it contains all IMPD

1. Presented by:Karthik P S
M Pharma 1st year
DEPARTMENT:Pharmaceutics

2. MY SEMINAR IS ON
 Investigation of medicinal products dossier (IMPD)

3. IMP 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.

4. 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.
 In many cases where the IMP has a marketing authorisation, an IMPD is not required.
 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, harmonizing 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.

5.  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.
 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.

6. 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 MarketingAuthorisation 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.

7. 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.

8. Substantial Amendment
 The 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. Certain amendments are considered substantial in which case the
competent authority has to be informed of the substantial amendment. This may be the
case for changes in IMP impurities, microbial contamination, viral safety , and in some
particular cases to stability when toxic degradation products may be generated. Further
information about substantial amendments can be found here.

9. 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.

10. 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 inArticle 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.

11. 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. The IMPD should not be unnecessarily
voluminous. It is preferable to present data in tabular form accompanied by brief narrative
highlighting the main salient points.

12. 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
when unexpected impurities are detected, the certificate of analysis for test products
Should be attached.

13. 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.

14.  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.

15. 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.

16. 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.

17.  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.

18. REFERENCES