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Regulatory Requirements For New Drug Approval

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Regulatory Requirements For New Drug Approval

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Regulatory Requirements For New Drug Approval.
This topic is from Industrial Pharmacy-II, B.Pharm Final year VIIth semester.
It include rule and regulations related to new drug approval for clinical use.

Regulatory Requirements For New Drug Approval.
This topic is from Industrial Pharmacy-II, B.Pharm Final year VIIth semester.
It include rule and regulations related to new drug approval for clinical use.

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Regulatory Requirements For New Drug Approval

  1. 1. Regulatory Requirements For New Drug Approval Prepared by- Shagufta Farooqui Assistant Professor Nanded Pharmacy College, Nanded
  2. 2. Regulatory Affairs Regulatory affairs in pharmaceutics are like vehicle inspectors in the automotive industry. They assess and perform quality checks to ensure that medicinal drugs, veterinary drugs and nutritional supplements rolled out by the pharmaceutical industry are safe and effective for the consumers to use. In other words, regulatory affairs are in place to protect public health by evaluating the processes of drug discovery, production, and promotion of pharmaceutical products. Regulatory affairs in the pharmaceutical industry comprise of a variety of functions. One of these functions includes staying abreast of the changes in the legislation of pharmaceutical drug research, manufacture, and marketing. This is a critical task as keeping updated on the rules and regulations of the pharmaceutical industry will govern the manufacturing and marketing practices of the pharmaceutical companies.
  3. 3. WHY? 1922 : JAUNDICE associated with the use of SALVARSAN, an organic arsenical used in the treatment of Syphilis. In 1937: In USA, 107 people died from taking an ELIXIR OF SULFANILAMIDE that contained the SOLVENT DIETHYLENE GLYCOL. Establishment of the FOOD AND DRUG ADMINISTRATION (FDA), which was given the task of enquiring into the safety of new drugs before allowing them to be marketed. 1958: Thalidomide marketed in West Germany as a non barbiturate hypnotic & for morning sickness during pregnancy based on animal toxicity report
  4. 4. In 1959 - 1961, it was reported in that there was an outbreak of PHOCOMELIA (hypoplastic and aplastic limb deformities) in the new born babies. The THALIDOMIDE INCIDENT led to a public outcry, to the institution all round the world of DRUG REGULATORY AUTHORITIES, to the development of a much more sophisticated approach to the preclinical testing and clinical evaluation of drugs before marketing. Such Tragic incidence led to introduction of regulations for new drugs
  5. 5. Sr no. Countries Regulatory body 1 USA FDA 2 UK Medicines and healthcare products Regulatory Agency(MHRA) 3 Australia Therapeutic Goods administration(TGA) 4 India (CDSCO) Central Drugs Standard Control Organisation 5 Canada Health Canada 6 Europe European medicines Agency 7 Japan Ministry of Health, Labour and welfare(MHLW) Regulatory Authorities:
  6. 6. Following acts and rules were passed: 1. Drug and cosmetic act,1940: It regulates the manufacturing, distribution, import and sale of allopathic, homeopathic, unani and siddha drugs. 2. Drug and cosmetic act,1945: This act regulates manufacture of ayurvedic drugs for sale only, not for consumptions and use or possession. 3. Pharmacy Act,1948 4. Drugs and magic remedies rule,1955: This rules regulates the advertisement of drugs in India. 5. Drug price control order (DPCO),1955: 6. Indian patent Act, 1970: 7.1980-1990: The Indian industry has started investing process development of API and created production for the same.
  7. 7. 8. 1990-2000: A rapid expansion in domestic market has observed in pharmaceutical industry. The companies started entering into Research and Development. 9. 2000-2010: This period is considered to be the innovation and Research activity, patenting of the drugs formula process. 10. Patent Amendment (minor change or addition designed to improve a text, piece of legislation) Act.2005: 11. Compulsory Licenses: Such licenses can be granted for manufacture and export of the drug products to any country having sufficient or no manufacturing capacity, for the said product to address public health problems
  8. 8. Drug Discovery Drug Development Preclinical and Clinical trials Marketing Application Compliance with regulatory requirement is necessary Process for New Drug Approval
  9. 9. Drug discovery is the process by which new candidate medications are discovered
  10. 10. Drug development is the process of bringing a new pharmaceutical drug to the market once a lead compound has been identified through the process of drug discovery.
  11. 11.  Preclinical Trials: Research using animals to find out if a drug, procedure, or treatment is likely to be useful. Preclinical studies take place before any testing in humans is done. During Preclinical drug development, the drugs toxicity and pharmacological effects need to be evaluated through in vitro and in vivo laboratory animal testing.  Clinical trials: Clinical trials are scientific studies of the safety and efficacy of a new medical drug or other treatment, conducted on human volunteers. Clinical trials(Human testing of drugs) are a set of procedure in medical research and drug development that conducted to allow safety (information about adverse effects) efficacy of data to be collected for health intervention.
