Regulations & Standards
EU IVD Regulation: Something Wicked This Way Comes?
The ride started on September 26, 2012, with the publication by the European Commission of the proposed new EU IVD regulation. So far, nothing much has happened at the official level, but industry has had enough time to attentively read the 143-page document. This led to nascent concerns and an uneasy feeling that some elements of the proposal, if wrongly interpreted and applied, could seriously jeopardize the EU regulatory framework for IVDs that has been in place for a dozen or so years and...
Proposed Guidance on IVD Clinical Evidence and Performance Evaluation
Manufacturers of IVD devices should be aware of three proposed Global Harmonization Task Force guidance documents on clinical evidence for IVD devices. The documents cover definitions and terminology, determining scientific validity, performance evaluation, and clinical performance studies. The Global Harmonization Task Force (GHTF), created in 1992 in an effort to promote the international harmonization of medical device regulation, is a voluntary group of representatives from national medical...
Pivotal Clinical Investigations Draft Guidance: IVD Applications
FDA issued draft guidance on August 15, 2011, that addresses design of pivotal clinical trials for medical devices. The comment period expired November 14, 2011. There are no surprises in this guidance. The principles of trial design that are discussed are standard techniques that have been used to evaluate clinical utility of medical devices for many years. The guidance does make clear that FDA expects device manufacturers to be as rigorous in design of clinical trials as drug and biologic...
In Vitro Diagnostic Performance Evaluation Studies: Part 2
IVD medical devices are extremely important products for which performance evaluation studies can provide necessary evidence on safety and performance. Part 1 of this article discussed European requirements related to performance evaluation studies. Part 2 discusses considerations when planning studies where results will be used for both CE marking and U.S. approval and clearance. European and U.S. terminology differences The term “performance evaluation studies” is used for...
IVD Performance Evaluation Studies: Part 1
IVDs are extremely important healthcare products for which performance evaluation studies can provide necessary evidence on safety and performance. Part 1 of this two-part column discusses European requirements related to performance evaluation studies. Part 2 will discuss issues to consider when planning studies, in which results will be used not only for CE marking but also for clearance or approval in the United States. European definitions and implications Article 1(e) of the European In...
Manufacturing equipment and supplies
The good news is that in a stagnant economy, the $37 billion global IVD market continues to grow at a compound rate, which is expected to approach 9% through 2012. The challenging news is that IVD manufacturers encounter a myriad of obstacles when considering their manufacturing solutions. IVD testing devices are much more sensitive and complex than in the past. Not only is the technology more complex, stringent per-piece pricing adds to that complexity. There is an ever-constant need to reduce...
Revision of Europe’s IVD Directive 98/79/EC
The European Directive 98/79/EC on in vitro diagnostic medical devices, or IVD Directive (IVDD), became operational in June 2000.1 It provides Europe with one single regulation for in vitro diagnostics (IVD). Devices receiving the CE mark after one successful conformity assessment procedure can be introduced into the member states of the European Union and the European Free Trade Association, and two countries with which mutual recognition agreements have been established (Switzerland and...
Exploring FDA-Approved IVDMIAs
The sequencing of the human genome in 2001 brought about rapid development of technologies to measure multiple genes, which resulted in the creation of gene arrays. These tests, and multianalyte protein marker panels, constitute a new type of advanced diagnostic that is rapidly entering the clinical laboratory.1 As a result of the vast information that was made available from the Human Genome Project, great expectations developed that we would be able to diagnose, target, predict, and treat a...
Quality Control in Molecular Diagnostics
New information on proficiency results and quality practices points to a continued gap in the standard of quality control (QC) practice between molecular diagnostic testing and that of other laboratory disciplines. Indications of quality issues have surfaced in several areas but most visibly in the direct-to-consumer (DTC) testing arena. A recent Government Accounting Office study, for example, showed evidence of inadequate quality of molecular testing following an analysis of the results of...
Why manufacturers should embrace error grids
To legally sell in vitro diagnostic assays, manufacturers must submit performance data to FDA that demonstrates that the assay meets specifications. However, FDA approval does not guarantee that serious problems do not lurk within the assay that could cause severe patient harm and subsequent financial loss to the manufacturer. A typical performance specification has limits for average bias and imprecision. The logic of this specification is that according to a popular model, average bias plus...