use, and particularly suitable for development, pilot phases or batch filtration, they offer ease of use that is much appreciated by operators.
They are used for pre-filtration, microbial load reduction, sterilising filtration and final filtration stages, from sample preparation to packaging of larger batches. The filtration unit is enclosed in a filter capsule, limiting set-up or maintenance operations and operator exposure. They can be ordered pre-sterilised for immediate use in an aseptic environment.
Find out more about filter capsules
Disposable filter capsules use media made from PES, PP, hydrophilic or hydrophobic PVDF, PTFE, glass microfibre, nylon or filled nylon. Suitable for gas and liquid filtration, they are available in different pore sizes, lengths and connection types, and cover a filtration threshold range from 0.1 to 20 μm. A wide range of filtration surfaces is available, from small 5 cm² capsules with very low retention volumes to 18,000 cm² filters for large-scale production.
For all filter capsules, the inlet/outlet connections are either standard or customisable. Capsule filter media are inserted into shells made of Polypropylene, Polyetherimide, Polycarbonate, etc.
Capsules with hydrophilic membranes in PES or PVDF are particularly recommended for sample preparation, clarification and microfiltration of cell culture media, both upstream and downstream. Whether sterilising filtration of pH adjusters, growth regulators, antibiotics or a vaccine, these sterilising membranes are compatible with ethylene oxide, γ-radiation and autoclave sterilisation methods.
Hydrophobic membrane filters are used for pressurised gas filtration or tank venting. Their PTFE or polyvinylidene fluoride (PVDF) membrane reliably removes contaminants and micro-organisms in sterilisation applications.
There are also filter capsules specially designed for higher flow rates. With a low protein adsorption rate, PES and PVDF media offer high chemical compatibility with extremely low extractables, both on a pilot scale and for larger production batches.
Filter capsules must be manufactured in a clean room (ISO class 7), under the control of a strict quality management system, to ensure total traceability and consistent production quality for the user. Each capsule must be accompanied by an individual certificate of conformity.
