Applying disposable technologies
Compounding of a biopharmaceutical product can be as simple as combining the contents of a few bottles of thawed material
or diluting a solution to a defined concentration. For small batches (i.e., volumes up to 20 L), standard bottles made of
glass, polypropylene, or polyethylene, or flexible bags may be used. If a custom design is required, these containers can
be developed in collaboration with suppliers. Agitation can be achieved easily with disposable magnetic followers, paddle
stirrers, or recirculation of the solution.
Larger batches (i.e., volumes in excess of 20 L) also can be manufactured using disposable technologies. Plastic and glass
bottles may be used, but the manual handling of such containers needs to be considered as the batch size increases. Tank liners
and large flexible containers supported in a specifically designed trolley may be a more suitable choice for the larger batch.
Agitation can be achieved by employing similar techniques as those used for the smaller batch sizes. Sophisticated, purpose-built,
disposable mixing systems are commercially available for batches of volumes of 200 L and larger, including features such
as jackets for temperature control.
Filter manufacturers have been providing disposable filters to the pharmaceutical industry for many years. Capsule filters,
with a range of filter membranes, are available in many different sizes and can be supplied presterilized. The capsules are
often used as replacements for filter cartridges in a stainless-steel housing. The filter manufacturers have taken the disposable
concept one stage further by supplying custom designed sterile-filtration systems, complete with filtration lines, molded
silicone fittings, plastic connections, and waste bags to contain the wetting fluids. This custom design has the advantage
of reducing the number of aseptic connections required, which significantly decreases the time to make up and sterilize the
filtration system in the manufacturing facility.
Most filling systems do not use disposable technologies for the dosing of the solution into the vial. For example, many filling
systems use displacement pumps that are made from stainless steel. These filling systems often can be modified to accommodate
disposable systems such as peristaltic pumps. Advances in peristaltic technology have improved the performance of peristaltic
pumps. The accuracy and precision of doses are ensured, as are reliable performance, easy and quick setup, fast line turnarounds
(with pre-prepared, sterilized disposable tubing, complete with filling needles), and low manufacturing losses. Peristaltic
pumps have other advantages compared with traditional displacement pumps such as suitability for shear-sensitive compounds
(e.g., proteins) and viscous solutions.
The solution can be filled from a disposable filling bag such as a flexible bag. Flexible bags are available in a wide range
of sizes, typically from 1 L to hundreds of liters, which can make scaling up a much simpler process. The flexible bags are
sterile and ready to use, thereby reducing the setup time by removing the need for autoclaving vessels. Companies can collaborate
with the manufacturers of the disposable bags to facilitate fewer and less complex aseptic connections. The disposable bags
can be designed to be physically strong and to have low gas permeability by using several layers of different plastics. Compatibility
with typical pharmaceutical ingredients is optimized by making the inner layer polyethylene, a plastic commonly used in many
dosage forms. Manufacturers of disposable bags have conducted extensive testing on the plastic components used to demonstrate
compatibility with biological systems and can demonstrate compliance with US Pharmacopeia Class VI requirements. For small batch sizes, flexible bags can be designed to hang toward the end of the batch, so the solution
is filled and gravity-fed to the dosing pump, thus reducing manufacturing losses.
Disposable equipment used to manufacture clinical-trial materials has certain advantages:
- Removes the need to clean product-contact equipment
- Eliminates the need for cleaning-verification methods
- Almost totally eliminates the risk of cross-contamination
- Reduces line changeover times
- Reduces the number of aseptic connections
- Simplifies the aseptic line build
- Reduces manufacturing losses
- Improves sterility assurance
- Improves waste management.
Although the advantages of disposable technologies may seem compelling, disposable technologies' disadvantages need to be
considered. The increased use of disposable technologies results in an increase in the quantity of solid waste, which frequently
requires incineration. Disposable technologies, however, also lead to a reduction in the quantities of water for injection
(WFI) and chemicals to clean reusable equipment. For example, in a study on the use of disposable technology in a concept
biomanufacturing system, the estimated saving in WFI usage was 80%. Substantial reductions in the use of cleaning chemicals
also were reported (3). The study also estimated a 72% saving in electrical power when compared with a similar manufacturing
facility (3). These benefits outweigh the costs associated with disposal and incineration. Moreover, reducing chemicals and
power not only produces cost savings, but also reduces the environmental impact of the manufacturing process.