Mayuri Ghavate Dept. of Pharmaceutics AISSMS College of Pharmacy PUNE

1. INVESTIGATIONAL MEDICINAL
PRODUCT DOSSIER
Presented by: Mayuri Ghavate
M.Pharm Pharmaceutics

2. Agenda
Key Topics
Investigational Medicinal
Product Dossier
Objectives of IMPD
Types of IMPDs
P
Data related to the IMP
Headings in IMPD
Documents to be submitted
alongwith IMPD

3. The Federal Food, Drug, and Cosmetic Act prohibits the shipment of a new drug into
interstate commerce unless there exists an approved NDA or an effective IND
application for that drug. In the European Union countries and countries that follow
the EUDirectives, the equivalent information that is required for a new product
application is an effective Investigational Medicinal Product Dossier (IMPD).
The European Union (EU) Clinical Trials Directive issued on May 1,2001, became
national law on May 1,2004. The Directive describes the regulatory and ethical
review processes and the information which now have to precede the initiation of
clinical trials in the EU.
This information has to be submitted to and approved by the Competent
Authorities ( C A ) and the IECs of each Member State (MS) where the trials will be
implemented. EUDirective 2001/20/EC (April 2001) sets out the new rules and
regulations for the approval and conduct of clinical trials in Europe.
The European Union (EU)

4. The Investigational Medicinal Product Dossier (IMPD) is a piece 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 (including reference product and placebo), and data from
non-clinical and clinical studies.
Investigational Medicinal
Product Dossier

5. Since clinical trials will often be designed as multi-center
studies, potentially involving different Member States, it is the
aim of this guideline to define harmonized requirements of
the documentation to be submitted throughout the European
Community
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
Objectives of IMPD

6. Guidance concerning IMP Dossiers can be found in the communication from the European
Commission titled “Detailed guidance on the request to the competent authorities for
authorisation of a clinical trial on a medicinal product for human use, the notification of
substantial amendments and the declaration of the end of the trial” which is based on
Regulation (EU) No 536/2014 on Clinical Trials on Medicinal Products for Human Use
(Repealing Directive 2001/20/EC) commonly referred to as the ‘Clinical Trials Directive’.
European Member States have transformed the requirements outlined in the Directive into the
respective national laws.
Article 2 ( d ) of Directive 2001/20/EC defines an IMP as ‘A pharmaceutical form of an active
substance or placebo being tested or used as a reference in a clinical trial, including products
already with a marketing authorisation but used or assembled (formulated or packaged) in a
way different from the authorised form, or when used for an unauthorised indication, or when
used to gain further information about the authorised form.’
Guidance and Legal Basis

7. As regards GMP compliance, in the following cases no documentation
needs to be submitted:
—the IMP has a marketing authorisation in the EUor in an ICH country, is
not modified, and is manufactured in the EU, or
—the IMP is not manufactured in the EU,but has a marketing
authorisation in the EU,and is not modified.
If the IMP does not have a marketing authorisation in the EUor an ICH
country and is not manufactured in the EU,the following documentation
should be submitted:
—a copy of the importation authorisation as referred to in Article 13(1) of
Directive 2001/20/EC, and
—a certification by the qualified person (QP) in the EUthat the
manufacturing complies with GMP at least equivalent to the GMP in the
EU.

8. Simplified IMPD
Full IMPD
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.
The SmPC will also be sufficient for
studies of dosing regimens where
the Sponsor can demonstrate that
information in the SmPC justifies
the safety of the new dosing
regimen.
Types of IMPDs

9. Data related to the IMP
1.Introductory remarks
The IMPD should be prefaced with a detailed table of contents and a glossary of
terms.
2.Quality data
Quality data should be submitted in a logical structure, such as the headings of the
current version of the Guideline on the requirements to the chemical and pharmaceutical
quality documentation concerning investigational medicinal products in clinical trials.
In exceptional cases, where impurities are not justified by the specification or when
unexpected impurities (not covered by specification) are detected, the certificate of
analysis for test products should be attached.

