ONLINE self-study

1. ONLINE self-study Shipping of Infectious Substances and Other Biomedical Materials Annual Update

2. Course Objectives The purpose of this program is to: • ensure the safe handling of hazardous materials using good sensible practices. • recognize hazardous materials and realize there are special requirements • Comply with Federal and International regulations The basic goal for this training is to provide a framework for decisions • Is material to be shipped a dangerous good, genetically modified, biological substance category B, or an exempt human specimen? Upon completion you will receive certification to ship hazardous materials

3. Course Objectives This training will increase your awareness of safety and compliance issues. If you need more information or help with shipping your package you can e-mail the EHS Shipping Specialist. The training will cover the topics listed below. Classification, identification, and packaging are three of the most important topics covered. • Regulatory Oversight • Dangerous Goods/Hazardous Materials • Training Requirements • Shipper’s & Operators’ Responsibilities • Classification, Identification • Packaging • Shipping with dry ice and Overpacks • Marking & labeling packages • Shipping documentation • Emergency Response • Laboratory Security • Accept or reject shipments by use of checklist

4. What is a Dangerous Good/Hazardous Material? Federal Regulations: U.S. Dept. of Transportation (DOT) – 49 CFROther federal requirements: CDC, OSHA, USDA, Department of Commerce, International Traffic and Arms (ITAR) and Toxic Substance Control Act (TSCA)      DOT regulations primarily cover ground transportation. DOT is the organization that has the authority to fine you for violations. Their authority extends well beyond US boundaries. Import permits from the CDC or USDA may be needed if you are importing human etiological organisms or plant or animal pathogens. Department of Commerce licenses may be needed to export organisms, genetic elements, chemicals, technology or other commodities. TSCA Certification may be needed to import or export certain chemicals. International Regulations (Air shipments) International Civil Aviation Organization (ICAO) International Air Transport Association (IATA) Dangerous Goods Regulations (DGR)      Internationally, the UN Committee of Experts (CoE) develops recommended procedures for the transport of all types of dangerous good except Radioactive material. The International Civil Aviation Organization (ICAO) uses the UN recommendations as the basis for developing the regulations for the safe transport of dangerous goods by air. IATA is the international trade organization that interprets ICAO regulations and provides the Dangerous Goods Regulations (DGR). The IATA regulations are more stringent than DOT. This training program follows the IATA regulations. IATA regulations are minimal requirements - your carrier can be more stringent.

5. What is a Dangerous Good/Hazardous Material? Fines and Penalties "Violations contrary to the U.S. Code of Federal Regulations (CFR) 49, if substantiated, may result in the assessment of a civil penalty of up to $37,500 per violation, and deliberate violations may result in criminal prosecution of up to $500,000 and 5 years in prison." • There has been an increase in the number of Federal Aviation Inspections (FAA) in response to the 1996 ValuJet crash, the September 11, 2001 attacks, and the UPS package bomb scare in November 2010. • If you are receiving a HazMat package it is your responsibility to ensure the sender packages it correctly. Oxygen-generating canister like the ones on board the ValuJet flight 592

6. Definition Infectious Substance - Class 6.2 Definition: Infectious substances are substances known to contain, or reasonably expected to contain, pathogens. Pathogens are defined as micro-organisms (including bacteria, viruses, rickettsia, parasites, fungi) and other agents such as prions which can cause disease in humans or animals. Critical to the infectious substance definition is the ability to cause disease. - Note the reliance on your professional judgment when the words “reasonably expected” are used.

