Industrial Perspectives on Assays (2025)

Quality Assurance Issues and Interpretation of Assays

Seminars in Hematology, 2007

The consequences of an erroneous thrombophilia diagnosis may be serious if it is used to determine clinical management. Therefore careful selection, assessment, and control of laboratory tests for thrombophilia are essential. As for other coagulation tests, the preanalytical phase must be carefully controlled with attention to the specific problems associated with each type of assay. The investigator must then recognize that for most laboratory tests of thrombophilia, there are a number of assay types available, often based on different principles of analysis. This creates the potential for different users to obtain varying results depending on the technique employed. Such problems can occur in assays of antithrombin activity, depending on whether the assay employs factor Xa, human thrombin, or bovine thrombin. In clot-based assays of protein C and protein S, there can be specificity problems related to interference by factor V Leiden (FVL), antiphospholipid antibodies, and other substances. Even genetic tests can give erroneous results and should not automatically be seen as absolute without supporting evidence and careful qualitycontrol measures. Whatever technique is selected, it is mandatory to incorporate sufficient concurrent quality-control samples to validate the results of thrombophilia tests. These should include assessment of the parameter at normal and abnormal levels to give confidence in results across the measurement range that would normally be encountered in routine practice. This should be used in conjunction with regular participation in external quality assessment (EQA) (which has been linked to improved laboratory performance in thrombophilia testing). Larger EQA programs can provide information concerning the relative performance of analytical procedures, including the method principle, reagents, and instruments. Herein, we describe many of the methodologic effects in detail. We use specific examples to illustrate the general principle that, in performing laboratory testing for thrombophilia, one must always consider the performance characteristics and limitations of the assay in use.

Ensuring quality of in vitro alternative test methods: Issues and answers

Regulatory Toxicology and Pharmacology, 2005

Many in vitro and ex vivo methods have been developed or are under development to reduce or replace animal usage in toxicity tests. Consistent with the goal of obtaining scientiWcally sound test data for hazard and risk assessment of chemicals, changes are being made in current policies and procedures to facilitate the acceptance of data developed using these methods. National and international organizations are developing policies and standards for scientiWc practice to assure quality in implementation of in vitro methods. Consensus is developing in the scientiWc community for the quality control measures needed for in vitro methods; including appropriate controls, data reporting elements, and benchmarks to be identiWed in test guidelines so that the potential risks of chemicals can be reviewed and reliably assessed. Additional guidance to the OECD's Good Laboratory Practice principles [Organization for Economic Cooperation and Development (OECD), 2004. Advisory Document of the Working Group on Good Laboratory Practice: The Application of the Principles of GLP to in vitro Studies. OECD Series on Principles of Good Laboratory Practice and Compliance Monitoring Number 14 (ENV/JM/MONO . Paris, France] will help to ensure that in vitro tests used for regulatory purposes are reproducible, credible, and acceptable. Generic test guidelines incorporating performance standards are being written to allow acceptance of proprietary test methods by regulatory agencies and to provide assurance that any in vitro system performs over time in a manner that is consistent with the test system as it was originally validated. Published by Elsevier Inc.

Ensuring quality of in vitro alternative test methods: Current practice

Regulatory Toxicology and Pharmacology, 2006

In Vitro toxicology methods are being validated and adopted by regulatory agencies for use as alternatives to animal testing. Such methods may use ex vivo tissues or bioconstructs, some of which may be proprietary. Users of the data from these methods need to be reassured that the assays or assay components used in their studies provide consistent, good quality data over time, matching the standards achieved during the validation process. This paper presents an overview of approaches currently used by representatives of a manufacturer and a contract testing laboratory to ensure that the results from in vitro alternative methods are reproducible and of high quality over time. These approaches include full characterization of cells or tissues, sampling of each lot of manufactured bioconstructs for performance, and regular use of controls and benchmark chemicals to provide assurance of consistency of assay performance.

