logging in or signing up INVESTIGATIONAL NEW DRUG , APPLICATIONS abdulrazzaqM.PHARM Download Post to : URL : Related Presentations : Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Uploaded from authorPOINT lite Insert YouTube videos in PowerPont slides with aS Desktop Copy embed code: Embed: Flash iPad Dynamic Copy Does not support media & animations Automatically changes to Flash or non-Flash embed WordPress Embed Customize Embed URL: Copy Thumbnail: Copy The presentation is successfully added In Your Favorites. Views: 1254 Category: Science & Tech.. License: Some Rights Reserved Like it (0) Dislike it (0) Added: December 23, 2010 This Presentation is Public Favorites: 2 Presentation Description No description available. Comments Posting comment... By: aa12 (22 month(s) ago) hello, sir i m doing my m.pharm ...we have ind, nda in our curriculum...so if u cud plz mail me dis ppt at firstname.lastname@example.org... Saving..... Post Reply Close Saving..... Edit Comment Close Premium member Presentation Transcript The IND Process : The IND Process Presented by: ABDUL RAZZAQ M.PHARM PHARMA CHEMISTRY FDA’s Mission : FDA’s Mission FDA has a broad public protection mission Ensure the safe use of regulated products that are themselves safe and efficacious Underlying this mission is FDA decision-making on product applications and labeling Based on complete and accurate information from well-designed, ethically-conducted, and well-monitored clinical research FDA’s Mission in Clinical Research : FDA’s Mission in Clinical Research Ensure Implementation of Good Clinical Practice Standards Embodied in FDA regulation and guidance since the 1960’s and ‘70’s International Standard (ICH E6) since 1996 Enforced through FDA’s review process and in its program of on-site inspections U.S. Clinical Investigator inspections from 1962 Ethics Committee (IRB) inspections from 1978 International CI inspections from 1980 GCP is Comprehensive : GCP is Comprehensive International ethical and scientific quality standard for designing, conducting, recording, and reporting trials that involve the participation of human subjects GCP embraces trial objectives, trial design, study oversight, data collection and quality assurance, study analysis, as well as human subject protection in studies that support product applications Good Clinical Practice : Good Clinical Practice GCP is most fundamentally a System of Shared Responsibilities Clinical Investigators Institutions/Institutional Review Boards Industry (Sponsors/Monitors) Government Regulators FDA’s Authority to Regulate : FDA’s Authority to Regulate Federal Food Drug and Cosmetic Act Requires that an FDA approved marketing or research permit be obtained before certain commodities (such as human drugs, medical devices, veterinary drugs, food additives, etc.) may move across state lines Pharmaceuticals may move across state lines during two stages of human use : Pharmaceuticals may move across state lines during two stages of human use Research prior to “approval” Requires research permit: e.g, Investigational New Drug Exemption (IND) Marketing after “approval” Requires marketing permit: e.g., New Drug Application (NDA) What is an IND/IDE ? : What is an IND/IDE ? An exemption from the law which otherwise requires that a drug (biologic, device) be approved before it can be transported across state lines The standard for approval is evidence of safety and efficacy The IND exemption is granted for purposes of clinical investigation (research) Importance of the IND : Importance of the IND Affirms a body of knowledge about the manufacturing, pharmacology, and toxicology of the drug to support its use in human testing Requires that the clinical investigation(s) be performed in accordance with Good Clinical Practice (GCP) Provides an additional level of protection through FDA oversight The FD&C Act Defines “Drug” Very Broadly : The FD&C Act Defines “Drug” Very Broadly Any of: Article recognized in the U.S. Pharmacopeia, official Homeopathic Pharmacopeia of the US, or official National Formulary, or any supplement Article intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals The FD&C Act Defines “Drug” Very Broadly : The FD&C Act Defines “Drug” Very Broadly Any of: Article (other than food) intended to affect the structure or any function of the body of man or other animals Article intended for use as a component of any article specified in clauses above