  12. 12. Non-Clinical Drug Development Preclinical/Non-Clinical Trials A laboratory test for novel drug or new medical device is usually done on animal subjects, to see the drug really work and if it is safe to test on humans IT INCLUDES VARIOUS STUDIES-  In silico: Via Computer simulation  In vivo: within the living  In vitro: within the glass(outside the living organism) This process of non-clinical development of medicine is very complex, time consuming and regulatory driven.
  13. 13. Aim of Non-Clinical drug development: 1. To analyse and determine which candidate has the greatest probability of success. 2. To asses its safety to proceed with human clinical trials. 3. To raise firm scientific foundation before transition to the clinical development phase. 4. To collect data to submit to the FDA for filing INDA.
  14. 14. Types of studies included in Preclinical trials: 1.Screening test/Test on animal models for human disease 2.Test on isolated organs, bacterial cell culture 3.Observational study 4.Mechanism of action 5.Pharmacokinetics 6.Toxicity test
  15. 15. Pharmacology: Study the effects of chemical substances on living system It holds all the aspects of drug discovery, ranging from details of interaction between drug molecule and its target to consequences of placing the drug in the market.
  16. 16. Safety Pharmacology  This includes the scientific evaluation and study of potentially life threatening pharmacological effects of potential drug which is unrelated to the desired therapeutic effect and therefore may present a hazard  These test are conducted at low doses/not too much in excess of the intended clinical dose.  Safety pharmacology seeks to identify unanticipated effects of new drugs on major organ function.  It is aimed at detecting possible undesirable or dangerous effects of exposure of the drug in therapeutic doses.
  17. 17. Toxicological Approaches To Drug Discovery Toxicology is the scientific study of adverse effects that occur in living organisms due to chemicals. It involves observing and reporting symptoms that arise following exposure to toxic substances. Acute toxicity- 14 days Sub acute toxicity- 28 days Chronic Toxicity- 90 days
  18. 18. 1. Acute toxicity: Acute toxicity refers to the adverse effects that occur on first exposure to a single dose of a substance. Usually two animal rat and mice will be used and same route will be used as intended in human. Mortality looked after 14 days. Fasted mice or rat Single dose Observed individually for 1hr,4hr and 24hr Behavioral, autonomical, neurological responses Mortality looked after 14 days.
  19. 19. 2. Repeated-dose toxicity studies: These studies have three main objectives: (i) to identify toxicity that develops only after a certain length of continuous exposure to the chemical, (ii) to identify the organs most affected and (iii) to determine the doses at which each effect occurs. Repeated-dose studies are conducted for various periods of time. The 28-day (sub- acute) study is most common, but studies of 90 days to one year are also regularly carried out. Rats and mice are generally used but for certain classes of chemicals, such as agrochemicals and pharmaceuticals, the tests may also be conducted in non-rodent animals such as the beagle dogs, pigs, marmosets or macaques. The test data allow an assessment of the highest dose without significant effects (the ‘no observed adverse effect level.
  20. 20. Different types of Drug Application that can be submitted to FDA • Investigational new drug IND • New drug Application NDA • Abbreviated new drug application ANDA • Biologic license application BLA
  21. 21. Investigational New drug application (INDA) Its application filed to FDA in order to start clinical trials in humans if the drug was found to be safe from the report of preclinical trials. A pre-IND meeting can be arranged with the FDA to discuss a number of issues: The design of Animal research. Protocol for conduction the clinical trials Review the chemistry, manufacturing and control of the investigational drug
  22. 22. 1. IND application is filled to provide the data showing that it is reasonable to begin tests of new drug on humans. 2. During a new drugs early preclinical development the sponsors primary goal is to determine if the product is reasonably safe for initial use in humans and if the composed exhibits pharmacological activity that justify commercial development. 3. When a product is identified viable candidates for further development, the sponsor then focuses on collecting the data and information necessary to establish that the product will not expose Humans to unreasonable risk when used in limits, early stage clinical studies. 4. FDA’s Role in the development of new drug begins when the drugs sponsor having screened the new molecule for pharmacological activity and acute toxicity potential in animals.
  23. 23. Types of IND application Investigator IND Application Emergency use IND Application Treatment IND Application
