Unveiling the Drug Development Journey through clinical trial

1. Unveiling the Drug Development Journey through clinical trial Have you ever wondered, how a drug developed and is available to you? What is the pipeline behind it? And how much time this process takes? What is FDA-approved drugs and what are the guidelines followed to develop a drug? Well, to answer all your questions, let’s try to find out the drug development process in clinical research. You all familiar with the term clinical trial, from the discovery of a drug to its commercial availability, there is vigorous clinical researches are conducted at various phases. The whole process generally takes 12-15 years and in all this process costs around eight hundred million dollars to more than one billion dollars. The drug development process comprises several stages that can span decades. Understanding these stages is crucial for comprehending how new therapeutics and vaccines reach the market. Let’s delve into the clinical trial of drug development.

2. Background The pharmaceutical industry has evolved significantly, transitioning from primarily curing diseases to manufacturing active ingredients for therapeutics at scale. This acceleration in pharmaceutical product development has facilitated treatments for chronic diseases and those previously without remedies. Moreover, it can take decades for a drug to progress from discovery to market, with only around 4% of launched drugs achieving a return on investment. Drug Discovery Advancements in chemistry and compound screening development have fueled drug discovery. Combinatorial chemistry has enabled the creation of vast compound libraries, searchable through High-throughput screening (HTS). HTS, an automated process, sifts through these libraries to identify potential hits for specific targets, such as proteins. Despite generating extensive data, HTS can be a high-effort, low-yield activity in the preclinical phase. Rational drug design, incorporating knowledge of biological targets, has gained traction as an alternative approach. The Drug Development Paradigm The drug development paradigm comprises two main phases: preclinical and clinical. Biotechnological companies typically specialize in the preclinical phase, developing multiple drug candidates/ New Chemical Entities (NCEs)and conducting preliminary studies to assess viability. Investigational New Drug applications are submitted, covering formulation development, pharmacology, and toxicology studies. The journey of drug discovery commences with the search for promising molecules or chemical compounds. This complex process demands both keen observation and extensive knowledge, as researchers navigate through evaluating various types of reactions and interactions.

3. Importance of pre-clinical studies in drug development Preclinical studies are a critical phase in drug discovery. But what exactly are preclinical studies? Preclinical studies mark the initial foray into the quest for new therapies, whether targeting emerging diseases or combating established ones. Serving as the initial stage in drug discovery, these studies are pivotal in evaluating the toxicity, efficacy, and safety of prospective drugs. The pre-clinical studies itself take around 4-5 years of the whole process of drug development (Figure 1) Figure 1: Drug development paradigm (26473190)

4. Work-flow for pre-clinical studies Upon identifying a promising target and confirming a lead compound, researchers delve into a realm where the chemistry of the treatment intersects with the biological system. This intersection forms the core of preclinical studies, representing a profound exploration of how the new drug interacts with living organisms. For this purpose, researchers may explore alternative animal models to glean insights into the drug’s effects. By examining every aspect of a potential treatment, from its mechanisms of action to its potential side effects, preclinical studies contributed to all transformative advancements in medical science. Search for alternative animal models A quest is driven by the desire for repeatable results while respecting ethical boundaries. The push for 3Rs solutions (Replace, Reduce, and Refine) in animal research has spurred interest in models that can offer viable alternatives without compromising on genetic homology to humans. In the realm of preclinical trials, there’s a growing trend toward exploring alternative animal models to enhance efficiency and ethical standards. While traditional models like rodents have long been prevalent, they come with inherent limitations, particularly regarding ethical considerations, interspecies difference and the need for reliable data. Zebrafish can be an alternative for rodents Zebrafish stands out as a promising candidate for preclinical studies in drug discovery. It share a remarkable similarity to humans in terms of disease genes, boasting upto 85% genetic homology. This makes them a compelling choice for researchers seeking insights into how new treatments may impact human biology. Unlike traditional animal models, Zebrafish produce hundreds of eggs daily, which develop outside the body within a week. This rapid reproductive cycle, coupled with their transparent embryos, provides

5. researchers with a non-invasive means of observing the effects of new treatments on biological systems. In preclinical studies, researchers test these factors The process of medicine discovery is not merely about identifying potentially useful drugs but also involves converting them into high-quality, effective, and safe formulations. This process generates valuable data regarding appropriate dosing, dosing intervals, and potential impacts and side effects of the treatment. The following are some aspects that should be checked in pre- clinical studies. Acute Toxicity Effect in a single large dose Sub-acute toxicity; involving multiple doses Chronic toxicity in case of prolonged usage Reproductive Toxicity of possible effect on Reproduction function Genetic toxicity for the possibility of mutagenicity Carcinogenicity To bridge the gap between in vitro studies and human clinical trials, preclinical studies often involve testing on animal models that closely mimic human biology. Ensuring alignment with human biology is essential for any drug candidate seeking to advance beyond the preliminary stages of discovery. The transition from early drug discovery to preclinical stages marks a pivotal juncture in a shift toward understanding the new treatment’s impact on human. As the precursor to clinical trials involving human subjects, preclinical studies wield significant influence over drug development. Approval for human trials hinges on a thorough understanding of the potential treatment’s effects. A comprehension that can only be achieved through comprehensive preclinical testing. What are clinical trials or clinical research? These two terms if used simultaneously may create confusion among readers. Well, let’s clear out the differences between clinical trials and clinical research.

6. Clinical trials revolve around pre-clinical research and clinical research. Moreover, clinical trials are defined as those studies that try to figure out the potential of a therapeutic drug in the management control, and prevention of disease. Whereas clinical research is an alternative terminology for medical research. It generally revolves around people, to evaluate the efficiency of drugs as a part of treatment and patient management. Drug development process in clinical research The drug development process in clinical research involves the testing of drug safety or toxicity on the human body. The primary objective was to establish best practices and provide regulators with practical criteria for effective monitoring, thereby ensuring reliable and useful trial outcomes and human safety. Researchers search for lead compounds that show promise in affecting these targets and have the potential to become targeted drug. They involve a series of progressively evolving experiments conducted on human volunteers to evaluate the effectiveness and safety of a new drug. Following rigorous study and completion of preliminary investigations, companies submit inquiries to regulatory authorities for Investigational New Drug (IND) approval, allowing clinical testing in human volunteers. Phases of clinical research Phases of clinical studies progress from preclinical testing, which evaluates experimental therapies before human clinical trials, to Phase 0, Phase I, Phase II, and Phase III trials. These phases involve increasingly larger numbers of participants and aim to assess the safety, effectiveness, and adverse effects (toxicity) of the treatment under investigation. They involve randomizing patients into different treatment groups, known as trial arms, to ensure unbiased outcomes. Automated processes are often used for random allocation of participants to experimental arms. In phase III trials, patients are closely monitored, and the trial may be stopped early if significant adverse effects occur or if one group shows substantial

7. improvement. These trials are typically necessary for FDA approval before a new medication can be widely distributed. Phase IV studies, meanwhile, evaluate FDA-approved treatments in real-world settings, involving thousands of participants. Conclusion Ethical considerations, such as patient history, care during the trial, and accessibility, are crucial. Despite the rigorous process, only around 10% of drug candidates undergoing trials are approved by regulatory agencies. Despite challenges, clinical trial participants play a vital role in advancing medical science. Through ethical conduct and rigorous research, clinical trials remain fundamental to modern medicine, driving innovation and improving patient outcomes globally. Kosheeka can be your trusted partner in preclinical drug discovery process. We provide high quality cell models for drug screening purposes. STAY UPDATED! www.kosheeka.com info@kosheeka.com +91-9654321400