Section 201(g) of the FD&C Act “Clinical Investigation” is also Defined Broadly : “Clinical Investigation” is also Defined Broadly Any experiment in which a drug is administered or dispensed to, or used involving, one or more human subjects. For the purposes of this part, an experiment is any use of a drug except for the use of a marketed drug in the course of medical practice 21 CFR 312.3 So When Is an IND Required ? : So When Is an IND Required ? In general: An IND is required when an unapproved drug (or biologic) is used in a clinical investigation What About Approved Products : What About Approved Products No IND is needed when an approved product is used in the course of medical practice (even for an indication different from the approved indication) But an IND may be required when an approved products is used in a clinical investigation What About Approved Products : What About Approved Products An IND is needed if: The clinical investigation is intended to be reported to FDA as a well-controlled study in support of a new indication or a significant change in the labeling of the drug The clinical investigation is intended to support a significant change in advertising for the product What About Approved Products : What About Approved Products With the above caveats, clinical investigation of an approved product may be exempt from IND requirements if: The investigation does not involve a route of administration or dosage level or use in a patient population or other factor that significantly increases risks AND The investigation is conducted in accordance with IRB and informed consent requirements What About Approved Products : What About Approved Products FDA has generally allowed the IRB to assess whether risk of an approved product is increased for a given protocol But FDA retains final authority for such determinations What About Approved Products : What About Approved Products It is also important to note that shelf chemicals which bear the same “name” as an approved product are not considered as “lawfully marketed” equivalents of the approved product Approval is specific to dose, formulation, and applicant Need for an IND/IDE:Who to Contact with Questions : Need for an IND/IDE:Who to Contact with Questions Drugs (CDER) Drug Information Branch: (301) 827-4573 Biological Products (CBER) (301) 827-0373 Medical Devices (CDRH) IDE Staff: (301) 594-1190 Food Safety (CFSAN): (202) 418-3126 Related Information : Related Information GCP Regulations IND/IDE Regulations: 21 CFR Part 312/812 IRB Regulations: 21 CFR Part 56 Informed Consent Regs: 21 CFR Part 50 All are accessible at: www.fda.gov/oc/gcp Related Information : Related Information IND Forms Available on-line through: www.fda.gov/cder/regulatory/applications/ IND: What is Required -1- : IND: What is Required -1- General Investigation Plan Investigator’s Brochure Protocol(s): Later protocols submitted as amendments Chemistry, manufacturing and control information Animal pharmacology and toxicology information IND: What is Required -2- : IND: What is Required -2- Previous human experience Additional information Dependence and abuse potential Plans for pediatric studies Amount of information required in each section depends on novelty of the drug, extent studied, and known or suspected safety concerns The FDA Form “1572” : The FDA Form “1572” IND sponsors are required to obtain a signed FDA Form “1572” from each clinical investigator, containing: Name and address of CI Name and code number of any protocol(s) Name and address of research facility and any clinical labs Name and address of responsible IRB Names of subinvestigators Signed commitment by the investigator Clinical Investigator Responsibilities* : Clinical Investigator Responsibilities* Personally conduct or supervise investigations Ensure all persons assisting in conduct of studies are informed of their obligations Ensure informed consent (21 CFR 50) and IRB review, approval , and reporting (21 CFR 56) requirements are met *(Form FDA 1572: #9. Commitments) Clinical Investigator Responsibilities* : Clinical Investigator Responsibilities* Conduct studies according to relevant, current protocol Make changes in a protocol only after notifying the sponsor Maintain adequate and accurate records Make records available for inspection Agree to comply with all other requirements in 21 CFR 312 *(Form FDA 1572: #9. Commitments) Review of IND Application : Review of IND