Biomedical Engineering Reference
In-Depth Information
The concerns about leachability or extractability remain to be challenged in
filed applications and, as with any new event, the industry is in a waiting
mode to see how the FDA or EMEA react to these submissions.
Regulatory Barriers
There are no extraordinary regulatory barriers in the deployment of dispos-
able systems except the need to validate leachables. Not surprisingly, even
the hard-walled manufacturing systems inevitably use plastic for such uses
as filtration, packaging, and storage. Whether these devices or components
are steam cleaned or not is irrelevant. So, there is already a precedent to
show the safety of plastics in manufacturing.
The use of disposables is supposed to reduce regulatory barriers substan-
tially. It has been clearly established that if the manufacturer does not have to
do any cleaning validation between batches, the cost will be reduced. There
are other features of a facility using disposables, including how this can
reduce regulatory barriers that should be considered.
One of the easiest and perhaps most robust means of assuring lack of
cross-contamination is to dedicate a facility for a single molecule; this way
only one cell line enters the facility and only one molecule goes out; all
equipment is dedicated, and nothing in the facility is shared with another
operation by the manufacturer. The cleaning between batches remains a
task, but its importance is significantly reduced as no new contaminants
are expected. Dedicating a facility to one molecule is not possible today for
most companies unless they happen to be the innovator producing very
large quantities of the product. However, the smaller footprint required in
a disposable facility can make it possible to dedicate facilities to individual
molecules. First, the elimination of sterilization-in-place (SIP)/cleaning-
in-place (CIP) reduces capital cost substantially, and the requirement of
the total space needed is also reduced substantially. Combining this with
adopting newer techniques in producing purified water (e.g., double reverse
osmosis (RO)/ electrodeionization (EDI), the company can completely elim-
inate the large engineering infrastructure needed to provide water in the
manufacturing area. It is projected that almost 90% of the water used in
traditional facilities is for CIP/SIP and autoclave use. Amgen uses 80,000
gallon of water per day in its Rhode Island facility, most of it for CIP/SIP.
The cost of water is very high; use of disposables brings the first savings in
terms of energy cost reduction (required in water distillation) and the capi-
tal costs of distillation and storage. The new RO systems do not have storage
vessels and work on an on-demand basis.
Another design element that reduces the footprint of a manufacturing
facility using disposables is the size of equipment installed; while many
