Cumitech 40: Packing and Shipping of Diagnostic Specimens and Infectious Substances

40 Packing and Shipping of Diagnostic Specimens and Infectious Substances GERALD A. DENYS, LARRY D. GRAY, AND JAMES W. SNYDER COORDINATING EDITOR

DAVID L. SEWELL

Cumitech CUMULATIVE TECHNIQUES AND PROCEDURES IN CLINICAL MICROBIOLOGY

Cumitech 1B

Blood Cultures III

Cumitech 2B

Laboratory Diagnosis of Urinary Tract Infections

Cumitech 3A

Quality Control and Quality Assurance Practices in Clinical Microbiology

Cumitech 5A

Practical Anaerobic Bacteriology

Cumitech 6A

New Developments in Antimicrobial Agent Susceptibility Testing: a Practical Guide

Cumitech 7B

Lower Respiratory Tract Infections

Cumitech 12A

Laboratory Diagnosis of Bacterial Diarrhea

Cumitech 13A

Laboratory Diagnosis of Ocular Infections

Cumitech 16A

Laboratory Diagnosis of the Mycobacterioses

Cumitech 18A

Laboratory Diagnosis of Hepatitis Viruses

Cumitech 19A

Laboratory Diagnosis of Chlamydia trachomatis Infections

Cumitech 21

Laboratory Diagnosis of Viral Respiratory Disease

Cumitech 23

Infections of the Skin and Subcutaneous Tissues

Cumitech 24

Rapid Detection of Viruses by Immunofluorescence

Cumitech 25

Current Concepts and Approaches to Antimicrobial Agent Susceptibility Testing

Cumitech 26

Laboratory Diagnosis of Viral Infections Producing Enteritis

Cumitech 27

Laboratory Diagnosis of Zoonotic Infections: Bacterial Infections Obtained from Companion and Laboratory Animals

Cumitech 28

Laboratory Diagnosis of Zoonotic Infections: Chlamydial, Fungal, Viral, and Parasitic Infections Obtained from Companion and Laboratory Animals

Cumitech 29

Laboratory Safety in Clinical Microbiology

Cumitech 30A

Selection and Use of Laboratory Procedures for Diagnosis of Parasitic Infections of the Gastrointestinal Tract

Cumitech 31

Verification and Validation of Procedures in the Clinical Microbiology Laboratory

Cumitech 32

Laboratory Diagnosis of Zoonotic Infections: Viral, Rickettsial, and Parasitic Infections Obtained from Food Animals and Wildlife

Cumitech 33

Laboratory Safety, Management, and Diagnosis of Biological Agents Associated with Bioterrorism

Cumitech 34

Laboratory Diagnosis of Mycoplasmal Infections

Cumitech 35

Postmortem Microbiology

Cumitech 36

Biosafety Considerations for Large-Scale Production of Microorganisms

Cumitech 37

Laboratory Diagnosis of Bacterial and Fungal Infections Common to Humans, Livestock, and Wildlife

Cumitech 38

Human Cytomegalovirus

Cumitech 39

Competency Assessment in the Clinical Microbiology Laboratory

Cumitech 40

Packing and Shipping of Diagnostic Specimens and Infectious Substances

Cumitechs should be cited as follows, e.g.: Denys, G. A., L. D. Gray, and J. W. Snyder. 2004. Cumitech 40, Packing and Shipping of Diagnostic Specimens and Infectious Substances. Coordinating ed., D. L. Sewell. ASM Press, Washington, D.C. Editorial Board for ASM Cumitechs: Alice S. Weissfeld, Chair ; Maria D. Appleman, Vickie Baselski, B. Kay Buchanan, Mitchell I. Burken, Roberta Carey, Linda Cook, Lynne Garcia, Richard M. Jamison, Karen Krisher, Susan L. Mottice, Michael Saubolle, David L. Sewell, Daniel Shapiro, Susan E. Sharp, James W. Snyder, Allan Truant. Effective as of January 2000, the purpose of the Cumitech series is to provide consensus recommendations regarding the judicious use of clinical microbiology and immunology laboratories and their role in patient care. Each Cumitech is written by a team of clinicians, laboratorians, and other interested stakeholders to provide a broad overview of various aspects of infectious disease testing. These aspects include a discussion of relevant clinical considerations; collection, transport, processing, and interpretive guidelines; the clinical utility of culture-based and non-culture-based methods and emerging technologies; and issues surrounding coding, medical necessity, frequency limits, and reimbursement. The recommendations in Cumitechs do not represent the official views or policies of any third-party payer. Copyright © 2004 ASM Press American Society for Microbiology 1752 N Street NW Washington, DC 20036-2904 All Rights Reserved 10 9 8 7 6 5 4 3 2 1

Packing and Shipping of Diagnostic Specimens and Infectious Substances Gerald A. Denys Clarian Health Partners, Inc., Methodist Hospital, Indianapolis, IN 46206-1367

Larry D. Gray TriHealth Laboratories, Cincinnati, OH 45206, and Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267

James W. Snyder Department of Pathology, Division of Laboratory Medicine, University of Louisville School of Medicine, Louisville, KY 40202

COORDINATING EDITOR: David L. Sewell Pathology & Laboratory Medicine Service, Veterans Affairs Medical Center, and Department of Pathology, Oregon Health and Sciences University, Portland, OR 97239

Governing Authorities and Regulations .................................................. 1 Classification of a Substance ................................................................. 3 Assignment of Substances to Risk Groups ............................................. 4 Naming a Substance ............................................................................ 5 Packaging of Substances ...................................................................... 5 Marking and Labeling Packages ............................................................. 7 Documentation .................................................................................... 9 Refrigerants ......................................................................................... 9 Select Agents and Forbidden Substances ............................................. 10 Personnel (Shipper’s) Training ............................................................. 10 Laboratory Procedures for Packing and Shipping ................................... 12 Appendix 1: Definitions ....................................................................... 13 Appendix 2: A Template for a Laboratory Protocol for Packing and Shipping Diagnostic Specimens and Infectious Substances .................... 14 References ......................................................................................... 15

industry from accidental exposure to the contents of the packages. Important non-safety-related benefits of adherence to these regulations are minimization of the potential for damage to the contents of the package during transport and reduction of the exposure of the shipper to the risk of criminal and civil liability associated with the improper shipment of dangerous goods. Shipping regulations are developed by and published by many governing authorities, the most notable of which are the following (Table 1):

GOVERNING AUTHORITIES AND REGULATIONS Laboratory workers who ship or transport dangerous goods, in general, and diagnostic specimens and infectious substances, in particular, by a commercial land or air carrier are required to follow a complex and often confusing set of national and international regulations (5, 8, 9). The purpose of these regulations is to protect the public, emergency responders, laboratory workers, and the employees in the transportation 1

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Table 1.