7. Definition The IATA definition for infectious substances leaves out toxins. Toxins are placed in a separate category. They are treated like chemicals. Toxins from plant, animal or bacterial sources which do not contain any infectious substances or toxins that are not contained in substances which are infectious substances should be considered for classification in Division 6.1 and assignment to UN 3172 (for liquids) or UN 3462 (for solids). Contact EHS if you are shipping toxins as instructions for shipping toxins is not covered in this training module. Please be aware that many toxins (if shipped out of the US) are regulated by the Department of Commerce. There are significant fines associated with exporting toxins without a license

8. Definition • Biological products are those products derived from living organisms which are manufactured and distributed in accordance with the requirements of appropriate national authorities, which may have special licensing requirements, and are used either for prevention, treatment, or diagnosis of disease in humans or animals, or for development, experimental or investigational purposes related thereto. They include, but are not limited to, finished or unfinished products such as vaccines.

9. Definition Cultures Laboratory stocks are the result of a process by which pathogens are intentionally propagated in order to generate high concentrations. This increases the risk of infection when exposure to them occurs. An example of this would be a patient sample of TB that has been cultured.

10. Definition Patient Specimens Patient Specimens are human or animal materials, collected directly from humans or animals, including, but not limited to, excreta, secreta, blood and its components, tissue and tissue fluid swabs, and body parts being transported for purposes such as research, diagnosis, investigational activities, disease treatment and prevention.

11. Classification of Infectious Substances The three proper shipping names for infectious substances are: • Infectious substances, affecting humans, UN 2814 • Infectious substances affecting animals, UN 2900 • Biological Substances Category B, UN 3373 (This does not require a Dangerous Good Declaration to ship)

12. Classification Category A Infectious Substances - an infectious substance which is transported in a form that when exposure occurs, is capable of causing permanent disability, life threatening or fatal disease in otherwise healthy humans or animals. Examples of substances that meet this criteria are located in this table: Table 3.6.D. NOTE: An exposure occurs when an infectious substance is released outside of the protective packaging, resulting in physical contact with humans or animals.

13. Classification of Infectious Substances Infectious substances meeting the Category A criteria which cause disease in humans or both in humans and animals must be assigned to UN 2814 (Infectious substance, affecting humans). Infectious substances which cause disease only in animals must be assigned to UN 2900 (Infectious substance, affecting animals).

14. Classification of Infectious Substances Assignment to UN 2814 or UN 2900 must be based on the known medical history and symptoms of the source human or animal, endemic local conditions, or professional judgment concerning individual circumstances of the source human or animal. Example: a patient from a foreign country is admitted to the hospital. You think they may have Ebola. You will ship all body fluids as infectious substances (Category A) using all the applicable packaging and paperwork.

15. Classification of Infectious Substances Category B, biological substance is an infectious substance which does no meet the criteria for inclusion in Category A. An example of a Category B biological substance would be a patient's body fluid infected with mycobacterium tuberculosis. A culture of this same organism would be a Category A infectious substance. You must use your professional judgment in deciding if an infectious substance is a Category A or Category B infectious substance. Contact EHS if you need assistance determining your classification.

16. Classification of Infectious Substances   Infectious substances in category B must be assigned to UN 3373 except those organisms on table 3.6.D - which must be assigned to UN 2814 or UN 2900. The proper shipping name of UN 3373 is Biological Substance Category B.

17. Classification of Infectious Substances Exemptions under Biological Substance Category B Substances which do not contain infectious substances or substances which are unlikely to cause disease in humans or animals are not subject to these Regulations unless they meet the criteria for inclusion in another class i.e. you add ethanol to the sample. Substances containing micro-organisms, which are non-pathogenic to humans or animals are not subject to these Regulations unless they meet the criteria for inclusion in another class. Substances in a form that any present pathogens have been neutralized or inactivated such that they no longer pose a health risk are not subject to these Regulations unless they meet the criteria for inclusion in another class. Environmental samples (including food and water samples), which are not considered to pose a significant risk of infection are not subject to these Regulations, unless they meet the criteria for inclusion in another class. Dried blood spots, collected by applying a drop of blood onto absorbent material, or faecal occult blood screening tests and blood or blood components which have been collected for the purposes of transfusion or for the preparation of blood products to be used for transfusion or transplantation and any tissues or organs intended for use in transplantation are not subject to these Regulations.

