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Is it possible to present preclinical data in IMPD and IB in different profundity? Date: 25. November 2008 Topics: Licensing Type: FAQ

If preclinical data are presented in the IB and the IMPD, both data sets should be equal or comparable. If in doubt, latest preclinical data should be presented in more detail or data in the IMPD.

Relevant differences of data in both …

Is it necessary to indicate changes in the new version of the IB and IMPD, regarding preclinical aspects? Date: 25. November 2008 Topics: Licensing Type: FAQ

Yes, providing only a brief list of changed sections is usually not sufficient for the assessment. The changes should be marked in the text of the new version (coloured, bold or underlined) or should be listed explicitly in detail.

What are the preclinical requirements for the IMPD layout? Date: 25. November 2008 Topics: Licensing Type: FAQ

IMPD layout should be in agreement with the layout suggestions in the 3. Notification on the clinical trial of medicinal products for human use.

For first in human studies is it necessary to submit safety margins based on exposure for the intended application? Date: 25. November 2008 Topics: Licensing Type: FAQ

Yes, the calculation of safety margins should be based on the estimated (upscaled) systemic exposure. In addition please give a statement about the expected therapeutic dose range in humans.

How to calculate the safe starting dose for first-in-human trials – does a European guideline exist? Date: 25. November 2008 Topics: Licensing Type: FAQ

Currently, a European guideline does not exist. Therefore, the FDA-guidance paper: ”Estimating the Maximum Safe Starting Dose in Clinical Trials for Therapeutics in Adult Healthy Volunteers” (July 2005) should be used. The dose calculation …

What kind of study design is expected if dosing of the investigational medicinal product in human is planned in cycles (e.g. for oncologic treatment) Date: 25. November 2008 Topics: Licensing Type: FAQ

In accordance with the ”Note for guidance on the pre-clinical evaluation of anticancer medicinal products“ (CPMP /SPW/997/96), drug application in repeated dose toxicity studies should be performed as similar as possible to the clinical study …

Are there any layout recommendations for presenting the results in the preclinical part? Date: 25. November 2008 Topics: Licensing Type: FAQ

Yes, tables are more suitable in reporting noteworthy findings, sorted by species, increasing duration of treatment, and increasing dose. These tables should also contain toxicokinetic data of the dose levels given as well as a statement on …

Is it possible to include women of childbearing potential in phase I/IIa trials without the assessment of embryo-foetal development? Date: 18. November 2008 Topics: Licensing Type: FAQ

Yes, this is possible in exceptional cases. If in the clinical trial

  • a life-threatening disease is treated and the patients involved are using highly effective contraception in accordance with Note 3 of the “Note for guidance on …

How should preclinical findings be presented and discussed? Date: 18. November 2008 Topics: Licensing Type: FAQ

Please do not present the findings sorted by target organs. Tables are more suitable in reporting noteworthy findings, sorted by species, increasing duration of treatment and increasing dose. Those tables should also contain toxicokinetic data …

Is it necessary to calculate safety margins for the intended application in humans? Date: 18. November 2008 Topics: Licensing Type: FAQ

Yes, it is necessary to present the calculated safety margins on the base of (free) exposure (AUC, Cmax) at the NOAEL in the animals to the expected exposure in the intended clinical trial. The safety margins should be calculated for the …