Regulations for Packaging and Shipping Laboratory Specimens

CE U P D A T E - R E G U L A T I O N S AND ACCREDITATION I Harold R. Beckala, MBA Regulations for Packaging and Shipping Laboratory Specimens Laboratories must maintain the integrity of patient specimens before the specimens are analyzed. Maintaining specimen integrity in the laboratory is not simple, and it becomes even more complex when specimens are transported by public conveyance. Specimens must be kept from leaking and from being crushed in unexpected accidents. They must be packed to protect both the specimens and those who handle them. The problem for most of us is to determine how to prepare specimens for transport in a transportation system that is outside of our day-to-day experience. The various dangerous goods regulations developed by government and international bodies provide guidelines based on the wisdom of experts who truly understand the transport system. If we follow the regulations, specimens should not leak or be crushed in transit. The regulations are more than guidelines. If a sample leaks from a package, an innocent bystander may be exposed to a pathogen. At that time a federal regulatory agency may investigate the incident and assign legal responsibility. Regulations provide a schedule of fines ( 107.329 and 107.333).i Fines can, in theory, be levied against the person packing the box, the employer, the carrier, and possibly the recipient of the package if the recipient's actions cause an incident. The civil penalties listed in the regulations may be as large as $27,000 for each violation, and in extreme criminal liability range up to $500,000 and 5 years in prison. The previously given penalties may seem to make shipping medical specimens a hazardous procedure, when in fact, it probably is not. Fortunately for our sendout staff the regulators are currently lenient in their enforcement procedures. For example, of the millions of shipments sent each year, the Federal Aviation Agency has levied only a handful ABSTRACT The US Department of Transportation (USDOT) requires anyone who causes specimens to be transported by public carrier to follow Dangerous Goods Shipping Regulations. That includes laboratory sendout staff, anyone who transports specimens, and, in my opinion, those who receive specimens. The responsibilities imposed on most laboratories are related to specimen packaging, labeling, documentation, and training of staff to follow regulations. This article concentrates on those aspects of the law and several of the most routinely used transport sources. The regulations are complex, and significant changes are being proposed by USDOT that may have an impact on courier services provided by laboratories. This is the first article in a three-part continuing education series on regulations and accreditation. On completion of this article, the reader will be able to describe regulations that affect shipping of medical specimens, apply that knowledge as needed, and locate additional pertinent information as necessary. of fines (see Hazardous Materials downloadable documents at: hazmat.dot.gov/ohmforms.htm). Still, to minimize risk, the sendout person should follow regulations. He or she must know which regulations to follow, and the employer must train that individual. Sources of Information The regulations that apply depend on how you send specimens (ie, mail, or ground, or air courier). Each mode of transportation has its own rules. For specimens sent by mail, follow the US Postal Service Dangerous Goods Regulations. Your local post office can provide a copy of a recent directive on shipping dangerous goods or refer you to an expert on hazardous materials. For specimens sent via ground courier, follow US Department of Transportation (USDOT) regulations. Its authority is derived from federal hazardous materials law, frequently called Hazmat From the Department of Laboratory Medicine and Pathology, Mayo Clinic and Mayo Foundation, Rochester, Minn. Reprint requests to Mr Beckala, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First St SW, Rochester, MN 55905. 663 0 y u c 0 1 9) w