18. Classification of Infectious Substances Exemptions: Patient Specimens Patient specimens for which there is minimal likelihood that pathogens are present are not subject to these Regulations if the specimen is packed to prevent any leakage and is marked with the words "Exempt human specimen" or "Exempt animal specimen", as appropriate. The packaging must meet the following conditions: The packaging must consist of three components: a leak-proof primary receptacle(s); a leak-proof secondary packaging; and an outer packaging of adequate strength for its capacity, mass and intended use, and with at least one surface having minimum dimensions of 100 mm x 100 mm; For liquids, absorbent material in sufficient quantity to absorb the entire contents must be placed between the primary receptacle(s) and the secondary packaging so that, during transport, any release or leak of a liquid substance will not reach the outer packaging and will not compromise the integrity of the cushioning material; When multiple fragile primary receptacles are placed in a single secondary packaging, they must be either individually wrapped or separated to prevent contact between them. Determining whether a patient specimen has a minimal likelihood that pathogens are present, should be based on the known medical history, symptoms and individual circumstances of the source, human or animal, and endemic local conditions. Examples of specimens which may be transported under this paragraph include the blood or urine tests to monitor cholesterol levels, blood glucose levels, hormone levels, or prostate specific antigens (PSA); tests required to monitor organ function such as heart, liver or kidney function for humans or animals with non-infectious diseases, or therapeutic drug monitoring; tests conducted for insurance or employment purposes and are intended to determine the presence of drugs or alcohol; pregnancy tests; biopsies to detect cancer; and antibody detection in humans or animals.

19. Other Classifications Biological Products For the purposes of these Regulations, biological products are divided into the following groups: Those which are manufactured and packaged in accordance with the requirements of appropriate national authorities and transported for the purposes of final packaging or distribution, and use for personal health care by medical professionals or individuals. Substances in this group are not subject to these Regulations. These include but are not limited to finished and unfinished products such as vaccines. Those which do not fall under paragraph (a) and are known or reasonably believed to contain infectious substances and which meet the criteria for inclusion in Category A or Category B. Substances in this group must be assigned to UN 2814, UN 2900 or UN 3373, as appropriate. Note:Some licensed biological products may present a biohazard only in certain parts of the world. In that case, competent authorities may require these biological products to be in compliance with local requirements for infectious substances or may impose other restrictions

20. Other Classifications Genetically modified microorganisms are: Organisms that do not meet the definition of infectious substances but posses genetic material that has been purposely altered through genetic engineering in a way that does not occur naturally. Assigned UN 3245 UN 3245 label: These items must be triple packaged (leak proof primary container, leak proof secondary container, strong outer container). Liquids must have sufficient absorbent material to absorb all contents outside of the primary container. Outer containers must have sender and receiver names, addresses, and phone number marked on the box. UN3245

21. Other Classifications Infected Animals A live animal which has been intentionally infected and is known or suspected to contain an infectious substance cannot be transported by air unless the infectious substance contained cannot be consigned by any other means. Infected animals can only be transported by certain carriers. With the shipment there must be a DOT letter of authorization. In order to receive infected animals you must obtain an import permit from the USDA. Both a DOT letter of authorization and USDA Permit take weeks to obtain.

22. Identification Category A Infectious Substance The table from the Dangerous Goods Regulations provides a lot of critical information. The entries for infectious substances are shown here. You will not find a microorganism listed by its scientific/technical name. There are two UN numbers: UN 2814 and UN 2900 for Category A Infectious Substances (Column A). The asterisk beside infectious substances means you must put the technical name (specific name of the organism) on any paperwork. You do not put the technical name on the outside of the package. Column C gives the class or division and Column D gives the hazard label that will be affixed to the package. Columns J and L give the quantity limits per package type. 2011 Update: Category A infectious substances are packed according to Packing Instruction 620