CUMITECH 40

Agencies governing transportation of dangerous goods

Governing authority

Agency

UN

ICAO

Commercial airline industry United States

IATA DOT

United States

USPS

Canada Other nations

Transport Canada

● ● ● ● ●

the International Civil Aviation Organization (ICAO) (a body of the United Nations [UN]), the International Air Transport Association (IATA) (an airline trade organization), the U.S. Department of Transportation (DOT), the U.S. Postal Service (USPS), and Transport Canada (Canadian government).

The ICAO regulates all international civil aviation matters. Specific ICAO regulations (The Technical Instructions for the Safe Transportation of Dangerous Goods by Air) govern the international shipment of dangerous goods by air (5a). The IATA regulations (Dangerous Goods Regulations) are derived from, based on, and easier to read than the ICAO Technical Instructions (2). Individual nations of the world may issue additional regulations for the shipment of dangerous goods. The DOT regulates the commercial transportation of dangerous goods within the United States by both air and ground commercial carriers. The DOT regulations are derived from IATA regulations (5, 7, 9). Recently (14 August 2002), the DOT revised its regulations for the transportation of diagnostic specimens and infectious substances to be in substantial agreement with IATA regulations (5, 9). For practical purposes, clinical microbiologists can consider IATA and DOT regulations to be essentially the same. The transportation of diagnostic specimens is exempted from DOT regulations if the specimens are transported by a private or contract carrier in a motor vehicle used exclusively to transport diagnostic specimens or biological products. The USPS is not subject to DOT regulations and publishes its own regulations in the USPS Domestic Mail Manual. Recently (19 December 2002), the USPS proposed to amend its regulations to be in substantial agreement with DOT regulations (10). In some cases (e.g., lower allowable volume limits), the proposed USPS regulations are more restrictive than those of the DOT or IATA. IATA and DOT regulations mandate the minimum requirements for packaging and shipping of diagnostic specimens and infectious substances that may pose

Regulations (reference) The Technical Instructions for the Safe Transport of Dangerous Goods by Air (5a) Dangerous Goods Regulations (5) United States Hazardous Materials Uniform Safety Act (Code of Federal Regulations 49) Hazardous materials: proposed domestic mail manual revisions for division 6.2 infectious substances and other related changes (10) Transportation of Dangerous Goods Regulations Individual regulations

a threat to humans or animals. The safe and legal transport of these substances is based on the following mandated activities: 1. classification and naming of the material to be shipped; 2. selection of packaging that will protect the shipped material and will not leak if the package is damaged; 3. packing of the shipment correctly; 4. placing of appropriate markings and labels on the outer package to alert carrier personnel to the hazardous contents of the package and to identify contacts if an accident occurs; 5. documenting of relevant aspects of each package and its contents; and 6. training of individuals on the requirements for appropriate packaging and shipping of diagnostic specimens and infectious substances. This Cumitech is a summary of the authors’ interpretation of the most recent regulations and guidelines; it is not an all-inclusive guide to shipping regulations. The regulations governing the transport of infectious substances and diagnostic specimens change frequently as federal agencies and international organizations attempt to coordinate their respective regulations. Shippers are responsible for adhering to the most current regulations. This Cumitech provides practical guidance to facilitate compliance with current national and international shipping regulations. Topics in this Cumitech include terminology, classification and naming of diagnostic specimens and infectious substances, marking and labeling of packages, packaging material, documentation (instructions for completing a Shipper’s Declaration for Dangerous Goods), training of personnel, practical suggestions and checklists to be used in preparing a procedure for packing and shipping, and resources for additional information. Definitions of terms used in this Cumitech are given in Appendix 1 (1, 3, 5, 8, 9).

CUMITECH 40 Table 2.

Shipping of Specimens and Infectious Substances

IATA-defined classes of dangerous goods

Class

Substance

1 ..........................Explosive 2 ..........................Gases 3 ..........................Flammable liquids 4 ..........................Flammable solids 5 ..........................Oxidizing substances and organic peroxides 6 ..........................Toxic and infectious substancesa Division 6.1: toxic substances Division 6.2: infectious substancesa 7 ..........................Radioactive materials 8 ..........................Corrosives 9 ..........................Miscellaneous dangerous goods (dry ice)a a

Addressed in detail in this Cumitech.

mens, infectious substances, biological products, or genetically modified organisms (GMO). Classification can be difficult and subjective. The IATA regulations, which contain detailed definitions of infectious substances, diagnostic specimens, biological products, and GMO, can be helpful to shippers (2, 5). Classification of a substance as diagnostic or infectious can be facilitated by finding the answers to a few important and helpful questions (3): ●

CLASSIFICATION OF A SUBSTANCE Classification is a mandatory three-step process to define dangerous goods that are shipped by commercial carriers (8). Classification serves two purposes: (i) it provides important information necessary to complete the Shipper’s Declaration for Dangerous Goods, and (ii) it allows the shipper to select the proper IATA packing instructions (PI) to use. First, the material must be placed into one of the nine IATA-defined classes (class 1 through class 9) of dangerous goods (Table 2). Infectious and toxic substances are class 6 dangerous goods; dry ice is a class 9 dangerous good. Generally, class 6 and class 9 substances are the only dangerous goods shipped by clinical microbiologists. Second, class 6 substances must be subclassified as either toxic (division 6.1) or infectious (division 6.2) substances. Third, division 6.2 substances must be placed into one of four subclasses: diagnostic speci-

3

●

● ●

● ● ● ●

Is the substance being shipped for diagnostic, clinical, or other purposes directly related to patient care? Does the sample contain or is it reasonably expected to contain pathogens in risk group 2, 3, or 4 (11)? Is the specimen being cultured or examined for a particular pathogen? Does the shipper (usually a laboratory worker) know relevant information regarding the patient’s medical condition such that the shipper has reason to believe the specimen is likely to contain a pathogen even if the specimen is to be tested for a noninfectious analyte? Does the sample contain a GMO? Is a pathogen in risk group 4 present (11)? Does the specimen contain a select agent or a forbidden substance? Does the shipper feel there is an unacceptable risk involved in shipping this specimen?

