TCI and the United States of America

 Steven L. Shafer, MD

The United States is the only developed country that does not have target controlled infusion devices. Why? The answer is that for many years the development of such devices was blocked by a combination of arcane regulatory issues (Is it a drug? Is it a device?) and a combination of ignorance and malfeasance on the part of the Food and Drug Administration.

I have great respect for the FDA. I have worked with the agency on many issues relating to anesthesia drugs and devices. Nearly all of the individuals associated with the FDA are dedicated to improving public health through advances in science and technology. Nearly all…

In the area of target controlled infusions, a single individual with the Anesthesia Devices branch of the Center for Devices and Radiological Health adamantly blocked development of these devices for more than a decade. This was compounded by a profoundly ignorant pharmacokinetic analysis conducted by a physician at the Center for Drug Evaluation and Research. This analysis concluded that TCI devices had the ability to profoundly increase the variability in concentration when compared to other types of infusions. As a reviewer, I responded with a mathematical proof that this was not possible. The individual never acknowledged that my proof was correct, but it was published in Anesthesiology several years later.

These two individuals created a poisoned environment for all efforts to develop TCI. Graseby submitted an application to market the Diprifusor in October 1995. The application went through a number of bizarre twists. The strangest was the FDA’s insistence in January 1997 that the device indicate a range rather than a number! In March 1998, 14 months later the FDA agreed that a target rather than a range was acceptable. The application then spent 4 years in limbo at the FDA, with constantly changing review teams. It was finally withdrawn in 2002, SEVEN years after submission.

In 2004 the individual who had worked so diligently to block development of TCI at the FDA was removed from his position after numerous complaints from the device industry about his bizarre behavior. The physician at CDER who performed the horrific PK analysis of TCI has long since retired from the agency. Additionally, the FDA has created an “Office of Combination Products” that specifically addresses drug-device combinations. Most critically, this office is headed by a very capable individual whose interest is not in defending the past, but in advancing the practice of medicine. These developments make it possible, and perhaps even probable, that a company that is willing to invest the time to deal with the paperwork will find a receptive audience at the agency.