Mold Control and Detection In Biological Drug Substance Manufacturing Facilities: An Industry Perspective

Abstract

The biopharmaceutical industry produces non-sterile and/or low-bioburden intermediates and bulk biologics (i.e. Drug Substances) using bioburden controlled processes in accordance to Q7A and Annex 2. In many cases, single mold isolation events have received a high level of scrutiny; the goal of this paper is to challenge this paradigm and provide the rationale for an enhanced control approach that focuses on trending of mold species as microbial indicators rather than on single isolation events. Molds, can also be part (in much lower numbers) of the normal microbial population of a biologics manufacturing facility and, therefore, mold isolation is not an unexpected event in non-aseptic processing environments. This presentation provides recommendations from a biopharmaceutical industry perspective on mold monitoring in biologics drug substance facilities and processes. Additionally, recommendations on subjects commonly encountered in the establishment of a monitoring program, such as mold trending, responding to mold isolation events and best practices on mold prevention, are included. These recommendations assist biologic manufacturers in refining their current mold control strategy, as well as developing control strategies for new processes, facilities and products. Establishing appropriate mold control programs is a key element of overall microbial control plans in biologics manufacturing facilities.