The following perspective was presented as an abstract by Fresenius-Kabi at the Second World Congress of TIVA-TCI held in Berlin, April 2009.

Developed in the 80’s the Target Controlled Infusion (TCI) theory was first commercially available in the 90’s associated to a unique molecule, the Diprivan. By combining a pre-filled syringe with an electronic tag, and a syringe pump integrating Diprifusor the technique was proposed to simplify IV anaesthesia and to provide a competitive and a clinical advantage to this molecule.

In 2003, Fresenius Kabi opened the TCI practice to the generic Propofol and to two opioids (Sufentanil and Remifentanil) with the launch of the Base Primea. Other companies then decided to propose their own so-called “open TCI” syringe pumps.

First driven and managed by a pharmaceutical company in collaboration with Infusion Pump companies the regulatory process was then in the hands of the Medical Devices companies to make the technique independent from a unique molecule and to allow its expansion.

Medical Devices companies are subject to the CE marking process and each company developed its own regulatory strategy mainly based on a review of the literature to select one (or more) pharmacokinetic model and based on the design of user interfaces that makes the use of the device safe by providing users with information they used to have with a standard administration mode, such as the flow rate profile associated to a change in the concentration target.

The main issue is associated with the choice of the pk/pd model for a specific IV drugs and to the corresponding patient population on which this model is validated. This has led to the availability of different pk/pd models for the same IV drugs depending on the syringe pump manufacturer, which is creating confusion for users who are not familiar with the TCI technique, and therefore limits the expansion of the technique despite its clinical benefits.

This could be overcome following 3 different strategies:

PK/PD models have to be integrated into the prescribing information provided by the pharmaceutical companies. In this case, these companies have to find an economical interest to justify the associated investment. This will reinforce the development of captive solutions and thus limits the expansion of the technique only to new IV drugs that are not yet in the public domain.

• The different IV pumps companies agree on the pk/pd models they integrate in their devices based on a consensus that could be found between their respective clinical advisory boards. This has the advantage to simplify the process but it limits its transparency.
• An independent clinical and scientific committee (TCI committee) under the umbrella of a scientific society such as the WorldSIVA defines the pk/pd models valid for a specific IV drugs and for a specified patient population. This committee could also review the dossier provided by a specific company and provide it with its recommendation that could be public.

The latter strategy is probably the more complex one to set up, but the most valuable on a long term basis. It will have the advantage to limit the number of pk/pd models available independently from the necessary competition between the device manufacturers. It will allow reinforcing teaching of the TCI techniques by providing the local scientific societies with clear guidelines.

But to really make the TCI technique a recognised and valuable administration technique it has to be expanded to IV drugs outside the single anaesthesia field and especially for IV drugs used in Intensive Care such as antibiotics for example. The clinical benefits have also to be more demonstrated and published to justify changes in the user’s habit.

Despite more than 25 years experience, the TCI technique is still in the development phase and both the scientific community and the medical device industry have to find a new way of collaboration to avoid seeing this technique remaining a technique for experts understood and supported only by a small group of scientists.

This collaboration could be based on:

• funding an independent TCI committee by all major players which will gain the right to use the results of its work (such as the Bluetooth consortium).
• having strong relationship between Medical Device industry official representative such as the Eucomed and the TCI committee to define short, mid and long term strategies.
• developing educational program using the EuroSIVA and other local or regional societies expertise.
• developing lobbying towards the pharmaceutical companies to integrate the development of pk/pd models when possible into the prescribing information.
• developing a research program to continue to demonstrate the clinical benefits of the TCI technique.

The TCI technique needs a new dynamic, only a joined action by both the industry and the scientific community can create this dynamic.

Stephane Ruton
Fresenius Kabi
Strategic marketing director for Acute Care IV Delivery Systems