Intense clinical monitoring of the human subject is expected after administration of the product. FDA requires sponsors to
report serious and unexpected adverse events associated with use of a product as soon as possible and within 15 calendar days.
Sponsors must report any unexpected fatal or life-threatening experience associated with the use of the product as soon as
possible and within seven days.
The need to have a well-defined clinical monitoring program is something FDA has emphasized for both cell-based and gene therapy
products in recent years.4,5 In terms of gene therapy products, which include genetically modified cells, FDA recently announced the "Gene Therapy Patient
Tracking System," which includes a provision for the collection of short- and long-term patient safety and outcome data.18 A similar system is under consideration for long-term patient follow-up for recipients of xenotransplantation products.19,20 Upon marketing approval, FDA expects ongoing postmarketing safety data collection and risk assessment based on observational
data, as it does for all approved products, as part of pharmacovigilance.22
SUMMARYProducts based on living cells appear to hold significant therapeutic promise for addressing unmet medical needs. In light
of the approximately 340 ongoing clinical trials involving cell therapies, perhaps this is an under- statement.23 However, such enthusiasm must be tempered by the potential biosafety risks these products present. Many of these risks,
such as those presented by infectious agents, are common to all biological products, and well-established procedures such
as donor screening and testing, as well as qualification of source and ancillary materials, should greatly minimize those
However, the very characteristics that many cells possess, such as the ability to proliferate, differentiate, and integrate
into a diseased or damaged body system, also elicit concerns regarding biosafety. Since there are a number of uncertainties
regarding the ability of in vitro and in vivo systems to address these issues, we are left to ponder the notion that "absence of evidence is not evidence of absence."24 An ongoing biosafety vigilance program (before, during, and after administration of the product) should significantly minimize
the actual biosafety risks inherent in CBTs.
DEDICATIONThis article is dedicated to my former colleagues in the Office of Cellular, Tissues and Gene Therapies (OCTGT), CBER, FDA.
The basis of the information presented in this article has been gleaned from conversations with many of you over the years,
as well as guidance documents you have written and presentations you have made. Thanks for so freely sharing your knowledge
and enthusiasm for these products with me.
REFERENCES1. FDA. Code of Federal Regulations, Title 21 Part 600, Section 3(p): Definition of safety for biological products. 2003 April
2. FDA. Code of Federal Regulations, Title 21 Parts 210 and 211: Good manufacturing practices. 2003 April 1.
3. Frey-Vasconcells J. Presentation on GMPs. Biotechnology Industry Organization (BIO) Annual Meeting; 2000 Mar 26-30; Boston,
4. FDA. Dear gene therapy IND or master file sponsor letter. 2000 Mar 3. Available at:
5. International Society for Cellular Therapy. Cel therapy regulatory requirements: recent developments. ISCT Telegraft 2002; 9(3):13-15. Available at:
6. FDA, CBER. Draft guidance for reviewers: instructions and template for chemistry, manufacturing, and control (CMC) reviewers
of human somatic cell therapy investigational new drug applications (INDs). 2003 August 15. Available at: