Work Item
ASTM WK81999

New Guide for Establishment of a Microbiological Quality Level for Pharmaceutical and Biopharmaceutical Products and Processes

1. Scope

This guides outlines the establishment and implementation of a mechanism to measure the state of control of each independent step within a manufacturing process to determine the collective level of risk to the overall microbiological quality of the process and product. The microbiological quality level will be:
a) Dependent upon the demonstrated level control for the Critical Quality Attributes
b) Dependent upon the microbiological risk to the patient from both the process and product perspective
c) Demonstrated control through QRM to limit, exclude or eliminate the probability of contamination
d) Be quantitated by assessing and measuring the risk associated with independent steps of the manufacturing process

2. This guide applies to sterile, non-sterile, and low bioburden processes and intermediates for pharma, biopharma, and combination products

3. This guide does not cover the overall evaluation for safety and efficacy of manufactured products.


microbiological; microbial control; contamination control; sterile; sterility assurance; environmental control; clean room


The manufacturing of advanced Pharmaceutical and BioPharmaceutical products has become increasingly complex and requires guidance for better determining "How clean is clean?" and "How sterile is sterile?" where the industry needs:
• To understand the Microbiological Quality Spectrum: from non-sterile to sterile; end to end—
• A mechanism to differentiate microbiological quality of end product.
• A quality stepwise for process (end to end) to support final product (E.g., Food HACCP programs)
• A standard approach for the measurement of each critical control point;
• Ability to differentiate level of micro control as it proceeds from start to final sterility
• A means of determining Probability/quantification of risk for each step and its contribution to the final product
• A standard approach for Trending vs. excursions to support demonstration of a state of control

The title and scope are in draft form and are under development within this ASTM Committee.


Developed by Subcommittee: E55.06

Committee: E55

Staff Manager: Travis Murdock

Work Item Status

Date Initiated: 05-25-2022

Technical Contact: John Logar

Item: 000