Table 1. Key Points.

Area	Key Points
Pharmaceutical Quality and Manufacturing Control Issues	Establishing and maintaining consistency and reliability of raw materials and the product throughout development stages and in the final commercial process is critical and presents a challenge for complex biological systems due to multiple factors that affect their viability and function.
	The leveraging of clinical data throughout development can occur only if the drug product has similar or comparable qualities throughout development. Thus, comparability for CGT therapy products is a critical aspect of process development and is required to link clinical data throughout progressive phases of product development.
	Assays measuring product potency are of central importance to all product development and quality control activities. Potency assays serve many functions. They help to identify and control sources of variation in product activity and to test for product comparability across lots, process changes, sites, scale changes, and stability testing.
Nonclinical Issues	The preclinical safety package is conducted in appropriate models to help understand and de-risk the potential toxicities to human patients. No preclinical model is perfect. Each model will have strengths and weaknesses. Developers should understand these limitations and seek regulatory advice if any questions arise when forming the species selection strategy and translating the results for the first-in-human (FIH) package.
	Potential tumorigenicity should be considered, depending on the level of perceived risk, the product’s attributes, the scientific literature, previous clinical experience, and in vitro assessments. In vitro studies can involve characterization of biological stability, including proliferation rate and number of population doublings before senescence and karyotyping or other genetic analysis to look for chromosomal abnormalities.
Intellectual Property (IP)	IP protection and IP ownership can be critical to ensuring that a viable development path exists and to protecting the value of invested time and resources. Universities and established companies have policies to determine IP ownership. When establishing a start-up, the founders should clearly agree on ownership of IP.
Communication and Technology Transfer	Developers should have clear development and regulatory paths and be able to communicate them to colleagues, health authorities, and potential partners. These components are critical to avoiding delays and inefficiencies in the development of a CGT product.
	Technology transfer should be planned, well understood, and carefully executed. As with IP, tension exists regarding the advantages of sharing information, the leveraging of partners’ or vendors’ experience, and the retention of confidential information.

SOURCE: Tsokas, K., R. McFarland, C. Burke, J. L. Lynch, T. Bollenbach, D. A. Callaway II, and J. Siegel. 2019. Reducing risks and delays in the translation of cell and gene therapy innovations into regulated products. NAM Perspectives. Discussion Paper, National Academy of Medicine, Washington, DC. doi: https://doi.org/10.31478/201909d