Dr. Mark Luscher
Senior Vice President of Scientific Affairs, Microbix
Times are changing in the clinical infectious diseases laboratory, particularly in the era of nucleic acid based testing.
The FDA is increasingly turning its attention to the important matter of controls as a fundamental element of the quality management system (QMS) ensuring patient safety. In its guidance1, regarding controls for nucleic acid amplification testing (NAAT) for respiratory pathogens, the FDA advises the need for the use of external controls, and further advises that positive controls should regulate the entire process, including nucleic acid extraction, amplification, and detection. The agency cites infected cell lines or packaged nucleic acids as acceptable examples, and recognizes the role of low-pathogenicity or inactivated samples.
Insights into future quality management trends
Our work as a provider of pathogen-derived materials to both major IVD companies and to providers of Proficiency Testing (PT) services has given us insight into some of the trends that are poised to affect quality management now and in the future. Among these is the increasing desirability of third-party controls, derived neither from the IVD manufacturer, nor from the testing laboratory, where ‘stored patient samples’ might formerly have been the gold standard. However, there are significant shortcomings in some contemporary third-party offerings, where providers are not using intact organisms, or are using chemically-inactivated organisms that can perform suboptimally or even interfere with the test methodology. Among the most common observations is that the market for quality controls is fragmented according to test methodologies, for example with controls designed to operate in the context of an immunoassay or a NAAT system, but not both. In fact, this fragmentation is amplified where providers of controls design toward specific testing platforms. From this, it is apparent to us that there is an emerging need for intact whole organism controls that are broadly compatible not only across the platforms of multiple IVD manufacturers, but also across technologies including immunoassay and NAAT.
The need for controls in the diverse environment of POCT
Another emerging trend is the move from central laboratory testing toward the increasing use of point-of-care testing (POCT), with its attendant advantages for efficient and effective patient management. The need for controls in such diverse and unspecialized environments is self-evident, but the nature of POCT provides some unique challenges for manufacturers of controls. For example, the immediate processing of patient samples using POCT obviates the need for sample transportation, stabilization, and preservation, and therefore of common transport media (TM). A consequence of this simplification is that POCTs are not necessarily compatible with TM, some of which are used as media for commercially-available controls.
A unifying concept for quality controls across the infectious diseases IVD sector is the metaphor of controls as ‘patient samples’. Patient samples are natively suitable for use on all platforms using all testing methods, where the choice of method is governed by availability and by the economic and clinical criteria. Furthermore, patient samples are suitable for verification across platforms, for example where an immunocard assay positive might be further assessed in a confirmatory test by NAAT. We feel strongly that the future of controls lies in such broad cross-compatibility spanning platforms and technologies.
Specialised quality control is essential
For these reasons, lab managers and professionals focussed on laboratory QMS should insist on quality controls that best match fundamental characteristics of patient samples, while simultaneously providing an unbiased, externally-provided challenge to testing systems. The important characteristics include cross-method and cross-platform performance, the presence of both antigenic and nucleic acid characteristics represented by the whole organism (including compatibility with nucleic acid extraction if applicable), inactivation for safe handling using non-chemical means, and the presentation of the samples in a TM that is universally compatible with testing methodologies, including POCT where a TM is not normally used.
These fundamentals are the underpinning of Microbix’ Quality Assurance Products, an expanding line of controls designed to meet the challenge of broad utility in infectious disease diagnostics. http://www.microbix.com/QAPs/AMR
1. Class II Special Controls Guidance Document: Respiratory Viral Panel Multiplex Nucleic Acid Assay – Guidance for Industry and FDA Staff. 2009. https://www.fda.gov/RegulatoryInformation/Guidances/ucm180307.htm