FIGURE 1. Algorithm for selecting PI. The information in this figure is the authors’ interpretation of current regulations. The purpose of this algorithm is to simplify the text of this protocol. It is not a substitute for interpretation of applicable regulations as they apply to individual situations, in which cases applicable governing regulations should be followed. (Courtesy of and adapted from SafTPak.)

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Table 3.

Examples of classifying shipped materials as infectious substances Infectious substance?

Example (reasoning) Shipping a blood specimen from Chicago to Atlanta for confirmation of HIVa antibodies (specimen likely contains a pathogen [HIV]) Shipping a blood specimen collected from a healthy patient to a reference lab for cholesterol and glucose testing (no reason to suspect presence of pathogens) Shipping a blood specimen from Africa to Dallas, Tex., for Lassa virus research (specimen likely contains a pathogen [Lassa virus]) Shipping a risk group 2 bacterial isolate in support of a national antimicrobial susceptibility surveillance study (pure culture of pathogen) Returning a recalled licensed diagnostic reagent to the manufacturer (reagents generally are not regulated) Outsourcing clinical microbiological specimens to a reference lab For routine culture (presence of specific pathogens in specimens is not known) To be cultured for Escherichia coli O157:H7 (specimen likely contains a particular pathogen [E. coli]) Shipping a clinical fungal isolate to a reference lab for identification (specimen likely contains a fungal pathogen) Shipping antimicrobial agent powder or disks to another clinical lab (reagents generally are not regulated) a

Yes No Yes Yes No No Yes Yes No

HIV, human immunodeficiency virus.

The answers to these questions and the use of the algorithm in Fig. 1 will help determine if a substance is infectious or diagnostic and which IATA PI should be used. Examples of classification of substances as infectious are shown in Table 3. Although this process can be difficult, the shipper must not arbitrarily classify all shipments as infectious. Such classification is illegal and is not cost-effective (8). It is also illegal to ship infectious substances under the diagnostic, biological, or GMO classification (8). Toxic and infectious substances are in IATA class 6, which is divided into division 6.1 (toxic substances) and division 6.2 (infectious substances). Infectious substances are defined as (i) pathogens and cultures of pathogens, (ii) substances that are known to contain or likely to contain a pathogen, and (iii) substances that are infectious to humans or animals. Shippers must assign infectious substances a UN identification number depending on the substance’s ability to cause disease in humans (UN 2814) or animals (UN 2900). Diagnostic specimens include any human or animal material, such as, but not limited to, secreta, blood and blood components, excreta, tissue, and tissue fluids, that is being transported for investigational or diagnostic purposes. A diagnostic specimen is a dangerous good and must be assigned UN identification number UN 3373 unless it is capable of causing or is reasonably likely to cause or to be capable of causing disease in humans (e.g., contains a risk group 4 organism) or animals, in which case it must be assigned UN 2814 or UN 2900, respectively. Certain IATA-defined substances are forbidden to be shipped as diagnostic specimens, in some cases in any form and in some cases in only certain forms (see “Select Agents and Forbidden Substances” [below] and Table 4). GMO are microorganisms that have had their genetic material purposely modified or altered through genetic engineering in a manner that does not occur naturally. For shipping purposes, GMO are danger-

ous goods and are assigned one of three UN identification numbers depending on whether the GMO meets the definition of an infectious substance affecting humans (UN 2814) or animals (UN 2900) or is not dangerous to humans or animals (UN 3245). Biological products generally are substances which originated from living organisms and have been manufactured and distributed in accordance with compliance requirements set forth by the federal government, including licensing requirements. Such products can be finished or unfinished; are intended for use in the prevention, treatment, or diagnosis of disease in humans or animals; and are used for investigational, experimental, or development purposes. Biological products include such common items as clinical microbiology reagents and kits, serological reagents, diagnostic reagents, and vaccines. In certain parts of the world, some licensed biological products are regarded as biohazardous and either are subject to compliance criteria specified for infectious substances or must adhere to other restrictions imposed by the government of that country. Biological products generally are not considered to be dangerous goods and are not subject to shipping regulations presented in this Cumitech unless they contain pathogens in risk group 2, 3, or 4, in which case the product must be classified under UN 2814 or UN 2900.

ASSIGNMENT OF SUBSTANCES TO RISK GROUPS Assignment of diagnostic substances, infectious substances, biological products, or GMO to one of four World Health Organization-defined risk groups is required to help the shipper select appropriate packaging for the substance and to determine if it is necessary to submit a Shipper’s Declaration for Dangerous Goods with the shipment (Fig. 1; Table 5) (11). The risk group to which a substance is assigned is deter-

CUMITECH 40

Shipping of Specimens and Infectious Substances

Table 4. Examples of infectious substances forbidden to be shipped as diagnostic specimens

pose a risk to the individual or community. Substances allocated to this group do not meet the IATA and DOT criteria for classification as an infectious substance and are not subject to IATA and DOT regulations. Risk group 2 contains pathogens which can cause human or animal disease, are unlikely to represent a serious health hazard, are not likely to be transmitted easily, and cause disease for which effective therapy and preventive measures are available. Pathogens in risk group 3 are regarded as high risks to individuals and low risks to the community. Organisms in this risk group often cause serious human or animal disease but are not easily transmissible from human to human. Effective therapy and preventive measures for the disease generally are available. Risk group 4 contains pathogens which have the highest health risk for humans, animals, and the community. The diseases caused by these pathogens are easily transmitted from person to person, either directly or indirectly, and are ones for which effective therapy and preventive measures usually are not available.

