This document provides an overview of an Investigational Medicinal Product Dossier (IMPD) and Investigator Brochure (IB). It begins with background on the European Medicines Agency and drug approval process. It then describes the contents and objectives of an IMPD, which includes quality, manufacturing, and clinical data submitted as part of a clinical trial application. Next, it introduces the IB and lists components like the product description, nonclinical study results, effects in humans, and guidance for investigators. The document aims to define harmonized IMPD requirements for clinical trials involving multiple EU member states.

1. Investigation of Medicinal Product Dossier (IMPD)
and Investigator Brochure (IB)
Guided by:
Dr. Vidya Sabale
Associate Professor
Department of
Pharmaceutics
Presented by:-
Tanvi D. Mhashakhetri
M. Pharm 1st Sem
Department of
Pharmaceutics
Dadasaheb Balpande College Of Pharmacy,
Besa , Nagpur -440037
2022-23
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2. Contents:
• European Medicines Agency (EMA)
• IMPD Introduction
• Contents of IMPD
• Objectives
• Scope
• Introduction of IB
• General Consideration
• Content of IB
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3. European Medicines Agency (EMA)
• It is a decentralized agency of the European union.
• The Management Board is the European Medicines Agency’s integral governance Body.
• The Agency is responsible for the scientific evaluation, supervision and safety monitoring of the
medicines developed by pharmaceutical companies use in EU.
• EMA protects public and animal health in 27 EU member states, as well as the countries of the
European economic area , by ensuring that all medicines available on the EU market are safe,
effective and of high quality.
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4. History
• European medical agency was found in 1995, has worked across the EU and globally to protect
public and animal healty by assessing medicines to rigorous scientific standards and providing
with independent, science-based informations on medicines.
• EMA has 20 year track record of ensuring efficacy and safety of human and veterinary
medicines across Europe, and promoting research and innovation in the developments of
medicines.
• In first two decades, the agency recommended the authorization of the total of 975 humans and
188 veterinary medicines.
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5. Drug approval process
There are two regulatory steps to go through before a drug is Approved to be marketed in the EU.
There two steps are:-
1. Clinical trial application
2. Marketing authorization application
• Clinical trial applications are approved at the member state level. Marketing authorization
applications are approved at both the member state or centralized levels.
• Qualified person has to certify that the investigation medicinal product (IMP) is manufactured
according to GMP.
• The component authority has the right to inspect the manufacturing facility for GMP
compliance, the preclinical facility for GLP compliance and the clinical trial sites for GCP
compliance.
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6. Clinical Trial Application
EU directive (April 2001) sets out the new rules and regulations for the approval and conduct of
clinical trials in Europe.
• A sponsor submits a clinical trial application to the competent Authority in each member state
where the trials are to be conducted.
• The competent Authority has 60 days to review and approve or reject the application.
• Application is in prescribed forms and cover the proposed clinical trials protocol, manufacturing
and quality controls on the drug and supporting data, such as:
1. Chemical,biological and pharmacological data
2. Non-clinical pharmacological and toxicological data
3. Previous human experience and clinical data
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7. • Dossier
A collection of documents about a particular person, event or subject
e.g. patient’s medical record
• Medicinal product dossier
File containing detailed records about a particular drug product
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8. Investigational Medical Product Dossier ( IMPD )
• The IMPD is the basic for approval of clinical trials by the competent authorities in the EU .
• The clinical trial directive came in force, harmonizing the laws, regulations and administrative
provisions of the member states relating to the implementation of GCP in the conduct of clinical
trials on medicinal products for human use.
• The directive introduced a harmonized procedure for the authorization to perform a clinical
study in any one of the EU member states.
• 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 competents authority
for approval.
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9. IMPD:
IMPDs are submitted as part of clinical trial application dossier. As the basic for approval of clinical
trials by competent regulatory authorities within European Union.
IND application are equivalent in U.S.
Contents: subsequent trial documentation
1.Protocols
2.Informed consent forms
3.Investigator brochure
4.Study reports
5.Subject narratives
6.Risk management
7.safety update reports
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10. The IMP dossier required will depend on many factor including:
• Risk aspects
• Nature of the product
• State of development
• Patient population
• Nature and severity of the illness
• Type and duration of the clinical trial itself
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11. What is IMPD ?
• The investigational medicinal product dossier (IMPD) is one of several pieces of
investigational medicinal product (IMP) related data required whenever the
performance of the 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 ( including reference product and placebo) , and data from non-
clinical and clinical studies.
Objectives :
• Since clinical trials will often be designed as multi center studies, potentially
involving different member states.
• It is the aim of the guideline to defined harmonized requirements of the
documentation to be submitted through the European community.
