this topic deals with the regulatory requirement of Investigation of Medical Product Dossiers

1. INVESTIGATION OF MEDICAL
PRODUCTS DOSSIERS (IMPD)
BY: SHRESTHA
M.PHARM 1ST YEAR
AL – AMEEN COLLEGE OF
PHARMACY
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2. INTRODUCTION
 The investigational medicinal product dossier is the basis for
the approval of clinical trials by the competent authorities in
the EU.
 The Clinical Trials Directive (2001/20/EC) came into force in
April 2001, harmonizing the laws, regulation and
administrative provision of member states relating to
implementation of GCP in the conduct 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. 2

3.  The IMPD, is requested whenever the performance of a
clinical study in any one the EU member states is intended.
 The IMPD includes summaries of information related to the
quality, manufacture and control of the IVESTIGATIONAL
MEDICAL PRODUCT (IMP), data from nonclinical studies
and its clinical use.
 An overall risk benefits assessment, clinical 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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4.  In certain situations e.g. where the IMP 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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5. WHAT IS IMPD?
 The Investigational Medicinal Product Dossier is one of the
several pieces of investigational medicinal product(IMP)
related data required whenever the performance of a clinical
trial is intended in one or more EU 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.
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6. REQUIREMENT OF IMPD?
 Although the IMPD compromise the main
component of the documentation provided to each
member states (MS) in order to obtain permission
to initiate clinical trials, there are other documents
that need to accompany the IMPD before approval
is granted by the component authorities of each
MS, as they may vary from country to country.
 The IB is a very comprehensive document that
contains much of the information in the IMPD.
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7.  Therefore an applicant may either provide a stand alone
IMPD or cross- refer to the IB for the preclinical and clinical
parts of the IMPD providing the IB has sufficient detail to
allow assessors to reach a decision about the potential
toxicity of the IMP and safety of its use in the proposed trial.
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8.  The following should accompany the IMPD:
 Receipt of confirmation of EudraCT number
 Covering letter
 Application form
 List of all CAs where application has been submitted
 Copy of IEC approval or comments
 Any letter 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
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9.  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
 IB
 Report of any trial with same IMP
 Example of label in the national language
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10. OVERALL CONTENT OF IMPD…?
 An IMPD should include summaries of information related to
the quality, manufacture, and control of the IMP.
 Data from nonclinical trials and from its clinical use, if any,
should be included.
 As with the recommended format of the IND presentation of
the data in tabular form with brief narratives of the main points
is acceptable.
 Although the format, as stated in the above reference , is
recommended, it is not mandatory and the list is exhaustive
 Sponsors are advised to use this detailed guidance as a
starting point in their IMPD submissions
 The following is a listing of the data that should be included in
the IMPD.
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11. 1. QUALITY DATA
 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 applicant should also supply the
following.
 A copy of manufacturing authorization stating the scope of the
authorization if the IMP is manufactured in the EU and does not
have 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.
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12.  Certification of the GMP status of any active biological
substance.
 Copy of the importers authorization
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13. 2. NON CLINICAL PHARMACOLOGY
 Nonclinical pharmacology and toxicology data
including summaries of nonclinical pharmacology
and toxicology data for any IMP to be use in the
clinical trial or justify why they have not.
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14. 3. PREVIOUS CLINICAL DATA
 Previous clinical trial and human experience data
section providing summaries of all available data
from previous clinical trial and human experience
with the proposed IMPs.
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15. 4. OVERALL RISK AND
ASSESMENT
 Overall risk and benefits assessment section
should provide a brief integrated summary that
critically analyses the nonclinical and clinical data in
relation to the potential risk and benefits of the
proposed trial.
 The test should identify any trial that terminated
prematurely and discuss the reasons.
 Any evaluation of foreseeable risk and anticipate
benefits for trials on minors or incapacitated adults
should be taken into account.
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16. SIMPLIFIED IMPD
 A simplified IMPD may be submitted if information
related to the IMP has been assesses previously as
part of a marketing authorization in any MS of the
community or as part of a clinical application to the
CA concerned.
 The test should include a discussion of the potential
risks and benefits of the proposed trial.
 Where appropriate, sponsors are allowed to cross-
reference to the IMPD submitted by another
applicant and held by the CA.
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17.  This may require a letter from the other applicant to
authorize the CA to cross-reference their data.
 The sponsor should have relevant information
about this IMP that can be included in the IB.
 In addition, an appropriate and adapted content of
the IMP dossier may be allowed occasionally by the
CA, provide that it is justified and agreed before the
application is submitted.
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18. POSSIBITY TO REFER THE SMPCS OR TO THE
ASSESSMENT OF THE IMPD IN ANOTHER
CLINICAL TRIAL APPLICATION
 The applicant may submit the current version of the
SmPC (or, as regards ICH countries, the documentation
equivalent to the SmPC) as the IMPD if an IMP has a
marketing authorization in any Member State or in an ICH
country.
 The exact requirements are detailed in Table
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20.  Moreover, the IMPD may have been submitted previously by the
same applicant or by another applicant and held by the national
competent authority of the Member State concerned. In these
cases applicants are allowed to cross- refer to the previous
submission. If the submission was made by another applicant, a
letter from that applicant should be submitted authorizing the
national competent authority to cross-refer to that data. The
exact requirements are detailed in Table.
 If the applicant is the MA holder and he has submitted an
application to vary the SmPC, which has not yet been
authorized, and which is relevant for the assessment of the
IMPD in terms of patient safety, the nature of the variation and
the reason for it should be explained. 20

21.  If the IMP is defined in the protocol in terms of active
substance or ATC code the applicant may replace the
IMPD by one representative SmPC for each active
substance/active substance pertaining to that ATC group.
Alternatively, he may provide a collated document
containing information equivalent to that in the
representative SmPCs for each active substance that
could be used as an IMP in the clinical trial.
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22. IMPD IN CASES OF PLACEBO
 If the IMP is a placebo, the information requirements can be
reduced in line with the requirements set out in Table 2.
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24. REFERENCE….
 www.impd.eu
 www.imp-dossier.eu
 New drug approval process fifth edition by
RICHARD.A. GUARINO,M.D.
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