UN no. and proper shipping name UN 2814: infectious substance, affecting humans

UN 2900: infectious substance, affecting animals

Organism Bacillus anthracis (cultures only) Brucella abortus (cultures only) Brucella melitensis (cultures only) Brucella suis (cultures only) Burkholderia mallei (cultures only) Burkholderia pseudomallei (cultures only) Chlamydia psittaci (avian) (cultures only) Clostridium botulinum (cultures only) Coccidioides immitis (cultures only) Coxiella burnetii (cultures only) Crimean-Congo hemorrhagic fever virus Dengue virus (cultures only) Eastern equine encephalitis virus (culture only) Escherichia coli, verotoxigenic (cultures only) Ebola virus Francisella tularensis (cultures only) Hantaan virus Hepatitis B virus (cultures only) Herpes B virus (cultures only) Human immunodeficiency virus (cultures only) Lassa virus Marburg virus Mycobacterium tuberculosis Poliovirus (cultures only) Rabies virus Rickettsia prowazekii (cultures only) Shigella dysenteriae type 1 (cultures only) Variola virus Venezuelan equine encephalitis virus West Nile virus (cultures only) Yellow fever virus (cultures only) Yersinia pestis (cultures only) Classical swine fever virus Bluetongue virus Foot-and-mouth disease virus Goatpox virus Lumpy skin disease virus Newcastle disease virus Sheeppox virus Swine vesicular disease virus Vesicular stomatitis virus

mined by (i) the virulence of the organism, (ii) the mode and relative ease of transmission of the organism, (iii) the degree of risk the organism presents to an individual and community, and (iv) the availability of effective treatment for the disease. Each country interprets the assignment of organisms to risk groups differently; therefore, the list of organisms in each group can differ from country to country. Risk group 1 consists of microorganisms that are unlikely to cause human or animal disease and do not

5

NAMING A SUBSTANCE After classifying the substance, the shipper must identify (officially name) the substance by assigning the substance one of the 3,000 IATA-specified proper shipping names, all of which are listed in the IATA regulations (5). This list provides 14 informational items (A through N) for each of the 3,000 shipping names (Table 6). The 14 items conveniently correspond to the information needed to complete the Shipper’s Declaration for Dangerous Goods. Fortunately, only 4 of the 3,000 proper shipping names are used by most clinical laboratories: two names for infectious substances and one name each for diagnostic substances and dry ice (Table 7).

PACKAGING OF SUBSTANCES DOT and IATA shipping regulations and PI describe the minimum standards for the safe transport of various biological materials. Shippers are legally responsible for complying with these regulations and for packing substances correctly to ensure the safety of the persons who handle the package before and during shipment and after shipment to the point of acceptance of the package by the consignee. Generally, the PI used in the clinical laboratory are those that relate to shipping of infectious substances (PI 602), diagnostic specimens (PI 650), GMO (PI 3245), and dry ice (PI 904). Assignment of a substance to a risk group helps a shipper decide which PI to use (PI 602 or PI 650). After determining if a specimen is being shipped for diagnostic or for investigational purposes and then assigning the substance to one of the four risk groups,

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CUMITECH 40

Table 5.

World Health Organization-defined risk groups of infectious substances

Risk group

Characteristics of organisms in the group

Examples

4

High (always causes severe disease; easily transmitted; treatment generally not available)

Ebola virus, smallpox virus, M. tuberculosis in broth, Y. pestis, alphaviruses, hemorrhagic fever viruses, unknown viruses

3

High (usually causes serious disease; usually not transmitted extensively; treatment generally available)

Sputum for M. tuberculosis culture, Francisella, Brucella, Coxiella, C. botulinum toxin, Burkholderia pseudomallei/mallei, HIV,a hepatitis C virus, B. anthracis, staphylococcal enterotoxin

2

Low (can cause serious disease but generally not a hazard; usually not transmitted; treatment available)

Most Enterobacteriaceae, typical clinical microbiology bacteria

1

Very low (negligible health hazard)

B. cereus, normal flora

a

HIV, human immunodeficiency virus.

the shipper must select the PI most appropriate for the substance being shipped. The appropriate PI to use can be determined by using the algorithm in Fig. 1. Both PI 602 and PI 650 mandate triple packaging for both diagnostic specimens and infectious substances. The triple packaging required by PI 602 and PI 650 consists of the following: ●

a primary receptacle (watertight, leakproof, and sealed) made of glass, metal, or plastic and sealed by a positive method (e.g., heat seal, metal crimp, or taped screw-cap lids). For infectious substances and diagnostic specimens, the maximum volume per total primary containers in a single package must not exceed 50 ml or 50 g. IATA Special Provision A81 permits shipment of up to 1 liter of fluid/ primary container and up to 4 liters of fluid/completed outer container if the substance is a body fluid that does not contain pathogens in risk group

Table 6. Information applicable to shipping of diagnostic specimens, infectious substances, GMO, biological products, and dry ice in the IATA Alphabetical List of Dangerous Goods Columna

Information

A.......................The UN identification no. of the proper shipping name/description B.......................Proper shipping name and description C.......................Class of dangerous good D.......................NAb E .......................The hazardous label required on the outer package F .......................NA (applicable only to dry ice) G.......................NA H.......................NA I ........................PI to use for passenger and cargo aircraft J .......................Maximum allowable amounts to be shipped in passenger and cargo aircraft K .......................PI to use for cargo aircraft only L .......................Maximum allowable amounts to be shipped in cargo aircraft only M......................Applicable special provisions or exceptions N.......................Emergency response code a

Refers to the 14 columns in the IATA Alphabetical List of Dangerous Goods (found in IATA Dangerous Goods Regulations [5]). b NA, not applicable unless otherwise noted.

●

●

●

●

4. If a shipper chooses to use A81 and ship these increased amounts, “A81” must be noted in the Authorization column on the Shipper’s Declaration for Dangerous Goods. absorbent material sufficient to absorb all liquid contained within the primary containers in case of breakage and placed between the primary and secondary receptacles. Absorbent material is not required if the material is a solid. a secondary container (watertight and leakproof) which contains the primary receptacle. The maximum quantity per outer packaging for diagnostic specimens must not exceed 4 liters. a durable outer package of adequate strength for its intended use and constructed of cardboard, wood, or “material of equivalent strength” and measuring ⱖ4 in. in the shortest dimension. For shipping of infectious substances, these containers must meet UN manufacturing and testing specifications (see below). A list of the contents of the primary container(s) must be attached to the secondary container.

