Scientific and Regulatory Policy Committee Best Practices: Documentation of Sexual Maturity by Microscopic Evaluation in Nonclinical Safety Studies.

The sexual maturity status of animals in nonclinical safety studies can have a significant impact on the microscopic assessment of the reproductive system, the interpretation of potential test article-related findings, and ultimately the assessment of potential risk to humans. However, the assessment and documentation of sexual maturity for animals in nonclinical safety studies is not conducted in a consistent manner across the pharmaceutical and chemical industries. The Scientific and Regulatory Policy Committee of the Society of Toxicologic Pathology convened an international working group of pathologists and nonclinical safety scientists with expertise in the reproductive system, pathology nomenclature, and Standard for Exchange of Nonclinical Data requirements.

A New Perspective on Scale-Down Strategies for Freezing of Biopharmaceutics by Means of Computational Fluid Dynamics.

Common approaches to scale-down freeze-thaw systems are based on matching time-temperature profiles at corresponding points; however, little is known about the differences in anisotropy between the 2 scales. In this work, computational fluid dynamics modeling was used to investigate these differences. The modeling of the convective flow of the liquid phase within ice porous structure and volume expansion caused by freezing enabled accurate prediction of the local temperature and composition, for evaluation of potential stresses on protein stability, such as cryoconcentration and time in the nonideal environment.

Challenges and strategies to facilitate formulation development of pediatric drug products: Safety qualification of excipients.

A public workshop entitled "Challenges and strategies to facilitate formulation development of pediatric drug products" focused on current status and gaps as well as recommendations for risk-based strategies to support the development of pediatric age-appropriate drug products. Representatives from industry, academia, and regulatory agencies discussed the issues within plenary, panel, and case-study breakout sessions. By enabling practical and meaningful discussion between scientists representing the diversity of involved disciplines (formulators, nonclinical scientists, clinicians, and regulators) and geographies (eg, US, EU), the Excipients Safety workshop session was successful in providing specific and key recommendations for defining paths forward.

Increased fear- and stress-related anxiety-like behavior in mice lacking tuberoinfundibular peptide of 39 residues.

Tuberoinfundibular peptide of 39 residues (TIP39) is synthesized by two groups of neurons, one in the subparafascicular area at the caudal end of the thalamus and the other in the medial paralemniscal nucleus within the lateral brainstem. The subparafascicular TIP39 neurons project to a number of brain regions involved in emotional responses, and these regions contain a matching distribution of a receptor for TIP39, the parathyroid hormone 2 receptor (PTH2-R). We have now evaluated the involvement of TIP39 in anxiety-related behaviors using mice with targeted null mutation of the TIP39 gene (Tifp39).

Endocannabinoids at the spinal level regulate, but do not mediate, nonopioid stress-induced analgesia.

Recent work in our laboratories has demonstrated that an opioid-independent form of stress-induced analgesia (SIA) is mediated by endogenous cannabinoids [Hohmann et al., 2005. Nature 435, 1108].