This document discusses the requirements and contents of an Investigator's Brochure (IB) and Investigational Medicinal Product Dossier (IMPD). The IB is intended to inform investigators about the investigational product and facilitate their understanding of the clinical trial. It includes summaries of nonclinical and clinical data, adverse reactions, and guidance for investigators. The IMPD provides the basis for approval of clinical trials in the EU. It includes quality, nonclinical, clinical, and risk-benefit data for the investigational product as well as other required documents and forms. Both the IB and IMPD aim to ensure the safety of clinical trials and protection of human subjects.

1. Presented by:
Naveen Balaji
1st M.Pharm
Department of
Pharmaceutics
SSCP
Tumkur.
Under guidance of:
Dr . P. Ashok Kumar,M.Pharm,Ph.D,
Associate Professor,
Department of
Pharmaceutics,
SSCP,
Tumkur.

2. THE INVESTIGATOR’S BROCHURE
 The IB is a compilation of the clinical and nonclinical data on the
investigational product that are relevant to the trial of the product
in human subjects.
 Its purpose is to provide the investigators and others involved in
the trial with the information to facilitate their understanding of
- The rationale (a set of reasons or a logical basis )
- Their compliance with many key features of the protocol, such
as the
dose, dose frequency/interval,
- Methods of administration, and safety monitoring procedures.

3. • The information should be presented in a concise(giving a lot
of information clearly ), simple, objective, balanced, and non
promotional form .
• It will enables a clinician or potential investigator to
understand it, and make his or her own unbiased(impartial)
risk-benefit assessment of the appropriateness of the proposed
trial.

4. •For this reason, a medically qualified person
should generally participate in the editing of an
IB, but the contents of the IB should be
approved by the disciplines that generated the
described data.
•The IB should be reviewed at least annually and
revised as necessary in compliance with a
sponsor’s written procedures The revised
version should be included in the
IND(Investigational New Drug) annual report..

5. • Generally, the sponsor is responsible for ensuring that
an up-to-date IB is made available to the
investigator(s).
• And the investigators are responsible for providing the
up-to-date IB to the responsible IRB(institutional
review board)/IEC(independent ethics committee ).
• The following information that should be included in
the IB
1. Title Page
2. Confidentiality Statement
3. Contents of the Investigator’s Brochure

6. TITLE PAGE
TITLE PAGE OF INVESTIGATOR’S BROCHURE (Example)
 Sponsor’s Name
 Product
 Research Number
 Name(s): Chemical, Generic (if approved)
 Trade Name(s) (if legally permissible and desired by the
sponsor)
 Edition Number
 Release Date
 Replaces Previous Edition Number
 Date

7. Confidentiality Statement
• The sponsor may wish to include a statement
instructing the investigator/ recipients to treat the IB as
a confidential document for the sole information and
use of the investigator’s team and the IRB/IEC.
• IRB-institutional review board
• IEC-independent ethics committee

8. Contents of the Investigator’s Brochure
• TABLE OF CONTENTS OF INVESTIGATOR’S BROCHURE
(An Example)
• Confidentiality Statement (optional)
• Signature Page (optional)
• 1. Table of Contents
• 2. Summary
• 3. Introduction
• 4. Physical, Chemical, and Pharmaceutical
Properties and Formulation

9. 5. Nonclinical Trials
5.1. Nonclinical Pharmacology
5.2. Pharmacokinetics and Product Metabolism in
Animals
5.3. Toxicology

10. • 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)]

11. Introduction
• A brief introductory statement should be provided that
contains
a. The chemical name (and generic and trade name(s) when
approved)
b. All active ingredients
c. Pharmacologic class and its expected position within this class
d. Anticipated prophylactic, therapeutic, or diagnostic
indication(s).
e. General approach to be followed in evaluating the
investigational product.