All outer packaging used to ship infectious substances must meet specifications established by the UN and must be marked as such by the manufacturer. Packaging that meets the UN specifications is marked by a U over an N and a series of letters and numbers which indicate the type of package, class of goods the package is designed to carry, manufacturing date, authorizing agency, and the manufacturer. The designation “class 6.2” in the marked code indicates that the container is approved for shipping of infectious substances. These containers are commercially available. The strict UN specifications for outer packaging do not apply when diagnostic specimens are being shipped. Outer boxes used to ship diagnostic specimens need to be only strong enough for their intended purpose. The components and assembly of complete triplepackage systems for shipping an infectious substance

9L 9L 6L No limit 200 kg 4 liters

602

913 904 650 b

a

III 6.2

6.2

affecting

affecting

9 9

6.2 affecting

D C 6.2 affecting

3245 1845 3373

2900

2900

2814

B Infectious substance, humansb (liquid) Infectious substance, humansb (solid) Infectious substance, animalsb (liquid) Infectious substance, animalsb (solid) GMO Dry ice Diagnostic specimen A 2814

PG, packing group. A technical name in parentheses must follow the proper shipping name, e.g., “Infectious substance, affecting humans (hepatitis B virus).”

No limit 200 kg 4 liters 913 904 650 Miscellaneous Miscellaneous None

50 g 602 Infectious substance

50 ml 602 Infectious substance

50 g 602 Infectious substance

J 50 ml I 602 H F E Infectious substance

G

PI Maximum net wt/ package

PGa

PI

or diagnostic specimen are shown in Fig. 2A through C. Figure 2D shows a simplified complete shipping package which could contain either a diagnostic specimen or an infectious substance and dry ice. For convenience and lower costs, one or more triple packages packed in full compliance with IATA regulations may be shipped within a single overpack which does not have to meet UN specifications. However, the overpack must be labeled “Inner Packages Comply with Prescribed Specifications” (Fig. 2D) and must be completely labeled according to applicable IATA regulations.

A47 A48

6L 4 kg

602

A81

6L 4 liters

602

A81

4 kg

K 602

A81

N 6L L 4 liters

PI

M A81

Special provision Maximum net quantity/ package Maximum net quantity/ package Limited quantity

7

MARKING AND LABELING PACKAGES

Hazard label(s) Subsidiary risk Class Proper shipping name/description UN identification no.

Cargo aircraft only Passenger or cargo aircraft

IATA Alphabetical List of Dangerous Goods most applicable to clinical and research microbiologists Table 7.

6L

Shipping of Specimens and Infectious Substances

Emergency response code

CUMITECH 40

Marking is the act of writing information on the surface of an outer package. Labeling is the act of placing informational labels or stickers onto the surface of an outer package. The shipper is responsible for the proper marking and labeling of the outer shipping container as described in the DOT and IATA regulations (5, 9). The marking and labeling on the outside container communicate essential information regarding the shipper and consignee of the package, nature and weight of the contents of the package, the potential hazard of the substance, how the substance is packed, and information to be used in case of an emergency. The outer package must display markings and labels appropriate for the particular shipment. These labels and markings include the following: ● ●

●

●

●

●

the shipper’s and consignee’s (receiver) names and addresses; name and telephone number of a responsible person who is knowledgeable about the contents of the shipment; if the substance is infectious: (i) the class 6 diamond-shaped label “Infectious Substance. In Case of Damage or Leakage. . .” (this label is identical for the regulatory groups except that the DOT version of the label specifies notification of the Centers for Disease Control and Prevention by telephone in case of damage or leakage) and (ii) the label “Infectious Substance, Affecting Humans. . .” (including the proper shipping name, technical name, UN number, and quantity) (Fig. 3 and 4); if the substance is a diagnostic specimen: the label “Diagnostic Specimen Packed in Compliance with IATA Packing Instruction 650 —UN 3373” (Fig. 5); if dry ice is used: a class 9 “Miscellaneous Dangerous Goods” label and the weight of dry ice (Fig. 6 and 7); package orientation label (Fig. 8) (orientation labels [arrows] must be placed on opposite sides of all packages which contain ⬎50 ml to indicate the correct orientation of the package);

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FIGURE 2. (A) Example of a correctly prepared triple package for a PI 602 shipment of an infectious substance. The secondary container is rigid, leakproof, and crushproof and can withstand an internal pressure differential of 14 lb/in2. A secondary container does not necessarily have to be a rigid container as suggested by this illustration. The secondary container can be a flexible, tough envelope-like device or other container as long as it (when properly used together and securely closed according to manufacturer’s instructions) is leakproof and can withstand an internal pressure differential of 13.8 lb/in2. See panels B and C. (B) Example of a correctly prepared triple package for a PI 602 shipment of an infectious substance. The secondary container is composed of two bags or envelopes which (when properly used together and securely closed according to manufacturer’s instructions) are leakproof and can withstand an internal pressure differential of 13.8 lb/in2. (C) Example of a correctly prepared triple package for a PI 650 shipment of a diagnostic specimen. Note (i) the use of an envelope system for the secondary container (see legend to panel B) and (ii) the outer package or box which does not have to meet UN specifications but, rather, has to be only adequate in strength for its intended purpose. (Panels A to C are courtesy of and adapted from SafTPak.) (D) Example of a correctly marked and labeled outer shipping container which contains an infectious substance and dry ice. Dashed outlines indicate labels which should be used if the contents are diagnostic specimens or if dry ice or overpacks are used.

CUMITECH 40

Shipping of Specimens and Infectious Substances

FIGURE 5.

FIGURE 3.

●

● ● ●

Label: infectious substance (class 6).

“Cargo Aircraft Only” label if applicable (used if more than 50 ml or 50 g of infectious substance is transported by air) (Fig. 9); “Inner Packages Comply” markings if overpacks are used (Fig. 10); and air eligibility marking or label (Fig. 11). A Shipper’s Declaration for Dangerous Goods must be attached to the outer package if the substance is infectious and was packed according to PI 602 (Fig. 12 and 13).

