Regulatory Perspective

Regulatory PerspectiveJohn Koerner, Ph.D.

Senior Pharmacologist

CDER, DCRP

DisclaimerThe views expressed are those of the presenter and do not necessarily reflect

those of the FDA

Objectives of SP Studies This (S7A) guideline was developed to help protect

clinical trial participants and patients receiving marketed products from potential adverse effects of pharmaceuticals, while avoiding unnecessary use of animals and other resources.

ICH Guidances ICH S7A – Safety Pharmacology

“Some safety pharmacology endpoints can be incorporated in the design of toxicology (studies) … “

ICH S6 – Biotechnology Products ICH S9 – Oncology Products

For First in Human Studies Capture relevant CV safety signals to prevent

catastrophic, life-threatening AEs HR, BP and ECG

Reduce attrition throughout development Worthwhile goal A regulatory issue when a safety concern to

clinical trial participants – say, negative contractility in a fragile patient population.

Stand-Alone CV Safety Pharm Study Conscious, telemeterized animals

Typically cross-over design Experience with standard drugs

Known (and predictable) sensitivity

CV Endpoints in Toxicology Studies Sensitivity compared to stand-alone study?

i.e., what can the study capture,

and is this good enough?

How best to demonstrate this sensitivity?

Safety Pharmacology Recommendations

SPS – Best Practices* HESI Cardiovascular Safety Committee ^

* Best Practice in the conduct of key nonclinical CV assessments…; Leishman, et.al. ^

Cardiovascular Function in nonclinical drug safety assessment…; Sarazan, et.al.

Thank you