Law.2 Regulations governing specimen transport are incorporated in a document frequently referred to as 49 CFR.1 It is several hundred pages long and is amended and modified periodically; changes are communicated through the Federal Register. Substantial changes have been proposed for the coming year; these changes may dramatically affect laboratory courier services. If you or your reference laboratory ships specimens by air, dangerous goods regulations from the International Air Transport Association (IATA, Montreal) and International Civil Aviation Organization (ICAO, Montreal) must be followed. Both IATA and ICAO provide a hazardous materials technical manual.3'4 As with 49 CFR, shipping and packaging instructions for specimens are interspersed with requirements for shipping many other dangerous goods. IATA and ICAO regulations are almost identical. I believe a working knowledge of IATA regulations is sufficient for Glossary Carrier Individual or organization engaged in hauling goods for hire (eg, Federal Express). Includes local couriers. 49 CFR Title 49, Code of Federal Regulations. "Diagnostic Specimen" Any human material, including, but not limited to, excreta, secreta, blood and its components, tissue, and tissue fluids, shipped for purposes of diagnosis. In common usage, a package that contains low-risk specimens. Federal Register Official daily publication of rules, proposed rules, and notices of federal agencies and organizations, and executive orders and other presidential documents. IATA International Air Transport Association (Montreal). Regulates dangerous goods, including "Infectious Substances," for all member airlines and anyone who tenders dangerous goods to those airlines. Most airlines and air freight couriers are members. ICAO International Civil Aviation Organization (Montreal). Regulates dangerous goods for all international civil air transport. Regulations are similar to IATA regulations. "Infectious Substances Affecting Humans" Substances known to contain or reasonably expected to contain pathogens capable of infecting humans. Stated on the label of packages containing high-risk specimens. Sendout person Person in the laboratory who packs specimens and prepares them for transport to another location. Shipper Anyone who sends goods via carrier. In the laboratory, these are the sendout persons, and the laboratory is responsible for their actions. UN-certified container Package that has passed United Nations certification tests and is labeled as such for transport of high-risk specimens. USDOT US Department of Transportation. 6 6 4 2018 on 07 January most shippers. For additional information, IATA has established a hotline (514-390-6770) and email address (Gerbers@iata.org). Overview of Regulations The IATA and ICAO rules are difficult to condense into an easily workable format. I treat IATA regulations as the standard, because USDOT is proposing changes5 that will make its regulations similar to those of IATA. These potential changes can be tracked on the USDOT Hazmat Web site (hazmat.dot.gov/), or by periodically calling the USDOT hotline (800-467-4922). As you read the IATA regulations, imagine applying them to a hospital laboratory courier service. In the current IATA system, all dangerous goods regulations concern the shipper, a sendout person, deciding how much risk a specimen presents to the public. Packaging, labeling, and documentation requirements flow from that decision. You may wonder, why not ship all specimens under full infectious precautions? At first glance, it sounds reasonable, but that decision will cause at least three problems: 1. When a specimen is considered an "infectious substance," the added paperwork and labeling become much more difficult to complete. Any error, even a trivial mistake, means that a lawabiding carrier cannot accept the package. 2. United Nations (UN)-certified containers must be used. These are expensive, often more than $20 each. 3. Shipping charges are higher; carriers pass along the cost for special handling of these packages. Rather than sending all specimens under infectious precautions, I favor following the classification process for each specimen. Risk Classification Schema Decades ago, infectious specimens were labeled as such in the laboratory, and a sendout person often knew which specimens contained a pathogen. Old regulations made use of that fact to decide which specimens were infectious for shipping purposes. Today sendout staffs generally do not know the status of each specimen. ICAO and IATA recognize this change and have developed a method for classifying risk to the outside world based on information available to a sendout person. That person should know which tests have been ordered and can use a list of pathogens classified by risk to humans to assign risk status. The list

required by IATA is taken from the World Health No-Risk Specimens Organization's Laboratory Biosafety Manual.6 Few no-risk specimens are seen in a laboratory. With these two pieces of information, IATA These specimens absolutely do not contain a devised a method that divides risk into three cate- pathogen, and are not regulated. However, if they gories ( 3.6.2.4).3 I will simplify the definitions. leak from a package, the carrier will be alarmed. USDOT regulations seem to be headed toward the Because of this, I suggest packing and treating same three-category framework. them as low-risk specimens. Before I describe the framework, let me warn you about a special requirement for US shippers. Packaging, Labeling, and The World Health Organization risk group 4 D o c u m e n t a t i o n pathogens, such as Ebola virus and certain stock cul-"infectious Substances Affecting Humans" tures, are very dangerous. Congress is concerned A UN-certified package must be used to protect about terrorists intercepting these agents in the mailhigh-risk specimens. Containers may be pur- Test Your and in 1996 passed a law that attempts to control chased for $10 to $20 each, or you can develop Knowledge the shipment of these pathogens.7 Routine samples your own. Certification testing costs about $2,000, Look for the CE for simple diagnostic testing are exempt. If you are if you develop your own original container. Update exam on Regulations and shipping something else, contact the Centers for Review the IATA requirements ( 6.5.0 and Accreditation (908) in 3 Disease Control and Prevention (Atlanta) before 6.5.3) and the 49 CFR regulations ( 178.609).' the December issue you ship the material. The package must be able to withstand a 30-foot of Laboratory With the above warning in mind, the sendout drop without breaking enclosed tubes and a punc- Medicine. Participants will earn 3 CMLE person in a laboratory must classify specimens as ture test with a 16-lb steel rod. credit hours. one of three types: If your laboratory provides testing for other facilities, it may be cost-effective to develop your own 1. High-risk specimens are labeled as "Infectious packaging. If you send work to a reference laborasubstances Affecting Humans" on the package tory, ask it to provide UN-certified containers. label. The packing of specimens in UN-certified con2. Low-risk specimens are labeled "Diagnostic tainers consists of two parts: Specimens" on the package label. 1. Prepacking, or placing primary containers into 3. No-risk specimens are not regulated. secondary containers, and Fig 1, Generic High-Risk Specimens 2. Packing the secondary containers for shipping. example of Specimens being sent to test for antigens of prepacking before pathogens or for many antibody tests, and certhe final package is the UN-certified box. shipment. UN tainly all cultures, are considered high-risk specifor prepacking, a watertight primary container indicates United mens. Screening tests for a pathogen should be must be used (Fig 1). Vials must be pressure tested Nations. included unless the test is unlikely to be positive (eg, a blood bank screen). A practical approach is to look at the name of the test requested. If it contains the name of a pathogen, consider the specimen high risk. Of course, some tests measure previous infection, and the specimens are not infectious. Let your laboratory medical director's opinion override generalities. High-risk specimens are regulated by law and are labeled as "infectious substances affecting humans." Low-Risk Specimens Most specimens are low risk. Tests ordered generally measure an analyte not related to an infectious pathogen. Low-risk specimens are now called "diagnostic specimens" and are regulated materials, but the regulations are easy to follow. Primary watertight vial pressure tested Absorbent around specimen Secondary watertight container hardened to withstand UN testing 665

