{"operation":"document","citation":"98-0303","title":"Glaxo Wellcome, Inc. — Hazardous Materials Safety Interpretation","source_type":"guidance","agency":"Pipeline and Hazardous Materials Safety Administration","status":"guidance","official":true,"published_on":"1998-11-19","effective_on":null,"summary":"98-0303 response to Glaxo Wellcome, Inc. concerning 173.134.","machine_formats":{"json":"https://regulus.evalyn.ai/document/phmsa-interpretation-98-0303.json","markdown":"https://regulus.evalyn.ai/document/phmsa-interpretation-98-0303.md"},"app_url":"https://regulus.evalyn.ai/document/phmsa-interpretation-98-0303","source_url":"https://www.phmsa.dot.gov/sites/phmsa.dot.gov/files/legacy/interpretations/Interpretation%20Files/1998/980303.pdf","body":"<<<PAGE 1>>>\n\nU.S. Department\nof Transportation\nWashington. D C\n400 Seventh Street, SW\n20590\nesearch an\nAdministration\npecial Program\nNOV | 9 1998\nMr. James R. Hendricks\nManager, Dangerous Goods Compliance\nRef. No. 98-0303\nGlaxo Wellcome, Inc.\nP.O. Box 13398\nResearch Triangie Fark, NC 27709-3396\nDear Mr. Hendricks:\nThis is in response to your letter in which you request clarification concerning the definition of\n\"biological product,\" as used in the Hazardous Materials Regulations (HMR; 49 CFR parts 171-\n180) and in the regulations of the Food and Drug Administration (EDA) of the Department of\nHealth and Human Services (21 CFR part 312 and parts 600 to 680). I apologize for the delay in\nresponding to your inquiry.\nYour letter is quoted, in part, as follows:\n•\nAn infectious material which meets the FDA definition of \"biological product,\" as\ndetined in 21 CFR Part 312 or 21 CFR Parts 600-680 may be shipped in any additional\npackaging; essentially non-regulated. Our question is whether an infectious material\nwhich does not meet the FDA definition of \"biological product\" while outside a \"medical\ndevice,\" automatically becomes a \"biological product\" when placed into a \"medical\ndevice?\"\nthat has been registered with the FDA as a \"medical device;\" with the implication that\nOur contusion results trom the tact a packaging manufacturer currently offers a package\nany biological material inside a registered medical device (including infectious materials)\nmay be treated as a biological product.\nOur understanding of the FDA definition of \"biological product\" does not include\nmention of \"medical devices.\" Furthermore, we do not believe the two terms are inter-\nrelated. Although our question may be more appropriately directed to the FDA, we\nwould appreciate RSPA's response/comments to the following question: Does an\ninfectious material that is not a \"biological product\" outside a FDA-approved medical\ndevice become a \"biological product\" when placed inside the medical device?\n\n<<<PAGE 2>>>\n\nWe agree that it does not appear that a medical device meets the FDA definition of \"biological\nproduct\" in 21 CFR 600.3(h). However, you are correct that it would be more appropriate to\naddress your question concerning this definition to the FDA.\nUnder the HMR, a material which meets the definition of \"biological product in 49 CFR\n173.134(a)(3) is excepted from regulation. With regard to FDA regulations, the HMR definition\napplies only to materials prepared and manufactured in accordance with 21 CFR part 312\n(Investigational new drug application) and 21 CFR 600 to 680 (Biologics). If a material is not\nprepared and manutactured in accordance with these regulations, it is not a biological product\nunder the HMR. An infectious material that is not a biological product does not become a\nbiological product by the act of placing it in an FDA-registered medical device and, unless\notherwise excepted, is fully subject to the HMR\nFor your information, we have been in contact with the packaging manufacturer and they have\nagreed to discontinue making claims that might imply that an infectious substance becomes a\nbiological product when shipped in their packaging.\n...-....