title: Development of safety qualification thresholds and their use in orally inhaled and nasal drug product evaluation.
abstract: Safety thresholds for chemical impurities and leachables in consumer products such as foods and drugs have helped to ensure public health while establishing scientifically sound limits for identification and risk assessment of these compounds. The Product Quality Research Institute (PQRI) Leachables and Extractables Working Group, a collaboration of chemists and toxicologists from the U.S. Food and Drug Administration (FDA), industry, and academia, has developed safety thresholds for leachables and extractables in orally inhaled and nasal drug products (OINDP), for application in United States pharmaceutical submissions. The PQRI safety concern threshold (SCT) is 0.15 microg/day, and the qualification threshold is 5 microg/day. OINDP are important in the treatment of lung diseases such as asthma and chronic bronchitis, as well as systemic diseases such as diabetes. Analysis of extractables and minimization of leachables in OINDP are vital to ensuring the quality and safety of the final product. It is expected that the thresholds developed by the PQRI Leachables and Extractables Working Group will be used by both industry and regulators to ensure and assess such quality and safety in OINDP applications. In this article, we describe the importance of the PQRI safety thresholds in the OINDP pharmaceutical development process; the background and context of safety thresholds for consumer products; how these safety thresholds were developed using well-established, robust databases and quantitative risk assessment approaches; and how these thresholds can be applied in a pharmaceutical safety qualification process, including FDA regulatory perspectives on the use of safety thresholds for OINDP.
authors: Safety Sciences, Groton Laboratories, Pfizer Global Research and Development, Groton, CT 06340, USA. douglas.j.ball@pfizer.com
authors: Douglas
authors: D
authors: Ball
authors: James
authors: J
authors: Blanchard
authors: David
authors: D
authors: Jacobson-Kram
authors: Roger O
authors: RO
authors: McClellan
authors: Timothy
authors: T
authors: McGovern
authors: Daniel L
authors: DL
authors: Norwood
authors: Wmark
authors: W
authors: Vogel
authors: Ron
authors: R
authors: Wolff
authors: Lee
authors: L
authors: Nagao
mesh_terms: D000280:Administration, Inhalation; D000281:Administration, Intranasal; D000818:Animals; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D007880:Legislation, Drug; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000592:standards*; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D004364:Pharmaceutical Preparations