CLEAN ROOM ENVIRONMENTAL MONITORING

Clean room used in the manufacturing of human drugs or medical devices must have appropriate HVAC designed to prevent objectionable organisms in non-sterile drug products and microbiological contamination of sterile drug products. Clean rooms used for manufacturing of drugs and devices must be validated and routinely tested.

MQA provides flexible services to help our customer validate and maintain the clean room areas in GMP compliance. MQA personnel have more than 25 years of clean room and environmental monitoring experience. No project is too small or too big for us.

Reference documents:

• FDA 2004 Guidance for Industry Sterile Drug Products Produced by Aseptic Processing

• ISO 14644-1:1999 Clean rooms and associated controlled environments -- Part 1: Classification of airborne molecular contamination

• EU Manufacture of Sterile Medicinal Products (May 2003)

• USP Microbiological Evaluation of Clean Rooms and Other Controlled Environments <1116>

Assay Description Service Code Surface sampling (Includes media, incubation, enumeration and documentation) EM01 Viable particulate air sampling (Includes media, incubation, enumeration and documentation) EM02 Non-viable particulate monitoring (Includes laser counter and documentation) EM03 PQ protocol generation EM04 Sampling labor (does not include materials or equipment EM05 PQ validation project management EM06 Data analysis and trend reports EM07 Clean room ISO certification EM08 Clean room certification based on grid system EM09 Plate Incubation (Includes incubation, enumeration and documentation) EM10 Equipment rental EM11 TSA-80 or SDA-80 contact plates gamma irradiated (Includes media and copy of vendor COA. MQA growth promotion and sterility will be an additional charge.) EM12 Settling plates gamma irradiated (Includes media and copy of vendor COA. Growth promotion and sterility tests for a particular lots will be an additional charge.) EM13

CLEAN COMPRESSED GASES

Clean compresses gases such as Nitrogen, Carbon Dioxide, Oxygen and compressed air are used in the manufacturing process of medical products, cosmetics and nutritional products. Compressed gasses systems must be free of harmful substances that may pose a serious risk to patients. The gas and the delivery system (compressed gas system) are typically tested for purity and the following contaminants: hydrocarbon (oil vapors), moisture (water vapor), bioburden, non-viable particulate contamination.

Reference documents:

• USP Medical Air monograph

• NFPA 99 breathing air systems

• ISO 8573-1:2001 Compressed air - Part 1: Contaminants and purity classes

• 21 CFR 10.90 Compressed Medical Gas Guidelines

Assay Description Service Code Compressed Gas aerobic bioburden monitoring using a liquid impinger (Includes media, incubation, enumeration and documentation CG01 Compressed Gas anaerobic bioburden monitoring (Includes media, incubation, enumeration and documentation CG02 Compressed Gas oil vapor test (Includes materials and documentation CG03 Compressed Gas moisture test (Includes materials and documentation CG04 Compressed Gas Non-viable particulate monitoring (Includes materials and documentation CG05 PQ protocol generation EM04 PQ validation project management EM06 Sampling labor (does not include materials or equipment EM05 Data analysis and trend reports EM07

CLEAN STEAM MONITORING

Clean steam contacting product or product contact parts used for manufacturing of sterile products must have the same microbiological and chemical quality as WFI water. MQA provides sampling and testing services for clean steam system.

Assay Description Service Code Sample volume USP Water Bioburden - membrane filtration method mHPC medium WT01 > 200 mL Standard Method Water Bioburden membrane filtration method R2A medium WT02 WFI > 200 mL Bioburden test for thermopile organisms WT07 > 200 mL Endotoxin test - LAL KQCL method ET11 > 10mL Endotoxin test - LAL gel clot ET01 > 10mL Endotoxin test - LAL Kinetic Turbidimetric method ET06 > 10mL USP TOC analysis WT10 > 40mL USP conductivity analysis WT11 >100mL PQ protocol generation EM04 NA PQ validation project management EM06 NA Sampling labor (does not include materials or equipment EM05 NA Data analysis and trend reports EM07 NA

WATER SAMPLING AND TESTING

Water is the most common raw material used to manufacture medicine, devises or nutritional products. The United States Pharmacopeia (USP) defines several types of water including: Purified Water, Water for Injection, Sterile Purified Water, Sterile Water for Injection, Sterile Bacteriostatic Water for Injection, Sterile Water for Inhalation, and Sterile Water for Irrigation. However, there are two basic types of water preparation, Water for Injection and Purified Water. The analytical standards for these two types of water are very similar, differing in the fact that Water for Injection has stricter bacterial count standards and must also pass the bacterial endotoxin test.

The source water supplied to the purification system for preparation of USP water must comply with drinking water standards as defined by the United States Environmental Protection Agency in the National Primary Drinking Water Regulations or equivalent international regulations. Although the water source must be safe to drink, there is quite a range of problematic contaminants that may be present in the water. Chlorine is most certainly present in the water and will have to be removed at some point in the purification process.

The following tests are required to meet USP and EP test requirements: Conductivity, Total Organic Carbon, and Bioburden (plus bacterial endotoxin in the case of WFI Water used to manufacture products for Europe must meet EP test requirements for heavy metals and nitrates.

MQA provides sampling, and microbiology and chemical testing services for water systems.

Test performed

• Lab Reagent water: Bioburden, Conductivity, pH, Silica and TOC

• Potable water: Bioburden, Chlorine, Coliform, Conductivity, Copper, Hardness, Iron, pH, Silica, Sodium and TOC

• Purified water: Bioburden, Conductivity, and TOC

• WFI: Bioburden, Conductivity, Endotoxin and TOC

WATER TESTING

Assay Description Service Code Sample volume Bioburden Tests USP Water Bioburden - membrane filtration method mHPC medium WT01 WFI > 200 mL Other type of water > 10mL Standard Method Water Bioburden membrane filtration method R2A medium WT02 WFI > 200 mL Other type of water > 10mL Standard Method Water Bioburden - plate count method mHPC, R2A or plate count agar WT03 WFI > 200 mL Other type of water > 10mL Water Coliform test - membrane filtration - m-Endo broth WT04 > 100 mL Water fecal coliform test(+/-) WT05 > 100 mL Pseudomonas screening WT06 > 100 mL Bioburden test for thermopile organisms WT07 >100 mL Other microorganisms WT08 > 100 mL Endotoxin tests Gel Clot Method, LAL - USP <85> ET01 > 100 mL Kinetic Turbidimetric Method - USP <85> ET06 > 100 mL Chromogenic (KQCL) Method USP <85> ET11 > 100 mL

WATER TESTING

Assay Description Service Code Sample volume Chemical aTests USP TOC analysis WT09 > 40 mL USP Conductivity analysis WT10 > 100 mL pH analysis WT11 >100 mL Water hardness test WT12 > 100 mL Water silica content WT13 > 100 mL Chlorine test WT14 > 100 mL Iron WT15 > 100 mL Copper WT16 > 100 mL Phosphate WT17 > 100 mL Water Sampling & Validation PQ protocol generation EM04 NA PQ validation project management EM06 NA Sampling labor (does not include materials or equipment EM05 NA Data analysis and trend reports EM07 NA Materials Sterile Bioburden sampling containers 200 mL WT18 NA Sterile Bioburden sampling containers 100 mL WT19 NA Sterile Bioburden sampling containers <100 mL WT20 NA Endotoxin free test tube WT21 NA Low TOC vials WT22 NA Coliform test with Sodium Thiosulfate pellet WT23 NA Potable water bioburden sampling container < 100mL with Sodium Thiosulfate pellet WT24 NA