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In Vitro Diagnostics
In Vitro Diagnostics
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FDA finalizes guidance on Molecular Diagnostic Instruments with Combined Functions
12 November 2014
The US Food and Drug Administration (FDA) has published the final version of its guidance document 'Molecular Diagnostic Instruments with Combined Functions: Guidance for Industry and Food and Drug Administration Staff', to replace the draft published for comment in April 2013.
The Introduction to the guidance explains that the "document provides FDA’s current thinking on regulation of molecular diagnostic instruments that combine in a single instrument both approved/cleared device functions and device functions for which approval/clearance is not required. It also provides advice on the type of information that should be provided in a premarket submission for a molecular diagnostic instrument that measures or characterizes nucleic acid analytes and has combined functions."
The guidance goes on the explain that: "Molecular diagnostic instruments, for example, real-time thermocyclers, are critical components of certain in vitro diagnostic devices (IVDs). One molecular diagnostic instrument is often used to perform multiple unrelated assays, such as those that detect methicillin resistant S. aureus (MRSA), Hepatitis C virus, and genetic markers of cystic fibrosis. These types of instruments are not generally approved/cleared alone, i.e., without an accompanying assay, because their safety and effectiveness or substantial equivalence cannot be evaluated without reference to the assays they run and the assay’s defined performance parameters. The same instruments may also be used for additional purposes that do not require FDA approval or clearance, such as for basic scientific research—purposes this document refers to as functions for which approval/clearance is not required. In the past, FDA has provided informal advice in response to individual inquiries regarding the permissibility of having functions for which approval/clearance is not required on an instrument intended to be used with approved/cleared in vitro diagnostic assays. This guidance is meant to communicate FDA’s policy regarding molecular diagnostic instruments with combined functions."
The European Scientific Committee on Emerging Newly Identified Health Risks (SCENIHR) has issued an updated opinion on the safety of medical devices that include plasticizers including DEHP for public comment.
The publication updates the Committee's previous opinion, issued in February 2008, to take account of the reults of further relevant research carried out during the intervening period. The original opinion concluded that:
"There is no conclusive scientific evidence that DEHP exposure via medical treatments has harmful effects in humans. But, it is recognised that especially the potentially high exposure during medical treatments may raise a concern, even in the absence of clinical or epidemiological evidence, for harmful effects in humans. Further studies are required to confirm or reject the suggestions of adverse effects of DEHP in humans."
The revised report states:
"Use of PVC medical devices may lead to a higher exposure to DEHP than everyday sources affecting the general population. Several procedures such as exchange transfusion of blood in neonates, extracorporeal membrane oxygenation (ECMO) treatment of neonates and adults, total parenteral nutrition (TPN) in neonates, haemodialysis, enteral nutrition in neonates and adults, heart transplantation or coronary artery bypass graft surgery, massive blood transfusion of red blood cells and plasma or peritoneal dialysis may lead to high exposure to DEHP. The extent of exposure largely depends upon the type of device, the number and duration of medical procedures."
And concludes that:
"DEHP causes the most severe reproductive toxicity in animal studies, when compared to other plasticizers such as DEHA, DINP and TOTM. However, the lack of data on their release from medical devices and consequent human exposure does not allow an appropriate risk assessment to be carried out, for which aggregate exposure should be taken into account, because dust and air samples may contain these plasticizers.
It should be realised that the benefit of medical devices has also to be considered: the survival of premature infants often depends on the availability of the same medical devices which result in a relatively high DEHP exposure due to treatment. Whenever possible, material with low release potential should be used. The potential for replacement of DEHP in these products should be considered against their efficiency in the treatment, as well as the toxicological profile and leaching properties of the alternative materials."
The report also explains that while extensive exposure to medical devices containing DEHP is considered 'high risk' for reproductive and developmental toxicity in neonates (by analogy with the results of studies with immature rats, mice, and hamsters), usage of such devices in adults is unlikely to result in a Tolerable Daily Intake (TDI) exceeding the established value of 48 μg per kg body weight per day, with the possible exception of dialysis patients.
While the clammer for an outright ban on DEHP in medical devices from some quarters continues, the scientific evidence does not support such a position, although it is recommended that research on alternative materials continues, to ensure that DEHP is not unjustifiably replaced by alternatives about which we have insufficient data to prove that they are safer.