CTGT Advisory Committee Meeting - 5/14/09

FDA asked the committee to consider current scientific data as it relates to the potential for infectious disease transmission of Chlamydia trachomatis, or CT, and Neisseria gonorrhoeae, or NG, by human cells, tissues, and cellular and tissue-based products that are recovered from the reproductive system or gestational tissues (e.g., amniotic membrane and placenta, cells recovered from menstrual blood, foreskin, and placental/umbilical cord blood derived cell products), or other sources. The recent increased use of these HCT/Ps in transplantation, and increased research to evaluate potential stem cells from these HCT/Ps for use in development of cellular therapy products, has raised questions regarding the potential for infectious disease transmission that have not been previously considered.

 

Examples of HCT/Ps Recovered from the Reproductive System or Gestational Tissues

 

Tissue

Description

Examples of Products/Uses

Amniotic membrane and cells recovered from amniotic membrane

Innermost layer of the placental membrane; often used decellularized, either as a surgical patch, or as a rich substrate for seeding other cell types (Ref. 1); decellularized amnion contains collagen fibers, glycosaminoglycans and elastin fibers

Wound dressing, treatment for leg ulcers, skin loss, reconstruction of the pelvic floor, vaginal epithelialization, oral cavity reconstruction, replacement of nasal mucosa, ear surgery, and in otolaryngology procedures (Ref. 2), ocular repair, stem cells (Ref. 3)

Placenta and cells recovered from placenta

Fetomaternal organ connected to the fetus by a fetal cord; has a role in transfer of gases and nutrients to the fetus and endocrine function

Used to replace or supplement damaged or inadequate integumental tissue;

stem cells (Refs. 4-5)

Cells recovered from menstrual blood

Shed menstrual blood collected into a container processed for long-term storage, and banked/stored

Stem cells (Refs. 6-8)

Foreskin and cells recovered from foreskin

Usually from infant foreskin but also may use adult foreskin

Fibroblast cells used as component of a cell/scaffold product (Refs. 9-10); Research ongoing re: potential for stem cells (Refs. 11-12)

Umbilical cord blood (HPC-C)

Blood which remains in the  umbilical cord of a newborn, after clamping, is collected, processed for long-term storage, and banked/stored (Ref. 13)

Hematopoietic stem cells derived from cord blood used for reconstitution of the hematopoietic system during the treatment of malignant and nonmalignant diseases, most commonly in pediatric patients (Refs. 14-15)

Placental blood derived stem cells

Extracted from placenta after placental/umbilical cord blood is recovered (Ref. 16)

Used in conjunction with cord blood for hematopoietic reconstitution (Refs. 17-19)

 

  

 

References can be found at http://www.fda.gov/ohrms/dockets/ac/09/briefing/2009-4436B1-01.htm.

 

FDA guidance for industry published in August 2007 — “Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products”provides current recommendations for determining donor eligibility as it relates to reproductive HCT/P donors:

VII. ADDITIONAL SCREENING AND TESTING REQUIREMENTS FOR DONORS OF REPRODUCTIVE CELLS AND TISSUES

             A.        Do I need to screen and test all donors of reproductive cells and tissue?

Except as provided in § 1271.90, you must screen and test all directed reproductive donors (as defined in § 1271.3(l)) and anonymous donors of reproductive cells and tissues (§§ 1271.75, 1271.80, and 1271.85) (Refs. 102 through 138).

            B.        What additional screening must I do for donors of reproductive cells and tissue?

In addition to the screening required for all cell and tissue donors and, if applicable, the screening requirements for viable, leukocyte-rich cell and tissue donors, you must review the relevant medical records of donors of reproductive HCT/Ps (who are not sexually intimate partners) for risk factors for and clinical evidence of infection due to relevant sexually transmitted and genitourinary diseases that can be transmitted with the recovery of the reproductive cells or tissue (§ 1271.75(c)). These include:

          §   Chlamydia trachomatis; and

          §   Neisseria gonorrhea.

Specific donor screening recommendations are described in section IV of this document.

            C.        What additional testing must I perform on donors of reproductive cells and tissue?

In addition to the testing required for all cell and tissue donors, and, if applicable, the testing required for donors of viable, leukocyte-rich cells and tissues, you must test donors of reproductive HCT/Ps (who are not sexually intimate partners) for evidence of infection due to relevant genitourinary disease agents (§ 1271.85(c)). These include:

          §   Chlamydia trachomatis; and

          §   Neisseria gonorrhea.

Special note on Chlamydia trachomatis and Neisseria gonorrhea testing: Although there are diagnostic tests available, there are currently no FDA-licensed, approved, or cleared tests for donor screening. In the absence of such screening tests, you must use an FDA-licensed, approved, or cleared diagnostic test labeled for the detection of these organisms in an asymptomatic, low-prevalence population (§ 1271.80(c)). FDA recommends Chlamydia trachomatis and Neisseria gonorrhea test kits utilizing NAT technology to adequately and appropriately reduce the risk of infectious disease transmission (Refs. 81, 139 through 148). You can find a listing of FDA-licensed or approved test kits for Chlamydia trachomatis and Neisseria gonorrhea at the following website: http://www.fda.gov/cber/tissue/prod.htm.

Exception from testing requirement:

If the reproductive cells or tissue are recovered by a method that ensures freedom from contamination of the cells or tissue by infectious disease organisms that may be present in the genitourinary tract, then tests for Chlamydia trachomatis and Neisseria gonorrhea are not required (§ 1271.85(c)). However, if these tests are performed and one or both results are reactive, the donor must be determined ineligible, regardless of the recovery method used (§ 1271.80(d)(1)).

(Examples of viable, leukocyte-rich HCT/Ps include hematopoietic stem/progenitor cells and semen.)


 

However, it was explained to the committee that current donor screening and testing requirements for these HCT/Ps do not require evaluation for CT and NG for the products under discussion by the committee because FDA interprets reproductive HCT/Ps to include semen, oocytes, and embryos to which the donor contributed the spermatozoa or oocyte. Because of their anatomical location, HCT/Ps collected from the reproductive system or from gestational tissues raise questions regarding the potential for infection or contamination with CT and NG.

 

After hearing a review of relevant infectious disease literature and a presentation on epidemiology and infectivity of the two organisms, the committee asked and received clarification that there have not been any reported cases of transmission of CT or NG by the tissues in question. Many commented that it appeared that current Good Tissue Practices and screening of potential donors, coupled with epidemiological trends in the U.S., appear to be providing adequate safeguards. Several members did express concern that the same may not be true for products that might be imported into the U.S. They did not make any recommendations for change to current practices