12. Nonclinical Trials
• The information provided may include the following, as appropriate, if known
or 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
• Information on systemic distribution
• Duration of post exposure follow-up
• 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

13. • Effects in Humans
• A thorough discussion of the known effects of the
investigational product in humans should be provided,
including information on Pharmacokinetics, metabolism,
Pharmacodynamics, dose response, safety, efficacy, and other
Pharmacologic activities.
• Information on the pharmacokinetics of the investigational
product, should be presented, including the following, if
available:
1. Pharmacokinetics (including metabolism, as appropriate, and
absorption, plasma protein binding, distribution, and
elimination)

14. • 2. Bioavailability of the investigational product
(absolute, where possible, or relative) using a
reference dosage form
• 3. Population subgroups (e.g., sex, age, and impaired
organ function)
• 4. Interactions (such as, product–product interactions
and effects of food)
• 5. Pharmacokinetic data (e.g., results of population
trials performed within clinical trial(s))

15. • Summary of Data and Guidance for the Investigator
• The overall aim of this section is to provide the
investigator with a clear understanding of the possible
risks and adverse reactions, and of the specific tests,
observations, and precautions that may be needed for a
clinical trial

17. INTRODUCTION
 The Investigational Medicinal Product Dossier is the basis for
approval of clinical trials by the competent authorities in the EU.
 The Clinical Trials Directive (2001/20/EC) came into force in April
2001, 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
 The Directive introduced a harmonised procedure for the
authorization to perform a clinical study in any one of the EU
Member States.

18. •In addition, it defines the documentation to be
submitted to the Ethics Committee as well as the
Investigational Medicinal Product Dossier (IMPD)
to be submitted to the competent authority for
approval.

19.  The IMPD includes summaries of information related to the
- Quality, manufacture and control of the Investigational Medicinal Product,
data from non-clinical studies and from its clinical use.
- An overall risk-benefit assessment
- Critical analyses of the non-clinical and clinical data in relation to the potential
risks and benefits of the proposed study have to be part of the IMPD.
 This Dossier will basically be composed of the information as was
previously presented for the IND (Investigational New Drug).
 The difference being that the format for the information presented in an
IMPD.

20. The following should accompany the IMPD:
• Receipt of confirmation of EudraCT number (see chap. 24)
• Covering letter
• Application form
• List of all CAs(competent authority) where application has been submitted
• Copy of IEC(Independent ethics committee) approval or comments
• Any letters of concern received from any MS
• Copy of any scientific advice
• A letter of authorization for use when applicant is not the sponsor
• Confirmation that CA will accept application in English
• Informed consent form
• Subject information (if any)
• Arrangement for recruitment of subjects
• Protocol with any amendments
• Summary of protocol in the national language
• Peer review of trial if available
• Ethical assessment by principal investigator
• Investigators Brochure (IB) (see IND for detail)
• Report of any trial with same IMP
• Example of label in the national language.

21. The following is a listing of the data that should be included in the IMPD:
a. Quality data including summaries of chemical, pharmaceutical and biological data
on the IMP. Data should be based on the IMPs to be used for a clinical trial whose
manufacture complies with the principle of Good Manufacturing Practice (GMP)
Applicants should also supply the following:
– A copy of the manufacturing authorization stating the scope of the
authorization if the IMP is manufactured in the EU and does not have a
marketing authorization in the EU.
– If the IMP is not manufactured in the EU and does not have a marketing
authorization in the EU
– Certification of the Qualified Person that the manufacturing site works in
– Compliance with GMP at least equivalent to EU GMP
– Certification of the GMP status of any active biological substance
– Copy of the importer’s authorization
b. Nonclinical pharmacology and toxicology data
c. Previous clinical trial and human experience data
d. Overall risk and benefit assessment section

22. Simplified IMPD
In certain situations, e.g. where the Investigational Medicinal
Product has already been authorized as a medicinal product in
one of the EU Member States or where clinical studies with
the IMP have already been approved by a Member State, a
simplified IMPD will be sufficient.

23. REFERENCES
• New Drug Approval Process, Edited By:
Richard Guarino. Page No: 136 – 144.