USP Microbial Limits Testing (<USP 61>)

Often, it is necessary to evaluate a non-sterile test article for the presence of objectionable organisms, depending on the intended use of the material. MDS offers Microbial Limits Testing (MLT) services for the evaluation of objectionable organisms to evaluate the bioburden (total aerobic organisms as well as the total number of yeasts, and molds) of given pharmaceutical manufacturing samples. The samples are tested per U.S. FDA criteria for "objectionable organisms." For minimum coverage, these criteria require testing for the following:

• The bacteria Escherichia coli (E. coli)
• The bacteria Staphylococcus auseus (S. auseus)
• The yeast Candida albicans (C. albicans)
• The bacteria Pseudomonas aeruginosa (Ps. aeruginosa)
• The fungus Aspergillus niger (A. niger)

Validation methods are in place to ensure that the product has no inhibitory effect on the recovery of organisms. If the total aerobic and total yeast and mold counts are acceptable and no objectionable organisms are found, then the release of the product or raw material will be pursued.

Biological Indicator Survival/Kill Time Determination
The resistance of Biological Indicators to various sterilants is measured as described in individual USP monograph for Biological Indicators.

Accelerated/Real-time Aging Incubation and Testing
Packaged products are exposed to extreme conditions of temperature and humidity-the performance of the product and/or packaging is evaluated. Using specialized exposure chambers, we can expose products to the chosen accelerated aging conditions and at the conclusion of the exposure period evaluate the packaging and in the case of pharmaceutical products, perform stability indicating analyses of the active ingredients. Products that complete this exposure with no damage can be labeled with extended expiration dates, as described in ISO 11607 and AAMI TIR No. 17--1997.

Cell Aging Characterization of MCB
Aged cell banks (16 passage beyond MCB) will be compared with MBC for the following characterization studies:

• Cytogenetic analysis (ploidy)
• Copy number of E1 and E4 insertions
• Chromosome localization of E1 and E4 insertions
• DNA sequence of inserted gene
• Protease sensitivity of inserted gene product
• PCR identity assay for genotyping

Package/Container Integrity Microbiology

• Sterility testing-uses the USP 40-item product immersion procedure described above under Pharmacopeial Sterility
• Microbial aerosol challenge as recommended in ISO 11607
• injected into the package near the seal and integrity of the seal is assessed visually.
• Package Burst Testing-air is injected into the sealed package and the pressure at which a seal fails is recorded. A modification of this procedure is called Creep to Burst Testing; in this test the package is pressurized to 80% of its theoretical burst value and held for a defined period of time. It is then further pressurized until it bursts and the final burst pressure is recorded.
• Vial Test