\nI trust this satisfies your inquiry. If we can be of further assistance, please contact us.\nSincerely,\nHe 17. Manzalle\nEdward T. Mazzullo,\nDirector, Office of Hazardous\nMaterials Standards\n:\n2\n\n<<<PAGE 3>>>\n\n1.\nGlaxoWellcome\nManager, Dangerous Goods Compliance\nOctober 20, 1997\nU.S. Department of Transportation\n400 Seventh Street, S.W.\nDirector-Office of Hazardous Materials Standards; DHM-10\nWashington, Dc 20590-0001\nSubject: Request for Clarification\nThe purpose of this correspondence is to request clarification regarding DOT and FDA criteria for\nclassification, packaging and transportation of infectious materials, including biological products.\nCFR Part 312 or 21 CFR Parts 600-680 may be shipped in any additional packaging; essentially non-\nAn infectious material which meets the FDA definition of \"biological product,\" as defined in 21\nregulated. Our question is whether an infectious material which does not meet the FDA definition of\n\"biological product\" while outside a \"medical device,\" automatically becomes a \"biological product\" when\nplaced into a \"medical device?\"\nOur confusion results from the fact a packaging manufacturer currently offers a package that has\nbeen registered with the FDA as a \"medical device,\" with the implication that any biological material inside\na registered medical device (including infectious materials) may be treated as a biological product.\n\"medical devices.\" Furthermore, we do not believe the two terms are inter-related. Although our question\nOur understanding of the FDA definition of \"biological product\" does not include mention of\nfollowing question: Does an infectious material that is not a \"biological product\" outside a FDA-approved\nmay be more appropriately directed to the FDA, we would appreciate RSPA's response/comments to the\nmedical device become a \"biological product\" when placed inside the medical device?\norganism Vibrio vulnificus, which has caused septic shock syndrome in the person from which the sample\nPerhaps a specific example may assist in your response: Could a blood sample containing the\nwas drawn, be shipped as a biological product, if shipped in a FDA-approved medical device? Vibrio\nvulnificus is not on the 42 CFR 72.3 list of certain etiologic agents, nor does the blood sample meet the\nFDA definition of \"biological product\" prior to preparation for shipment.\nThank you for your consideration. We anxiously await your response.\nRegards,\nGames tendrich\nJames R. Hendricks\nGlaxo Wellcome Inc.\nPO Box 13398\nFive Moore Drive\nTelephone\n27709-3398\nResearch Triangle Park, NC\n919 483-6595\n599315-5713\n\n<<<PAGE 4>>>\n\nResponse to 10/20/97 Letter from James R. Hendricks\nISSUE PAPER\nof Glaxo Wellcome, Inc. (GWI)\nRE: Can an infectious substance that is not a biological product become a\nbiological product solely because it is placed in an FDA-approved medical device?\nG WI Issues:\nGWI says Pro-Tech-Tube (PTT) presented them with literature that makes it appear to GWI that an\ninfectious substance that is not a biological product, such as a diagnostic specimen, becomes a biological\nproduct if it is placed in an FDA-approved medical device. PTT also presented GWI with their packaging,\nE10148/ RESTRICTED: BODYFLUIDS AND EXCRETIONS ONLY.\" On the bottom of the\nwhich GWI presented to RSPA. This packaging was stamped \"UN1H2V/X.2/S/92/USA/M4578/DOT-\npackaging is the wording \"Supreme Plastics Inc. White Oak, Texas\"\n*\nThe written materials GWI submitted are from Andwin Scientific, a Division of the Andwin Corporation,\n6636 Variel Avenue, Canoga Park, CA 91303, (818)999-2828, FAX 818(999-0111). They contain\npromotional literature on how to use the Safetex clinical shipper, which is really PTT's device. The\nmaterials also include a letter and instructions from PTT. In these materials are the phrases:\n\"You really can ship infectious substances, in limited quantities (50 ml or less),\nin the Safetex ™ Clinical Shipper as biological products.