ABSTRACT
CONTENTS 4.1 Introduction ............................................................................................... 59 4.2 What Is Good Science?............................................................................. 61 4.3 Origins of Microbial Contaminants ....................................................... 61 4.4 Evaluating the Possible Effects of Microbial Content ........................ 62 4.5 Microbial Growth and Characteristics .................................................. 62 4.6 Detection Methods and Capabilities ..................................................... 63 4.7 Evaluating Recovered Organisms.......................................................... 64 4.8 How to Perform a Risk Assessment Using Compendial Guidance .... 64 4.9 Use of the Product: Hazard Varies According to the Route
of Administration (Eye, Nose, Respiratory Tract) .............................. 66 4.10 Method of Application............................................................................. 67 4.11 Intended Recipient: Risk May Differ for Neonates, Infants,
and the Debilitated ................................................................................... 67 4.12 Use of Immunosuppressive Agents, Corticosteroids ......................... 67 4.13 Presence of Disease, Wounds, Organ Damage.................................... 68 4.14 Microbiological Control ........................................................................... 68 4.15 People.......................................................................................................... 68 4.16 Raw Materials and Other Components ................................................ 69 4.17 Equipment.................................................................................................. 69 4.18 Environment .............................................................................................. 70 References ............................................................................................................. 71
Virtually all pharmaceutical manufacturing is performed under non-sterile conditions. Even for sterile products (aseptically filled or terminally sterilized), the majority of operations are carried out in non-sterile environments.
The finished product (either sterile or non-sterile) is stored under non-sterile conditions. What is sterility? The scientific definition is absence of life. In pharmaceuticals, the definition for products labeled sterile is based on the probability of a single unit having viable contaminants. The minimal acceptable standard is 1 in 10,000 for aseptic fills and 1 in 1,000,000 for terminally sterilized products. Risk and the actual contaminated product are not synonymous terms. However, current technology cannot support 100% sterility checks.
