cGMP Facility

The cGMP facility encompasses four distinct production rooms, two centrifuge rooms, a common equipment hallway, gowning room, anteroom, and tank room. Single pass air flows into each room through an inline High Efficiency Particle Arrestor (HEPA) filter in the ceiling and is exhausted through the laminar flow hood directly to the outside. The gowning, production, and centrifuge rooms, as well as the equipment hallway, are monitored weekly for air quality and general environmental cleanliness, in accordance with established standard operating procedures. Air quality is maintained within parameters for Class 100,000 in the gowning room, Class 10,000 in the common equipment hallway, production rooms, and centrifuge rooms, and Class 100 in each laminar flow hood.

The anteroom is accessed from the seventh floor riverside corridor of the hospital through an M-card controlled door. All attempts at entry to the anteroom are logged by security. A work area, cordless phone, and computer are located in the anteroom for use by HAL technicians and staff. One side of the pass-through validated sterilizer can be accessed from the anteroom for the removal of decontaminated waste or the loading of clean supplies to be sterilized.

The gowning room is accessed from the anteroom through an M-card controlled door. The gowning room is under positive pressure. Both gowning room doors may not be open at the same time. HEPA-filtered air flows out of the gowning room into either the anteroom or the common equipment hallway, depending on which door is open. Cleanroom gowning materials are stocked in the cabinet and on the shelves in the gowning room. HAL technicians don appropriate barrier clothing in the gowning room before entering the common equipment hallway. Proper gowning procedures are posted. Sticky mats cover the floor surrounding the entrance and exit to the gowning room in order to prevent carry-over of particulates on shoe and boot cover soles. When leaving the HAL, all personnel must wash their hands using the gowning room sink.

The common equipment hallway serves several purposes. It is a buffer zone between the four separate production rooms, a staging area for waste decontamination, a storage area for supplies and finished products, and a secondary gowning area prior to entrance into any of the dedicated production rooms. The equipment hallway is at a greater pressure than any of the production rooms, causing air to flow from the equipment hallway into any production room with an open door. In this way, the production rooms are prevented from contaminating each other. Waste that has been securely bagged is collected in the hallway before being loaded in the sterilizer for decontamination. In order to facilitate the secure storage of supplies and products that require low temperatures, the equipment hallway contains three liquid nitrogen freezers, four -70°F freezers, a dual chamber -30°C freezer, and two 4°C refrigerators, as well as a controlled-rate step-down freezing chamber. The HAL staff stocks the two equipment hallway metal cabinets with general and sterile supplies. The staff also stocks the secondary gowning cabinets, located outside the entrance to each of the production rooms, with sterile gloves, gowns, and miscellaneous small supplies. All personnel must re-gown before moving from one production room to another.

Each production room is independently keyed. Keys for the appropriate production rooms are issued to HAL technicians by the HAL staff. Upon entry and exit from a production room that is active, all personnel must sign the production room log located on the room's door. Two sizes of production rooms are available, depending on the requirements of the procedures to be performed. Within each room approximately 12 square feet of stainless steel benchspace is available for the housing of equipment and other prepackaged sterile reagents. Equipment within each room includes a six foot laminar flow hood, stacking CO₂ incubators, an inverted microscope, a table top centrifuge, a high volume floor centrifuge, a triple arm laboratory balance, and a free standing refrigerator/freezer for storage of media, serum, and supplements. The two smaller production rooms have fewer incubators than the two larger rooms. Shelf space is located immediately adjacent to each room's laminar flow hood. All HAL incubators are continuously monitored for temperature, humidity, and CO₂ concentrations using electronic sensors linked to a computer-based data storage and alarm system. All refrigerators and freezers are also monitored for temperature using the same electronic monitoring system. Each production room within the cGMP facility of the HAL can be used for the performance of a single protocol only. No other laboratory procedures (including the growth of other eukaryotic cells, bacteria, or viruses) are performed in a designated room. Only one cell type, either from or intended for a single patient, may manipulated in a production room at a time. Technicians must re-gown and the room must be decontaminated between different cell types or patients. Cleaning of the room before and after performance of protocol-related activities is performed in accordance with established laboratory standard operating procedures.

Two dedicated centrifuge rooms are located between the production rooms. Centrifuge room A links production rooms 1 and 2, and centrifuge room B links production rooms 3 and 4. Each centrifuge room is accessible to only one of its attached production rooms at a time. Each centrifuge room must be cleaned and validated before it may be used by the other adjoining production room. Centrifuge A contains a super-speed centrifuge and an ultra-speed centrifuge. Centrifuge B has the capacity to have either a super-speed or an ultra-speed centrifuge, as well as ample shelf space for supplies.

The tank room, located outside the production area of the cGMP facility, is accessible only from the hospital corridor. Gas tanks are changed by the HAL staff without entering the cleanroom portions of the facility. Dedicated piping carries required gases and liquid nitrogen into the cleanroom production areas of the cGMP facility without the risk of introducing contamination from the gas tanks.

QA/QC Laboratory

The QA/QC portion of the Human Applications Laboratory provides the HAL staff with the laboratory and office space required to perform assays on products from the cGMP facility, maintain records, and perform environmental testing of the cGMP facility. The HAL staff stores all current production and maintenance records in the QA/QC area. The automated data monitoring and alarm systems for both equipment and environmental controls are located in the QA/QC portion of the HAL. Fire-safe cabinets are used for the storage of records, both paper and electronically archived. In order to ensure the integrity of the data which is maintained in the QA/QC space, only HAL staff are allowed access to the QA/QC portion of the laboratory.

One wall of the QA/QC laboratory is bench space dedicated to performing assays on products from the cGMP facility. A 4°C refrigerator, -30°C freezer, and -70°C freezer provide low temperature storage for test samples and for Biopharmacy products. The small Biopharmacy area allows for the final preparation of viral and plasmid products in a laminar flow hood cleanspace.