\"\n\"...you are allowed to ship an infectious substance as a biological product and be\nexempt from DOT hazmat regulations.\"\n\"Shipped quantities of medical specimen, limited to the Directions for Use, are\n\"biological products'as defined by FDA, and are to be treated just as you would\nvaccines.\"\ntreat the transportation of a potentially dangerous attenuated live virus\n\"The FDA definition for biological product means any virus ... Paragraph (1)\nstates a virus is interpreted to be a product containing the minute living cause of\nan infectious disease... The manufacturer's claim to FDA states:\nmicroorganisms placed in the shipper are FDA regulated biological products.\"\n\"Biological products are products made from living organisms. They consist of\nprevention of diseases in man.\"\nsubstances that can be part of an aid to diagnosis, mitigation, treatment or\n[RSPA Note: The \"directions for use\" do not define biological product but forbid the packaging\nindividual risk of aerosol-transmitted laboratory infections and life threatening disease\" and any\nto contain volumes exceeding 50 ml or 50 g; Biosafety level 4 materials \"which pose a high\nmaterial with a close or identical antigenic relationship to these materials; agents found in 42 CFR\nPart 72 as select agents, Appendix A to Part 172, or in NIH publications Biosafety in\nMicrobiological and Biomediçal Laboratories or \"Actions Under the Guidelines.\"]\n*\nmake this call. They may be encountering difficulty obtaining this information from FDA. Historically,\nGWI recognizes it needs FDA to define biological product, but has approached RSPA asking its staff to\nFDA has been slow to respond to RSPA on definition and packaging issues involving biological products.\nThe response RSPA formally submitted to FDA's Dr. Katherine Nzoom, Director of the Center for\nE. Edmonson 10/5198 11/18/97 EF.\n\n<<<PAGE 5>>>\n\n2\nBiologics and Research several years ago asking for clarification on how the agency defines biological\nproducts and ensures packaging integrity for these materials in transportation was never answered.\n*\nGWI doesn't believe PTT's claims that its packaging meets UN performance standards. GWI is reluctant\nto use f'I's packagings without assurances from DOT that it is acceptable. GWI reported in\nconversations with RSPA staff that it is concerned about any liability it may experience from using the\npackagings, and stated other shippers of Division 6.2 materials are also reluctant to use PTT's packagings\nwithout further assurances from DOT.\nPTT's Issues:\n*\nOn October 30, 1997, PTT sent RSPA several of their packagings stamped \"UN 1HH2U Class 6.2\n96/M4395 USA,\" directions for using the packaging, and the FDA letter approving the packaging as a\nsubmitted a copy of their test results, patent information and diagram to RSPA on August 20, 1997.\nmedical device (which includes a description of the product and the results of the penetration test). PTT\n*\nIn an 11/97 conversation with Ms. Edmonson, Mr. Warder said he once spoke with Dr. Richard Knudsen,\nKnudsen objected to its design. Mr. Warder said Dr. Knudsen informed him that the design of packages\nChiet, Biological Safety, Centers for Disease Control and Prevention, about the PTT packaging and Dr.\nfor diagnostic specimens must meet CDC requirements. Ms. Edmonson told Mr. Warder Dr. Knudsen's\nstatement was correct.\n*\nOn 11/17/97, Mr. Warder stated in a telephone conversation with Ms. Edmonson that the packagings PTT\nsent RSPA on October 30, 1997, were the result of a run of incorrectly marked packagings. He provided a\nml)/S/97/USA/ M4578,\" which meets ICAO marking requirements for a Division 6.2 packaging. The\nfacsimile of the markings currently in use, which describe the packaging as a \"UN 6HH1U/class 6.2 (50\nthe notation for packing group.