CLSI Provides Strategies For The Design And Validation Of Immunoassays For The Assessment Of Human Allergenicity Of New Biotherapeutic Drugs
The Clinical and Laboratory Standards Institute (CLSI) recently published Design and Validation of Immunoassays for Assessment of Human Allergenicity of New Biotherapeutic Drugs; Approved Guideline (I/LA34-A). This document provides guidance for the design, validation, analytical performance, and quality assurance of laboratory assays used in the measurement of human immunoglobulin E (IgE) antibodies specific for new biotherapeutic drugs.
When a new drug is developed and evaluated in clinical trials, pharmaceutical companies establish assays early in the drug development process to monitor subjects for possible drug immunogenicity. The development of a drug-specific antibody response is used as the principal indicator for a drug's ability to induce a humoral immune response in humans.
However, development of an assay to detect human IgE antibodies is more demanding than its companion drug-specific immunoglobulin G (IgG) antibody assay. To this end, I/LA34 addresses the technical challenges that are uniquely associated with the development of this type of assay, which detects drug-specific IgE antibody in human blood and tissue extracts. It also provides an approach for validation of an assay in the absence of a positive drug-specific human IgE antibody serum, which involves a feasibility study phase and then development and validation, using a concomitantly established drug-specific human IgG antibody assay as part of its quality control program.
"The document was created to address outstanding issues of confusion regarding validation, use, and application of human IgE antibody assays for new drugs," says Robert G. Hamilton, PhD, D.ABMLI, Professor of Medicine and Pathology at Johns Hopkins University School of Medicine in Baltimore, Maryland, USA, and chairholder of the committee that developed the document. "IgE antibody assays pose unique problems that differ from IgG and immunoglobulin M antibody assays. IgE antibody assays are being increasingly performed to identify the causes of adverse reactions to new drugs in phase II and III clinical trials."
This guideline is intended to complement existing comprehensive immunogenicity (IgG assay)-based recommendations by selectively addressing unique aspects of therapeutic drug-specific human IgE antibody assay development, validation, and performance specifications.
Where possible, validation techniques presented in the IgG antibody documents are used to minimize redundancy.
I/LA34 is designed for use by academic and industrial laboratory scientists and clinicians, and drug manufacturers. "The principal audience includes all drug manufacturers who must examine new drugs that they are filing with the US Food and Drug Administration for immunogenicity and allergenicity," Dr. Hamilton explains. This includes clinical and laboratory investigators who are involved in generating preclinical data and performing clinical trials involving new biotherapeutic drugs. It is also intended as a guideline for administrators of manufacturer safety programs, and government regulators to assess the validity of allergenicity data that have been submitted by innovator pharmaceutical investigators as part of the governmental licensing process for a new drug.
CLSI is a volunteer-driven, membership-supported, nonprofit organization dedicated to developing standards and guidelines for the health care and medical testing community through a consensus process that balances the perspectives of industry, government, and the health care professions. For more information, visit www.clsi.org.
SOURCE: The Clinical and Laboratory Standards Institute