![NEW DRUG APPLICATION
A New Drug Application (NDA) expresses the full story of a drug molecule . Its purpose is
to verify that a drug is safe and effective for its Proposed use in the people studied. A drug
developer must include all about a drug starting from preclinical data to Phase 3 trial data
in the NDA. Developers must include reports on all studies, data, and analysis .[26]Beside
with clinical trial outcomes, developers must include:
Proposed labeling
Safety updates
Drug abuse information
Patent information
FDA Review
Once FDA obtains a complete NDA then FDA team of review may require about 6 to 10
months to take a pronouncement on whether to approve the NDA. If Once FDA obtains a
incomplete NDA then FDA team of review refuse the NDA.](https://image.slidesharecdn.com/variousprocessofdrugdevelopment-210718170709/85/Various-process-of-drug-development-10-320.jpg)
Various process of drug development
- 1. VARIOUS PROCESS OF NEW DRUG DISCOVERY AND DEVELOPMENT Presented by AYAN PAL M.PHARM, 1st SEM DEPARTMENT OF PHARMACEUTICS CALCUTTA INSTITUTE OF PHARMACEUTICAL TECHNOLOGY AND AHS
- 2. CONTENTS 1. INTRODUCTION 2. STAGES OF DRUG DISCOVERY AND DEVELOPMENT 3. SUCCESS RATE OF DEVELOPING A NEW DRUG 4. TIME REQUIRED TO DEVELOP A NEW DRUG 5. REFERENCES
- 3. INTRODUCTION Drug discovery is a multifaceted process, which involves identification of a drug chemical therapeutically useful in treating and management of a disease condition. The process of drug discovery includes the identification of drug candidates, synthesis, characterization, screening, and assays for therapeutic efficacy. Drug discovery and development is an expensive process due to the high budgets of R&D and clinical trials. It takes almost 12-15 years to develop a single new drug molecule from the time it is discovered when it is available in market for treating patients. The average cost for research and development for each efficacious drug is likely to be $900 million to $2 billion. This figure includes the cost of the thousands of failures: For every 5,000- 10,000 compounds that enter the investigation and development pipeline, ultimately only one attains approval.
- 4. STAGES OF DRUG DISCOVERY AND DEVELOPMENT Target identification Target validation lead identification lead optimization Product characterization Formulation and development Preclinical research Investigational New Drug Clinical trials New Drug Application Approval
- 5. TARGET IDENTIFICATION The first step in the discovery of a drug is identification of the biological origin of a disease, and the potential targets for intervention. Target identification starts with isolating the function of a possible therapeutic target (gene/nucleic acid/protein) and its role in the disease. APPROACHES Data mining using bioinformatics Genetic association Expression profile Pathway and phenotypic analysis Functional screening TARGET VALIDATION Target validation is the process by which the expected molecular target –for example gene, protein or nucleic acid of a small molecule is certified. Target validation includes: determining the structure activity relationship(SAR)of analogs of the small molecule; generating a drug- resistant mutant of the presumed target. IDENTIFICATION OF LEAD A chemical lead is defined as synthetically stable, feasible, and drug like molecule active in primary and secondary assays with acceptable specificity, affinity and selectivity for the target receptor. This requires definition of the structure activity relationships well as determination of synthetic feasibility and preliminary evidence of in vivo efficacy and target engagement.
- 6. LEAD OPTIMIZATION Lead optimization is the process by which a drug candidate is designed after an initial lead compound is identified. The process involves iterative series of synthesis and characterization of a potential drug to build up a representation of in what way chemical structure and activity are related in terms of interactions with its targets and its metabolism. PRODUCT CHARACTERISATION When any new drug molecule shows a promising therapeutic activity, then the molecule is characterized by its size, shape, strength, weakness, use, toxicity, and biological activity. Early stages of pharmacological studies are helpful to characterize the mechanism of action of the compound. FORMULATION AND DEVELOPMENT Pharmaceutical formulation is a stage of drug development during which the physicochemical properties of active pharmaceutical ingredients(APIs) are characterized to produce a bioavailable, stable and optimal dosage form for a specific administration route. During preformulation studies the following parameters are evaluated: Solubility in different media and solvents Dissolution of the active pharmaceutical ingredient (API) Accelerated Stability Services under various conditions Solid state properties (polymorphs, particle size, particle shape etc.) Formulation services and capabilities. Formulation development of new chemical entities (NCE) . Optimization of existing formulations Process development for selected dosage forms Novel formulations for improved delivery of existing dosage forms
