Introduction to the EQIPD quality system.

While high risk of failure is an inherent part of developing innovative therapies, it can be reduced by adherence to evidence-based rigorous research practices. Supported through the European Union's Innovative Medicines Initiative, the EQIPD consortium has developed a novel preclinical research quality system that can be applied in both public and private sectors and is free for anyone to use. The EQIPD Quality System was designed to be suited to boost innovation by ensuring the generation of robust and reliable preclinical data while being lean, effective and not becoming a burden that could negatively impact the freedom to explore scientific questions. EQIPD defines research quality as the extent to which research data are fit for their intended use. Fitness, in this context, is defined by the stakeholders, who are the scientists directly involved in the research, but also their funders, sponsors, publishers, research tool manufacturers, and collaboration partners such as peers in a multi-site research project. The essence of the EQIPD Quality System is the set of 18 core requirements that can be addressed flexibly, according to user-specific needs and following a user-defined trajectory. The EQIPD Quality System proposes guidance on expectations for quality-related measures, defines criteria for adequate processes (i.e. performance standards) and provides examples of how such measures can be developed and implemented. However, it does not prescribe any pre-determined solutions. EQIPD has also developed tools (for optional use) to support users in implementing the system and assessment services for those research units that successfully implement the quality system and seek formal accreditation. Building upon the feedback from users and continuous improvement, a sustainable EQIPD Quality System will ultimately serve the entire community of scientists conducting non-regulated preclinical research, by helping them generate reliable data that are fit for their intended use.

CNS safety pharmacology: A focus on cognitive functions.

INTRODUCTION: The guidelines from different agencies do not include studies on cognitive functions as part of safety pharmacology. This is unfortunate as it seems important to verify that drugs entering into the central nervous system (CNS) are devoid of detrimental effects on cognition. Our aim is to show examples on how an evaluation of unwanted effects of drugs on cognitive functions may be included in preclinical studies. Rather than a review of the scientific context, the present text is an appeal for a wider consideration of cognition as a safety pharmacology endpoint. METHODS: The following procedures provide an index of the ability of substances to induce cognitive deficits in rodents. In the passive avoidance (PA) test, rats receiving an electric shock show on a later occasion an avoidance of the shock-associated environment. In the social recognition (SR) test, rats recognize familiar congeners. In the Morris water maze (MWM) test, rats placed into a tank containing water learn to find an invisible escape platform using extra-maze visual cues. In the delayed alternation (DA) test, rats placed in a Skinner box learn to alternate their pressing behavior between two levers in order to obtain food rewards. In the operant reversal (OR) test, rats adapt their behavior following a change of the reinforcement rule. RESULTS: Standard reference agents were used to confirm that the different assays were able to detect pharmacologically induced cognitive impairments. Diazepam decreased associative memory performances in the PA test. MK-801-induced memory deficits in SR. Haloperidol increased escape latencies in the MWM test. Scopolamine decreased the number of correct responses in the DA test, and nicotine decreased the number of correct responses in the OR test. The relationship between the doses administered and the effects observed was also evaluated. DISCUSSION: Cognitive assays may provide utility in determining potential undesirable effects or discharging perceived risks with novel CNS drugs under development.