23. Identification Category A Infectious Substance This slide shows the packing instruction and maximum quantity per package. The limits are different for passenger and cargo aircraft. You are only allowed to ship 50mg/g per package on a passenger and cargo aircraft. You are only allowed to ship 50mL (liquid) or 50g (solid) per package on a passenger and cargo aircraft. With the "cargo aircraft only" label you can ship up to 4L (liquid) or 4 kg (solid) on a cargo aircraft only. Cargo Aircraft Only Label

24. Identification Biological Substance, Category B The UN number 3373 is in Column A. When shipping biological substances you have to use packing instruction 650 and you can ship up to 4 L per outer package (primary containers cannot exceed 1 L.) The 4L quantity excludes ice, dry ice or liquid Nitrogen when keeping specimens cold.

25. Identification Biological Products There is no UN number in the left hand column for biologicals. It states they are not restricted.   You do not need diamond shaped labels and you can ship as much as you want as long as no chemicals or infectious agents are present.

26. Chemical Preservatives Solutions used to preserve biological samples may be regulated as dangerous goods. • Ethanol, greater than 24% is assigned to UN1170, Class 3, Ethanol, PGII • 10% to <25% Formaldehyde is assigned to UN3334, Class 9, Aviation regulated liquid, n.o.s. • Formaldehyde, not less than 25% assigned to UN2209, Class 8, Formaldehyde solution PGIII • Formaldehyde combined with a flammable substance may qualify as UN1198, Class 3 (Sub risk 8), Formaldehyde solution, flammable. Call EHS for specific packaging and training before shipping chemicals

27. Packing Groups Packing groups apply to toxic substances and chemicals but not infectious substances, biological products or Category B biological substances. Here is an example of the packing group criteria for class 3 materials (flammable liquids). The packing groups pertain to performance test requirements. They are assigned with regard to the relative degree of danger of the article or substance. The IATA DGR establishes packing group assignments for all applicable classes based on the type of hazard. For example Class 8 materials are assigned packing groups based on corrosivity and Class 6.1 materials are assigned based on toxicity.

28. Packing Groups The packing group for a material is indicated on the table in the Dangerous Goods Regulations. Here is an example using the listing for Ethanol. Ethanol has two packing groups listed (column E). The flashpoint of your ethanol solution will determine which packing group and packing instructions to use. Check the MSDS for flashpoint information.

29. Shipping With Formalin Shipper's Declaration for Dangerous Goods Many people ship large amounts of formalin to preserve their specimens. Here is an example of the Shippers Declaration for Dangerous Goods when shipping formalin. If you are shipping formalin or any other chemical, you need to call EHS at 962 - 5507 for more in-depth training.

30. Dangerous Goods in Excepted Quantities • There is a provision in the Dangerous goods regulations that allows small quantities of some dangerous goods to be shipped as "dangerous goods in excepted quantities.“ • This is very useful for small amounts of hazardous chemicals. • Check the EQ column (column F) on the Dangerous Goods Table for the material to find the Excepted Quantity code. • Reference table 2.7 to determine the quantity allowed under your item's code. • Some materials are not allowed to ship as Excepted Quantities. These will have an E0 in column F • For the EQ table, click here: table 2.7

31. Dangerous Goods in Excepted Quantities This form can be downloaded at http://ehs.unc.edu/ih/lab/docs/excepted.pdf. It needs to be printed on a color printer. In the upper box you will type the Class number(s), with sub risks in parenthesis. This is found in column C of the Dangerous Goods table. In the lower box you will type either your name and address or the recipient's name and address IF it is not already marked ON the package. This label along with an address label placed on a strong outer box is what is needed for shipping excepted quantities of chemicals not forbidden for transport. The material must be in a leak proof primary container. The primary container needs to be taped closed. This primary container must be securely packed in a secondary container with absorbent/cushioning material in such a way that the primary container will not break, puncture, or otherwise release its contents. The secondary container must be securely packed in a strong rigid outer packaging (wood, cardboard, or other equally strong material). Each outer package must be large enough to apply all necessary markings.

