[AUDIO LOGO] NARRATOR: The biologics production facility is located on the main campus of Nebraska Medicine in Omaha, Nebraska. The 12,000-square foot cleanroom facility operates as a critical venue for researchers to transition small scale, basic science research findings to useful therapeutics at the bedside. Through phase I and II clinical trials. The biologics production facility supports our clinical blood and marrow transplant and immune effector cell programs, as well as providing manufacturing support for novel cell and gene-based therapies. 

The facility is designed and operated to comply with GTP and GMP regulatory requirements. The biologics production facility is a secure site, with each entry point requiring authorized badge access to enter. The main entrance remains unlocked during normal business hours, Monday through Friday, 8:00 AM to 5:00 PM, to allow visitors and unauthorized personnel to enter the main lobby. 

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Once inside the main lobby, visitors are required to sign in to the visitor log and must be escorted by an employee at all times. Access to office areas, locker rooms, and processing areas are restricted to authorized badge access only. Visitors requiring unaccompanied access to the facility must undergo lab safety and basic GMP training before being issued a visitor badge. The visitor training is good for one year, and must be refreshed annually. All of these requirements are designed to help us comply with D 2.1.3 of the FACT standards. 

All supplies and reagents entering the biologics production facility are controlled by our materials management program per section D 6 of the FACT effect standards. The receiving room is kept clean and sanitary, and materials are stored in a way that prohibits contamination. 

When materials enter the facility, they are placed in quarantine, which is designated by the orange shelves, as well as an orange quarantine sticker on the material. Packaging materials then undergo a visual examination for evidence of damage or contamination. They are entered into our inventory control system, which captures the material, name, quantity, manufacturer, lot number, date of receipt, acceptability, and expiration date. 

Supplies and reagents are purchased from approved vendors and require an acceptable certificate of analysis upon receipt. All materials also undergo an initial qualification and approval before being used in manufacturing. The storage shelves are up off the floor and organized in a way that doesn't block the fire sprinkler system. Once materials are approved for use, they enter into the classified space via designated pass through. Non-electronic items are wiped down with sporicidin disinfectant wipes, and electronic devices are wiped down with 70% IPA prior to being placed in the pass through. These disinfecting measures help reduce bioburden in the processing area. 

Materials are stored inside the classified space in designated supply rooms in accordance with the manufacturer's storage recommendations. The supply rooms are kept orderly to make materials easier to find and to prevent mix ups. Temperature and humidity levels are continuously monitored in the supply storage rooms. Supplies and reagents requiring cold storage are kept in temperature-controlled walk-in coolers under the appropriate environmental conditions, which are also continuously monitored. 

Entrance into the clean room areas is restricted to trained personnel having defined tasks in the area and to escorted visitors. Employees enter the classified clean space through designated locker rooms. The locker rooms are considered unclassified space, but serve as a transition space from unclean to clean. The locker rooms are cleaned regularly and monitored as part of our environmental monitoring program per section D2 of the FACT standards. The locker rooms are equipped with lockers for storage of personal items, as well as access to sinks to promote proper hand washing and disinfection. 

Food, drink, candy and tobacco products are prohibited in the processing facility. Storage shelves within the locker rooms contain all of the necessary PPE required to enter the classified clean space, including hairnets, beard nets, shoe covers, face masks, coveralls, and gloves. PPE is for clean room-use only and is not to be worn outside of the clean room per the 2.9 of the FACT standards. Procedures for proper gowning and personal hygiene are documented in our gowning and working in the biologics production facility procedure, as well as posted on the wall in each locker room for reference. 

The biologics production facility has class 100,000 and class 10,000 clean rooms. The production environment is controlled by our building management system that provides continuous monitoring, control, trending, data archiving, and alarm capabilities for five HVAC air handling units, various exhaust fans, USP water purification, hot and chilled water supply, vacuum system, process utilities, and other related systems. The building management system is maintained, verified and calibrated in accordance with applicable regulations and standards. 

The clean room environments comply with section D 2.1 of the FACT standards, as well as 21 CFR part 211 GMP regulations and are constructed with smooth, hard surfaces that are easily cleanable. The layout of the rooms allow for proper cleaning, maintenance, and operations. There is adequate space for the equipment in the room, and plenty of lighting for employees to perform their duties safely and effectively. There are separate and clearly defined areas for different operations to prevent contamination and mix ups. 

Non-biohazardous waste is removed from our facility on a daily basis by our contracted cleaning service. Biohazardous waste and sharps are removed from our facility by separate specialized medical waste contractors on a regular basis. Safety manuals are located throughout the facility and are readily accessible to staff in accordance with section D 2.7 of the FACT standards. 

The safety manuals include information on behavioral emergencies, blood and body fluid exposure, bomb threat, cardiac arrest, disaster response, earthquake and explosion, fire emergency, STS retrieval, hazardous materials spill, including chemical and radiological hazards, and severe weather plan. The safety manuals also include emergency contact information for key departments. 

There is a designated room for QC functions that is separate from processing and storage areas. The QC room is designed and constructed to the same standards as the rest of the facility, with adequate lighting, air filtration and smooth, impervious cleanable surfaces. The facility has a media prep room that is separate from the main processing areas. This room serves primarily as a backup to the main class 100,000 processing rooms, and houses redundant critical equipment that can be utilized if the main processing equipment fails or is needed due to an increased demand. 

The biologics production facility maintains seven separate class 10,000 processing suites. The separation of processing suites helps minimize risk of improper labeling, contamination, cross-contamination, and mix ups. The separate suites also allow us to accommodate research activities that can be completely separated from processing of human cellular therapy products. 

The processing facility maintains a separate room for the cryopreservation and storage of cellular therapy products. The product storage room is accessible via keycard access only and is off limits to unauthorized personnel and visitors. Each freezer unit is continuously monitored to ensure appropriate storage conditions are maintained per section D 9.5 of the FACT standards. Visual and audible alarms are in place if storage condition failures occur. Temperature, humidity, air control, and surface contamination are also monitored in the product storage areas. 

An electronic inventory control system is used to help maintain product segregation, i.e. quarantine versus release status, as well as product identification and location within the freezer units. Compressed CO2, gas and liquid nitrogen are stored in secured locations where access is restricted. All areas in the facility where liquid nitrogen is used are continuously monitored by oxygen sensors, per D 2.1.2 of the FACT standards. The processing facility is cleaned on a regular basis in accordance with D 2.4 of the FACT standards and our internal cleaning SOPs and cleaning schedules. 

Cleaning and sanitation procedures were developed based on room classification and the type of processing taking place. The cleaning procedures are validated for their intended purpose, and cleaning effectiveness is monitored on an ongoing basis through our environmental monitoring program. Records of cleaning activities, as well as environmental monitoring results are maintained. EM results are trended and analyzed to ensure the facility is maintained in an appropriate state of cleanliness. 

Records are stored and maintained in accordance with section D 1.3 of the FACT standards. Physical record, storage of SOPs, validations, occurrence reports, change requests, and processing records are kept in a secure location that is only accessible by keycard. Records are also scanned and stored electronically on a backed up server. 

We utilize an electronic document control system that manages document creation and revision, change requests and approval, staff training on documents, and periodic review. The electronic document control system is backed up daily on an external server. A downtime binder that contains current copies of all SOPs, forms, and worksheets is available in both physical and electronic format in the event of a system failure. 

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