\nfacsimile included a second marking \"UN 6HH1U/50ml/97/USA/M4578\", which appears to be missing\nFDA Issue:\n*\nMr. Steve Falter, Director, Regulations and Policy Staff, Center for Biologics Evaluation and Research,\n(301)827-6210, FAX (301)443-3874, in a 11/18/97 conversation with Eileen Edmonson stated that an\nHFM-17, Food and Drug Administration, 1401 Rockville Pike, Suite 200N, Rockville, MD 20852-1448,\ndoes not determine whether a material meets the definition of a biological product. He said a biological\nFDA-approved medical device is approved to transport biological products for humans. He said the device\nfor the prevention and treatment of injuries of man; that it must be licensed in interstate commerce; and\nproduct is defined in Section 351 of the Public Health Service Act and, in general, is a material developed\nthat it must be safe, pure and potent for its intended use. He said the statements in the Andwin literature\nare incorrect and requested copies of them to present to FDA's enforcement office. Ms. Edmonson\nsupplied him with these materials by facsimile on 11/18/97.\nRSPA Issues:\n*\nRSPA denied PTT the reissuance of the exemption DOT-E 10148 because it was for biological products\nand diagnostic specimens, products that are not currently regulated under the HMR.\n*\nGWI doesn't believe PTT's claims that its packaging meets UN performance standards. GWI is reluctant\nto use PTT's packagings without assurances from DOT that it is acceptable. We can respond to this issue,\nPTT has supplied us with their test data, directions for use, and an example of the packaging.\nE. Edmonson 10/5/98\n\n<<<PAGE 6>>>\n\n\". 4\n3\n*\nUnited States. However, there are package marking requirements under the International Civil Aviation\nCurrently, there are no package specification marking requirements for Division 6.2 packagings in the\nOrganizations (ICAO) Technical Instructions. In a 4/9/97 conversation with Mr. Bill Warder, President of\nPTT, Ms. Eileen Edmonson informed him there was no UN specification 1HH2 and the manufacturer's\nmarking \"M4395\" represented the Cooper Drum, Co., in South El Monte, CA. Ms. Edmonson informed\nMr. Warder the correct packaging specification reference was either 1H2 (removable head plastic drum) or\n6HH2, that she incorrectly informed him was a removable head composite plastic drum. Mr. Warder stated\nthe correct reference was 6HH1 for a plastic receptacle within a protective plastic drum. Also, Ms.\nEdmonson informed Mr. Warder that the correct manufacturer's marking for PTT was \"M4578.\" The\nsymbol \"U\" represents special packaging under Section 6.4 of ICAO's Technical Instructions. The \"\"\nsymbolizes that the inner receptacles of any type may be assembled within an intermediate (secondary)\npackaging and transported without testing in the outer packaging under certain conditions.\nQuestions:\nDoes DOT have the authority to say the definition of a biological product is determined by the type of\npackaging used? Although, historically, we have excepted hazardous materials from regulation based on\npackaging safety, the answer is no.\n*\nDoes the Pro-Tech-Tube packaging meet the performance criteria in § 178.609 (for infectious substances)?\nIn § 178.522 (for composite packagings with inner plastic receptacles)? Materials and packagings\nsubmitted to RSPA by PTT were forwarded to DHM-20 on 11/18/97 for their review.\n*\nDoes it matter that the packaging meet the criteria in § 178.609 to be an acceptable packaging for\nbiological products since we currently do not regulate biological products? No.\n*\nWhat specifically is the FDA's definition for biological product; is it tied to its use in a medical device?\nOn 11/13/97, Ms. Ann Wion, Deputy Chief Counsel for Program Review (301-827-1143) referred me to\nthis question. Mr. Falter responded on 11/18/97. See FDA Issue.\nMr. Steve Falter, FDA Center for Biologics and Research (301-827-6210, ext. 5) to obtain an answer to\nRecommendations for response to GWI:\nClarify that the biological products definition is solely FDA's to determine.\n*\nProvide our comments on the packaging and its test results.\nE. Edmonson 10/5/98","truncated":false,"body_characters":15009}