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〈 1111 〉 MICROBIOLOGICAL EXAMINATION OF NONSTERILE
PRODUCTS: ACCEPTANCE CRITERIA FOR PHARMACEUTICAL
PREPARATIONS AND SUBSTANCES FOR PHARMACEUTICAL USE
The presence of certain microorganisms in nonsterile preparations may have the potential to reduce or even inactivate the
therapeutic activity of the product and has a potential to adversely affect the health of the patient. Manufacturers have therefore to
ensure a low bioburden of nished dosage forms by implementing current guidelines on Good Manufacturing Practice during the
manufacture, storage, and distribution of pharmaceutical preparations.
Microbial examination of nonsterile products is performed according to the methods given in the texts on Microbial Enumeration
Tests 〈61〉 and Tests for Speci ed Microorganisms 〈62〉. Acceptance criteria for nonsterile pharmaceutical products based upon the
total aerobic microbial count (TAMC) and the total combined yeasts and molds count (TYMC) are given in Tables 1 and 2. Acceptance
criteria are based on individual results or on the average of replicate counts when replicate counts are performed (e.g., direct plating
methods).
When an acceptance criterion for microbiological quality is prescribed, it is interpreted as follows:
101 cfu: maximum acceptable count = 20;
102 cfu: maximum acceptable count = 200;
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103 cfu: maximum acceptable count = 2000; and so forth.
Table 1. Acceptance Criteria for Microbiological Quality of Nonsterile Dosage Forms
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Total Combined
Total Aerobic Microbial Yeasts/Molds Count (cfu/g or
Route of Administration Count (cfu/g or cfu/mL) cfu/mL) Speci ed Microorganism(s)
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Nonaqueous preparations for 103 102 Absence of Escherichia coli (1
oral use g or 1 mL)
Aqueous preparations for oral 102 101 Absence of Escherichia coli (1
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use g or 1 mL)
Rectal use 103 102 —
Oromucosal use 102 101 Absence of Staphylococcus
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aureus (1 g or 1 mL)
Absence of Pseudomonas
aeruginosa (1 g or1 mL)
Gingival use 102 101 Absence of Staphylococcus
aureus (1 g or 1 mL)
Absence of Pseudomonas
aeruginosa (1 g or 1 mL)
Cutaneous use 102 101 Absence of Staphylococcus
aureus (1 g or 1 mL)
Total Combined
Total Aerobic Microbial Yeasts/Molds Count (cfu/g or
Route of Administration Count (cfu/g or cfu/mL) cfu/mL) Speci ed Microorganism(s)
Absence of Pseudomonas
aeruginosa (1 g or 1 mL)
Nasal use 102 101 Absence of Staphylococcus
aureus (1 g or 1 mL)
Absence of Pseudomonas
aeruginosa (1 g or 1 mL)
Auricular use 102 101 Absence of Staphylococcus
aureus (1 g or 1 mL)
Absence of Pseudomonas
aeruginosa (1 g or 1 mL)
Vaginal use 102 101 Absence of Pseudomonas
aeruginosa (1 g or 1 mL)
Absence of Staphylococcus
aureus (1 g or 1 mL)
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Absence of Candida albicans
(1 g or 1 mL)
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Transdermal patches (limits 102 101 Absence of Staphylococcus
for one patch including aureus (1 patch)
adhesive layer and backing)
Absence of Pseudomonas
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aeruginosa (1 patch)
Inhalation use (special 102 101 Absence of Staphylococcus
requirements apply to liquid aureus (1 g or 1 mL)
preparations for nebulization)
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Absence of Pseudomonas
aeruginosa (1 g or 1 mL)
Absence of bile-tolerant
Gram-negative bacteria (1 g or
1 mL)
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Table 2. Acceptance Criteria for Microbiological Quality of Nonsterile Substances for Pharmaceutical Use
Total Aerobic Microbial Count (cfu/g or Total Combined Yeasts/Molds Count
cfu/mL) (cfu/g or cfu/mL)
Substances for pharmaceutical use 103 102
Table 1 includes a list of speci ed microorganisms for which acceptance criteria are set. The list is not necessarily exhaustive, and
for a given preparation it may be necessary to test for other microorganisms depending on the nature of the starting materials and
the manufacturing process.
If it has been shown that none of the prescribed tests will allow valid enumeration of microorganisms at the level prescribed, a
validated method with a limit of detection as close as possible to the indicated acceptance criterion is used.
In addition to the microorganisms listed in Table 1, the signi cance of other microorganisms recovered should be evaluated in
terms of the following:
The use of the product: hazard varies according to the route of administration (eye, nose, respiratory tract).
The nature of the product: does the product support growth? does it have adequate antimicrobial preservation?
The method of application.
The intended recipient: risk may differ for neonates, infants, the debilitated.
Use of immunosuppressive agents, corticosteroids.
The presence of disease, wounds, organ damage.
Where warranted, a risk-based assessment of the relevant factors is conducted by personnel with specialized training in
microbiology and in the interpretation of microbiological data. For raw materials, the assessment takes account of the processing to
which the product is subjected, the current technology of testing, and the availability of materials of the desired quality.
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< 1111 > MICROBIOLOGICAL Radhakrishna S Tirumalai GCM2015 General Chapters-Microbiology
EXAMINATION OF NONSTERILE Principal Scienti c Liaison 2015
PRODUCTS: ACCEPTANCE CRITERIA FOR
PHARMACEUTICAL PREPARATIONS AND
SUBSTANCES FOR PHARMACEUTICAL
USE
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Most Recently Appeared In:
Pharmacopeial Forum: Volume No. 29(5)
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