32. Dangerous Goods in Excepted Quantities Excepted Quantity Package Test The complete package must be capable of withstanding the following drop and load tests. This must be demonstrated by testing and appropriately documented using this form. Excepted Quantity Package Test Verification Form (http://ehs.unc.edu/ih/lab/docs/eq_test_form.pdf) For the purposes of testing you will use a substance with similar physical characteristics (mass, grain size, density, etc.) to the item you intend to ship. Fill the primary container to 98% capacity. Triple package this substance in identical primary, secondary (including absorbent/cushioning), and outer containers to what you intend to use for shipping and perform the following tests:

33. Dangerous Goods in Excepted Quantities Drop Test: From a height of 1.8 m (5.9 feet), perform each of the following drops onto a rigid, non-resilient flat and horizontal surface: Flat on the base Flat on the top Flat on the longest side Flat on the shortest side On a corner Load Test: Calculate the mass of identical size and weight packages as your test sample if stacked to a height of 3 m (10 feet). Apply this amount of force to the top surface of your package for 24 hours.

34. Dangerous Goods in Excepted Quantities A successful package test results in no leakage or breakage of the inner containers and no significant reduction in effectiveness of any of the 3 layers of packaging. Remember to document this package test using this form (http://ehs.unc.edu/ih/lab/docs/eq_test_form.pdf) If you are using packing materials and specimens that you have previously tested and documented you do not need to re-test the package. You may use a copy of the package test verification form from a previous test of the same materials. Make sure you keep a copy of the package test verification form in your shipping records.

35. Dangerous Goods in Excepted Quantities Here is an example of the label for a package containing an excepted quantity of a Class 3 flammable liquid.

36. Dangerous Goods in Excepted Quantities Many people ship their biological samples in formalin or ethanol to preserve them. Packing instructions 620 (UN2814 and 2900 Category A infectious substances) and 650 (UN3373 Biological Substances, Category B) allow for a quantity of 30mL or less of dangerous goods in classes 3, 8, or 9 to be packed in each primary receptacle containing infectious substances. This includes commonly used preservatives such as formalin, ethanol, or formaldehyde. When these small quantities are packed with infectious substances using the packing method for that infectious substance, the excepted quantity label is not required. The infectious substance packaging will be sufficient. This does not include phenol which is a class 6 chemical.

37. Biological Specimens Category B Packaging Selecting Proper Packaging Selecting the proper packaging is one of the most important functions of the shipper. The shipper is responsible for all aspects of the packing of dangerous goods. The carrier (FedEx, DHL, World Courier, etc.) will not help you package your material.

38. Biological Substance Category B Packaging Selecting Proper Packaging The shipper must comply with the following packing instructions: When shipping UN2814 or UN2900 Category A infectious substances use Packing Instruction 620 pdf When shipping UN3373 Category B infectious substances use Packing Instruction 650 pdf When shipping dry ice use Packing Instruction 954 pdf Make sure the responsibilities for packing are complete when the package is given to the carrier for shipment

39. Biological Substances Category B Packaging Category B Infectious Specifications These are the minimum packaging requirements for Packing Instruction 650: • The packagings must be of good quality, strong enough to withstand the shocks and loadings normally encountered during transport, including trans shipments. • "Packagings must be constructed and closed so as to prevent any loss of contents that might be caused under normal conditions of transport, by vibration or by changes in temperature, humidity or pressure." The packaging must consist of three components: Primary receptacle(s) Secondary packaging(s) Rigid Outer Packaging

40. Biological Substance Category B Packaging Packaging Materials for Category B Substances This picture was taken from FedEx's Points to Consider brochure for mailing Category B substances. Category B substances can be shipped in a cardboard mailing tube or a plastic container. You do not need special absorbent. Cotton balls or paper towels may be used.

