MPH104T

LH 43
Investigation of Medicinal Products Dossier (IMPD)
Session leader
[Link]@[Link]

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Learning Objectives

At the end of this session, student will be able to:

• Define IMP and IMP dossier

• Explain the significance of IMP dossier

• Identify the situations where full and simplified IMPD are applicable

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IMP (Investigational Medicinal Product)- Definition

• A pharmaceutical form of an active substance or placebo being tested or used as a

reference in a clinical trial

• Includes products already with a marketing authorisation but used or assembled

(formulated or packaged) in a way different from the authorised form

• Products used for an unauthorised indication

• Products used to gain further information about the authorised form

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IMP Dossier

Gives information related to

the quality of any IMP (i.e. including reference product and placebo)

manufacture and control of the IMP

data from non-clinical studies and from its clinical use

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IMP Dossier (IMPD)

• The IMPD is the basis for approval of clinical trials by the competent authorities in
the EU (European Union)

• 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

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IMP Dossier

• Member States were obliged to transform the requirements outlined in the

Directive into the respective national laws by May 2004

• The Directive introduced a harmonised procedure for the authorisation to perform

a clinical study in any one of the EU Member States

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IMP Dossier

• 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

• Thus, an IMPD is requested whenever the performance of a clinical study in any

one of the EU Member States is intended

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IMP Dossier

• 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

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IMP Dossier

• In certain situations, e.g. where the Investigational Medicinal Product has already
been authorised 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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Full and simplified IMPDs

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

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Full and simplified IMPDs

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

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Full and simplified IMPDs

• There are also situations where the SmPC (Summary of product characteristics) 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

• 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
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Format of an IMPD
• IMPD can also follow the structure of a Common Technical Document

• 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

• Certain products such as vaccines, antibodies and gene therapy, are also covered
by other EU guidelines and have additional data requirement

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Substantial Amendment

• 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

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GMP compliance

As regards GMP compliance, in the following cases no documentation needs to be

submitted:

• The IMP has a marketing authorisation in the EU or in an ICH country, is not

modified, and is manufactured in the EU

• The IMP is not manufactured in the EU, but has a marketing authorisation in the
EU, and is not modified

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GMP compliance

If the IMP does not have a marketing authorisation in the EU or 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

• A certification by the qualified person (QP) in the EU that the manufacturing

complies with GMP at least equivalent to the GMP in the EU

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 Data related to IMPD

• The IMPD should be prefaced with a detailed table of contents and a glossary of
terms

• The information in the IMPD should be concise

• Should not be unnecessarily voluminous

• Preferable to present data in tabular form accompanied by brief narrative

highlighting the main salient points

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Quality data

• Quality data should be submitted in a logical structure. This document should also
contain guidance for quality of placebos

• Biotechnological IMPs - Guideline on virus safety evaluation

• In exceptional cases, where impurities are not justified by the specification or

when unexpected impurities are detected, the certificate of analysis for test
products should be attached

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Non-clinical pharmacology and toxicology
data
• Summaries of non-clinical pharmacology and toxicology data for any IMP used in
the clinical trial should be provided

• Should provide a reference list of studies conducted and appropriate literature

references

• The summaries of the studies conducted should allow an assessment of the

adequacy of the study and whether the study has been conducted according to an
acceptable protocol

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Non-clinical pharmacology and toxicology
data

• The protocols should meet the requirements of Good Laboratory Practice (GLP)
guidelines where appropriate

• 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

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Previous clinical trial and human experience
data
• Clinical trial and human experience data should be submitted

• Statement of the GCP compliance of the clinical trials

• Where a clinical trial referred to has been performed in third countries, a reference
to the entry of this clinical trial in a public register, if available. Where a clinical trial
is not published in a register, this should be explained and justified

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Overall risk and benefit assessment

• 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

• Should identify any studies that were terminated prematurely and discuss the
reasons

• Any evaluation of foreseeable risks and anticipated benefits for studies on minors
or incapacitated adults

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Overall risk and benefit assessment

• The sponsor should discuss safety margins in terms of relative systemic exposure
to the IMP, preferably based on area under the curve (AUC) data, or peak
concentration (C max ) data, whichever is considered more relevant, rather than in
terms of applied dose

• The sponsor should also discuss the clinical relevance of any findings in the non-
clinical and clinical studies along with any recommendations for further monitoring
of effects and safety in the clinical trials

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Summary
• IMP – investigational Medicinal Product

• IMP Dossier - Gives information related to the quality of any IMP (i.e. including
reference product and placebo), manufacture and control of the IMP, and data
from non-clinical studies and from its clinical use

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, when there is no MA in the
Community
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Summary…

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

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