Development of a validated molecular analytical method to determine the viral safety of F(AB´)2 products: A novel application for a well-known technique.
Abstract: The immunotherapy agents derived from horses are biological products that allow the neutralization of clinically relevant immunogens, such as the SARS-CoV-2 virus that causes COVID-19, or the neutralization of toxins present in the venoms of snakes, spiders, and other poisonous animals. Due to their importance, detecting adventitious viruses in equine hyperimmune serum (raw material in industrial processes) is a critical step to support the safety of products for human use, and, in consequence, it is a requirement for commercialization and distribution. The safety of the finished product is based on three complementary approaches: (i) testing of the source material (horse serum) donations, (ii) release of the starting material (i.e., pool of horse serum) based on non-reactivity for a range of human infectious or pathogenic viruses, and (iii) validate (selected) steps of the manufacturing process for their capacity to inactivate and/or remove a wide range of viruses potentially present in the starting material. Orthogonal approaches to reduce viral contamination risk include implementing a reliable and validated system for detecting adventitious viruses. Thus, it is necessary to establish trustworthy and sufficiently sensitive analytical methods to evidence the lack of viruses to assure the safety of the therapeutic product. Therefore, in this research, an analytical method based on end-point Reverse Transcription Polymerase Chain Reaction (RT-PCR) was developed, implemented, and validated in hyperimmune equine serum samples to detect Venezuelan equine encephalitis virus, West Nile virus, and Rabies virus.
Copyright © 2023. Published by Elsevier B.V.
Publication Date: 2023-02-22 PubMed ID: 36822561PubMed Central: PMC9943559DOI: 10.1016/j.jviromet.2023.114694Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The researchers developed an effective and verified technique to ensure the viral safety of therapeutics derived from horse serum against harmful toxins and the SARS-CoV-2 virus. They achieved this by using end-point Reverse Transcription Polymerase Chain Reaction (RT-PCR) to reliably identify the absence of the Venezuelan equine encephalitis virus, West Nile virus, and Rabies virus in horse serum samples.
Objective of the Study
- The study’s objective was to develop, implement, and validate an analytical method to certify the absence of harmful viruses in horse serum used to make immunotherapy agents. This B-certain strategy is crucial to affirm the safety of products made for human consumption, which is a prerequisite for distribution and commercialization.
Relevance of the Study
- Immunotherapy agents derived from horse serum are significant in neutralizing harmful immunogens like the SARS-CoV-2 virus, which causes COVID-19, or harmful toxins from venoms of poisonous animals, making them effective therapeutic agents.
- Given their vital role, it is imperative to guarantee the safety of these agents by ensuring the absence of adventitious viruses. This makes the detection of these impurities in the equine hyperimmune serum, the raw material for these agents, a critical validation step towards product safety and hence, commercialization.
Mechanisms of Ensuring Product Safety
- The researchers ensured the safety of the finished product using three complementary approaches: testing of the source material (horse serum) donations, confirming the non-reactivity of the starting material (i.e., pool of horse serum) for a range of human infectious or pathogenic viruses, and validating the steps of the manufacturing process for their potential to inactivate and/or remove a wide range of viruses possibly present in the starting material.
- Furthermore, the study highlights the importance of establishing reliable and sensitively sufficient analytical methods for ascertaining the absence of viruses, effectively assuring the safety of the therapeutic product.
Method Used
- The researchers developed an analytical method based on end-point Reverse Transcription Polymerase Chain Reaction (RT-PCR). This technique was implemented and validated in hyperimmune equine serum samples with the goal to detect Venezuelan equine encephalitis virus, West Nile virus, and Rabies virus.
Cite This Article
APA
Sánchez-Pacheco UA, Bahena-Mondragón BM, Hernández-Piedras FR, Soria-Osorio R, Meneses-Acosta A.
(2023).
Development of a validated molecular analytical method to determine the viral safety of F(AB´)2 products: A novel application for a well-known technique.
J Virol Methods, 315, 114694.
https://doi.org/10.1016/j.jviromet.2023.114694 Publication
Researcher Affiliations
- Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Chamilpa, C.P. 62209 Cuernavaca, Morelos, Mexico; Inosan Biopharma S.A. Arbea Campus Empresarial, Km. 3.8, C.P. 28108 Madrid, Spain.
- Inosan Biopharma S.A. Arbea Campus Empresarial, Km. 3.8, C.P. 28108 Madrid, Spain.
- Inosan Biopharma S.A. Arbea Campus Empresarial, Km. 3.8, C.P. 28108 Madrid, Spain.
- Inosan Biopharma S.A. Arbea Campus Empresarial, Km. 3.8, C.P. 28108 Madrid, Spain. Electronic address: rsoria@inosanbiopharma.com.
- Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Chamilpa, C.P. 62209 Cuernavaca, Morelos, Mexico. Electronic address: angelica_meneses@uaem.mx.
MeSH Terms
- Animals
- Horses
- Humans
- COVID-19
- SARS-CoV-2
- Viruses / genetics
- West Nile virus
- Encephalitis Virus, Venezuelan Equine
Conflict of Interest Statement
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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