Investigator brochure
- 1. INVESTIGATOR’S BROCHURE(IB) INTRODUCTION Investigator brochure is a collection of the clinical and non-clinical data on the investigational product that are relevant to the study of the product in human subject. IB is a comprehensive document summarizing the information about the investigational product obtained during a clinical trials. The information should be presented in a short, simple, objective, and non-promotional form that enables a clinical or potential investigator to understand it.
- 2. IB is prepared by the sponsor who also controls the distribution of the document. The sponsor is responsible for ensuring that an up-to- date IB is made available to the investigator and investigators are responsible for providing the up-to-date IB to the responsible IRB/IEC. IB provides the investigator and other staff with background information about the investigational medicinal product.`
- 3. GENERAL COSIDERATION The IB should include: Title page This should provide the sponsor ‘s name, the identity of each investigational product(i.e., research no. ,chemical or approved generic name, trade name and the release date). It also suggested that an edition no. ,reference no. and date of edition. For example….
- 4. TITLE PAGE (Example) SPONSOR'S NAME Product: Research Number: Name(s): Chemical, Generic (if approved) Trade Name(s) (if legally permissible and desired by the sponsor) INVESTIGATOR'S BROCHURE Edition Number: Release Date: Replaces Previous Edition Number: Date
- 5. Confidentiality statement The sponsor may include a statement instructing the investigator to treat the IB.
- 6. Contents of the Investigator’s Brochure The IB should contain the following sections.. Table of Contents An example of the Table of Contents is given in Appendix 2 .
- 7. TABLE OF CONTENTS OF INVESTIGATOR'S BROCHURE (Example) -Confidentiality Statement (optional)........................................................................... - Signature Page (optional)............................................................................................. 1 Table of Contents ......................................................................................................... 2 Summary ...................................................................................................................... 3 Introduction .................................................................................................................. 4 Physical, Chemical, and Pharmaceutical Properties and Formulation .................... 5 Nonclinical Studies ...................................................................................................... 5.1 Nonclinical Pharmacology .......................................................................................... 5.2 Pharmacokinetics and Product Metabolism in Animals
- 8. 6 Effects in Humans ........................................................................................................ 6.1 Pharmacokinetics and Product Metabolism in Humans ............................................ 6.2 Safety and Efficacy ....................................................................................................... 6.3 Marketing Experience .................................................................................................. 7 Summary of Data and Guidance for the Investigator ................................................ NB: References on 1. Publications 2. Reports These references should be found at the end of each chapter Appendices (if any)
- 9. Summary A brief summary should be given highlighting the significant physical, chemical, pharmaceutical, pharmacological, toxicological, pharmacokinetic, metabolic, and clinical information of the investigational product. Introduction A brief introductory statement should be provided that contains … The chemical name (and generic and trade name(s) ) of the investigational product. All active ingredients
- 10. The investigational product Pharmacological class and its expected position within this class (e.g. advantages), Therapeutic, or diagnostic indication. The introductory statement should provide the general approach to be followed in evaluating the investigational product.
- 11. Physical, Chemical, and Pharmaceutical Properties and Formulation A description should be provided of the investigational product substance( the chemical and/or structural formula(e)), and brief summary should be given of the physical, chemical, and pharmaceutical properties. To permit appropriate safety measures to be taken in the course of the trial, a description of the formulation(s) used.
- 12. Instructions for the storage and handling of the dosage form(s) should also be given. Any structural similarities to other known compounds should be mentioned. Nonclinical studies Introduction: The results nonclinical pharmacology, toxicology, pharmacokinetic, and investigational product metabolism studies should be provided in summary form. This summary should address the methodology used, the results, possible unfavourable and unintended effects in humans.
- 13. The information provided may include the following, as appropriate, if known/available: Species tested Number and sex of animals in each group Unit dose (e.g., milligram/kilogram (mg/kg) Dose interval Route of administration Duration of dosing Duration of post-exposure follow-up
- 14. Results, including the following aspects: − Nature and frequency of pharmacological or toxic effects Severity or intensity of pharmacological or toxic effects Time to onset of effects Reversibility of effects Duration of effects Dose response
- 15. (A) Non-clinical pharmacology A summary of the pharmacological aspects of the investigational product , its significant metabolites studied in animals, should be included. (B)Pharmacokinetics and product metabolism in animals A summary of the pharmacokinetics and biological transformation of the investigational product in all species studied . The discussion of the findings should address the absorption and the local and systemic bioavailability of the investigational product and its metabolites, and their relationship to the pharmacological and toxicological findings in animal species.
- 16. (C) Toxicological A summary of the toxicological effects in different animal species should be described under the following headings where appropriate: Single dose Repeated dose Carcinogenicity Special studies (e.g. irritancy and sensitisation) Reproductive toxicity Genotoxicity (mutagenicity)
- 17. Effects in Humans Introduction Effects of the investigational product(s) in humans should be provided, including information on pharmacokinetics, metabolism, pharmacodynamics, dose response, safety, efficacy, and other pharmacological activities. (A) Pharmacokinetics and Product Metabolism in Humans − A summary of information on the pharmacokinetics of the investigational product(s) should be presented… Pharmacokinetics (including metabolism, as appropriate, and absorption, plasma protein binding, distribution, and elimination).
- 18. Bioavailability of the investigational product (absolute, where possible, and/or relative) using a reference dosage form. Population subgroups (e.g., gender, age, and impaired organ function). Interactions (e.g., product-product interactions and effects of food). Other pharmacokinetic data (e.g., results of population studies performed within clinical trial.
- 19. (B) Safety and Efficacy A summary of information should be provided about the investigational product's/products' (including metabolites) safety, pharmacodynamics, efficacy, and dose response that were obtained from preceding trials in humans (healthy volunteers and/or patients). Tabular summaries of adverse drug reactions for all the clinical trials (including those for all the studied indications) would be useful.
- 20. Important differences in adverse drug reaction patterns/incidences across indications or subgroups should be discussed. A description should also be provided of the precautions or special monitoring to be done as part of the investigational use of the product.
- 21. (C)Marketing Experience The IB should identify countries where the investigational product has been marketed or approved. Any significant information arising from the marketed use should be summarised (e.g., formulations, dosages, routes of administration, and adverse product reactions). The IB should also identify all the countries where the investigational product did not receive approval/registration for marketing or was withdrawn from marketing/registration.
- 22. Summary of data and guidance for the investigator This section should provide an overall discussion of the nonclinical and clinical data, and should summarise the information from various sources of the investigational product(s), wherever possible
- 23. The overall aim of this section is to provide the investigator with a clear understanding of the possible risks and adverse reactions of the specific tests, observations, and precautions that may be needed for a clinical trial. This understanding should be based on the available physical, chemical, pharmaceutical, pharmacological, toxicological, and clinical information on the investigational product.
- 24. THANK YOU KANCHAN GUPTA M.PHARM(Pharmacology) Advance institute of biotech and paramedical sciences