The discovery and development of live biotherapeutic products have revolutionized and continue to reshape the medical and pharmaceutical industries. This exciting frontier of science involves leveraging microorganisms for therapeutic purposes to treat or prevent diseases. The process involves the significant quartet of isolation, cultivation, and identification of strains, safety evaluation of these strains, dedicated drug efficacy studies, and detailed mechanism research.
Fig.1 Graphical pathway for live biotherapeutic products development. (O'Toole, 2017)
Live Biotherapeutics harness the therapeutic potential of living microorganisms to establish and maintain the human microbiota. The initial step in the development process, therefore, entails the isolation of strains from various sources which are examined for biotechnological potential. This stage is conducted under sterile conditions and often involves techniques such as streaking on antibiotic agar plates, polymerase chain reaction (PCR) or through the use of selective media and microscopy.
Once isolated, the next step encompasses the cultivation of these strains under optimal conditions to facilitate their growth and proliferation. This phase requires precision and utmost diligence as variables such as temperature, pH, and oxygen levels significantly impact organism success.
Lastly, the identification of strains is conducted using methods like 16S rRNA sequencing, next-generation sequencing, or MALDI-TOF mass spectrometry. This ensures the right strain is selected for the development of the final product.
Before conducting clinical trials or releasing a live biotherapeutic product into the market, it is mandatory to conduct a thorough safety assessment of the strain. This safety evaluation seeks to uncover any potential risk factors, toxicities, or adverse effects associated with the utilization of the strain in question.
Various tests such as antibiotic susceptibility tests, cytotoxicity assays, and genotoxicity tests are conducted during this phase. Also, thorough genomic analysis for potential pathogenic determinants is a fundamental step towards understanding the safety profile of the strain. The retrieved results are then evaluated against regulatory guidelines to ensure the strain poses no risk to human health.
Following the comprehensive safety evaluation, subsequent steps involve the examination of the strain's therapeutic efficacy. This requires rigorous in vitro assays and in vivo studies often using suitable animal models. It provides useful insights into the biotherapeutic's effectiveness in disease treatment or prevention, dosage requirements, pharmacological properties, and potential interactions.
Furthermore, human clinical trials are executed in phases. Phase I evaluates safety and tolerability, Phase II investigates the efficacy, and Phase III confirms its effectiveness, closely monitors side effects and compares it to commonly used treatments. If the trials are successful, the drug may proceed to regulatory approval.
Understanding the underlying mechanism of action is paramount. It can be notably complex in live biotherapeutics given their interaction with the human microbiota and immune systems. Mechanism research aids in determining how the strain exhibits its therapeutic effects providing a basis for dosage determination, identifying potential side effects, and directing development of the biotherapeutic.
Modern techniques such as multi-omics analyses, in vitro model systems, and gene editing tools like CRISPR-Cas provide substantial depth to understanding the intricate network of interactions within live biotherapeutics.
The discovery and development of live biotherapeutics is a laborious, intricate, and multi-disciplinary endeavor. It requires an amalgamation of experts in microbiology, systems biology, pharmacology, bioinformatics, immunology, and clinical medicine. This process, although daunting, is fundamental to releasing a safe and effective live biotherapeutic onto the market.
Creative Biolabs provides comprehensive services and products for all processes of live biotherapeutics development. Please feel free to contact us if you have any questions.
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