6. Biological Specimen

6.1 Provide a list of documents needed for export permit relevant to biological specimen shipment.

49CFR173.134 provides for the shipment of biological materials. Biological specimens fall into Division 6.2 – infectious substances. {(“Infectious substances”, per 49CFR173, “means a material known or reasonably expected to contain a pathogen. A pathogen is a microorganism (including bacteria, viruses, parasites, and fungi) or another agent, such as a proteinaceous infectious particle (prion) that can cause disease in humans or animals”)}.

(4) Patient specimens are those collected directly from humans or animals and transported for research, diagnosis, investigational activities, or disease treatment or prevention. Patient specimens include excreta, secreta, blood and its components, tissue and tissue swabs, body parts, and specimens in transport media (e.g., transwabs, culture media, and blood culture bottles).

Infectious substances are broken down into:

• Category A: An infectious substance in a form capable of causing permanent disability or life-threatening or fatal disease in otherwise healthy humans or animals when exposure to it occurs; and
• Category B: An infectious substance that is not in a form generally capable of causing permanent disability or life-threatening or fatal disease in otherwise healthy humans or animals when exposure to it occurs. This includes Category B infectious substances transported for diagnostic or investigational purposes. 

For the purposes of this guidebook, we shall address only Category B.

A Category B infectious substance must be described as a “Biological substance, Category B” and assigned identification number UN3373.

The U.S. International Trade Administration indicates that an export permit is unlikely to be needed for patient specimens. The Export Control Classification Number (ECCN) under the U.S. Department of Commerce provides help to determine whether a given class of item has an Export Control Classification Number (ECCN), i.e. if it is on the Commerce Control List (CCL): “The majority of commercial products are designated EAR99 and generally will not require a license to be exported or reexported.”

Please refer to Exhibit [A] at the end of this page. It provides a detailed list of packaging requirements. The National Centre for Biotechnology Information has published detailed and helpful guidance “Domestic and International Shipping of Biospecimens”, stating that the following are required:

1. An itemized list of contents
2. Class 9 label of Miscellaneous Dangerous Goods/UN1845 Dry Ice label (where dry ice is used in the package)
3. Blue “C” stickers
4. Air Waybill
5. Declaration of Dangerous Goods
6. Customs invoice
7. Centers for Disease Control and Prevention permit [(import only)]
8. UN3373 label

6.2 Does local regulation require any separate consent for biological specimen collection, storage, and future research? If yes, please explain if there are any templates and/or links to be followed.

IRBs tend to provide ICF templates. From the research conducted, it seems that wording about biological specimen collection, storage, and any future research tends to be embedded within the main participant information sheet, unless the samples are conducted for an optional sub-study in which, in some cases, may have a separate consent.

Normally, the expectation of the type of information to be included would be as follows:

• What diseases/conditions will be the focus of the research. 
• What types of testing will be conducted (e.g., genetic, creation of cell lines, etc.) 
• If genetic research: whether subjects/investigators will receive results. 
• Whether the samples will be coded/de-identified. 
• Who will have access to the samples/data. 
• How long samples will be stored/how long data will be used (may be indefinite). 
• Whether samples/data will be shared with secondary researchers, including submission to public databases.
• Whether the sample/data collection is optional or mandatory, and whether participants may withdraw. 
• That unspecified future research with identifiable samples must be made optional. 

It will also be expected that the study protocol describes all research, including future research, in sufficient detail for the IRB to make all regulatory requirements, including assessing confidentiality and risks.

6.3 Does the local authority require any specific documents for customs clearance?

Please refer to Section 6.1 above for export requirements.

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Exhibit A – Packaging requirements for biological specimens 

(See: https://www.ecfr.gov/current/title-49/subtitle-B/chapter-I/subchapter-C/part-173/subpart-E/section-173.199)

• 49CFR173.199 Category B infectious substances

(a) Category B infectious substances. Except as provided in this paragraph (a), Category B infectious substances are excepted from all other requirements of this subchapter when offered for transportation or transported in accordance with this section. Category B infectious substances offered for transportation or transported under the provisions of this section are subject to the incident reporting requirements in [49CFR171.15, 49CFR171.15, 49CFR171.15, 49CFR.171.15 and 49CFR171.16 and to the requirements in [49CFR175.75(b) concerning cargo location. Except as provided in paragraph (a)(9) of this section, a Category B infectious substance meeting the definition of a hazard class other than Division 6.2 must be offered for transportation or transport in accordance with the applicable requirements of this subchapter. 

