Managing documents to aid product compliance

1st April 2013

Before any therapeutic product or device is approved for use in humans, it has to undergo a battery of pre-clinical and clinical studies to ensure the safety and efficacy.

Ellen-Patricia Zimmermann reports.

Pre-clinical studies can be performed in laboratory cell cultures (in vitro) or in animal systems (in vivo). The ideal animal system is as close as possible to the human system and predictive of responses expected in human patients.

Pre-clinical safety and toxicity studies provide assurance of safety by demonstrating biocompatibility of the product in appropriate animal models. Identifying the safe dose ranges for clinical studies in humans is mandatory.

Other studies are designed to demonstrate a product's effectiveness and provide the aproof of concept'.

Good practice

All studies have to be conducted in accordance with Good Manufacturing Practices (GMP) and all toxicology studies have to be completed in compliance with the Good Laboratory Practices (GLP).

In addition the study design should be based on the proposed clinical trial. In accordance with the Good Clinical Practices (GCP) the results of all relevant non-clinical pharmacology, toxicology, pharmacokinetic and investigational product metabolism studies should be provided in the Investigator's Brochure (IB) in summary form.

This summary should address the methodology used, the results and a discussion of the relevance of the findings to the investigated therapeutic, the possible unfavourable and unintended effects in humans.


As a result the chemical, pharmaceutical and biological testing is a very important part in the marketing authorisation application (MAA). It is an integral part of GMP-compliant manufacturing of drug substances and products.

Prior to submission of the MAA, the following information has to be available and presented in Modul2.4,2.6,3 and 4 of the Common Technical Document (CTD) :

* Composition of drug substances and products

* Method of preparation, including GMP-related information

*Quality control of starting materials and intermediates

* Quality control of the finished product

* Stability of the active substance and the product

*Virological documentation.

Each step in the drug development process, from screening to MAA, is regulated by law, directives and guidelines. It has to be validated and documented. All these documents should demonstrate the aquality' aspects of the quality, safety and efficacy criteria that have to be met in the development of a new pharmaceutical product.

After all substantial documentation and data are required in marketing application submissions, resulting in large, complex applications.

Applicants have used many different approaches to organise the information, but differences in the organisation of each application make regulatory agency's review more difficult. It may lead to gaps of critical data or analyses. In the worst case the gaps may result in a decision by the regulatory agency to refuse the filing of an application.

A good way to get a correct path to compliance is the use of a Document Management System like COI-PharmaSuite for handling the substantial documents from the first written words in the drug development department to last written words in the regulatory affairs department through the complete lifecycle of an authorised product. u

Ellen-Patricia Zimmermann is Product Manager with

COI GmbH, Herzogenaurach, Germany.





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