& Total Antibody
Measuring potential anti-drug antibody (ADA) generation as an immune response to therapeutic types, such as small peptides, antibodies, bispecifics or gene therapies, is a required part of both pre-clinical and clinical development. Neutralizing antibody (NAb) assays can be cell-based or non-cell-based depending on MOA of the therapeutic.
Precision recommends and delivers the optimal assays based on the appropriate stage of development and risk profile, and develops a quality system to successfully meet regulatory requirements. Notably for AAV-based gene therapy development, we have supported co-development of neutralizing antibody assays as companion diagnostics to support commercial testing.
Recommendations for the Development of Cell-Based Anti-Viral Vector
Neutralizing Antibody (NAb) Assays by Precision’s Eugen Koren, MD
Gorovits Boris,* Michele Fiscella,* Mike Havert,* Eugen Koren,† Brian Long,* Mark Milton,* and Shobha Purushothama*
AAPS J. 2020 Jan 6;22(2):24.
†Precision for Medicine
Assessing safety and activity with anti-drug antibody assays
We support pre-clinical through phase 3 studies with ADA assays for biologic, biosimilar, gene therapy, and companion diagnostic development
Our offerings include method development or transfer, validation, and sample testing, and includes a thorough strategic assessment.
ADA assays, often for neutralizing or total antibodies, are generally conducted using ELISA or MesoScale Discovery (MSD) technologies. Other platforms such as Biacore™ are available if required.
ADA Assay development strategy
- Identify positive control antibodies
- Select optimal assay formats/platforms for binding antibodies
- Select optimal assay formats for neutralizing antibodies
- Design appropriate monitoring strategies
Example ADA assay types
- Screening assay
- Confirmatory assay
- Titer assay
- Neutralizing assay (functional cell-based and non cell-based)
Our ADA assay services also support development and commercialization of total antibody and neutralizing antibody companion diagnostics, including:
- FDA diagnostic pre-submission and modular PMA submissions
- Complete LDT analytical studies under full design control
Our experience speaks for itself-we’ve already successfully completed over 100 CDx regulatory filings globally
Global reach, multi-site support
Our ADA assay services support pre-clinical and clinical research, including multi-site global studies.
Working with Precision
Precision’s specialty lab scientists take a collaborative and consultative approach to projects and can provide recommendations on biomarker assay strategies and implementation, including comprehensive plans for immunogenicity testing.
Services can be provided individually or as part of a comprehensive therapeutic development package including biomarker assays and clinical trials.
Case Study: Development of a NAb CDx for a gene therapy
Because preexisting antibodies may hamper transduction efficiency and reduce efficacy of AAV5 vector-based therapy, the sponsor wanted us to develop and validate an AAV5 NAb CDx to identify patients most likely to benefit from treatment.
We developed and optimized a cell-based luciferase reporter assay that could detect and measure anti-AAV5 capsid antibodies capable of neutralizing viral transduction of HEK 293 cells. This project included maintenance of the cell bank, running the assay, and testing clinical samples.
We are also developing a single-site CDx using our ISO 13485-certified and FDA 21 CFR 820-compliant laboratory facilities. As of early 2019, this project included full regulatory, biostatistical, and commercial services for the CDx, including both strategic and tactical support for all activities throughout the product life cycle.
Optimizing gene therapy development
Understand current FDA guidance and regulations for gene therapy development, and plan for the concurrent development of a companion diagnostic including development of an AAV NAb assay
Integrating biomarker and clinical trial data
To help researchers understand and interpret biomarker assay data in the context of other assays as well as the clinical trial data, Precision provides the option to manage and analyze data using our proprietary QuartzBio Translational Informatics platform.
Learn more about the sample management, informatics, and computational capabilities of QuartzBio>
We offer assay development, validation, and implementation using ELISAs and MesoScale Discovery (MSD) assays for biologics; flow cytometry and Droplet Digital™ PCR (ddPCR) for cell-based therapies; and Quanterix SIMOA® for ultrasensitive detection.
MesoScale Discovery (MSD) Assays
Measure a range of analytes in complex samples matrices consistently and at high sensitivity with our MSD assay capabilities. Applications include ADA, NAb, and TAb assays, PK assays, and more.
ELISA is generally recognized as a gold standard for quantitative, antibody-based analysis. Precision’s ELISA services include assay development or transfer, validation, and implementation