I Inter shipper's name and address on the box. The UN number 2814 must also be on the box. Infectious Substance label with additional information and fields to complete. Enter name of responsible person. You must also have the recipient's address on the box. Enter Shjpger_n ma & Addrew Below: Dry Ice label. Use if shipping dry ice. Enter dry ice weight in kilograms. Volume of If volume i Cargo Aircraft Only label is used if more than 50 ml of infectious substance is sent by air. The name of the infectious substance must be on the box Fig 2. United Nations-certified package with proper labels, ready for shipment. / ^^ «^_. _ Fig 3. Standard "Infectious Substance" label with additional information required for shipment. By permission of the International AirTransport Association (Montreal) and courtesy of Mayo Foundation (Rochester, Minn). UN indicates United Nations. Message shows transport workers that the package contains Low-risk specimens. It is a "handle with care" message. _ 5^=^f 1., :.. Primary wa tert lght vial, pressure tes ted Secondary watertight cont ainer (bag) with absorbent Fig 4. Prepackage low-risk specimens in a secondary container or bag. Dry ice label. Use if shipping dry ice. Enter dry ice weight in kilograms. Fig 5. Example of "Diagnostic Specimens" box with proper labeling. IATA indicates International AirTransport Association (Montreal). to 13.8 lb/in2 or about a 55,000-foot altitude. Absorbent material is placed inside a secondary watertight container. The UN-certified box consists of the primary and secondary containers, placed in a shipping box. The shipping box must be marked and labeled. A standard "Infectious Substance" label, described in the IATA manual ( 7.3.15),3 must be placed on the box. A "Dry Ice" label must be used 6 6 6 2018 on 07 January if dry ice is being shipped, and a "Cargo Aircraft Only" label must be added if more than 50 ml of an infectious substance is enclosed (Fig 2). IATA Packing Instruction 602 requires the shipper to write additional information on each box. The amount of dry ice in each package must be noted if dry ice is used. Many specimens have been damaged because it is difficult to remember

all the information required. To assist clients of Mayo Clinic, I developed a modified box label around the official label (Fig 3). This version of the label has been used for 4 years. Special documentation is also required for shipping high-risk materials. Some carriers provide special airbills; others require the shipper to fill out a "Dangerous Goods Declaration." Each of these documents is a legal document, and any error will cause the shipment to be rejected. We preprint part of each declaration and underline the critical fields for our clients to complete on site. The high-risk specimens, packed and labeled according to regulations, are now ready for shipping. A courier picks up the box. Usually that courier is not fully versed in the regulations, and a hazardous materials specialist, at a central processing location, accepts or rejects the box several hours later. If the box is rejected, the sendout person will see the box the next day. "Diagnostic Specimens" Training Staff To Follow Regulations Both IATA ( 1.5)3 and USDOT ( 172.700 and 172.704)' require active training of anyone who packs or carries specimens. Basically, each regulator requires that each person be given training necessary to follow the regulations correctly. Proper documentation is required, and a test must be administered to the training participants. Conclusion Whether specimens are shipped by mail, or ground or air courier, various dangerous goods shipping requirements must be followed. Specific regulations apply. Contact the appropriate agency for help. USDOT is proposing to make its ground regulations consistent with IATA regulations, and these changes would affect laboratory courier services. High-risk specimens ("infectious substances") are tightly controlled. Low-risk specimens ("diagnostic specimens") are less dangerous, and the regulations are correspondingly less complicated. The requirements for packaging, labeling, and documentation are much less stringent for low- References 1. Title 49 Code of Federal Regulations. Washington, DC: risk specimens. Although the packaging does not Office of the Federal Register National Archives and Records need to be UN-certified, IATA Packing Group 650 Administration, Government Printing Office; 1997. specifications must be followed. 2. 49 USC 5101 et seq (formerly, Hazardous Materials The specimen must be placed in a watertight Transportation Act, 49 App USC 1801 thet seq). 3. Dangerous Goods Regulations, 40 ed. Montreal, Canada: primary container, a vial or a bottle. Absorbent is International Air Transport Association; 1999. then placed around or at least between it and a 4. Technical Instructions for the Safe Transport of Dangerous secondary leakproof container or bag (Fig 4). The Goods by Air. Montreal, Quebec, Canada: International Civil Aviation Organization; 1997-1998. prepacked specimen simply needs to be placed in 5. 63 Federal Register 46843-46859 (1998), proposed rules. a protective outer box, which does not need to be 6. Laboratory Biosafety Manual, 2 nd ed. Geneva, Switzerland: UN-certified. The box must be marked as "Diag- World Health Organization; 1993. 7. Pub L No. 104-132, The Antiterrorism and Effective Death nostic Specimens packed in compliance with Penalty Act of 1996, 511, Sub 8. IATA Packing Instruction 650" (Fig 5). If dry ice is used, the weight must be marked on the box. The documentation for low-risk specimens consists of a routine airbill containing the information described above and other shipping information. This documentation is not generally inspected by a hazardous materials specialist.