DOCUMENTATION A Shipper’s Declaration for Dangerous Goods is used to document the shipment of an infectious substance, is a legal contract between the shipper and carrier, and must be accurate and legible or the carrier may reject the package for transport (Fig. 12 and 13). Some carriers require the Shipper’s Declaration for Dangerous Goods to be typed. The shipper must retain one copy and give two copies to the carrier with the shipment. All corrections must be neatly “lined out,” and all changes must be signed by the same person who signed the document. The carrier may reject the shipment if each field on the document is not completed exactly as specified or if punctuation and spelling are not correct. The carrier and Federal Aviation Administration often exercise their authority at airports to examine the Shipper’s Declaration for Dan-

FIGURE 4. Marking (example): proper shipping name, technical name, UN identification number, and quantity.

9

Marking (example): diagnostic specimen.

gerous Goods for compliance with applicable regulations and to open and inspect any package which contains or is suspected to contain an infectious substance or diagnostic specimen. Figure 13 shows a completed and acceptable Shipper’s Declaration for Dangerous Goods. Essentially all of the IATA-specified technical information required to complete the “Nature and Quantity of Dangerous Goods” section of a Shipper’s Declaration for Dangerous Goods can be found in Table 7. If a Shipper’s Declaration for Dangerous Goods is not absolutely 100% correct (including all spelling and punctuation), it is subject to being rejected by the carrier (3).

REFRIGERANTS Two common refrigerants used to ship diagnostic specimens and infectious substances are wet and dry ice. The DOT requires that the packaging must be leakproof when wet ice is used. Dry ice is a class 9 dangerous good and must meet all requirements for shipping of dangerous goods. Dry ice should never be placed into a sealable container (explosion hazard!). Dry ice must be placed outside the secondary container, and the outer packaging must permit the release of CO2. The secondary container must be secured such that it doesn’t become loose as the dry ice sublimates. Outer packages must be labeled “Dry Ice,” and the net weight of the dry ice must be indicated on the outside of the outer package (Fig. 6 and 7) and be recorded on the Shipper’s Declaration for Dangerous Goods. The maximum permitted net weight of dry ice per outer package is 200 kg.

FIGURE 6.

Label: miscellaneous dangerous goods (class 9).

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FIGURE 7.

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FIGURE 9.

Marking (example): dry ice weight.

SELECT AGENTS AND FORBIDDEN SUBSTANCES Select agents are microorganisms, biological agents, or biological toxins which have been deemed by the U.S. Government to be major threats to public health and safety because they could be used as agents of bioterrorism (4, 6). Examples of select agents are hemorrhagic fever viruses, encephalitis viruses, Bacillus anthracis, Yersinia pestis, Brucella spp., Francisella tularensis, smallpox virus, Clostridium botulinum toxin, Coccidioides immitis, and all agents of bioterrorism. If a select agent or a specimen or item suspected of containing a select agent must be shipped or otherwise transported from one facility to another, the shipper must contact appropriate state and federal authorities for guidance and instructions before doing so. In addition, the shipper must confirm that the reference laboratory is approved for receiving select agents. The select agent regulations and a list of select agents can be found at www.cdc.gov/od/sap/docs /42cfr73.pdf. Certain ICAO-defined pathogens likely to be injurious to public health are forbidden to be shipped as diagnostic specimens in any form— culture, specimen, or otherwise (Table 4). Others are forbidden to be shipped only if they are in culture form (Table 4); these pathogens must be shipped as infectious substances (UN 2814 or UN 2900). Live infected animals are forbidden to be shipped, even for diagnostic purposes.

FIGURE 8.

Label: package orientation.

Label: cargo aircraft only.

PERSONNEL (SHIPPER’S) TRAINING Anyone involved in the shipping or transportation of dangerous goods (including diagnostic specimens and infectious substances) must be trained in the shipment of dangerous goods (3, 5, 8). Acceptable training materials and methods include compact disks, manuals, and training courses, all of which are commercially available from professional organizations (e.g., IATA training manuals) and commercial suppliers of packaging materials for dangerous goods (e.g., SafTPak). Alternatively, a training program or workshop which includes hands-on training and demonstrations can be developed by any hospital, laboratory, school, institution, or other facility through the direction of a certified trainer. All training programs should be designed to provide initial and regular follow-up training to each employee responsible for shipping and packing infectious substances. The essential components of a training program should include the following: (i) general awareness and familiarity with the many aspects of shipping dangerous goods; (ii) importance, nature, and contents of IATA and DOT regulations; (iii) function-specific training (hands-on and/or demonstrations) on packaging, marking, labeling, and documentation of shipments of dangerous goods; (iv) safety training; (v) testing; and (vi) issuance of a certificate after successful completion of the training. Documentation of all aspects of training is required by IATA. Employers must keep records of the training courses (location, dates, and name of the certified trainer), employees trained, course content, testing, a statement of certification, and follow-up training. IATA and DOT certifications are valid for 2 and 3 years, respectively. The Federal Aviation Administration has authority to inspect facilities (e.g., clinical laboratories) that ship dangerous

FIGURE 10.

Marking: inner packages comply (used only on overpacks).

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Shipping of Specimens and Infectious Substances

FIGURE 11.

Marking: air eligibility.

11

goods for compliance with the training regulations and to inspect training records at these facilities. Anyone who receives appropriate training from any source and is tested as such is considered trained. However, a trained person must be certified before the person may legally pack, document, and ship dangerous goods. A trained person is certified only after the person’s employer states in writing (i.e., “signs off”) that the person is certified. In other words, a person can ship diagnostic specimens and infectious substances only after that person is trained by a trainer and certified by the employer. Training material for

FIGURE 12. Example of a blank Shipper’s Declaration for Dangerous Goods showing the 13 sections which must be completed. Sections 3, 6, and 7 usually are completed by the carrier.

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FIGURE 13.

