Page 1730 - Hematology_ Basic Principles and Practice ( PDFDrive )

1536 Part IX Cell-Based Therapies

which tests are required for certain products. Establishing postship- have a centralized independent data safety monitoring board (DSMB)
ment acceptance criteria is critical for the use of many cell therapy that is often convened by the sponsor (NIH or a pharmaceutical
20
products. Practice runs are recommended for shipment of the company). A monitoring plan must be developed for the collection
product, especially if the timing of the administration is crucial. For and reporting of adverse events to the SMC/DSMB and the FDA.
example, if a product is to be administered during a surgical proce- This is another step where good communication is essential. The trial
dure, it will be important to know the product viability if there are investigator and the cell-processing facility must meet regularly to
delays in shipment or postshipment testing, or during the surgical discuss any adverse events and events that occur during product
procedure. administration to determine if they are attributable to the cellular
In addition to a product meeting the appropriate release criteria, product or the subject’s underlying disease. The FDA and the SMC/
the product administration process needs to be monitored. Patient DSMB must be informed of these events to determine if a prespeci-
baseline and postadministration evaluations are conducted, adverse fied stopping boundary has been crossed.
events are documented, and any deviations from the product admin-
istration procedures/processes are recorded. Such documentation can
allow the cell-processing laboratory to evaluate common elements CONCLUSIONS
across different products as well as observe any product-specific
trending. The development of novel cellular therapeutics is a long and complex
process requiring an IND. There are many translational steps to be
completed before exposure to humans is feasible. These steps range
Quality Control/Quality Assurance from practical issues such as the shipment of cells to the complicated
issues of setting acceptable product specifications and conducting
A parallel process to the manufacturing process and pre-clinical pre-clinical studies in animal models to predict product safety profile.
studies is QC and QA. QA begins before the manufacture of the Investigators need to develop good working relationships with the
cellular therapeutic begins. It is based on the manufacturing process cell-processing facility staff and statistical staff in order to conduct a
and confirms that each step from raw material procurement to technical and scientifically robust clinical trial. The key to a successful
product release can be performed in a consistent and regulation- IND is early and frequent communication with the FDA.
compliant manner. QC is product based and confirms whether or
not the final cell therapy product satisfies the preestablished specifica-
tions for final release. Managers and third-party auditors are respon- SUGGESTED READINGS
sible for QA through the development of process documentation,
establishing SOPs, conducting audits, and training. Inspectors and Gee A, editor: Cell therapy cGMP facilities and manufacturing, New York,
area supervisors perform QC by performing and receiving inspection 2009, Springer-Verlag.
reports at all points throughout the manufacturing process. Gee AP, Sumstad D, Stanson J, et al: A multicenter comparison study between
the Endosafe® PTS™ rapid-release testing system and traditional
methods for detecting endotoxin in cell-therapy products. Cytotherapy
Data and Adverse Event Monitoring 10:427, 2008.
Guidance for Industry: Eligibility Determination for Donors of Human
In addition to the QC/QA of the cellular therapeutic, there is also Cells, Tissues, and Cellular and Tissue-Based Products (HCT/P’s) Final
the QC of data collection. Case report forms must be tailored to the Guidance, August 2007.
study and need to be linked to the source data collected during the Guidance for Industry: Guidance for Human Somatic Cell Therapy and
manufacture and delivery of the cells, and throughout the clinical Gene Therapy, March 1998.
trial. The forms should be tested for ease of completion so that data Preti RA: Bringing safe and effective cell therapies to the bedside. Nature
coming in from the clinical sites will be easy to collect and interpret. Biotechnol 23:801, 2005.
Data coordinators and/or research nurses should be given rigorous
training on the completion of these forms and should know how long
each form takes to complete so they will be able to give a reasonable REFERENCES
estimate of how many subjects they can follow within a given time
period. 21 For the complete list of references, log on to www.expertconsult.com.
Single-center trials are often monitored by an institutional safety
monitoring committee (SMC), whereas multicenter trials typically