Quality assurance for in vitro alternative test methods: quality control issues in test kit production

Alternatives to laboratory animals : ATLA, 2004

In vitro toxicology methods are being adopted by regulatory agencies worldwide. Many of these methods have been validated by using proprietary materials, often in the form of test kits. Guidelines for the use of Good Laboratory Practice methods for in vitro methods have been proposed. However, users of the data from these methods also need to be reassured that the proprietary materials and the test kits will provide consistent, good quality data over time, not just during the validation process. This paper presents an overview of the methods currently used by representatives of kit manufacturers and contract testing laboratories to ensure that the results from methods that utilise test kits are reproducible over time and across different types of test materials. This information will be valuable as a basis for future discussion on the need for formalised oversight of the quality of these materials.

Focus Issue Articles on Diagnostic Assay Development and Validation: The Science of Getting It Right

PhytoFrontiers, 2023

Bioassay development

Materiomics

Combinatorial chemistry and high-throughput synthesis of novel materials wa1Tant a parndigm shift in cunent methods to analyse biologi'c.:al responses. This chapter will provide an overview on bioassay development mid how novel assays amenuble to hightbroughput screening platfonns can be adapted to more complex systems. Special emphasis will be devoted to the development of assays that can be used in plationns that closely mimic the in vivo complexity of tissues and organs. Jn that respect, nssays thut can cope with co-cultun: systems as well as JD environments will be discusst.:d. M1)reover, modifications or development of new assays and techniques wiU be described as well as their rei;pectivc advantages and disadvantag~. Basic principles of assay development The ability ttl meAsure the speed of light changt!d the Geld of physics and tbc world. Chemical reacltons led to the Big Bang and the creation oftJJe Universe, but the ahility !I) measure and control those reactions changed the face of the Earth. We can surely Nay that the need to see more, and in more detail, led to the development of technologies that made tbal possible and ultimately contributed to the advance of science 1md society. In the eighteenth century, Antoni van Leeuwenhoek was the tlrst to sec organi.ms aud cells under a micro~cope that he built. This observation paveJ the way to Lhe high-resoll1ti011 microscopes we use to<luy which allow us to see strands or DNA and ot11er nauoscopic components in cells such as single molecules. Despitl! the rapid development of van Leeuwenhoek's microscope, measuring techniques lagged for many years until their implementation in today's laboratories. Monitoring cells und cellular activity in vitro and in vivn allows us to identify cellular processes characlciistic of normal and/or abnormal development such as those occu1Ting in cancer. Numerous cell and non-cell based assays have been developed during 1hc past decades, driving our understanding of bio1ogical processes. F'or example, the development of monoclonal antibodies gave us the possibility to identify specifi1.: proteins in comp le;< tissues (1, 2). The identification of 1.:ellular components mvol ved in intracellular Mate.r1' 0111i' "'': Htgl1-n1ro11g'1µ11f Scret~1i11g ef Biumorerla/ Pmpertil~~. ed Jan de Boi:r and Clemens van Ulilterswijk. Puhl1shcd h)' C1m1bridge Univcn;ity Prc.qs, © C11mbrirlge Univrnsiry Press 2013.

FORUM Are In Vitro Tests Suitable for Regulatory Use

Point: Legitimate and Illegitimate Tests of Free-Analyte Assay Function

Clinical Chemistry, 2009

Applying Good Laboratory Practices (GLPs) to in vitro studies, one laboratory's perspective

The steady increase in industry use and regulatory acceptance of in vitro test methods has resulted in an increased need to apply Good Laboratory Practice (GLP) regulations to these systems. The original GLP regulations, developed to address the conduct of animal studies, are concerned with many special conditions that apply to animal housing and care, and the relatively long duration of animal studies, that are not present in the shorter in vitro studies. In animal studies, for example, emphasis is placed on the isolation of species and periodic analysis of feed and water; whereas in non-animal studies, there is increased importance on the justification of the test system. Recently, the Organization for Economic Cooperation and Development (OECD) has published advisories (No. 7, The Application of the GLP Principles to Short-term Studies, 1999; No. 14 The Application of the Principles of GLP to in vitro Studies, 2004) to clarify the application of the GLP principles to both short-t...

Basics of Assay Equipment and Instrumentation for High Throughput Screening

2016

This chapter contains a synopsis of general and specialized instrumentation used in screening and lead optimization laboratories. The instrument type is described along with the general principles of operation to familiarize readers considering equipping drug discovery laboratories, principally directed to new investigators. The descriptions are introductory and detailed information on installation and applications should be obtained from instrument vendors and experienced drug discovery scientists and engineers.