Cell Tissue Bank DOI 10.1007/s10561-013-9408-7
BRIEF COMMUNICATION
How can we improve tracking of transplanted tissue in the United States? Reena Mahajan • Matthew J. Kuehnert
Received: 1 May 2013 / Accepted: 13 November 2013 Ó Springer Science+Business Media Dordrecht (outside the USA) 2013
Abstract Currently an estimated two million tissues are distributed for transplantation annually. With increasing use of recovered tissue, clusters of transplant-transmitted infection have shown the difficulty of tracking tissues from an infected donor to the recipient. The challenge of tissue tracking to multiple transplant recipients was illustrated in a recent investigation of transmission of hepatitis C virus infection from a donor of organs and tissues. When a tissue bank issued a recall of the donated tissue, the Centers for Disease Control and Prevention was notified to assist public health authorities; the mean time to locate and notify the physicians who had transplanted the tissue was 13 days, while the mean time to notify, inform, and test the patients was 29 days. Lack of common coding and nomenclature was one of the key challenges in tracking
CDC Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. R. Mahajan M. J. Kuehnert Centers for Disease Control and Prevention, Atlanta, GA, USA e-mail: [email protected] M. J. Kuehnert (&) Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Mailstop A-07, Atlanta, GA 30333, USA e-mail: [email protected]
tissue to the recipient. Some changes that could improve timeliness in the event of a recall includes: (1) standardized tissue nomenclature and coding through unique donor identifiers; (2) tissue traceability requirements using systems similar to that used for blood products; (3) a surveillance system for adverse events that provides feedback at the provider level. Keywords Safety
Tissue Transplantation Tracking
In the United States, the amount of tissue provided for implantation has doubled over the last 20 years, with an estimated two million tissues distributed for transplantation annually (American Association of Tissue Banks 2010). This increase has resulted in the routine use of a variety of tissue grafts, including musculoskeletal, cardiovascular, skin, and cornea, for transplantation throughout the world. However, clusters of transplant-transmitted infections have highlighted the difficulty of tracking tissues from an infected donor to potentially many recipients. Since over 100 tissue grafts may be provided for transplantation from a variety of types of tissue donated by one person, standardized tracking and reporting mechanisms in the healthcare setting are needed in the event a problem is identified. The challenge of tissue tracking was illustrated in a recent investigation of transmission of hepatitis C virus (HCV) infection from an infected donor to multiple
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organ and tissue transplant recipients (CDC 2011). The donor had a negative HCV antibody result using a donor screening test, and a positive nucleic acid test (NAT) suggesting recent infection; however, the NAT results were misread as ‘‘negative’’ due to a laboratory error. After two kidney recipients were diagnosed with post-transplant HCV infection, the donor was suspected as a source. Tissue for transplantation produced from this donor totaled 43 musculoskeletal tissue grafts and one cardiopulmonary patch graft. Of the donated tissues, 28 grafts had not yet been distributed by the tissue bank and were quarantined. The remaining 16 tissue grafts—15 musculoskeletal and one cardiopulmonary patch—had been distributed to 11 facilities in nine states. Based on data collected by the Centers for Disease Control and Prevention (CDC), the mean time to locate and notify each physician who had transplanted a tissue graft was 13 days, while the mean time to notify, inform, and test the patient was 29 days (Table 1). The tissue bank initiated a recall of all distributed tissue grafts 1 day after receiving the report from the organ procurement organization about Table 1 Number of days from CDC notification to physician contact, and number of days from CDC notification to testing of patient receiving potentially HCV-infected transplanted tissue in 9 states, 2011 Site
Number of days from CDC notification to physician contact
Number of days from CDC notification to testing of patient
1
6
9
2
4
12
3
13
15
4
13
40
5
14
28
6
13
34
7
12
15
8
14
27
9
14
27
10
14
27
11 12
14 14
27 27
13
14
27
14
20
59
15
6
34
16
16
34
Centers for Disease Control and Prevention (CDC) (2011)
123
the two kidney recipients who had tested positive after receiving organs from the donor who had tested positive for HCV NAT. A total of 16 tissue grafts were implanted between the time the first tissue graft was distributed and the time of the recall notification. (CDC 2011). According to routine protocol, the cardiopulmonary patch graft had not been irradiated or chemically treated except with an antimicrobial solution due to the need to preserve the vascularity of the tissue. This infected graft was implanted into an infant in Massachusetts, who was tested by HCV NAT after the donor’s HCV NAT positive result was identified. There are a few challenges complicating how tissue grafts can be identified and recalled quickly in the healthcare setting when transplant-associated adverse events are recognized as linked to a common donor. First, the most fundamental gap is the lack of common coding and nomenclature for tissue (World Health Organization 2006; Warwick et al. 2013). Currently, each tissue bank decides how each graft type they distribute is named; tissue graft names can be proprietary, but most often the graft is simply named differently by tissue banks (i.e. an iliac crest wedge can also be named a tricortical wedge). In contrast, a common coding and nomenclature system, known as ISBT 128, exists for most other healthcare products of human origin, such as blood and blood products, and it is being developed for cellular therapy products, human milk banking, ocular tissue, and other tissue types. Secondly, tissue banks are only required to track tissue to the facility level, and may be unaware of whether tissue has been implanted, stored, or discarded. The FDA is responsible for regulating cells, tissues, and cellular and tissue-based products and has direct oversight of tissue banks that screen and/or test donors, and those that recover, process, store and/or distribute tissues; the FDA does not have jurisdiction over entities that use these tissues until an event becomes a concern for public health (CDC 2011). Unless healthcare facilities are mandated to report information regarding tissue use through standards issued by an accrediting organization for healthcare such as the Joint Commission, notification of tissue use to the supplier by end users is voluntary. Notification of tissue use by a healthcare facility is not required by current standards, and reporting of tissue implantation with ‘‘implant cards’’ is voluntary with variable rates of return (AATB 2010; Kuehnert et al.