Example of a completed Shipper’s Declaration for Dangerous Goods.

the transportation of dangerous goods and infectious substances is available at the following sites: ● ● ●

● ●

American Society for Microbiology (www.asm .org) IATA (training manuals) (www.iata.com) regional clinical microbiology meetings (often have workshops on packing and shipping diagnostic specimens and infectious substances) SafTPak (training courses and compact disks) (www .saftpak.com) World Courier Training Course (Infectious Substances & Diagnostic Specimens) (www.world courier.com)

LABORATORY PROCEDURES FOR PACKING AND SHIPPING Laboratory personnel can use the information in this Cumitech and from other sources to develop a practical laboratory procedure for packing and shipping diagnostic specimens and infectious substances. A template for a laboratory protocol for packing and shipping diagnostic specimens and infectious substances is provided in Appendix 2. The template can be adapted to suit the needs of any laboratory. Checklists for packing and shipping and for completing a Shipper’s Declaration for Dangerous Goods can be

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Shipping of Specimens and Infectious Substances

FIGURE 14.

13

Checklist for packing.

incorporated into a packing and shipping procedure to facilitate the process (Fig. 14 and 15). APPENDIX 1 DEFINITIONS biological product A licensed material or product which is derived from living organisms and is manufactured and distributed for prevention, treatment, or diagnosis of disease in humans or animals or for research or investigational purposes (e.g., diagnostic reagents, antitoxin, blood, blood components, allergenic products, vaccines, and similar material); not an IATA-defined dangerous good unless it contains a risk group 2, 3, or 4 microorganism (11). Most Food and Drug Administration-approved biological products are exempt from shipping regulations. carrier (operator) Individual or organization engaged in the commercial transportation of goods (e.g., Airborne Express, Federal Express, and Northwest Airlines). Code of Federal Regulations U.S. laws published in the Federal Register.

FIGURE 15. applicable.

Checklist for completing a Shipper’s Declaration. N/A, not

consignee The receiver of the shipment (e.g., a reference laboratory). consignor The company or health care facility responsible for the shipment (e.g., a clinical microbiology laboratory). cultures and stocks Microorganisms cultured, grown, and maintained for growth and storage; can be classified as a risk group 2, 3, or 4 infectious substance. dangerous goods Material which, when not properly handled and contained, can cause harm to human or animal health, safety, property, or the environment. Dangerous Goods Regulations A commercially available book of regulations published by the IATA; is based on and incorporates ICAO regulations; provides packaging and shipping regulations for dangerous goods (e.g., diagnostic specimens and infectious substances). diagnostic (clinical) specimen Any human or animal ma-

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terial, including but not limited to, excreta, secreta, blood and its components, tissue and tissue fluids, shipped for diagnosis or investigational purposes but excluding live infected animals (an IATA-defined dangerous good). Generally, diagnostic specimens are considered minimal threats to public health and do not require a Shipper’s Declaration for Dangerous Goods. If a diagnostic specimen is known to contain or is reasonably suspected of containing a risk group 2, 3, or 4 pathogen (11), it is classified as an infectious substance, assigned UN identification number UN 2814 or UN 2900, and packed according to PI 602 (Table 7). Otherwise, the diagnostic specimen is assigned UN identification number UN 3373 and packed according to PI 650 (Table 7). GMO A microorganism in which genetic material has been purposefully altered in a way which does not occur naturally (an IATA-defined dangerous good); can be classified as a diagnostic specimen, infectious substance, or GMO. IATA A trade organization of the commercial airline industry; governs international aviation; publishes Dangerous Goods Regulations for use by the airline industry and by anyone who offers goods to commercial airlines for transport. ICAO An agency of the UN; governs international aviation; regulates the transportation of dangerous goods for all international civil air carriers; the original source of commercial airline shipping regulations. infectious substance Material known to contain or reasonably suspected of containing a pathogen and which has the potential to cause disease in humans or animals (an IATA-defined dangerous good). Infectious substances include (i) pathogens and cultures of pathogens, (ii) diagnostic specimens known to contain or reasonably suspected of containing a pathogen or to be cultured (examined) for a pathogen, and (iii) a diagnostic specimen from a patient with a serious illness of unknown etiology. An infectious substance is assigned UN identification number UN 2814 or UN 2900 and is packed according to PI 602 (Table 7). overpack The outmost packaging used to enclose more than one complete package, each of which contains dangerous goods; usually used for convenience and to reduce shipping costs. package End product of the packing process. packaging All of the numerous materials used to contain a shipped substance and to prepare the substance for shipping; the container (receptacle) and its associated components (e.g., tubes, containers, absorbent material, boxes, and labels) used to contain and pack a substance and to ensure compliance with packing requirements. packing The physical action and method by which packaging is used to secure articles or substances for shipment. PI IATA- and DOT-defined directions shippers must follow to select, assemble, mark, label, and document the packing process for shipping of dangerous goods, including diagnostic specimens and infectious substances; includes manufacturing testing and performance specifications for packaging materials. pathogen A microorganism (bacterium, mycobacterium, fungus, parasite, virus, plasmid, genetic element, protein-

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aceous infectious particle [prion], or GMO) that is known to cause or is reasonably expected to be able to cause disease in humans or animals. primary specimen container The innermost packaging containing a dangerous good; composed of glass, metal, or plastic and sealed. risk group A ranking of a microorganism’s ability to cause disease. Four risk groups (1 through 4) have been defined by the World Health Organization (Table 5) (11). The risk groups are based on the microorganism’s virulence, mode and ease of transmission, risk to individuals and the community, and availability of effective treatment and preventative agents (11). IATA recognizes three of the four risk groups: 2, 3, and 4. secondary specimen container The leakproof container that contains the primary specimen container. shipper Anyone who ships goods by a commercial carrier (usually an employee of a company or health care facility [e.g., a laboratory staff member]); anyone who offers goods for transport to a member of IATA; anyone who completes and signs the Shipper’s Declaration for Dangerous Goods. The person who signs the Shipper’s Declaration for Dangerous Goods is a representative of the shipper and is the person who accepts responsibility for the accuracy of the information on the document. Shipper’s Declaration for Dangerous Goods (Shipper’s Declaration) An IATA-defined and -mandated form which must accompany each shipment of dangerous goods; contains information which describes the dangerous goods and which is helpful to persons who handle the shipment; must be completed by the shipper. UN-certified container Packaging material (usually a cardboard box) that has passed UN certification tests (and IATA’s construction and testing criteria) and is labeled by the manufacturer as such for the transport of certain dangerous goods. DOT Regulates domestic transportation of all dangerous goods within the United States through regulations published in the Federal Register; incorporates and is in substantial agreement with IATA regulations.

