Biomedical Engineering Reference
In-Depth Information
except for the highest-volume drugs that support nearly continuous fill-
ing operations. Most filling lines today support multiproduct operations.
Traditional multiproduct operations require validation of the level of prod-
uct carryover after cleaning operations to ensure subsequent products are
not contaminated. Certain product-contact parts are hard to clean to accept-
able levels, and are therefore dedicated to specific products.
An alternative to filling equipment dedication is the use of single-use parts
and assemblies. These systems can include components such as bulk prod-
uct bags, capsule filters, silicone tubing, and other plastic fittings and parts.
Many of these parts can already be purchased precleaned and presterilized,
and double or triple bagged for easy use within clean rooms. However, fill-
ing operations are critical enough to require entire single-use systems be
assembled and sterilized together rather than having to piece individual
components together at the point of use. The dosing system used for filling
also affects the characteristics of the single-use components.
The presterilized, single-use concept has already been realized with sev-
eral off-the-shelf filling systems using peristaltic or gravimetric dosing.
Many existing systems, however, are designed for low-speed, small-batch
filling operations. Scale-up of these systems for high-speed filling have cre-
ated technical obstacles that include a relatively slow dosing speed, lower
filling accuracy and precision, and difficulty dosing products with variable
temperature and viscosity characteristics.
Peristaltic dosing is ideally suited for disposables, as peristaltic tubing is
used for much of the product path. Single-use peristaltic systems typically
comprise a product hold bag, supply tubing, and a filling needle, which are
bagged together and sterilized using gamma irradiation. The assembly is
removed from the bag and connected to the filling system, which can be
as simple as a single peristaltic pump, immediately before use. High-
quality peristaltic pumps can be very precise at dosing water-like solutions.
However, the tubing directly influences accuracy. The tubing that is located
in the pump head changes shape over time due to wear, so accuracy drift is
common. Characterizing and compensating for the drift is required. Some
peristaltic pumps also dose at slower speeds, which means that high-speed
peristaltic systems require more pump heads to dose at the same rate as the
equivalent piston, time pressure, or rolling diaphragm systems.
Gravimetric dosing uses optical sensors to dose a given volume based
on a calculation of the interior volume of a given length of tubing or glass.
The entire product path is supplied as a single-use, presterilized assembly.
Accuracy and precision of the system with water-like solutions is comparable
to other dosing systems. However, dosing speed and accuracy can be directly
related to fluid temperature and viscosity. Dosing time is based on the speed
at which a liquid will flow through the tubing based on gravity. Thicker solu-
tions flow more slowly and are therefore dosed at a slower rate. Relatively
small temperature changes over the course of a filling event can affect prod-
uct viscosity enough to have a significant effect on the volume filled. Similar
