The Cost of Sterile Operations

The production of drugs, especially those that cannot be sterilized after being sealed in a vial or other container, is an area in which Cedric and similar systems could play a significant role in reducing cost. Pharmaceutical manufacturing often entails the assembly of sterile drug product and pre-sterilized container components such as rubber stoppers and glass vials under "aseptic" or sterile processing conditions ("sterile" in this context is often stated, somewhat simplistically, to mean that there is less than a one-in-a-million chance of a contamination event).

Thousands of clean rooms currently in operation in the US use technology that's perceived by many industry professionals to be deficient in meeting cGMPs (current good manufacturing practices) set forth by FDA (Food and Drug Administration). These "conventional" clean rooms involve operators coming to work, stripping down to underwear, donning scrubs and dedicated shoes or shoe covers, hair and beard cover and washing their hands and arms with sanitant and/or disinfectant.

Suitably prepped the operators then enter a "pass-through", a small room in which they don a "bunny suit" fabricated from Tyvek^TM or other breathable material along with a second set of shoe covers, a second hair net, sterile gloves and protective goggles. This level of gowning then suffices for operations that do not involve the handling of sterile materials or working in the vicinity of open drug product.

For the most critical operations, personnel must then perform another sanitization/disinfection routine during entry into the sterile gowning room. Here, the gowning process involves donning laced booties and climbing into a hooded gown without letting any part of the gown touch the floor or walls. Addition of a facemask, vented goggles and another pair of sterile gloves typically completes the suit. Another sanitation of the gloves and it is off to work; 20-40 minutes per operator has now been spent simply preparing to begin work. Another 10-15 minutes of production time is lost as operators de-gown on the way out for lunch or break, after which the arduous process to reenter classified spaces starts anew.

Product Contamination Risk and Preventative Measures

Even with the rigorous gowning procedures outlined above, it is estimated that 80% of contamination events are due to operators inadvertently bringing in viable organisms or other particulates. For this reason, there is considerable push in the pharmaceutical industry to install equipment and processes that facilitate human intervention into the sterile work zone through the use of glove ports rather than operators opening glass barrier doors to perform physical manipulations. Unfortunately, fallen vials or stoppers can occur almost anywhere on a production line. For this reason the installation of glove ports rarely provides sufficient coverage for the full potential range of interventions. To make matters worse, glove ports are far from ergonomically optimal solutions.

In the process of upgrading to the newer glove-port technology pharmaceutical companies generally review and revise many aspects of their current operation. This is usually done in anticipation of regulatory scrutiny for cGMP compliance by the regulatory agencies once the changes are submitted for licensing. In extreme cases, project "scope creep" can lead to entire facilities being renovated or replaced at costs of 50-100 million dollars.

Competitiveness in Bio-Pharma Manufacturing

There was a time when patented drugs and pharmaceuticals with difficult-to-replicate therapeutic effect allowed manufacturers to pass exorbitant costs directly to the consumer. Now, patents are expiring and international generic drug producers are beginning to challenge blockbuster drugs in the US with lower cost substitutes. Increasing competition among drug manufacturers, a need to curb rising costs and demands by patients to reduce time-to-market has both pharmaceutical producers and regulatory agencies moving to a "risk-based" approach to manufacturing drugs as opposed to the historical prescriptive approach. As a result, alternative technologies and processes that can be substantiated or "validated" as effective and safe are now routinely being considered as viable options for license submittal.

Cedric and similar telerobots could be installed within existing facilities to remove the most persistent rationale for facility upgrade; the issue of viable and non-viable particle ingress by operators. Bio-pharmaceutical manufacturers will need to get past historical reticence to install cameras in classified spaces in order to fairly consider the benefits teleoperations will bring to their businesses.

Following is a partial list of advantages that derive from implementation of Cedric-based telerobots in clean rooms:

• Substantial reduction in the cost of sterile operations by minimizing or eliminating both operator gowning processes and the cost of disposable supplies (the telerobot will be covered with a reusable, sterilizable silicone skin).
• Relocation of operators to a more comfortable environment (i.e. cubicles or, potentially, their home office) with ergonomic improvement in task execution.
• Automation of certain physically difficult tasks, such as sanitizing floors and walls.
• Improved access for managers, engineers, quality operations personnel and other professionals that do not routinely enter clean rooms to view all aspects of the manufacturing operation.
• Improved access by qualified service technicians to remotely diagnose and, in some cases, repair equipment.
• Creation of a video record of daily operations, critical for troubleshooting and root cause analysis as well as for keeping workers exceptionally alert and mindful of their actions. It should be noted that this aspect of telepresence is often seen as a negative attribute; "If the regulatory agencies know we are recording, what is to stop them from coming in and auditing the record at any time"?