1. A Category B infectious substance must be packaged in a triple packaging consisting of a primary receptacle, a secondary packaging, and a rigid outer packaging. 
2. Primary receptacles must be packed in secondary packaging in such a way that, under normal conditions of transport, they cannot break, be punctured, or leak their contents into the secondary packaging. 
3. Secondary packaging must be secured in rigid outer packaging with suitable cushioning material such that any leakage of the contents will not impair the protective properties of the cushioning material or the outer packaging. 
4. The completed package must be designed, constructed, maintained, filled, its contents limited, and closed so that under conditions normally encountered in transportation, including removal from a pallet or overpack for subsequent handling, there will be no release of hazardous material into the environment. Package effectiveness must not be substantially reduced for minimum and maximum temperatures, changes in humidity and pressure, and shocks, loadings, and vibrations normally encountered during transportation. The packaging must be capable of successfully passing the drop test in § 178.609(d) of this subchapter at a drop height of at least 1.2 meters (3.9 feet). Following the drop test, there must be no leakage from the primary receptacle, which must remain protected by absorbent material, when required, in the secondary packaging. At least one surface of the outer packaging must have a minimum dimension of 100 mm by 100 mm (3.9 inches). 
5. The following square-on-point mark must be displayed on the outer packaging on a background of contrasting color. The width of the line forming the border must be at least 2 mm (0.08 inches) and the letters and numbers must be at least 6 mm (0.24 inches) high. The size of the mark must be such that no side of the diamond is less than 50 mm (1.97 inches) in length as measured from the outside of the lines forming the border. For transportation by aircraft, the entire mark must appear on one side of the package. The proper shipping name “Biological substances, Category B” must be marked on the outer packaging adjacent to the diamond-shaped mark in letters that are at least 6 mm (0.24 inches) high. 

(i) Transitional exception - A marking in conformance with the requirements of this paragraph in effect on December 31, 2014, may continue to be used until December 31, 2016.

(ii) For domestic transportation, packaging marked prior to January 1, 2017, and in conformance with the requirements of this paragraph in effect on December 31, 2014, may continue in service until the end of its useful life. 

6. When packages are placed in an overpack, the package markings required by this section must be either clearly visible or reproduced on the outside of the overpack. 
7. The name and telephone number of a person who is either knowledgeable about the material being shipped and has comprehensive emergency response and incident mitigation information for the material, or has immediate access to a person who possesses such knowledge and information, must be included on a written document (such as an air waybill or bill of lading) or on the outer packaging. The telephone number must be monitored during a company's administrative hours (i.e., the company's operational business hours). 
8. For transportation by aircraft, each package, overpack, pallet, or unit load device containing a Category B infectious substance must be inspected for leakage when it is unloaded from the aircraft. If evidence of leakage is found, the cargo compartment in which the package, overpack, pallet, or unit load device was transported must be disinfected. Disinfection may be by any means that will make the material released ineffective at transmitting disease. 
9. A packaging containing inner packaging of Category B infectious substances may not contain other hazardous materials except:

(i) Refrigerants, such as dry ice or liquid nitrogen, as authorized under paragraph (d) of this section; 

(ii) Anticoagulants used to stabilize blood or plasma; or 

(iii) Small quantities of Class 3, Class 8, Class 9, or other materials in Packing Groups II and III used to stabilize or prevent degradation of the sample, provided the quantity of such materials does not exceed 30 mL (1 ounce) or 30 g (1 ounce) in each inner packaging. Such preservatives are not subject to the requirements of this subchapter. 