Cell Tissue Bank
2007). Finally, in most healthcare facilities, tissue is managed in a decentralized process, depending on the type of graft; this is different from the centralized process used in the distribution of blood products or solid organs. Thus, most hospitals have a nonstandardized tracking system to the patient level, resulting in difficulty with locating physicians and delays in notification and testing of patients. This was evident in the recent HCV investigation in which a 2-week time frame was needed to notify physicians, and 1 month was needed to test the patients. A voluntary public health surveillance system to monitor in real-time adverse events associated with blood products, the Hemovigilance Module of the National Healthcare Safety Network, already exists; at this point, a limited number of institutions are currently using this system. However, there is no standardized real-time tracking system that can provide feedback to users of tissue if potential transmissions occurred that involved a common donor (DePaolo and Barbeau 2013). Other than the requirement for tissue banks to report recognized problems to FDA, there is no mandated national surveillance for providers to report adverse events if they suspect a transmission-related event; MedWatch-the FDA Safety Information and Adverse Event Reporting Program—is a reporting system voluntary for clinicians. Although not currently operational, the Transplantation Transmission Sentinel Network, a pilot reporting program developed by the CDC, demonstrated that enhanced infrastructure and standardization will be needed for success of such an effort on a national level (Strong et al. 2010). The issues of tissue tracking and standardized coding systems are not unique to the United States. The European Tissue Directive 2004/23/EC and their technical appendices discuss the problem of tracking and tissue traceability including the demand for a common basic nomenclature and a single coding system (The European Parliament and the Council of the European Union 2004). More recently, the ICCBBA in the United States has released a document for public comment regarding the need for uniform labeling of cellular therapy products (ICCBBA 2013), but challenges remain for implementation. Changes to improve patient safety for tissue recipients will require addressing gaps in the healthcare setting that cannot be easily fixed given the lack of infrastructure for tissue traceability in most
healthcare facilities. Three key changes that could improve timeliness in the event of a recall include: (1) common tissue nomenclature and coding that is specific to the donor; (2) tissue traceability requirements that are similar to ones used for blood products; (3) a surveillance system for adverse events that provides feedback at the provider level. Until these key components are implemented, preventable transplant-transmitted infections likely will continue to threaten patient safety. Acknowledgments The authors thank Susan Hocevar, MD, Division of Healthcare Quality Promotion, and Scott D Holmberg, MD, MPH, Division of Viral Hepatitis, Centers for Disease Control and Prevention for their assistance with this investigation. Conflict of interest No conflicts of interest have been declared for the authors on this manuscript.
