The Food and Drug Administration's (FDA) regulations for human cells, tissues, and cellular and tissue-based products (HCT/Ps) refer to this step as a 'pre-distribution' shipment. Refer to § 1271.265(b) in the Current Good Tissue Practice Final Rule as well as § 1271.60(b) and (c) from the HCT/P Donor Eligibility Final Rule. A corresponding AATB standard in the 13th edition of the Standards for Tissue Banking (2012) is found at D5.900 Transportation of Tissue Following Recovery.

Delays when transporting these boxes can occur and refusal to carry the container onboard commercial aircraft has happened. The cause has been discovered to be due to common wording used for labeling the outside of the shipping box that may cause alarm to airline or transportation safety personnel who check the box upon receipt at the airport.

A recommendation is now being issued to tissue banks that labels used for the outside of these shipping boxes should not contain the term "Quarantined." Identification that the tissue is currently in a state of quarantine is expected to be prominently displayed inside the box. We are also advising you that a description "Donor Eligibility Has Not Been Completed" must also be included in records inside the box that accompany the tissue, but this status is not necessary or advised to be indicated on the outside of this box. Inside the box, you may also include descriptions such as "Not Tested for Infectious Disease" or "Not Suitable for Transplant in Current Form" but this is not required.Use of any of these terms on the outside of this type of transport box may delay a pre-distribution shipment or refusal to transport can occur. The result can be disastrous in that tissue requiring time-sensitive processing will not be received in time to fulfill established processing parameters, and the desires of the donor and/or the donor's authorizing person may not be met.

To be certain federal regulations do not expect the term "quarantined" to appear on the outside of a pre-distribution shipment, we sent an inquiry to FDA to obtain current thinking on labeling pre-distribution shipments of tissue for transplantation. We received this reply:

Your inquiry was forwarded within CBER to the Office of Cellular, Tissue and Gene Therapies (OCTGT) and the Office of Compliance and Biologics Quality (OCBQ) who provided the following:

As I understand your questions, AATB membership has asked what is FDA's current thinking regarding the method a tissue establishment should use to clearly identify that tissue within a pre-distribution shipment is quarantined. In addition, AATB membership has asked whether there is an expectation that the term "quarantined" appear on the outside of the shipping container (the shipping box), or whether it can prominently appear inside this box instead.

In accordance with 21 CFR Part 1271.60 (b) Identification of HCT/Ps in quarantine, "You must clearly identify as quarantined an HCT/P that is in quarantine pending completion of a donor-eligibility determination. The quarantined HCT/P must be easily distinguishable from HCT/Ps that are available for release and distribution." 21 CFR Part 1271.60(c) further states that "If you ship an HCT/P before completion of the donor eligibility determination, you must keep it in quarantine during shipment."

According to 21 CFR Part 1271.3(q), "quarantine means the storage or identification of an HCT/P to prevent improper release, in a physically separate area clearly identified for such use, or through use of other procedures, such as automated designation." FDA does not prescribe how a tissue establishment must identify an HCT/P that is in quarantine, nor require that the word "quarantine" specifically appear on a label or shipping container. Rather, the establishment may determine by what means it will store or identify HCT/Ps in quarantine. To be in compliance with the regulations, the HCT/P must be accompanied by the records specified in 1271.60(c)(1), (2), and (3) during shipment.

For easy reference, here is § 1271.60:

§ 1271.60 What quarantine and other requirements apply before the donor eligibility determination is complete?

(a) Quarantine. You must keep an HCT/P in quarantine, as defined in § 1271.3 (q), until completion of the donor-eligibility determination required by § 1271.50.

(b) Identification of HCT/Ps in quarantine. You must clearly identify as quarantined an HCT/P that is in quarantine pending completion of a donor eligibility determination. The quarantined HCT/P must be easily distinguishable from HCT/Ps that are available for release and distribution.

(c) Shipping of HCT/Ps in quarantine. If you ship an HCT/P before completion of the donor-eligibility determination, you must keep it in quarantine during shipment. The HCT/P must be accompanied by records:

(1) Identifying the donor (e.g., by a distinct identification code affixed to the HCT/P container);

(2) Stating that the donor-eligibility determination has not been completed; and

(3) Stating that the product must not be implanted, transplanted, infused,

or transferred until completion of the donor-eligibility determination, except under the terms of paragraph (d) of this section.

In regard to expectations of the International Air Transport Association (IATA), there should be no concerns regarding this type of labeling appearing on the outside or inside of a pre-distribution shipment. Per IATA's Dangerous Goods Regulations, "any tissue or organs intended for use in transplantation are not subject to these Regulations." Recovered tissue for transplantation from a screened donor is considered an "Exempt Human Specimen" so no specific labeling on the outside of a shipping package is required. Refer to DGR Classifications, Biological Substance, Category B, Exceptions (see 3.6.2.2.3.5).

Contact Scott Brubaker if you have any questions.