Who good manufacturing practices for sterile pharmaceutical products Introduction

Examples of operations to be carried out in the various grades

Grade

Examples of operations for terminally sterilized products

(see sections 4.12–4.15 )

A

Filling of products when unusually at risk

C

Preparation of solutions when unusually at risk. Filling of products

D

Preparation of solutions and components for subsequent fi lling

Grade

Examples of operations for aseptic preparations

(see sections 4.16–4.20)

A

Aseptic preparation and fi lling

C

Preparation of solutions to be fi ltered

D

Handling of components after washing

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4.8  To control the microbiological cleanliness of Grades A–D in 

operation the clean areas should be monitored. Where aseptic operations 

are performed, monitoring should be frequent using methods such as 

settle plates, volumetric air and surface sampling (e.g. swabs and contact 

plates). Sampling methods used in operation should not interfere with zone 

protection. Results from monitoring should be considered when reviewing 

batch documentation for fi nished product release. Surfaces and personnel 

should be monitored after critical operations. Additional microbiological 

monitoring  is also required outside production operations, e.g. after 

validation of systems, cleaning and sanitization.

4.9  Levels of detection of microbial contamination should be established 

for the purpose of setting alert and action limits and for monitoring the 

trends  in environmental cleanliness  in the facility.  Limits expressed in 

colony-forming units (CFU) for the microbiological monitoring of clean 

areas in operation are given in Table 3. The sampling methods and numerical 

values included in the table are not intended to represent specifi cations, but 

are for information only.

Table 3