Application FDA also has responsibilities under GCP The focus of FDA’s IND Review is on safety for human research subjects and ensuring that the studies will produce useful information to assess safety and efficacy of the test product Reviews are Conducted by Teams of Specialists : Reviews are Conducted by Teams of Specialists Medical Officer Consumer Safety Officer/Project Manager Statistician Chemist Pharmacologist Human Biopharmaceutics (Microbiologist) Review of IND Application : Review of IND Application Review team has 30 days to review Focus of review is always on safety/ human subject protection No News = Good News IND Application: If Problems.. : IND Application: If Problems.. “Clinical Hold” Legal order to delay or stop the study in the U.S. Subjects may not be given the investigational drug May be imposed if: Exposure of subjects to unreasonable risk (includes manufacturing problems) Investigator brochure is misleading, erroneous, or materially incomplete Investigator is not qualified Drug Development Under an IND : Drug Development Under an IND Review Team Monitors New Protocols (IND amendments) Safety reports Annual reports Additional chemistry, animal toxicology, microbiology data Review team is available to consult/meet with sponsors: advise on protocol design, advise on drug development plan IND and Non-US Studies : IND and Non-US Studies Studies performed outside of the U.S. may be conducted with or without IND With an IND: Test article can be exported from the U.S. Study must conform to U.S. IND regulations (including U.S. IRB and informed consent rules) IND and Non-US Studies : IND and Non-US Studies Studies performed outside of the U.S. may be conducted with or without IND Without an IND May be acceptable for FDA review in support of a marketing application Export of the test article from the U.S. must conform to FDA regulations Export of an Investigational Drug : Export of an Investigational Drug Mechanisms (21 CFR 312.110) FDA authorization of a written request from the person that seeks to export Adequate information; investigational purposes only; can be legally used in the importing country for investigation; specifies quantity/frequency of shipment FDA authorization of a formal request from the government of the receiving country Export of an Investigational Drug : Export of an Investigational Drug 1996 law also allows drug export for investigational use without prior FDA approval if intended for use in one of 25 countries Australia; Canada; Israel; Japan, New Zealand; Switzerland; European Union Member States (15), Iceland, Norway, and Liechtenstein IND Content/Submission:Who to Contact with Questions : IND Content/Submission:Who to Contact with Questions Center for Drugs ODE I Cardio-Renal (110) 301-594-5300 Neuropharm (120) 301-594-2850 Oncology (150) 301-594-2473 Center for Drugs ODE II Anesthetic, Critical Care & Addiction (170) 301-827-7410 Metabolic/Endocrine (510) 301-827-6430 Pulmonary (570) 301-827-1050 IND Content/Submission:Who to Contact with Questions : IND Content/Submission:Who to Contact with Questions Center for Drugs ODE III Medical Imaging & Radiopharm (160) 301-827-7510 GI & Coagulation (180) 301-827-7310 Repro/Urologic (580) 301-827-4260 Center for Drugs ODE IV Anti-Infective (520) 301-827-2120 Antiviral (530) 301-827-2330 Special Pathogens & Immunologic (590) 301-827-2336 IND Content/Submission:Who to Contact with Questions : IND Content/Submission:Who to Contact with Questions Center for Drugs ODE V Derm/Dental (540) 301-827-2021 Anti-Inflammatory, Analgesic & Ophthalmic (550) 301-827-2040 Over-the-Counter (OTC) (560) 301-827-2222 IND Content/Submission:Who to Contact with Questions : IND Content/Submission:Who to Contact with Questions Center for Biologics (CBER) Office of Vaccines Research and Review (301) 827-0654 Office of Blood Research and Review (301) 827-3524 Office of Therapeutics Research and Review (301) 827-5099 Office of Generic DrugsWho to Contact with Questions : Office of Generic DrugsWho to Contact with Questions OGD Regulatory Support Branch (301) 827-5862 IDE Content/Submission:Who to Contact with Questions : IDE Content/Submission:Who to Contact with Questions Center for Devices and Radiological Health (CDRH) General, Restorative, and Neurological Devices: (301) 594-1184 Clinical Laboratory Devices: (301) 594-3084 Cardiovascular and Respiratory Devices: (301) 443-8320 IDE Content/Submission:Who to Contact