- 7. Controlled release and sustained release formulations Self-emulsifying drug delivery systems Colloidal drug delivery systems Sub-micron and nano-emulsions PRECLINICAL TESTING Pre-clinical research in drug development process involves evaluation of drug‘s safety and efficacy in animal species that conclude to prospective human outcome. The pre-clinical trials also have to acquire approval by corresponding regulatory authorities. THE INVESTIGATIONAL NEW DRUG PROCESS (IND) Drug developers must file an Investigational New Drug application to FDA before commencement clinical research. In the IND application, developers must include: Preclinical and toxicity study data Drug manufacturing information Clinical research protocols for studies to be conducted Previous clinical research data(if any) Information about the investigator/ developer
- 8. CLINICAL TRIALS Clinical trials are conducted in people (volunteer)and intended to answer specific questions about the safety and efficacy of drugs, vaccines, other therapies, or new methods of using current treatments. Clinical trials follow a specific stud protocol that is designed by the researcher or investigator or manufacturer. Phase 0 clinical trial Phase 0 implicates investigative, first-in-human (FIH) trials that are conducted according to FDA guidelines. Phase 0 trials besides termed human micro dose studies, they have single sub-therapeutic doses given to 10 to 15 volunteers. Phase 1: Safety and dosage Phase I trials are the first tests of a drug with a lesser number of healthy human volunteers. In most cases, 20 to 80 healthy volunteers with the disease/condition participate in Phase 1. Phase 2: Efficacy and side effects Phase II trials are Conducted on larger groups of patients (few hundreds) and are aimed to evaluate the efficacy of the drug and to endure the Phase I safety assessments. These trials aren‘t sufficient to confirm whether the drug will be therapeutic. Phase 2 studies provide with additional safety data to the researchers. Phase 3: Efficacy and adverse drug reaction monitoring Researchers plan Phase 3 studies to prove whether a product deals an action benefit to a specific People or not . Sometimes known as pivotal studies, these studies comprise 300 to 3,000 volunteers . Phase 3 studies deliver most of the safety data
- 9. Phase 4: Post-Marketing Drug Safety Monitoring Phase 4 trials are conducted when the drug or device has been approved by FDA . These trials are also recognized as post-marketing surveillance involve in pharmacovigilance and continuing technical support after approval. Phase IV studies may be required by regulatory authorities (e.g. change in labelling, risk management/minimization action plan) or may be undertaken by the sponsoring company for competitive purposes or other reasons.
- 10. NEW DRUG APPLICATION A New Drug Application (NDA) expresses the full story of a drug molecule . Its purpose is to verify that a drug is safe and effective for its Proposed use in the people studied. A drug developer must include all about a drug starting from preclinical data to Phase 3 trial data in the NDA. Developers must include reports on all studies, data, and analysis .[26]Beside with clinical trial outcomes, developers must include: Proposed labeling Safety updates Drug abuse information Patent information FDA Review Once FDA obtains a complete NDA then FDA team of review may require about 6 to 10 months to take a pronouncement on whether to approve the NDA. If Once FDA obtains a incomplete NDA then FDA team of review refuse the NDA.
- 11. Success Rate Of Developing A New Drug Not every compound that is tested in lab is marketed. Before a drug is marketed, it has to undergo several stages of development. A company has to screen through many thousand compounds that show promising result before it could take on the task of development of a promising compound. For every 1,000 compounds that are identified by a company, only about 30 show promising results. And for every 30 compounds that show promise, three get past the first round of clinical trials and finally, only one hit the market. Sometimes compounds are to be dropped off during regulatory approval process . Thus, to introduce one new drug, a company needs to start with many thousands of compounds. Time Required To Develop A New Drug It may take anywhere between 12 to 15 years to develop a new drug according to PhRMA (Pharmaceutical Research and Manufacturers of America -pharma industry trade group of America). This slowness of drug development is attributed to numerous steps a drug has to go through before it is ultimately launched in the market. Drug development includes about six-and-a-half years of discovery, preclinical testing, and toxicity studies.
- 12. REFERENCES 1. Shayne CG. Introduction: drug Discovery in the 21st Century . Drug Discovery Handbook, Wiley Press, 2005;1-10. 2. Smith GC, Oí Donnel JT. The Process of New Drug Discovery and Development, Eds., 2nd edition, Informa Healthcare, New York 2006. 3. Moffat J, Vincent F, Lee J, Eder J, Prunotto M. Opportunities and challenges in phenotypic drug discovery: an industry perspective . Nature Reviews Drug Discovery, 2017; 16(8):531-543 4. DiMasi JA, Hansen RW, Grabowski HG. The price of innovation: new estimates of drug development costs. Journal of Health Economics, 2003;151-185. 5. Gashaw I, Ellinghaus P, Sommer A, Asadullah K. What makes a good drug target. Drug Discovery Today, 2012; 17:S24-S30 6. http://www.mindbranch.com/products/R198-014 (accessed 30-09-2005) 7. http://www.businessworldindia.com/ (accessed 15-06-06)