The safety pharmacology core battery is the set of investigations described in ICH S7A regarding the adverse effects of an investigational product on vital functions. It typically includes the central nervous system, the cardiovascular system, and the respiratory system. This core battery is not a single study type, but a professionally defined scope of investigation that should be available prior to the first use in humans.
Objective and Integration of the Core Battery
Safety pharmacology searches for adverse pharmacodynamic effects on physiological functions within the therapeutic exposure range and above. Its core battery focuses on organ systems whose acute disruption can pose an immediate hazard. ICH S7A identifies the central nervous system, cardiovascular, and respiratory systems as the vital systems normally to be investigated.
Depending on the question, the investigation can be carried out using in vivo, ex vivo, or in vitro systems. For the central nervous system, ICH S7A mentions, for example, motor activity, behavioral changes, coordination, sensory-motor reflexes, and body temperature. For the cardiovascular system, blood pressure, heart rate, and electrocardiogram are among the relevant parameters. Respiratory function requires quantitative measurement methods; mere clinical observation of an animal is generally not sufficient according to the guideline.
Supplementation Instead of Rigid Testing Routine
The core battery is a starting point, not an inflexible package of identical experiments. Scientific reasons may necessitate supplementation with additional organ functions, for example, if pharmacology, structural class, findings from general toxicology, or clinical signals give cause for concern. Conversely, an investigation may be omitted if a plausible justification is provided.
Supplemental safety pharmacology investigates other systems, such as renal function, the gastrointestinal tract, or endocrine functions, when a specific risk exists. Follow-up studies clarify a previously observed adverse effect mechanistically or in greater detail. This differentiation prevents the core battery from being wrongly misunderstood as a complete safety assessment.
Distinction from Study Type
The safety pharmacology core battery refers to the defined set of investigations, not an organizationally separate study. Its components can be combined in different models or studies, provided the questions, systems, and endpoints are appropriate. The term therefore describes which vital functions are to be covered, not the format of a single study protocol.
There is also a difference compared to general non-clinical development. Repeated-dose toxicity studies capture a broad spectrum of clinico-pathological and histological findings; the core battery specifically searches for functional pharmacodynamic risks. ICH S7B supplements ICH S7A for the non-clinical evaluation of delayed ventricular repolarization and shows that a specific cardiac risk requires its own testing strategy alongside the general core battery.
The results of the core battery must be interpreted in relation to the planned human exposure. An effect that occurs only at a very high concentration in an isolated system has a different significance than a finding that is reproducible in vivo near the expected clinical exposure. The temporal relationship between concentration and functional change is also relevant, for example, if a change in heart rate occurs only shortly after the exposure maximum.
The core battery can utilize existing data from general toxicity studies if they adequately cover the required functional endpoints. Nevertheless, it must be clear for each function which method was used for assessment and whether the data are suitable for the safety pharmacology question. For example, a random observation without quantitative respiratory measurement does not replace a targeted investigation of respiratory function.
For active substances with known central nervous system sedation, the choice of model and observation time points can significantly influence the detectability of changes in coordination or reflexes. The core battery therefore requires not only the naming of an organ system, but appropriate measurements for its vital function.
The decision regarding supplements should follow from a specific risk. For a substance with indications of gastrointestinal motility disorders, for example, a targeted additional investigation would be justifiable without changing the scope of the core battery itself.
Relevance for clinical trials
Prior to a First-in-Human study, the core battery data must be available in the overall non-clinical overview. Findings on blood pressure, heart rhythm, respiratory parameters, or central nervous system effects can determine which baseline examinations, measurement time points, and stopping rules are necessary in the clinical protocol. The EMA requires additional investigations in individual cases if there is cause for concern for these or other organ systems.
Full-service CROs like Mediconomics support the mapping of safety pharmacology results to clinical monitoring plans, such as ECG recordings, vital sign measurements, or neurological examinations. The Nonclinical, Medical Monitoring, and Regulatory Affairs teams can use this to develop the risk-adapted safety sections of the study protocol and the Investigator’s Brochure.
Frequently Asked Questions (FAQ)
Which organ systems normally belong to the core battery?
ICH S7A identifies the central nervous system, the cardiovascular system, and the respiratory system as the vital systems usually to be covered.
Is the core battery identical to a GLP toxicity study?
This equating would be incorrect. It is a safety pharmacology scope of investigation with functional endpoints and can supplement other studies.
When are additional investigations required?
If the pharmacological profile, findings, or other data suggest a risk to further organ systems, supplemental or follow-up studies should be planned based on scientific justification.
Regulatory References
- ICH S7A, Safety Pharmacology Studies for Human Pharmaceuticals – defines the purpose, organ systems, and adaptation possibilities of the core battery.
- ICH S7B, The Nonclinical Evaluation of the Potential for Delayed Ventricular Repolarization – supplements the cardiac risk assessment according to S7A.
- EMA, Guideline on strategies to identify and mitigate risks for first-in-human and early clinical trials – requires core battery data prior to the first use in humans.