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Profil starts in-house production of tubing sets for ClampArt®, reinforcing the quality of world-class glucose clamp trials

Dr.
Posted by Dr. Carsten Benesch on Sep 8, 2020 4:02:00 PM

The euglycemic, hyperinsulinemic glucose clamp is the gold standard for the determination of pharmacokinetic and pharmacodynamic (PK/PD) effects of (new) anti-diabetic drugs, in particular insulins. In a typical glucose clamp experiment, a drug-induced decline in blood glucose (BG) concentrations is prevented by infusing glucose with a variable glucose infusion rates (GIR) to keep blood glucose concentrations (BG) as closely as possible to a pre-defined target level. 

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Glucose clamps can be done either manually or in an automated fashion. In manual clamps the investigator performs BG measurements and manually adjusts GIR every 3–10 minutes, whereas in automated clamps, BG is measured continuously and GIR is adapted every minute by an algorithm. To measure BG continuously it is necessary to provide the glucose sensor continuously with blood via pumps and tubes of the clamp device, i.e. the ClampArt® device used at Profil since 2013. The ClampArt® device was designed to use as little blood as possible to determine the actual BG concentration. For the investigation of PK/PD effects of basal insulins the ClampArt® device needs about 1 ml blood per hour. This is a challenge for the pumps as well as for the tubes because of their very small inner diameter. In the past Profil purchased the tubing system specifically designed for the ClampArt® device from a subcontractor specialized in manufacturing blood glucose catheters. Profil decided to manufacture the tubes called “double lumen catheter (DLC)” and some other accessory tubes and adapters by our own in order to 
  • be more independent from subcontractors in order to ensure availability at all times
  • have better control of the quality of the tubes for offering consistently high standards to our clients
  • control the know-how of this core part of the ClampArt® system
  • get the opportunity to optimise these tubes in different ways
    so we can continue to offer our clients the best Clamp solutions.

The DLC mainly consists of two tubes with a small inner diameter that are connected together at one end in a Y-shape. One of the tubes at the Y-connector is linked to a small capillary, which can be placed into an intravenous cannula and therefore has direct contact to the blood in the vein. The blood is pumped through the tube of the DLC towards the device with the glucose sensor where the BG concentration is determined. These facts make the DLC itself a medical product.

EC-Certificate_angepasstAs a first step before starting the production of the DLC systems a risk analysis was performed to ensure that the DLC would be manufactured as a safe and reliable medical product. Because the DLC is used within an intravenous cannula, the DLC has to be a sterile medical product for single use only. To produce a sterile medical product Profil uses a two-step approach: The DLC is manufactured by trained associates in a new cleanroom at Profil. All critical components are purchased at certified manufactures in medical grade quality and all components need to pass a strict inspection upon arrival. This enables Profil to produce ultra-clean but not yet sterile DLC systems. In a second step these clean DLCs are sterilised in a validated ethylene oxide sterilisation process and are then ready to be used by Profil’s clinical staff for automated glucose clamps with the ClampArt® device.

This entire manufacturing process, all documentation and validation including the implementation and maintenance of a full quality assurance system was inspected by a notified body and in August 2019 Profil obtained the EC-Certificate for a CE mark and subsequently to place the DLC tubing set on the market. For all future glucose clamp with the ClampArt® device Profil will use certified, self-manufactured DLC tubing sets.

 

Topics: Clinical Trial Methods, Diabetes Technology