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12. Scope
• Guideline addresses the documentation on the chemical and pharmaceutical quality of IMPs
containing chemically defined active substances, synthetic peptides, herbal substances
herbal preparations and chemically defined radio active/radio labelled substances to be
submitted to be competent authority for approval prior to beginning a clinical competent
authority a clinical trials in humans.
• It includes the requirements for IMPs to be tasted in phase I, phase II and phase III studies as
well as the requirements for modified and unmodified comparator requirements for modified
and unmodified comparator products and IMPs to be tested in generic bioequivalenvce
studies and [and placebo products].
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13. • 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 medicinal 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.
• 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.
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14. Procedure :
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15. Investigator’s Brochure ( IB ) :
• Investigator brochure is a collection of the clinical and non-clinical data of 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.
• 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 to the
responsible IRB ( Institutional Review Board ) / IEC( Institutional Ethics Committee) .
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16. General Considerations
Title page
1. Sponsor name
2. The identity of each investigational product (i.e., research
number, chemical or approved generic name, and trade name where legally
permissible and desired by the sponsor).
3. The release date.
4. Confidential statement
Confidential statement
The sponsor may wish to include a statement instructing the investigator to treat the IB as a
confidential document for the sole information and use of the investigators team and the IRB
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17. Contents of IB
The investigator brochure should include :
1. Table of contents
2. Summary :-preferably not exceeding two pages . Should highlighting the significant physical,
chemical, pharmaceutical, pharmacological, pharmacokinetic, metabolic and clinical information
available that is relevant
to the stage of clinical development of the investigational product(IP).
3. Introduction :- A brief introductory statement should be
provided that contains –
• The chemical name ( and generic and trade name ) of the
investigational product.
• All active ingredients
• The investigational product
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18. • Pharmacological class and its expected position within this class
• Therapeutic or diagnostic indication.
• The introductory statement should provide the general approach to be followed in
evaluating the investigational product.
4. Description of investigational product (IP) :-
• A brief summary should be given of the relevant physical, chemical , and pharmaceutical
properties.
• A discription of formulation to be used, including
excipients, should be provided and justified if clinically relevant.
• Instructions for the storage and handling of the dosage form should also be given.
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19. 5. Nonclinical Studies
The result of all relevant nonclinical pharmacological ,toxicology, pharmacokinetic and
investigational prouct metabolism studies should be provided in summary form.
The information provided may include:-
• Species tested
• Number and gender of animal in each group
• Unit dose (e.g., mg/kg)
• Dose interval
• Route of administraton
• Duration of dosing
• Information on systemic distribution
• Duration of post-exposure follow up
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20. Result including following aspects:-
• Nature and frequency of pharmacological or toxic effect
• Severity or intensity of pharmacological or toxic effects.
• Time to onset of effects
• Duration of effects
• Dose response
(A) Non-clinical pharmacology
A summary of the pharmacological aspect of the investigational product, its significant
metabolites
studied in animal should be included.
(B) Pharmacokinetic and product metabolism in animal
• A summary of the pharmacokinetic and biological transformation and deposition of the
investigational product in all species studied should be given.
•Single dose 20

21. • Repeated dose
• Carcinogenicity
• Special studies (e.g., irritancy and sensitization )
• Reproductive toxicity
• Mutagenicity
Effects in Humans
Introduction :- Effects of the investigational product in humans should be provided, including
information on pharmacokinetc, metabolism , pharmacodynamics, and 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 should be
presented.
• Pharmacokinetics ( including metabolism , absorption, plasma protein binding, distribution
and elimination ).
• Bioavailability of the investigational product using a reference dosage form .
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22. • Population subgroups. (e.g., gender, age , and impaired organ function). Interactions (e.g., effect
of food ).
• Other pharmacokinetic data (e.g., result of population studied performed within clinical trial).
B) Safety and Efficacy
A summary of information should be provided about the investigational products ( including
metabolites), safety, pharmacodynamics, efficacy and dose response that were obtained from
preceding trial in humans ( healthy volunteer / patient ).
C) Marketing Experience
• The IB should identify countries where the investigational product has been marketed or
approved.
• The IB should also identify all the countries where the investigational product did not receive
approval/
registration for marketing .
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23. 6. Summary of Data and Guidance for the Investigator
• This section should provide an overall discussion of the nonclinical and clinical data of IP.
• IB provide the investigator a clear understanding of
- The possible risk
- Adverse reaction
- Observation &precaution needed for the clinical trial.
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24. References :
1. Richard A. Gaurino , M.D., New Drug Approval Process , Fifth Edition,
2. http;//www.imp-dossier.eu/
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25. THANK YOU
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