IND enabling studies is recommended to conduct a clinical trial to evaluate potential risks related to toxicity and to assess initial doses for clinical trials. An IND (Investigational New Drug) is needed to conduct clinical trials for unapproved drugs or approved products for a new implication.
We require IND enabling to conduct a clinical trial when the drug is a
-new chemical material,
-which is unapproved during investigation in a new dosage mode.
-which is dispensed at an unknown dose level
-which is in conjugation with a different drug and the combination remains unapproved.
The different types of drugs and biologics need to undergo IND enabling studies, even before the clinical studies are initiated. The various entities are small molecule drugs, large molecules, and cellular therapies. Usually, a small molecule drug entails an organic compound that is synthetically derived, inorganic compounds to are involved.
A Small Molecule (or a metabolite) is a low molecular weight organic compound that plays a crucial role in a biological process as a substrate or a product. Metabolomics is a study that deals with small molecules within a range of 50-1500 Daltons (Da). Few examples of small molecules such as sugars, lipids, amino acids, fatty acids, phenolic compounds, alkaloids, etc.
Biologics are large molecules such as peptides, antibody-drug conjugates, antibodies, fusion proteins, and gene therapies. Cellular therapies are composed of cells or tissues obtained from a donor (e.g., islet cells for treating type1 diabetes) and are engineered for therapeutic purposes.
A classic example of a Small Molecule IND enabling studies involves basic research that shows a target involved possesses a disease-modifying effect. The target is identified, and the next few steps are:
-Synthesize and screen compounds to detect the ones that interact with the target through screening via structure-activity relationship screening.
-Methods to improvise compounds through in-vitro assays.
-Choose one among several compounds to proceed further based on physicochemical and pharmacokinetic properties.
The Development plan comprises of various tasks for unique New Chemical Entity (NCE) and the IND enabling filing with FDA are listed below:
-Metabolism, Pharmacokinetics, Range-Finding Studies
-GMP Manufacturing of Drug Substance
-Develop Formulated Drug for in vivo Toxicology Studies
-Definitive non-clinical toxicology studies, GLP toxicology studies, toxicokinetic studies, and Safety Studies
-Analytical Methods Development and Validation
-Clinical Trials Materials Manufacturing
-Preparation of IND enabling documentation
-Shelf product of Drug Substance and Drug Product.
The above listed significant tasks should be conducted sequentially; these tasks can be undertaken in parallel to accelerate clinical trials' initiation. Suppose many non-GMP batch drugs are synthesized in parallel. In that case, complementary tasks can be proposed, which include Preformulation, development of analytical and bioanalytical methods, formulation, and non-clinical toxicology toxicokinetic studies, and pharmacokinetic studies.
Nonetheless, a GMP batch of the drug is needed to manufacture the formulated drug for GLP toxicology study and genetic toxicology. The lead required towards IND can be tedious, and for successful progress, a thorough understanding to support the clinical program is a must. It requires a complete awareness regarding manufacturing and preclinical development, also abstaining from overestimates that may lead to a delayed development program.
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