10. 3.Non-clinical pharmacology and toxicologydata
The applicant should provide summaries of non-clinical pharmacology and toxicology data for
any IMP used in the clinical trial. He should also provide a reference list of studies conducted and
appropriate literature references.
This section should provide a critical analysis of the data and an assessment of the safety of the
product in the context of the proposed clinical trial.
The protocols should meet the requirements of Good Laboratory Practice (GLP) guidelines.
The test material used in the toxicity studies should be representative of that proposed for clinical
trial use in terms of qualitative and quantitative impurity profiles.
4. Previous clinical trial and human experience data
This section should provide summaries of all available data from previous clinical trials and human
experience with the proposed IMPs.
All studies should have been conducted in accordance with the principles of Good Clinical Practice
(GCP).
The applicant should submit the following:
— a statement of the GCP compliance of the clinical trials
—where a clinical trial has been performed in third countries, a reference to the entry of this clinical
trial in a public register, if available.

11. 4. Overall risk and benefit assessment
This section should provide a brief integrated summary that critically analyses the non-
clinical and clinical data in relation to the potential risks and benefits of the proposed
trial
5.Simplified IMPD by referring to other documentation
The applicant has the possibility to refer to other documentation which may be
submitted
alone or with a simplified IMPD to contain the information
Possibility to refer to the SmPC or to the assessment of the IMPD in another
clinical trials application
The applicant may submit the current version of the SmPC as the IMPD if an IMP has a
marketing authorisation in any Member State or in an ICH country
Possibility to refer to the IB
The applicant may either provide a stand-alone IMPD or cross-refer to the IB for the
preclinical and clinical parts of the IMPD.

13. IMPD in cases of placebo
If the IMP is a placebo, the information requirements can be reduced in line with
the requirements

14. The table of contents for a full IMPD follows the headings as given by the relevant guidelines. The
IMPD headings are based on the assumption that detailed information will be provided by the
Investigational Brochure. Only relevant information will have to be provided and several
headings can in general remain empty.
DRUG SUBSTANCE
General Information
1.Nomenclature Structure General Properties
2.Manufacture: Manufacturer(s) Description of Manufacturing Process and Process Control of
Materials Controls of Critical Steps and Intermediates Process validation and/or Evaluation
Manufacturing Process Development
3.Characterisation: Elucidation of Structure and Other Characteristics Impurities
4.Control of Drug Substance: Specification Analytical Procedures Validation of Analytical
Procedures Batch Analyses Justification of specification Reference Standards or Materials
5.Container Closure System
6.Stability
Headings in IMPD

15. INVESTIGATIONAL MEDICINAL PRODUCT UNDERTEST
1.Description and Composition of the Medicinal Product
2.Pharmaceutical Development: Components of the Medicinal Product, Medicinal Product,
Manufacturing Process Development
3.Container Closure System,Microbiological Attributes,Compatibility
4. Manufacture: Batch Formula, Description of Manufacturing Process and Process
Controls, Controls of Critical Steps and Intermediates
5.Process Validation and/or Evaluation, Control of Excipients
6.Specifications: Analytical Procedures, Validation of Analytical Procedures, Justification of
Specifications
7.Reference Standards or Materials
8.Container Closure System
9.Stability
APPENDICES
1.Facilities and Equipment
2.Adventitious Agents Safety Evaluation
3.Novel Excipients
4.Solvents for Reconstitution and Diluents

16. Although the IMPD comprises the main component of the documentation provided to
each MS in order to obtain permission to initiate clinical trials, there are other documents
that need to accompany the IMPD before approval is granted.
1.Receipt of confirmation of EudraCT number
2. Covering letter
3. Application form
4. List of all CAs where application has been submitted
5.Copy of IEC approval or comments
6. Any letters of concern received from any MS
7.Copy of any scientific advice
8. A letter of authorization for use when applicant is not the
sponsor
9.Confirmation that CA will accept application in English
Informed consent form
10.Subject information (if any)
11.Arrangement for recruitment of subjects Protocol with any
amendments
12.Summary of protocol in the national language
13.Peer review of trial if available
14. Ethical assessment by principal investigator
15.Investigators Brochure (IB)
16. Report of any trial with same IMP
17.Example of label in the national language
Documents to be submitted alongwith IMPD

17. Thank you!

18. Resources https://www.imp-dossier.eu/
New Drug Approval Process, Fifth Edition edited by Richard A.
Guarino