QCS-008 - Quality Operations Procedures for Pharmaceutical, API, and Biotechnology - page 31

SOP No. QCS-008.00 Effective date: mm/dd/yyyy
Approved by:

iii. Carry out investigational analysis of OOS microbiological results

iv. If the new sample is OOS the sampling point is rejected

2. Trend analysis: Trend—periodic printouts or tabulations of results for their purified water
systems. These printouts or data summaries should be reviewed. A trend analysis is used
to facilitate decision-making for requalification of a controlled environment or for mainte-
nance and sanitization schedules.

Interpretation of the significance of fluctuations in counts or a change in flora should be
based on the experienced judgment of qualified personnel.

3. Limits: Limits are conservative measures designed to signal potential or actual drift from
historical or design performance characteristics. They are not extensions of product speci-
fications, but are intended to flag changes so that corrective action may be taken before
product quality is adversely affected.

Not all situations require use of both alert and action limits.

4. Alert levels: Alert levels are specific for a given facility and are established on the basis of
a baseline developed under an environmental monitoring program. These levels are usu-
ally reexamined for appropriateness at an established frequency. When the historical data
demonstrate improved conditions, these levels can be reexamined and changed to reflect
the conditions.

Exceeding the alert level is not essential for definitive corrective action, but it should at least
prompt a follow-up investigation that could include sampling plan modifications.

5. Action levels: An action level in microbiological environmental monitoring is that when
the level of microorganisms exceeds requires immediate follow-up and, if necessary, cor-
rective action. The evaluation does not depend on the number of colonies only but also on
the types of microbes isolated and the suspected hazard that may result.

Regarding microbiological results, for pure steam and water for injection, it is expected that they be
essentially sterile. Since sampling is frequently carried out in nonsterile areas and is not truly asep-
tic, occasional low-level counts due to sampling errors may occur. Agency policy is that less than
5 CFU/100 mL is an acceptable action limit.

type of Water alert limit action limit

Pure steam ≤1 CFU/100 mL

Endotoxin : LT 0.06 USP EU/mL

≤5 CFU/100 mL
Endotoxin : LT 0.125 USP EU/mL

Water for injection ≤3 CFU/100 mL

Endotoxin : LT 0.125 USP EU/mL

≤5 CFU/100 mL
Endotoxin : LT 0.25 USP EU/mL

Ultra pure water ≤5 CFU/100 mL

Endotoxin : LT 0.125 USP EU/mL

≤10 CFU/100 mL
Endotoxin : LT 0.25 USP EU/mL

Purified water used highly
bacteria critical products

≤10 CFU/100 mL ≤20 CFU/100 mL

Pseudomonas : absence in 100 mL
Coliform : absence in 100 mL

Purified water used for
rinsing

≤50 CFU/100 mL ≤100 CFU/100 mL

Pseudomonas : absence in 100 mL
Coliform : absence in 100 mL

continued