ASEPTIC PROCESSING: ONE - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 221

ASEPTIC PROCESSING: ONE

JAMES P. AGALLOCO AND JAMES E. AKERS

9.1 INTRODUCTION

Sterile products are given to millions of patients daily around the world, and in
every instance there is a belief that the drug being administered is actually “ster-
ile.” This might seem like a valid assumption considering that every container is
labeled “sterile”; the product has passed a sterility test (or been parametrically
released); and appropriate control measures have been taken throughout to assure
that the product is “sterile.” Attaining “sterility” for parenteral products has been
the goal of both industry and regulators for many years.
It is useful to understand the origins of “sterility” to fully understand
pharmaceutical industry approaches and how existing expectations evolved.
In the 1800s as canned foods became more prevalent, deaths were attributed
to foods contaminated with the anaerobic pathogen Clostridium botulinum .
It was determined that treatment at temperatures near 250 ◦ F could make the
canned goods safe for human consumption. The knowledge gained from that
experience with retort processing of canned foods led to sterilization concepts
still in use in pharmaceuticals and other industry. [1,2] A major component
of that knowledge transfer is the establishment of the sterility assurance level
(SAL), which is an estimation of a process' effectiveness against the target
microorganism. ∗ The minimum expectation for a sterilization process across
the global healthcare industry is 1

10 − 6

× [3]. This value is essentially a

∗ Many practitioners prefer to use an alternative term—probability of a nonsterile unit (PNSU), which
is considered substantially more intuitive.