10. Clear instructions on filling and closing a packaging used to transport a Category B infectious substance must be provided by the packaging manufacturer and subsequent distributors to the consignor or person who prepares the package to enable the package to be correctly prepared for transport. A copy or electronic image of these instructions must be retained by the manufacturer and subsequent distributors for at least one year from the date of issuance, and made available for inspection by a Federal or state government representative upon request. Packaging must be filled and closed in accordance with the information provided by the packaging manufacturer or subsequent distributor. 

(b) Liquid Category B infectious substances. Liquid Category B infectious substances must be packaged in conformance with the following provisions: 

1. The primary receptacle must be leakproof. 
2. Absorbent material must be placed between the primary receptacle and secondary packaging. If several fragile primary receptacles are placed in a single secondary packaging, they must be either individually wrapped or separated to prevent contact between them. The absorbent material must be of sufficient quantity to absorb the entire contents of the primary receptacles and not compromise the integrity of the cushioning material or the outer packaging. 
3. The secondary packaging must be leakproof. 
4. For shipments by aircraft, the primary receptacle or the secondary packaging must be capable of withstanding without leakage an internal pressure producing a pressure differential of not less than 95 kPa (0.95 bar, 14 psi). 
5. For shipments by aircraft, the maximum quantity contained in each primary receptacle, including any material used to stabilize or prevent degradation of the sample, may not exceed 1 L (34 ounces), and the maximum quantity contained in each outer packaging, including any material used to stabilize or prevent degradation of the samples, may not exceed 4 L (1 gallon). The outer packaging limitation does not include ice, dry ice, or liquid nitrogen when used to maintain the integrity of the material. 

(c) Solid Category B infectious substances. Solid Category B infectious substances must be packaged in a triple packaging, consisting of a primary receptacle, secondary packaging, and outer packaging, conforming to the following provisions: 

1. The primary receptacle must be siftproof. 
2. If several fragile primary receptacles are placed in a single secondary packaging, they must be either individually wrapped or separated to prevent contact between them. 
3. The secondary packaging must be siftproof. 
4. If residual liquid may be present in the primary receptacle during transportation, then the material must be transported in accordance with the requirements in paragraph (b) of this section. A solid material that may become liquid during transportation must be transported in accordance with paragraph (b) of this section. 
5. Except for packages containing body parts, organs, or whole bodies, for shipment by aircraft, the outer packaging may not contain more than 4 kg (8.8 pounds), including any material used to stabilize or prevent degradation of the samples. The outer packaging limitation does not include ice, dry ice, or liquid nitrogen when used to maintain the integrity of the material.

(d) Refrigerated or frozen specimens (ice, dry ice, and liquid nitrogen). In addition to complying with the requirements in paragraph (d), dry ice and liquid nitrogen must be offered for transportation or transported in accordance with the applicable requirements of this subchapter.

1. Ice or dry ice must be placed outside the secondary packaging or in an overpack. Interior supports must be provided to secure the secondary packaging in the original position. If ice is used, the outside packaging must be leakproof or must have a leakproof liner. If dry ice is used, the outside packaging must permit the release of carbon dioxide gas and otherwise meet the provisions in [49CFR173.217]. The primary receptacle and secondary packaging must maintain their integrity at the temperature of the refrigerant used, as well as the temperatures and pressures of transport by aircraft they could be subjected to if refrigeration were lost, and sufficient absorbent material must be provided to absorb all liquid, including melted ice. 
2. The package is marked “Carbon dioxide, solid” or “Dry ice” and is an indication that the material being refrigerated is used for diagnostic or treatment purposes (e.g., frozen medical specimens). 

(e) Training. Each person who offers or transports a Category B infectious substance under the provisions of this section must know about the requirements of this section. 

[67 FR 53142, Aug. 14, 2002, as amended at 71 FR 32261, June 2, 2006; 72 FR 55693, Oct. 1, 2007; 78 FR 1088, Jan. 7, 2013; 80 FR 1160, Jan. 8, 2015; 80 FR 72927, Nov. 23, 2015; 81 FR 35542, June 2, 2016; 85 FR 83399, Dec. 21, 2020; 87 FR 44994, July 26, 2022]