Seminar Slides on IMPD and IB of Regulator Affaires M. Pharm. 1st sem (Pharmaceutics)

1. IMPD & IB
Presented by – Snehankit Satish Gurjar
Guide – Dr. S. D. Pande
Seminar for completion of M. Pharm. 1st sem.
(Pharmaceutics)
VBCP, Amt.

2. IMPD
 IMPD or Investigational Medicinal Product Dossier is one of the several pieces of Investigational Medical
Product (IMP)and it is the basis for approval of clinical trials by the competent authorities in the European
Union Member State.
 The directive introduced a harmonized procedure for the authorization to perform a clinical study in any one of
the European Union Member State after Clinical Trial Directive (2001/20/EC) came into force in April 2001.
 The IMPD includes summaries of information related to
- Critical analysis 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.
- Investigational Medicinal Product’s manufacture and clinical data, quality, data from clinical use and
non-clinical studies
- An overall assessment of risk to benefit
- Presented by Snehankit Satish Gurjar 2

3. Additional components which should accompany the IMPD:
o Application form
o Covering latter
o Receipt of confirmation of EudraCT number
o List of all Competent authorities (CAs) where application has been submitted
o Copy of any scientific advice
o Any letter of authorization for the use when application is not the sponsor
o Any letter of concern received from any of Member State
o Information content form
o Confirmation that CA will accept application in English
o Protocol with any amendment
- Presented by Snehankit Satish Gurjar 3

4. o Subject information (If any)
o Arrangement for recruitment of subjects
o Peer review of trial if available
o Ethical assessment by principle investigator
o Report of any trial with sample IMP
o Investigators Brochure (IB)
o Example of label in the national language
- Presented by Snehankit Satish Gurjar 4

5. Following is a listing of the data that should be included in the IMPD:
1. 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 trials whose manufacturing complies with the principle of Good
Manufacturing practices (GMP)
Applicants should also supply the following-
i) A copy of the manufacturing authorization stating the scope of the authorization if the IMP is manufactured
in EU and does not have a marketing authorization in the EU
ii) If the IMP is not manufactured in the EU and does not have a marketing authorization in the EU
iii) Certification of the GMP status of any active biological substance
iv) Compliance with GMP at least equivalent to EU GMP
v) Certification of the Qualified Person that the manufacturing site works in
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6. 2. Previous clinical trial and human experience data
3. nonclinical pharmacology and toxicology data
4. Overall risk and benefit assessment section
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7. Simplified IMPD
In certain situation, e.g. where the Investigational Medical 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.
Substantial amendments to IMPD
 The assessment of an IMPD is focused on patient safety and any risk associated with the IMP
 Whenever any potential new risks are identified the IMPD has to be amended to reflect the change
 This may be the case for changes in IMP impurities, microbial contamination, viral safety, TSE and the some
particular cases to stability when toxic degradation products may be generated
- Presented by Snehankit Satish Gurjar 7

8. INVESTIGATIONAL BROCHURE (IB)
Investigation Brochure (IB) is a compilation of the clinical and non clinical data on the investigational
product/products that are relevant to the study of product/products in human subjects.
• Its purpose is to provide the investigators and other involved in the trial with the information to
facilitate their understanding of the following:
I. The rational (The set of reason or a logical basis)
II. Their compliance with many key features of protocol, such as the – dose, dose frequency or dose intervals
III. Methods of administration , and safety monitoring procedures.
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9. • The information should be presented in concise and simple manner.
• I.B. enables a clinician, or a potential investigator , to understand it and make his/her own unbiased risk
benefit assessment of appropriateness of purposed trials.
• For this reason, a medically qualified person should generally participate in the editing of an I.B.
• The I.B. should be revived at least annually and revised as necessary in compliance with the spencer's
written procedures. The revised version should be included in IND (Investigational New Drug) annual
report.
• Generally sponsor is responsible for ensuring that an up-to-date I.B. is made available to the
Investigator(s).
• The following should be included in the I.B.:
i. Title page
ii. Confidentiality statement
iii. Contents of the I.B.
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10. TITLE PAGE
Title page should include following components:
 Spencer's name
 Product
 Research number
 Name(s)- Chemicals, Generic (if approved)
 Trade name(s) – If legally permissible and approved by sponsor
 Edition number
 Release date
 Replaces previous edition number
 date
- Presented by Snehankit Satish Gurjar 10

11. Contents of I.B.
 Table of contents of investigational broacher-
• Confidentiality statement (optional)
• Signature page (optional)
1. Table of contents
2. Summary – not exceeding 2 pages – highlight the significant physical, chemical, pharmaceutical,
pharmacological, toxicological, pharmacokinetic, metabolic and clinical information available on Investigational
product.
3. Introduction – Chemical name, active ingredient, pharmacological class, anticipated therapeutic/ diagnostic
indicator(s), general approach to be followed in evaluating of Investigational Product.
4. Description of physical, chemical and pharmaceutical properties of product – storage and handling of
Investigational Product, any structural similarities with the other known compounds.
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12. 5. Non clinical trials :
i. Nonclinical pharmacology –
A summery of pharmacological the investigational product studied in animal should be included.
ii. Pharmacokinetics and product metabolism in animals –
A summery of ADME and biological transformation and disposition of the investigational product in all species
studied should be given
iii. Toxicology –
A study of toxicological effects found in relevant studies conducted in different animal species like,
• single dose
• Repeated dose
• Carcinogenicity
• Special studies (irritancy, sensitization)
• Reproductive toxicity
• Genotoxicity (Mutagenicity)
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13. 6. Effect in humans :
A through discussion of the known effects of the investigational product(s) in human should be provided,
including information on pharmacokinetics, metabolism, pharmacodynamics, dose response, safety, efficacy and
other pharmacological activities.
i. Pharmacokinetics and product metabolism in humans -
A summery of information on pharmacokinetic of the investigational product(s) should be presented
ii. Safety and efficacy -
A summery of information should be provided about the investigational product’s safety, efficacy and
pharmacodynamics
iii. Marketing experience -
The I.B. should identify countries where investigational product has been marketed or approved
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14. 7. Summary of data and guidance for the investigator –
This section should contain nonclinical and clinical data of Investigational Product (I.P.)
• Investigational Broacher provide investigator a clear understanding of
a) the possible risks
b) Adverse reaction
c) Observation and precautions needed for the clinical trials
• It should also contain
i. NB: Reference no.
ii. Publications
iii. Reports [this references should be found at the end of each chapter Appendices (if any)]
- Presented by Snehankit Satish Gurjar 14

15. REFERTENCES
 New Drug Approval Process, By: Richard Guarino, Page no.:136-144
 https://www.slideshare.net/Zahid1392/impd-amp-ib
 https://www.slideshare.net/NaveenBalaji32/investigators-bronchure-investigational-medicinal-product-dossier-ib-
amp-impd-naveen-balaji
- Presented by Snehankit Satish Gurjar 15

16. THANK YOU!!
- Presented by Snehankit Satish Gurjar 16