ABSTRACT
Orally inhaled and nasal drug products (OINDP) are regulated in Europe via national (country) legislation and guidelines and/or legislation established in the European Union and resulting guidelines developed by the European Medicines Agency (EMA). Recent movement in EMA guidance and European Commission legislation implies potential significant changes in OINDP regulation. The UK exiting the European Union ("Brexit") has also raised a number of questions related to OINDP development and regulation in the region. The International Pharmaceutical Aerosol Consortium on Regulation and Science (IPAC-RS) European outreach working group provides and overview and analysis of the current state of European regulatory activity for OINDP (International Pharmaceutical Aerosol Consortium on Regulation and Science (IPAC-RS) 2018).
Subject(s)
Aerosols , Drug and Narcotic Control , Administration, Inhalation , Administration, Intranasal , Aerosols/standards , Europe , European Union , HumansABSTRACT
The purpose of this article is to document the discussions at the 2010 European Workshop on Equivalence Determinations for Orally Inhaled Drugs for Local Action, cohosted by the International Society for Aerosols in Medicine (ISAM) and the International Pharmaceutical Consortium on Regulation and Science (IPAC-RS). The article summarizes current regulatory approaches in Europe, the United States, and Canada, and presents points of consensus as well as ongoing debate in the four major areas: in vitro testing, pharmacokinetic and pharmacodynamic studies, and device similarity. Specific issues in need of further research and discussion are also identified.
Subject(s)
Aerosols/pharmacokinetics , Lung/metabolism , Administration, Inhalation , Biological Availability , Canada , Drug and Narcotic Control , Dry Powder Inhalers , Europe , Humans , Metered Dose Inhalers , Models, Theoretical , Particle Size , Therapeutic Equivalency , United States , United States Food and Drug AdministrationABSTRACT
INTRODUCTION: Outcomes after endoscopic sphincterotomy (ES) and subsequent laparoscopic cholecystectomy (LC) versus laparoscopic bile duct exploration (LBDE) during LC are comparable in fit patients with choledocholithiasis. This randomized, clinical trial aimed to determine the optimum treatment in patients with higher medical risk. MATERIALS AND METHODS: Ninety-one higher risk patients with evidence of bile duct stones were randomized to ES/LC (group A) or LBDE during LC (group B). The primary outcome measure was duct clearance. Secondary outcome measures were complications, number of procedures per patient, conversion, and postoperative hospital stay (POS). RESULTS: Forty-seven patients were randomized to ES/LC and 44 to LBDE. The median age was 74.56 years. On an intention-to-treat basis, duct clearance was achieved in 29 of 47 of group A and 44 of 44 of Group B patients (P < 0.001). Clavien Grade II-V complications occurred in 8 of 47 and 8 of 44 patients (P = 0.884), the median number of procedures was 2 (2-3) and 1 (1-1) (P < 0.001), 2 of 47 and 4 of 44 patients required conversion (P = 0.676), and the median POS was 3 (2-7) and 5 (2-7) days (P = 0.825), respectively. CONCLUSIONS: There was no difference between approaches to duct clearance in terms of postoperative stay, complications, or conversion in higher risk patients, but the laparoscopic approach was more effective and efficient and avoided unnecessary procedures.