API REMOVAL FROM PHARMACEUTICAL MANUFACTURING WASTEWATER – RESULTS OF PROCESS DEVELOPMENT, PILOT-TESTING, AND SCALE-UP

Wyeth embarked on a project to identify and pilot test a wastewater treatment system effective at removing individual Active Pharmaceutical Ingredients (APIs) from pharmaceutical manufacturing wastewater to low levels. During 2002 and 2003, Wyeth conducted technology-screening evaluations and, working with Villanova University, developed analytical methods for measuring trace levels of soluble and solids-bound APIs in wastewater and biosolids. Following technology screening and analytical method development, Wyeth and Parsons conducted bench-scale treatability studies from which membrane bioreactor (MBR) treatment followed by high-level ozone oxidation was identified as the best candidate for API removal. The treatment concept involves using an MBR to remove bulk organics and suspended solids and effect the removal of sorbable and/or biotransformable APIs where possible followed by ozone oxidation of non-sorbable, biologically recalcitrant APIs.A five-month pilot study was conducted to evaluate the treatment concept. The MBR provided excellent removal of total chemical oxidation demand (94%), total biochemical oxidation demand (>99%), and total suspended solids (>98%). As such, the pilot tests demonstrated that MBR treatment achieved its primary objective of providing a solids-free, low organic strength permeate feed to the ozone oxidation system. Removal of select hormones and oral contraceptives; including 17-α-estradiol, 17-α-estradiol (E2), 17-α-dihydroequilin, trimegestone, estriol (E3), medrogestone, norgestrel, and estradiol valerate; to near and below analytical detection levels were realized by the MBR system. Several key APIs, including estrone (E1), ethinyl estradiol (EE2), and venlafaxine, a selective serotonin re-uptake inhibitor (SSRI), were found to be resistant to MBR treatment. Ozone oxidation was demonstrated to successfully remove residual APIs following MBR treatment at the relatively high doses and contact times studied. In addition, it was demonstrated that ozone oxidation was effective at removing all of the APIs tested to their respective detection levels.Design and construction of a full-scale system based on the pilot results commenced in 2004 and is due to be complete by the end of 2005.