Workpackage 6


Work package number


Start date or starting event:


Work package title

Preclinical and regulatory affairs

Activity Type[1]


Participant number








Participant short name








Person-months per participant:











Preclinical toxicology will be carried out prior to the final submission of a clinical trial application (CTA).


Description of work (possibly broken down into tasks), and role of participants

Preclinical toxicology testing is required for all material which will be used in human studies. The regulatory framework is described in the following documents;

ICH Document S6 (CPMP/ICH/302/95): Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals.

CPMP/SWP/2145/00 Note for guidance on non-clinical local tolerance testing of medicinal products.

CPMP/SWP/465/95 Note for Guidance on Preclinical Pharmacological and Toxicological Testing of Vaccines


Task 6.1: Preclinical testing (IQUR[s/c], M25-M30)

Although the vaccine guidance document CPMP/SWP/465/95 suggests that a single dose study in at least one species would be sufficient for many new vaccine products, including combined vaccines, the guidance also states that recombinant DNA protein vaccines should be addressed by ICH S6 ( CPMP/ICH/302/95). This guidance for biotechnology derived pharmaceuticals states that safety evaluation programmes should normally include two relevant species. As a result of this apparent inconsistency, we propose to carry out studies in two species approach in the first instance.

We will carry out repeated dose study designs in two species, to cover the potential repeated dosing in the clinic. Immunogenicity assessment will been included to look for immunological toxicity. Local tolerance to the vaccine can be assessed as part of the repeated dose toxicity study.

These studies will be carried out in GLP approved subcontractor’s facility and will be designed in accordance with regulatory advice.


Task 6.2: Regulatory application (IQUR/ICS [s/c], M24-M28)

Prior to the submission of any CTA, clinical advice will be sought from the Spanish regulator. A regulatory professional will be subcontracted to act for the consortium in preparation for this meeting and also to assist in the preparation of the final CTA.

Once a complete set of preclinical data has been collected a final CTA application will be submitted which will enable clinical trials to begin.




Deliverables** (brief description and month of delivery)


D 6.1: Preclinical safety report. (M30)

Safety testing will be carried out in two species and a suitable GCP compliant report prepared by the CRO. This will be used as part of the CTA process.


D 6.2: Regulatory application. (M30)

When sufficient laboratory and preclinical data has been generated, a formal filing to being clinical studies will be made with the Spanish Agency of Medicines and Medical Devices.


[1]   Please indicate one activity per work package: RTD = Research and technological development; DEM = Demonstration; MGT = Management of the consortium; OTHER = Other specific activities, if applicable (including any activities to prepare for the dissemination and/or exploitation of project results, and coordination activities).