with Questions : IDE Content/Submission:Who to Contact with Questions Center for Devices and Radiological Health (CDRH) Ophthalmic and ENT Devices: (301) 594-2205 Reproductive, Abdominal, and Radiological Devices: (301) 594-5072 Dental, Infection Control, and General Hospital Devices: (301) 443-8879 Sponsor Responsibilities : Sponsor Responsibilities Selecting Qualified Investigators Providing investigators with information they need to conduct an investigation properly. Ensuring proper monitoring of the investigation(s) Conduct per protocol Ethical considerations Control of investigational product(s) Safety reporting Sponsor Responsibilities : Sponsor Responsibilities Review Ongoing Investigations A sponsor who discovers that an investigator is not complying with the signed 1572, general investigation plan, or regulations shall promptly either: secure compliance or end the investigator’s participation in the investigation (discontinue shipment and require return/disposal of drug; notify FDA). Sponsor-Investigators : Sponsor-Investigators FDA regulations allow an individual to be both study sponsor and clinical investigator The Dilemma: Many sponsor-investigators believe that the lack of external monitoring and oversight means that they can perform to a lower standard Sponsor-Investigators : Sponsor-Investigators The Dilemma -2- Where a sponsor and an investigator are the same, the number of GCP control points is reduced from four to three A sponsor-investigator therefore needs to be more (not less) informed of responsibilities and more attentive to standards of study conduct and subject protection Subject Education : Subject Education Subject Education is an often neglected facet of GCP; yet, an educated, fully informed, and inquiring subject may be the best resource for ensuring ethical and quality performance in a clinical trial The IRB and institution should pay particular attention to informing subjects where to go with questions or complaints Reporting to FDA : Reporting to FDA Sponsors are required to report serious non-compliance But anyone can report complaints in FDA-regulated clinical trials to FDA FDA’s GCP website (www.fda.gov/oc/gcp) highlights where to report complaints in clinical trials New At FDA : New At FDA FDA has recently established a new Office for Good Clinical Practice to coordinate GCP across FDA and beyond... OGCP: Structure : OGCP: Structure Small Office Strategically located Office of the Commissioner and its Office of Science Coordination and Communication Key Positions David A. Lepay, MD PhD: Senior Advisor for Clinical Science and Director Stan W. Woollen: Associate Director for Bioresearch Monitoring Bonnie Lee: Associate Director for Human Subject Protection Policy OGCP: Functions : OGCP: Functions Centralized (Commissioner’s Office) Role in: GCP Policy Bioresearch Monitoring of Clinical Trials GCP Initiatives International GCP (harmonization) activities GCP Education and Outreach OGCP and Quality Assurance : OGCP and Quality Assurance OGCP will reflect FDA’s Commitment to Quality Assurance Internally Coordinating QA for the Agency’s clinical Bioresearch Monitoring Program of on-site inspections Externally Coordinating Agency GCP policy and initiatives to enhance the quality of clinical research Clinical Trial QA: What We Should Strive For : Clinical Trial QA: What We Should Strive For Building quality in upfront Assuring quality throughout Developing capacity for continuous quality improvement now and in the future Working Together: Plentiful Opportunities : Working Together: Plentiful Opportunities Well-designed, well-conducted clinical trials are not easy If you don’t want to “do it right”, you should not be conducting clinical trials The best systems can only emerge from the broadest possible participation Working Together: Plentiful Opportunities : Working Together: Plentiful Opportunities Quality assurance and quality improvement are integral to development of the best systems ! REFERENCES: : REFERENCES: CDER Guidance: IND Application Process (interactive session) http://www.fda.gov/cder/regulatory/applications/ind_page_1.htm A Review for OCRA US RAC Study Group September 2005, Ginger Clasby, MS, Promedica International European journal of pharmacology. Crystal clinical services (regulatory affairs) modules 3 You do not have the permission to view this presentation. In order to view it, please contact the author of the presentation.