Program in Novel Biotherapeutics (PINB) Initiatives
Clinical Translation and Operations
Clinical Translation and Operations: A clear, integrated, and coordinated regulatory and clinical development path is necessary to accelerate translation of novel biotherapeutics, particularly cell, gene and regenerative therapies, at the investigator-initiated and investigator-sponsored level. The Clinical Translation group, directed by Anne Chew, PhD. and Gwendolyn Binder-Scholl, PhD, has demonstrated that a promising candidate can progress from lab to in-human testing within a period of 9-18 months depending on the complexity of the investigational agent. A primary focus of the group is to reduce the hurdles associated with early phase translational trials by navigating the complex regulatory submission process of IND applications, and coordinating critical institutional, inter-institutional, and industry resources and partnerships necessary for preclinical experimentation and translational validation, GLP correlative assay development, and GMP manufacturing. These functions include serving as liaisons between the investigator and the FDA, shared core facilities, the Office of Research Services (ORS), Office of General Counsel (OGC), Office of Human Research (OHR) and Center for Technology Transfer (CTT). Investigators are encouraged to contact the Clinical Translation group by submitting inquiries to firstname.lastname@example.org
GLP/GMP Resources:GLP/GMP Resources: The Clinical Cell and Vaccine Production Facility (http://www.med.upenn.edu/bmcrc/CCVPF/?CCVPF), a PINB shared resource and accredited facility directed by Bruce Levine, PhD, continues to expand its technical capabilities in producing GMP quality cell, vaccine, and gene therapy products for Penn and CHOP investigators. One long term goal is to better understand the collective need and demand among the CTSA institutions for cGMP reagent development and manufacturing services that comply with FDA guidelines to establish a consortium of manufacturing centers. This manufacturing consortium will leverage existing investments and expertise by creating a centralized and accessible shared infrastructure to support early phase clinical trials across the CTSAs. In the past few years, the CVPF has developed inter-institutional agreements that permit the production and shipping of investigational biological products for external clinical sites, as well as trained staff from other GMP facilities on particular cell processing and manipulation procedures. These activities can be a model that is replicated on a larger scale, including conducting all aspects of validation and manufacturing scale-up and the production of clinical grade cellular products for CTSA trials, pending the availability of funding.
The recent recruitment of Michael Kalos, PhD to the Human Immunology Core, another PINB shared resource, provides for cell-based immune assessment capabilities at FDA mandated levels of GLP quality that are now available for Penn and CHOP investigators.
In order to increase the pool of translational investigators, a training program will be formalized that allow junior investigators, post-docs, medical residents or fellows to complete short rotations in the each of the PINB infrastructure cornerstones in which they have no prior experience in. Physicians may rotate through the Core Facilities to gain experience in bench research and/or learn to work under GLP and GMP conditions. Post-docs engaged in basic research would benefit from being exposed to the BRSO/Clinical Translation group to learn about the regulatory, contractual, and financial complexities in conducting clinical trials. This type of hands-on exposure will complement the training and certificate programs and resource modules offered by the Office of Human Research. Additionally, the pairing of junior investigators with more senior faculty who have diverse expertise in the different therapeutic modalities serve as mentoring opportunities, which the PINB will work to promote.
PINB, in collaboration with Penn's Office of Human Research, is completing the development of a university-wide seven-module training program on the elements of Good Laboratory Practices (GLP). The intent of this training program is to educate faculty and staff on how to design GLP-compliant pre-clinical studies and generate reliable and reproducible laboratory data in support of INDs, as well as FDA accepted, GLP-compliant assays for endpoint analysis of patient samples. This training program could be made available to other CTSA institutions. Another training module for GMP manufacturing practices is planned to be developed soon.
Synergistic interactions between lab and clinic:
Close interactions between the research lab and clinical studies offer a unique opportunity for rapid and effective clinical progress. This is notably important for many biological therapies, where animal models offer substandard reflections on therapeutic potential and safety. The PINB provides a matrix structure within which basic research investigators are brought together with clinical researchers. In this setting, emerging technological advances brought forward for evaluation for clinical application, and clinicians have the opportunity to communicate needs back for development. Data emerging from assessment of clinical samples is fed back to the translational research laboratory for next generation developments, and forwarded to the clinical investigator for assessment of the treatment. Moving forward with the support of the CTSA, this type of synergistic interaction will be enhanced by inclusion of a broader scope of basic research and clinical investigators. This will be facilitated in part through connecting investigators via the CTSA website and through investigators being placed together within this matrix during the preclinical development step by operational and regulatory components supported by the CTSA.