Terms and Definitions

• CBER – Center for Biologics Evaluation and Research; a center within the FDA whose goal is to “protect and enhance the public health through the regulation of biological and related products including blood, vaccines, allergenics, tissues, and cellular and gene therapies.”

• cGTP – Current Good Tissue Practices. This refers to a part of the HCT/P regulations 1271.150 (Subpart D and E). Reproductive clinics are exempt (so far) from this section except for 1271.15, ensuring the quality of contractors (those doing the actual disease testing) and 1271.155, which covers exemptions and alternatives. In the very near future, reproductive clinics will be required to follow the cGTPs

• Guidance – Method to comply with regulations; minimum requirements. Guidances are the FDA’s current thinking and “does not create or confer any rights for or on any person and does not operate to bind FDA or the public. You can use an alternative approach if the approach satisfies the requirements of the applicable statutes and regulations.”

• Departure – a change in your standard operating procedures. These changes must be justifiable and recorded. The responsible person must determine that this departure did not increase a risk for disease. Departures are consistent with the regulations. For example, you were supposed to use HTF medium but the manufacturer ran out of it so you used G1 medium. This is not where you forgot to test a donor for Chlamydia and now you want to transfer the donor tissue anyway. Also, “recipients signing a release saying that they know that an anonymous donor was not tested but they accept the risks and agree to the transfer” is not a departure. It is a deviation and could result in severe fines of up to $250,000 and imprisonment of up to 1 year. Bad doodoo!

• Deviation – When you do not follow requirements. This could increase the risk of a patient getting a disease. This is bad doodoo! Don’t ever deviate! For example, you forgot to run a test for HBV on an egg donor, or the lab you use pooled blood for testing for HIV 1 and 2.

• Donor Eligibility (DE) Determination – This is required for all donor tissues, including directed donor tissue. This is a determination by a Responsible Person regarding whether the tissue (donor eggs, embryos or sperm) is suitable for transfer and meets all FDA requirements as listed in 21 CFR Part 1271 and any addendums. In FDA terms this includes screening (the questionnaires, physical and review of relevant medical records) and testing (disease testing). Donor eligibility is also not required for reproductive tissue donated by a sexually intimate partner of the recipient or frozen embryos from SIPs that are later made available for either directed or anonymous donation. For the latter, “appropriate measures should be taken to screen and test the semen and oocyte donors before transfer”.

• HCT/Ps – Human Cells, Tissues, and Cellular and Tissue-Based Products; this is all donor tissue including donor sperm, donor eggs and donor embryos.

• Label – Required elements of labels are usually so large for the size of cryostorage containers that we use that these labels are usually stickers affixed to paperwork or a sheet of paper that contains warnings. Current labels are: “For Autologous Use Only,” “Not Evaluated for Infectious Substances”, “Warning: Advise recipient of communicable disease risks”, “Warning: Reactive test results for (name of disease agent or disease)” and “Advise recipient that screening and testing of the donor(s) were not performed at the time of cryopreservation of the reproductive cells or tissue, but have been performed subsequently.”

• Manufacturer – IVF clinics. Those of us that make embryos through the use of donor eggs. The term is actually much wider to include anyone who is involved in “any or all steps in the recovery, processing, storage, labeling, packaging, or distribution of any human cell or tissue, and the screening or testing of the cell or tissue donor.” Basically, if you are doing almost anything with donor tissue, you are a manufacturer.

• Most Responsible Person – The person that is ultimately responsible for the donor tissue program and must make sure the FDA regulations are complied with. This is where the buck stops. Must be someone with medical training and knowledgeable about the FDA regulations.

• Recommended – Not necessary – really, you don’t have to.

• RCDADs – Relevant Communicable Disease Agent or Disease; this list of diseases can change at any moment and you need to keep up to date with CBER’s list. Subscribe to their list server to get updates. HIV 1 and 2, HBV, HCV, WNV, Spesis (not for us really), Vaccinia, CJD/vCJD, syphilis, Chlamydia trachomatis, Neisseria gonorrhea, and HTLV I and II. SARS has been removed. HTLV I and II for donor embryos and donor sperm.  CMV testing is required for donor embryos and sperm but is not a RCDAD. You must test and have an SOP for CMV results.

• Regulation – The actual FDA requirements that must be followed, as opposed to Guidances, which are methods to comply with these regulations.

• Responsible Person(s) – Those that can determine eligibility and release donor tissue for use. Must be someone with medical training.

• SIPs – Sexually Intimate Partners. To be defined by each “manufacturer”. Tissue from SIPs is not exempt from these FDA regulations. SIPs can be transferred without testing or screening. SIPs do not need eligibility determination. The FDA leaves the definition of sexually intimate to each manufacturer.

• SOP – Standard operating procedures. Your manuals of how you do things.

• Summary of Records – This record records whether the donor tissue is eligible for transfer. It also is a summary of all of the disease tests. It must follow the tissue wherever it goes (shipping), even within the same facility. It should accompany the tissue when it is shipped. It must have the following five items: 1) The statement, “Communicable disease testing was performed by a laboratory that is CLIA certified or meets equivalency requirements as determined by CMS.” 2) A list and interpretation of all RCDADs and CMV, if applicable. 3) Name and address of the establishment making the donor eligibility determination. 4) The statement noting the reason for donor ineligibility for a directed donor. 5) Tissue number.

Copyright © 2008 AAB-CRB