APPENDIX 2 A TEMPLATE FOR A LABORATORY PROTOCOL FOR PACKING AND SHIPPING DIAGNOSTIC SPECIMENS AND INFECTIOUS SUBSTANCES (Name of Laboratory or Health Care System) Laboratory Procedure for Packing and Shipping Diagnostic Specimens and Infectious Substances I. PRINCIPLE The DOT issues strict regulations which govern the private and commercial transportation of what it considers dangerous goods. The purpose of these regulations is to protect the persons who handle the shipment during all segments of the transportation process. Two of the nine classes (class 1 through class 9) of DOT-defined dangerous goods are relevant to clinical microbiology laboratories: class 6 (toxic and infectious substances) and class 9 (miscellaneous dangerous goods). Examples of class 6 dangerous goods are clinical

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Shipping of Specimens and Infectious Substances

specimens and pure cultures of microorganisms. An example of class 9 dangerous goods is dry ice. The aforementioned regulations mandate that we must do the following if we ship class 6 and class 9 dangerous goods by a commercial carrier: (i) train all individuals who pack the goods, (ii) classify and name the goods being shipped, (iii) select appropriate packaging materials, (iv) pack the goods exactly according to the regulations, (v) mark and label the packages appropriately, and (6) document the entire process for each shipment. Failure to comply with the regulations can result in exposure of carrier personnel to dangerous substances and exposure of a shipper to the risk of criminal and civil liability and/or severe financial penalties. The purpose of this procedure is to provide guidelines for trained laboratory personnel to use as they pack substances commonly shipped from this laboratory, specifically, diagnostic specimens and infectious substances.

VII. METHODS

II. EXAMPLES OF SUBSTANCES TO WHICH THIS PROCEDURE APPLIES A. Body fluids: serum, plasma, whole blood, bone marrow, urine, cerebrospinal fluid B. Other fluids: broth cultures of microorganisms C. Solid items: tissue, biopsies, pure cultures of microorganisms, fixed tissue D. Other: dry ice

III. TRAINED PERSONS WHO ARE RESPONSIBLE FOR SHIPPING Only the following laboratory persons who have been trained and certified to pack class 6 and class 9 dangerous goods may do so: , , and .

IV. REFERENCE PERSONS Consult the following laboratory persons when you need technical or clinical information to help you decide if a substance is a diagnostic specimen or an infectious substance or for any other information regarding the purpose for shipping the substance, what tests are being ordered, the pathogenicity of the substance, or any other danger associated with the substance: , , and .

V. CARRIERS Use the following commercial carriers (and telephone numbers for pickup) to transport goods: (###-####), (###-####), and (###-####).

VI. SUPPLIES Use the following packaging materials (stored in the laboratory storeroom) to pack and ship diagnostic specimens and infectious substances: A. diagnostic specimens: packaging product/kit (catalog number and manufacturer) B. infectious substances: packaging product/kit (catalog number and manufacturer) C. other substances: packaging product/kit (catalog number and manufacturer) Notify when the supply of packaging products is low.

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A. Determine the commercial carrier to be used and schedule a pickup. B. Determine if the specimen is a diagnostic specimen or an infectious substance. Determine the inherent danger (if any) in the specimen. C. Use the algorithm in this procedure to determine which PI must be used (602 or 650). D. Select the packaging appropriate for the substance. E. Pack the substance. Use the checklists in this procedure to make sure all required steps are performed and the Shipper’s Declaration is filled out completely and correctly. Do not forget to (i) place reference laboratory test requisitions outside the secondary container and (ii) fill out a Shipper’s Declaration if the substance is an infectious substance. Attach the original Shipper’s Declaration and a copy to the completed package, and place a copy of the Shipper’s Declaration in the “Declaration Box” in the packing area. F. Fill out a carrier’s air waybill, and place the shipper’s copy in the box by the window at the laboratory reception area.

VIII. REFERENCES A. All training materials received during training courses and workshops B. IATA Dangerous Goods Regulations, 44th ed., 2003 C. Code of Federal Regulations 49 (U.S. DOT regulations published in the Federal Register) REFERENCES 1. Beckala, H. R. 1999. Regulations for packaging and shipping laboratory specimens. Lab. Med. 30:663– 667. 2. Bennett, C. 2003. HAZMAT training: 101. Advance/ Laboratory March:42– 45. 3. Cook, D. 2001. Practical aspects of shipping specimens. Advance/Laboratory March:52–54. 4. Gilchrist, M. J. R., W. P. McKinney, J. M. Miller, and A. S. Weissfeld. 2000. Cumitech 33, Laboratory Safety, Management, and Diagnosis of Biological Agents Associated with Bioterrorism. Coordinating ed., J. W. Snyder. ASM Press, Washington, D.C. 5. International Air Transport Association. 2003. Dangerous Goods Regulations, 44th ed. International Air Transport Association, Montre´ al, Que´ bec, Canada. 5a.International Civil Aviation Organization. 2003. The Technical Instructions for the Safe Transportation of Dangerous Goods by Air, 2003–2004 ed. International Civil Aviation Organization, Montre´ al, Que´ bec, Canada. 6. McKay, J., and D. O. Fleming. 2000. Packaging and shipping biological materials, p. 411– 423. In D. O. Fleming and D. L. Hunt (ed.), Biological Safety: Principles and Practices, 3rd ed. ASM Press, Washington, D.C.

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7. Mooney, B. 2002. “Wrapped up” in shipping specifics. Advance/Laboratory October:72–76. 8. Snyder, J. W. 2002. Packaging and shipping of infectious substances. Clin. Microbiol. Newsl. 24:89 –93. 9. U.S. Department of Transportation, Research and Special Programs Administration. 2002. Hazardous materials: revision to standards for infectious substances and genetically modified organisms; final rule.

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Fed. Regist. 67:53117–53144. 10. U.S. Postal Service. 2002. Hazardous materials: proposed domestic mail manual revisions for division 6.2 infectious substances and other related changes. Fed. Regist. 67:77726 –77737. 11. World Health Organization. 1993. Laboratory Biosafety Manual, 2nd ed. World Health Organization, Geneva, Switzerland.