Impd & ib

For pharmacy students.

1. IMPD & IB Zahid Husain M.Pharm (Pharmaceutics) Faculty of Pharmacy, IU, Lucknow

2. The Investigational Medicinal Product Dossier (IMPD) is one of several pieces of Investigational Medicinal Product (IMP) related data required whenever the performance of a clinical trial is intended in one or more European Union Member States. The IMPD includes summaries of information related to the quality, manufacture and control of any IMP, and data from non-clinical and clinical studies. What is an IMPD ?

3. Guidance concerning IMP Dossiers can be found in the communication from the European Commission titled . The guidance is based on Regulation (EU) No 536/2014 on Clinical Trials on Medicinal Products for Human Use (Repealing Directive 2001/20/EC) on the approximation of laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use. Guidance and legal basis

4. The Regulation comes into force in 2016, harmonising the laws, regulations and administrative provisions of the Member States relating to the implementation of Good Clinical Practice (GCP) in the conduct of clinical trials on medicinal products for human use .

5. When applying for a clinical trial authorisation, a full IMPD is required when little or no information about an IMP has been previously submitted to competent authorities, when it is not possible to cross-refer to data submitted by another sponsor and/or when there is no MA in the Community. A simplified IMPD may be submitted if information has been assessed previously as part of a Marketing Authorisation in any MS or a clinical trial to that competent authority. Full and simplified IMPDs

6. There are also situations where the SmPC of a Marketed Product will suffice as the IMPD. A SmPC may be submitted if the IMP has a Marketing Authorisation in any EU Member State and is being used in the same form, for the same indication and with a dosing regimen covered by the SmPC. 

7. There exists guidance on the section headings to be used in a full IMPD, although the format is not obligatory.  The IMPD can also follow the structure of a Common Technical Document (Module 3).  The IMPD need not be a large document as the amount of information to be contained in the dossier is dependent on various factors such as product type, indication, development phase etc.  If limited or no data is provided within the technical headings, then this must be properly justified . What is the format of an IMPD?

8. The assessment of an IMPD is focussed on patient safety and any risks associated with the IMP.  Whenever any potential new risks are identified the IMPD has to be amended to reflect the changes . This may be the case for changes in IMP impurities, microbial contamination, viral safety, TSE and in some particular cases to stability when toxic degradation products may be generated.  What is a Substantial Amendment?

9. Investigator’s Brochure  The Investigator's Brochure (IB) is a compilation of the clinical and nonclinical data on the investigational product(s) that are relevant to the study of the product(s ) in human subjects.

10.  Its purpose is to 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 . The IB also provides insight to support the clinical management of the study subjects during the course of the clinical trial. The information should be presented in a concise and simple manner. Purpose of I.B.

11. I.B. enables a clinician, or potential investigator , to understand it and make his/her own unbiased risk benefit assessment of the appropriateness of the proposed trial . For this reason, a medically qualified person should generally participate in the editing of an IB.

12.  The Investigator Brochure should include : 1 ) Title Page A. Sponsor name B. The identity of each investigational product (i.e., research number, chemical or approved generic name, and trade name(s ) where legally permissible and desired by the sponsor), C. The Release Date. D. Confidentiality Statement Contents of I.B

13. 1. Table of contents 2 . Summary – not exceeding 2 pages. highlighting the significant physical, chemical, pharmaceutical, pharmacological, toxicological, pharmacokinetic, metabolic, and clinical information available of IP 3 . Introduction: chemical name, active ingredients, pharmacological class, anticipated therapeutic / diagnostic indication(s). General approach to be fallowed in evaluating the IP CONTENTS OF IB

14. 4. Description of I.P. Physical, Chemical and pharmaceutical properties of I.P. Storage and handling of I.P. Any structural similarity with the other known compound given.

15.  The results of all relevant nonclinical pharmacology , toxicology, pharmacokinetic , and investigational product metabolism studies should be provided in summary form.  The information provided may include:  Species tested,  Number of sex in each group  Unit dose (e.g., milligram/kilogram (mg/kg),  Dose interval,  Route of administration and  Duration of dosing. 5. Non clinical studies

16. 5.1 NON CLINICAL PHARMACOLOGY: A summary of the pharmacological aspects of the investigational product studied in animals , should be included. 5.2 PHARMACOKINETICS AND PRODUCT METABOLISM IN ANIMALS A summary of the pharmacokinetics(ADME) and biological transformation and disposition(getting a drug into its appropriate position in the body and in an appropriate concentration ) of the investigational product in all species studied should be given.

17. 5.3 TOXICOLOGY (The study of the adverse effects of chemicals on animals )  A summary of the toxicological effects found in relevant studies conducted in different animal species .  Single dose  Repeated dose  Carcinogenicity  Special studies (irritancy, sensitisation)  Reproductive toxicity  Genotoxicity (mutagenecity)

18. 6. EFFECTS IN HUMANS  A thorough discussion of the known 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. (b ). Safety and Efficacy: A summary of information should be provided about the investigational product's safety, efficacy , pharmacodynamics. (c ). Marketing Experience: The IB should identify countries where the investigational product has been marketed or approved .

19. 7. Summary of Data and Guidance for the Investigator This section should contain nonclinical and clinical data of IP.  IB – provide the investigator a clear understanding of- The possible risks Adverse reactions Observations & precautions needed for the clinical trial .

20. THANK YOU