Authored By Mark Levi, PhD, and Mo Heidaran, PhD, PAREXEL® Consulting
In the world of good practices, far less is known about GTP than its more well-known counterparts, GLP and GMP.
The origin of GTP is 21 CFR 1271 Subpart D as well as Subpart E; however, the Donor Screening and Testing requirements originate from Subpart C. The GTP and Donor Eligibility requirements are designed to prevent the spread of communicable diseases.
The FDA guidance document “Current Good Tissue Practice (CGTP) and Additional Requirements for Manufacturers of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps)” was issued back in Dec. 2011. However, CGTP and CGMP have recently come to the forefront with enforcement actions against certain stem cell clinics and the FDA’s intent to exercise enforcement discretion for the 36 months following the issuance of final guidance, “Regulatory Considerations for Human Cells, Tissues, and Cellular and Tissue-Based Products: Minimal Manipulation and Homologous Use,” updated December 2017.
HCT/Ps are defined in 21 CFR 1271.3(d) as articles containing or consisting of human cells or tissues that are intended for implantation, transplantation, infusion, or transfer into a human recipient.
Certain HCT/Ps are minimally manipulated and used for homologous indications and do not require premarket approval as per §361 of Public Health Service Act; however, many others are not exempt. FDA’s current thinking on the 21 CFR 1271.10(a)(1) criterion of minimal manipulation and the (a)(2) criterion of homologous use is described in “Regulatory Considerations for Human Cells, Tissues, and Cellular and Tissue-Based Products: Minimal Manipulation and Homologous Use” which was corrected in Dec. 2017.
The following are core CGTP requirements:
Facilities (21 CFR1271.190(a) and (b))
Environmental control (21 CFR1271.195(a))
Equipment (21 CFR 1271.200(a))
Supplies and reagents (21 CFR1271.210(a) and (b))
Recovery (21 CFR1271.215)
Processing and process controls (21 CFR1271.220)
Labeling controls (21 CFR1271.250(a) and (b))
Storage (21 CFR 1271.260(a) through (d))
Receipt, predistribution shipment, and distribution of an HCT/P (21 CFR 1271.265(a) through (d)
While GTP may at first resemble GMP and GLP regulations, GTP is a stand-alone set with its own deviation reporting requirements and does not supersede GMP and GLP but applies in addition to those regulations. Thus, some companies with certain HCT/Ps are regulated under §351 are subject to all three sets.
Some stem cell clinics are making a “practice of medicine” argument in an attempt to avoid their products being regulated as biologics under §351. FDA’s concern is that these types of stem cell products could be manufactured under non-CGMP conditions and not meet the minimum regulatory standards for product quality.
PAREXEL is currently supporting clients in developing regulatory strategies and submissions for HCT/Ps and has experts who can help you thrive while being subject to all three sets of regulations.