  24. 24. Investigator’s Brochure (IB) It is a compilation of the clinical and non-clinical data on the investigational product that are relevant to the study of the product in human subject. Provide information to the investigators and others involved in the trial such as the dose, dose frequency/interval, methods of administration and safety monitoring procedures. Provides insight to support the clinical management of the study subjects during coarse of the clinical trial. This information should be presented in a concise and simple manner.
  25. 25. Content of Investigator’s Brochure (IB) 1 • Table of contents 2 • Summary not exceeding 2 pages 3 • Introduction: Chemical name API, Pharmacological class, therapeutic indication 4 • Description of Investigational product: Physical, chemical and pharmaceutical properties of IP, storage and handling of IP. And clinical data of IP 5 • Non clinical studies: The results of all relevant non-clinical pharmacology, toxicology, pharmacokinetic and investigational product metabolism studies should be provided in summary form. 6 • Effects in Humans: ADME, Safety, efficacy and other pharmacological activities 7 • Summary of Data and Guidance for the investigator
  26. 26. New Drug Application (NDA) It is an application submitted preclinical and clinical data for analyzing the drug information and description of manufacturing procedures. The goals of the NDA are to provide enough information to permit FDA reviewers to establish the complete history of the candidate drug. Among facts needed for the application are:  Patent and manufacturing information.  Drug safety and specific effectiveness for its proposed use(s) when used as directed  Reports on the design, compliance, and conclusions of completed clinical trials by the Institutional Review Board.  Drug susceptibility to abuse  Proposed labeling (package insert) and directions for use
  27. 27. Once the application is submitted, the FDA has 60 days to conduct a preliminary review which will assess whether the NDA is “Sufficiently complete to permit a substantive review” If everything is found to be acceptable, FDA will decide if NDA will get a standard or accelerated review and communicate the acceptance of the application and their review choice in another communication known as 74-days letter.
  28. 28. Bio-Equivalence Studies Bioequivalence study: A bioequivalence study refers to a human study, which applies bioavailability study methods with pharmacokinetic parameters as indicators to compare active ingredient absorption rate and extent of the preparations in the same or different dosage forms of a drug in terms of statistical differences under the same experimental condition. Bioequivalence is the biochemical similarity of two (or more) drugs that share the same active ingredient(s) and desired outcome(s) for patients. Pharmacokinetic studies must be done to determine whether a commercially available brand and a potential generic version share core attributes. Bioequivalence or pharmaceutical equivalence must be present showing that the two drugs release the active ingredient into the bloodstream at the same amount, the same rate, and have the same quality.
  29. 29. Bioavailability: Rate and Extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of action Equivalence: It is relative term that compares drug products with respect to a specific characteristic or function or to a defined set of standard.
  30. 30. Clinical Research protocol Research protocol is a document that describes the background, rationale, objectives, design, methodology, statistical considerations, and organization of a clinical research project. It is a complete written description and scientific rationale for a research activity involving human subjects It also states the condition under which the study shall be performed and managed.
  31. 31. 1. To raise the question to be researched and clarify its importance. 2. To collect existing knowledge and discuss the efforts of other researchers who have worked on the related questions (Literature review). 3. To formulate a hypothesis and objectives. 4. To clarify ethical considerations. 5. To suggest the methodology required for solving the question and achieving the objectives. 6. To discuss the requirements and limitations in achieving the objectives. Aim of Clinical Research Protocol
  32. 32. A Clinical Research Protocol should include the following: 1. Protocol title and date 2. Name, address and phone number of the principal investigator and co-investigators, if applicable 3. Site(s) where the study will be performed 4. Sponsor of the study 5. Introduction: Background-Rational-Literature Review: Describe the background, including human subjects or animal research studies, results and references that are relevant to the design and conduct of the study. 6. Research Objectives and Hypothesis: State the precise objectives of the study in the form of a hypothesis. The protocol should be designed to answer the questions posed by the objectives.
  33. 33. 7. Study Design and Research Methods: i. Primary and secondary endpoints ii. Design of the study (double-blind, placebo controlled, etc.) iii. Measures taken to minimize bias (randomization, blinding) 8. Anticipated Results and Potential Pitfalls 9. Discussion of Next Steps 10. References:
  34. 34. THANK YOU

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