Translational Cancer Imaging Facility (TCIF)
The TCIF at the Beth Israel Deaconess Medical Center (BIDMC) fills a major unmet need at Harvard Medical School and all of Massachusetts, namely, the cGMP manufacture and aseptic fill-finish of non-radioactive and radioactive pharmaceuticals to enable first-in-human trials of novel molecules. Construction of the facility was funded by an ARRA grant from the NIH and was completed in August of 2013.
The TCIF is a state-of-the-art 1,400 sq ft facility designed for the cost-efficient, time-efficient, and safe cGMP manufacturing and aseptic fill-finish of novel non-radioactive or radioactive in vivo diagnostic and therapeutic agents for cancer and other diseases. Unlike traditional facilities, which are over twice the size and quadruple the cost, the TCIF was engineered for maximal efficiency. Indeed, as one enters the facility and moves in a clockwise direction, one is able to achieve regulatory compliance with over 8 different (and sometimes conflicting) regulatory standards (Figure 1 and Table 1).
Capabilities: The TCIF is capable of taking virtually any molecule from the bench to the bedside. Of particular importance is the TCIF’s radiolabeling capabilities. The FDA has recently stated that prior to high mass dose injection of diagnostic and therapeutic proteins, quantitative biodistribution and pharmacokinetic studies in human volunteers are typically mandated. The TCIF is capable of radiolabeling any molecule with SPECT or PET radioisotopes, and in collaboration with the adjacent Longwood Small Animal Imaging Facility, can coordinate the rodent studies that are necessary to support first-in-human injections. Some of the TCIF’s many capabilities include:
- FDA-compliant log-in and controlled storage of precursors and supplies
- Controlled storage of regulatory documents
- ISO-7 cGMP manufacturing of small molecules, peptides, and proteins
- ALARA-compliant radiolabeling of small molecules, peptides, and proteins with SPECT or PET isotopes
- ISO-5 aseptic fill-finish of vials or syringes with non-radioactive or radioactive API
- Controlled long-term storage of non-radioactive APIs at 4˚C or -20˚C
- Quality assurance/quality control room
- Collaboration with the Longwood Small Animal Imaging Facility (www.centerformolecularimaging.org/lsaif) for quantitative biodistribution and pharmacokinetic studies in rodents (separate charges apply)
- Expert consulting on cGMP manufacturing processes, aseptic fill-finish processes, and CMC regulatory document preparation
Operational Model: The TCIF is operated as a core facility of the BIDMC and is open to all academic and corporate entities with a need for first-in-human clinical translation. Only one project at a time is accepted into the facility, with a minimum project period of 3 months and no maximum. The monthly core charge includes 24/7 facility access for the user’s team, use of the TCIF staff listed below, air quality certifications, facility cleaning, environmental monitoring, and all routine consumables and sterile gases. The user only needs to provide the equipment needed for their particular cGMP manufacturing process (e.g., bioreactors) and for their particular quality assurance/quality control processes (e.g., endotoxin detectors, GC with headspace, etc.). The user’s team then works with the TCIF staff to create standard operating procedures (SOPs), work instructions (WIs), and validated processes to for eIND or IND submission to the FDA. The TCIF staff will perform all aseptic fill-finish processes, including radioactive ones, to ensure full regulatory compliance.
Leveraging the BIDMC Clinical Infrastructure: The BIDMC is a 566-bed teaching hospital of the Harvard Medical School. It is JCAHO-compliant and underwent its last JCAHO accreditation inspection in July 2013. The BIDMC receives over $150 million per year in research support, and conducts clinical research under the supervision of the Committee on Clinical Investigations, New Procedures and New Forms of Therapy (CCI), which is the institutional review board (IRB), and reviews all Medical Center research involving human subjects. The CCI conforms to requirements set forth in 45 CFR Part 46 and 21 CFR Parts 50 and 56. In addition to these mandates, the CCI safeguards the rights and welfare of human subjects by making determinations regarding ethical standards and by evaluating the risk/benefit ratio of all studies. Users of the TCIF should inquire about clinical trial opportunities at BIDMC.