41. Biological Substance Category B Packaging Biological Substance, Category B Packaging Requirement • Primary receptacle(s) must be leakproof and contain no more than 1L • Secondary packaging must be leakproof • If multiple fragile receptacles are in a single secondary package they must be individually wrapped or separated to prevent contact • Sufficient absorbent material must be placed between the primary and secondary receptacles.

42. Biological Substance Category B Packaging Biological Substance, Category B Packaging Requirement • Water tight packaging (above in photo) • Pressure tested packaging (tyvek bag; below in photo) • The primary receptacle or the secondary packaging must be able to withstand without leakage an internal pressure test of 95 kPA in the range of -40° C to 55° C. When you are ordering shipping materials make sure you order primary or secondary containers that meet the 95 kPA. • Notice the bio hazard symbol on the packaging. It is an OSHA (not an IATA) requirement when shipping blood or other potentially infectious material.

43. Biological Substance Category B Packaging Biological Substance, Category B Packaging Requirement • Secondary packaging • Itemized list of contents • Placed in outer packaging • Outer packaging must be marked with the following:The name, address and telephone number of a responsible person. UN 3373 must be marked on the outside of the box adjacent to the words Biological Substance Category B. • The completed package must be able to pass a drop test of 1.2 M on all sides. • The biohazard symbol is not required on the outer box.  • Make sure your specimens do not move about loosely in the box. • It is useful many times when shipping out of the country to put "For Research Purposes Only" on the outside of the box.

44. Biological Substance Category B Packaging

45. Biological Substance Category B Packaging US Postal Service Label Requirement for Specimens OSHA "Biohazard Label" The U.S. Postal Service accepts Biological Substance Category B. You no longer display the Biohazard symbol on the outside. If you are shipping chemicals or blood or other potentially infectious materials using the U.S. postal service please call EHS at 962 - 5507.

46. Shipping With Dry Ice Use Packing Instruction 954 • Dry ice is always considered a • Dangerous good • It must always be declared by marking, labeling, (Class 9) and documentation. • If there are no other dangerous goods in a shipment, a Shipper’s Declaration is not required (red hatch-mark form). • It is very important that dry ice is never placed in a sealed container. The build-up in pressure will cause violent failure of the container. • When shipping dry ice the following needs to be on the outside of the box: "#9 misc label, UN 1845 and # kg" •  The package must be able to release vapor at all times. The lid of a Styrofoam cooler should not be taped in place. Tape the outer cardboard box.  Even when transporting dry ice by ground, basic safety precautions should be followed. Allow ventilation of the cooler and the vehicle. CO2 can build up in a car with the windows rolled up.

47. Shipping With Dry Ice Identification Several of these entries for dry ice look alike. The one you want is UN 1845, Class 9. The Packing Instruction when filling out the Dangerous Goods Declaration is 954. 2011 Update: Dry Ice is packed according to Packing Instruction 954

48. Shipping With Dry Ice Here is an example of the "Special Handling" box of the Air Waybill (FedEx): • The proper Shipping Name box should be checked • The Class Number 9 (misc) is printed on the form-fill in the amount of dry ice • The UN Number UN1845 should be on the form • One of the following boxes must be checked • Does this shipment contain dangerous goods? Wet ice or blue ice packs are not considered dangerous goods. Pack both so the package does not leak. If you are shipping Biological Substances Category B with wet ice, blue ice, dry ice, or at ambient temperatures you need to check the box. "Yes" (Shippers declaration not required). If you are shipping Infectious Substance Category A on dry ice you will check 'yes' (as per attached shipper's Declaration).

49. Shipping With Overpacks Overpacks are large packages capable of containing one or more smaller packages. Many people use the MediPak diagnostic shipper with an inner UN 6.2 infectious shipper box. Dangerous goods packages within the overpack must be correctly packed, marked, labeled and in proper condition.

50. Shipping With Overpacks The overpack must have on the outside of the box: • All necessary marks and labels. • If the UN package specification marks are not visible, a statement that says "Overpack" must appear on the outside package. UN Package Specification MarksRequired on inner package of overpack containing infectious substances.