Creating a cgmp Facility for Early Clinical Trials of Molecular Imaging and Therapeutic Agents

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1 Designing for the Frontiers of Research Creating a cgmp Facility for Early Clinical Trials of Molecular Imaging and Therapeutic Agents Richard J. Mohr What if it were possible to treat a cancer patient with a regimen tailored not only to their specific disease, but also to that individual patient s genetics? What if that treatment were able to deliver an effective cancer-fighting drug directly to tumor cells while avoiding the devastating effects of traditional chemotherapy? Thanks to researchers at the Johns Hopkins Medical School, this vision is quickly becoming reality. The Center for Translational Molecular Imaging (CTMI) will provide researchers the tools they need to conduct first-in-human trials of targeted molecular imaging agents and drug delivery systems. Center for Translational Molecular Imaging l page 1

2 One of the greatest challenges in treating cancer effectively is minimizing the damage to normal tissue during therapy, while ensuring a sufficient amount of agent is delivered to the tumor. Often, otherwise effective drugs fail in clinical trials because they cannot be administered in high enough doses to the malignant tissue. However, researchers at this facility may have overcome this challenge. One of their experimental treatment systems encapsulates anticancer drugs within nanoparticles, coating them with miniscule targeting or affinity agents that act as selective filters. Once the drug-filled particles are injected into a subject s system, the targeting agent, which is often a small molecule such as a peptide, allows the nanoparticle to attach only to malignant cells. This not only concentrates the cancer-fighting drug at the tumor site, but prevents the highly toxic drug from interacting with and harming the rest of the patient s system. The benefits of this revolutionary therapy are not limited only to cancer treatment. Therapeutic regimens across a wide range of diseases could be transformed through the various processes developed at the CTMI facility. In addition to the targeted nanoparticle drug delivery system, the CTMI provides research and validation capability for radiopharmaceutical To accomplish this mission effectively, the researchers require a first-of-its-kind facility for single patient treatment with the necessary environment and equipment. The facility, while meeting current Good Manufacturing Practice (cgmp) production standards (not normally applied at this stage of development), allows researchers to prepare, deliver, and track individual doses of molecular imaging and therapy agents. The 4,000-gross-square-foot facility will be located in vacated laboratory space on the lower level of an existing building with external access on one side. The complete renovation of the space will result in 3,500 net square feet of cgmp process rooms laboratories and support facilities the CTMI s imaging center, which includes a clinical PET/MRI scanner The facility is designed to provide flexibility to accommodate a variety of product types and manufacturing processes in the future, allowing researchers to investigate a host of process areas, including production of plasmid DNA products cell therapy products monoclonal antibodies protein therapeutics magnetic resonance nanoparticles optical and cellular imaging agent discovery and development and radioisotope products an imaging center for verification of the agents developed on-site, in patients Center for Translational Molecular Imaging l page 3

3 In the past, firstin-human test facilities such as this would not have been designed to cgmp standards, as they require the flexibility to test products, adjust the processes, and re-examine the results. However, the Food and Drug Administration (FDA) is more closely examining the clinical trial phase for compliance with cgmp standards as the increased interest in bench-to-bedside therapies circumvents the traditional scaleup and validation processes. As a result, earlier stages such as Phase 1 and first-in-human trials have to establish a plan to be compliant without knowing the complete set of requirements for the type of drug or process being researched. Adapting to these unknowns poses a distinct challenge when creating a cgmp processing space. To achieve the flexibility required by the researchers and still provide the qualified cgmp space, the design team selected the appropriate instrumentation based on a variety of possible research needs. The team then focused on validating the mechanical support, utilities, and all of the researcher s equipment in this space for: Installation Qualification (IQ) Demonstrating that the equipment meets all specifications, is installed correctly, and all necessary components and required documentation is in place. Operational Qualification (OQ) Demonstrating that all aspects of the equipment are operating correctly. Performance Qualification (PQ) Demonstrating that the equipment performs as intended in a consistent manner over a period of time. By ensuring the environment of the process rooms, and all the equipment is validated and can be used as the researcher s needs dictate, the facility meets cgmp standards without tailoring the entire facility to a single manufacturing process. The design team utilized the concept of multiple process rooms for the separation of products, while outsourcing some quality control testing (QC) operations to another campus facility near the site. The facility was separated into three distinct sections a cgmp cellular production space a cgmp radio isotope area and a non-cgmp imaging suite This separation allowed the design team to better control cross contamination issues and to accommodate the various cleanroom requirements of the production processes in a very constricted space allotment. Center for Translational Molecular Imaging l page 5

4 CTMI The facility is accessed through a single route for both patients and researchers, and the design incorporates a progressive tiered approach to cleanroom organization. The elevator opens into a vestibule that leads to a corridor providing access to the entire facility. This corridor, the patient prep rooms, and the imaging suite (shown in blue on floor plan) comprise the unclassified areas that allow for public/patient space and access to the controlled areas of the facility. PET/MRI Scanner As a result of this layout, the single point of entry to the facility accommodates the controlled access for patient and imaging technicians in the unclassified space, while also providing the necessary progression and classification of spaces to access the cleanrooms required for this cgmp facility. Another consideration for the planning of the facility was the challenge of bringing the PET/MRI scanner into the imaging suite. The sheer size of the equipment prohibited its delivery through interior corridors or the elevator. The solution was to locate this suite adjacent to the accessible exterior wall and create a temporary opening to bring the equipment As demonstrated by the various shades of green, yellow, and orange, the researchers must pass through a series of progressively cleaner laboratories and gowning areas, moving from Class 100,000 through to Class 10,000 cleanrooms. These final-stage cleanrooms are equipped with Class 100 clean cabinets, depending upon the production needs of the room. LEGEND CLASS 100 (ISO 5) CLASS 1,000 (ISO 6) CLASS 10,000 (ISO 7) CLASS 100,000 (ISO 8) CONTROLLED UNCLASSIFIED (CNC) single point of entry directly into the treatment area from the outside and then sealing the scanner inside the imaging suite. As with any cutting-edge research at the frontiers of science, the facility must be able to adjust and accommodate many unknown factors. Flexibility was addressed by creating independent process rooms supported with validated mechanical systems and utilities as required by cgmp. Providing a variety elevator Center for Translational Molecular Imaging l page 7

5 of equipment and supporting each process that could conceivably be used, enhances this flexibility. This will allow CTMI researchers to continue with their mission, taking the vital next steps in transforming how disease is treated. The promise of translational medicine is that treatments can be created and administered for the specific genetics of the patient. This facility takes that promise one step further with a bench-to-bedsideback-to-bench concept of taking the information gathered during treatment and feeding it back into the research process. Flad Architects has earned a reputation for outstanding client service, fiscal responsibility, and design excellence over its 85-year history. Specializing in the planning and design of innovative science facilities for academic, healthcare, government, and corporate science and technology clients, Flad is nationally known and honored for its planning and design expertise. In addition to traditional architectural services, Flad provides strategic facility planning and programming, laboratory planning, interior design, landscape architecture, and structural engineering Flad Architects