Nonclinical Dose Formulation: Out of Specification Investigations
Journal Title: The AAPS Journal - Year 2012, Vol 14, Issue 3
Abstract
Nonclinical safety studies are required to follow applicable Good Laboratory Practice (GLP) regulations. Nonclinical dose formulations are required to be analyzed to confirm the analyte concentration, homogeneity, and stability. Analytical samples that fall outside of the acceptance criteria are considered out of specification (OOS), and an investigation should be conducted. The US FDA has issued a guidance document for GMP studies on conducting OOS investigations. However, no regulatory guidance has been issued regarding nonclinical safety study (GLP) OOS investigations, which often vary in regard to content, assessment, and impact statements. There is opportunity to improve the quality of OOS investigations by defining expectations and providing guidance in several areas including root cause assessment, impact statements, and acceptable paths forward. This paper will provide recommendations of best practices for nonclinical dose formulation OOS investigations.
Authors and Affiliations
Troy Appleton, Peter Bryan, Denise Contos, Teresa R. Henry, Paul Lehmann, Susan Ohorodnik, Dave Reed, Chantal Robichaud, John Schetter, Natalie South, John Weissmann, Monica Lee Whitmire
Keywords
Related Articles
- EP ID EP681251
- DOI 10.1208/s12248-012-9347-4
- Views 59
- Downloads 0
Guidelines for the Quality Control of Population Pharmacokinetic–Pharmacodynamic Analyses: an Industry Perspective
Quality population modeling and simulation analyses and reports are something every modeler desires. However, little attention in the literature has been paid to what constitutes quality regarding population analyses. Ve...
Evaluation of USP apparatus 3 for dissolution testing of immediate-release products
We sought to evaluate whether U.S. Pharmacopeia (USP) apparatus 3 can be used as an alternative to USP apparatus 2 for dissolution testing of immediate-release (IR) dosage forms. Highly soluble drugs, metoprolol and rani...
NonClinical Dose Formulation Analysis Method Validation and Sample Analysis
Nonclinical dose formulation analysis methods are used to confirm test article concentration and homogeneity in formulations and determine formulation stability in support of regulated nonclinical studies. There is curre...
Bladder Tissue Pharmacokinetics of Intravesical Mitomycin C and Suramin in Dogs
Suramin, at non-cytotoxic doses, reverses chemoresistance and enhances the activity of mitomycin C (MMC) in mice bearing human bladder xenograft tumors. The present study evaluated the pharmacokinetics of the intravesica...
Peptide Kappa Opioid Receptor Ligands: Potential for Drug Development
While narcotic analgesics such as morphine, which act preferentially through mu opioid receptors, remain the gold standard in the treatment of severe pain, their use is limited by detrimental liabilities such as respirat...