References American Association of Tissue Banks (AATB) (2010) Annual survey of accredited tissue banks in the United States. AATB, McLean, VA Centers for Disease Control and Prevention (CDC) (2011) Transmission of hepatitis C virus through transplanted organs and tissues—Kentucky and Massachusetts, 2011. MMWR Morb Mortal Wkly Rep 60:1697–1700 DePaolo JS, Barbeau JM (2013) Enhanced tracking of tissue for transplantation. JAMA 309:443–444 ICCBBA (2013) http://www.iccbba.org. Accessed October 4, 2013 Kuehnert MJ, Yorita KL, Holman RC, Strong DM (2007) For the AABB Tissue task force. Human tissue oversight in hospitals: an AABB survey. Transfusion 47:194–200 Strong DM, Seem D, Taylor G, Parker J, Stewart D, Kuehnert MJ (2010) Development of a transplantation transmission sentinel network to improve safety and traceability of organ and tissues. Cell Tissue Bank 11:335–343 The European Parliament and the Council of the European Union (2004) Official Journal of the European Union. http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri= OJ:L:2004:102:0048:0058:en:PDF. Accessed October 4, 2013 Warwick RM, Chapman J, Pruett TL, Wang H (2013) Globally consistent coding systems for medical products of human origin. Bull World Health Organ. http://www.who.int/ bulletin/volumes/91/5/12-116988/en/index.html#.UYETS4 dhdS8.email. Accessed May 1, 2013 World Health Organization (2006) Second global consultation on regulatory requirements for human cells and tissues for transplantation: towards global harmonization through graduated standards. http://www.who.int/transplantation/ 2dHTTGHreport.pdf. Accessed February 26, 2013
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BRIEF COMMUNICATION
How can we improve tracking of transplanted tissue in the United States? Reena Mahajan • Matthew J. Kuehnert
Received: 1 May 2013 / Accepted: 13 November 2013 Ó Springer Science+Business Media Dordrecht (outside the USA) 2013
Abstract Currently an estimated two million tissues are distributed for transplantation annually. With increasing use of recovered tissue, clusters of transplant-transmitted infection have shown the difficulty of tracking tissues from an infected donor to the recipient. The challenge of tissue tracking to multiple transplant recipients was illustrated in a recent investigation of transmission of hepatitis C virus infection from a donor of organs and tissues. When a tissue bank issued a recall of the donated tissue, the Centers for Disease Control and Prevention was notified to assist public health authorities; the mean time to locate and notify the physicians who had transplanted the tissue was 13 days, while the mean time to notify, inform, and test the patients was 29 days. Lack of common coding and nomenclature was one of the key challenges in tracking
CDC Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. R. Mahajan M. J. Kuehnert Centers for Disease Control and Prevention, Atlanta, GA, USA e-mail: [email protected] M. J. Kuehnert (&) Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Mailstop A-07, Atlanta, GA 30333, USA e-mail: [email protected]
tissue to the recipient. Some changes that could improve timeliness in the event of a recall includes: (1) standardized tissue nomenclature and coding through unique donor identifiers; (2) tissue traceability requirements using systems similar to that used for blood products; (3) a surveillance system for adverse events that provides feedback at the provider level. Keywords Safety
Tissue Transplantation Tracking
In the United States, the amount of tissue provided for implantation has doubled over the last 20 years, with an estimated two million tissues distributed for transplantation annually (American Association of Tissue Banks 2010). This increase has resulted in the routine use of a variety of tissue grafts, including musculoskeletal, cardiovascular, skin, and cornea, for transplantation throughout the world. However, clusters of transplant-transmitted infections have highlighted the difficulty of tracking tissues from an infected donor to potentially many recipients. Since over 100 tissue grafts may be provided for transplantation from a variety of types of tissue donated by one person, standardized tracking and reporting mechanisms in the healthcare setting are needed in the event a problem is identified. The challenge of tissue tracking was illustrated in a recent investigation of transmission of hepatitis C virus (HCV) infection from an infected donor to multiple
123
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organ and tissue transplant recipients (CDC 2011). The donor had a negative HCV antibody result using a donor screening test, and a positive nucleic acid test (NAT) suggesting recent infection; however, the NAT results were misread as ‘‘negative’’ due to a laboratory error. After two kidney recipients were diagnosed with post-transplant HCV infection, the donor was suspected as a source. Tissue for transplantation produced from this donor totaled 43 musculoskeletal tissue grafts and one cardiopulmonary patch graft. Of the donated tissues, 28 grafts had not yet been distributed by the tissue bank and were quarantined. The remaining 16 tissue grafts—15 musculoskeletal and one cardiopulmonary patch—had been distributed to 11 facilities in nine states. Based on data collected by the Centers for Disease Control and Prevention (CDC), the mean time to locate and notify each physician who had transplanted a tissue graft was 13 days, while the mean time to notify, inform, and test the patient was 29 days (Table 1). The tissue bank initiated a recall of all distributed tissue grafts 1 day after receiving the report from the organ procurement organization about Table 1 Number of days from CDC notification to physician contact, and number of days from CDC notification to testing of patient receiving potentially HCV-infected transplanted tissue in 9 states, 2011 Site
Number of days from CDC notification to physician contact
Number of days from CDC notification to testing of patient
1
6
9
2
4
12
3
13
15
4
13
40
5
14
28
6
13
34
7
12
15
8
14
27
9
14
27
10
14
27
11 12
14 14
27 27
13
14
27
14
20
59
15
6
34
16
16
34
Centers for Disease Control and Prevention (CDC) (2011)
123
the two kidney recipients who had tested positive after receiving organs from the donor who had tested positive for HCV NAT. A total of 16 tissue grafts were implanted between the time the first tissue graft was distributed and the time of the recall notification. (CDC 2011). According to routine protocol, the cardiopulmonary patch graft had not been irradiated or chemically treated except with an antimicrobial solution due to the need to preserve the vascularity of the tissue. This infected graft was implanted into an infant in Massachusetts, who was tested by HCV NAT after the donor’s HCV NAT positive result was identified. There are a few challenges complicating how tissue grafts can be identified and recalled quickly in the healthcare setting when transplant-associated adverse events are recognized as linked to a common donor. First, the most fundamental gap is the lack of common coding and nomenclature for tissue (World Health Organization 2006; Warwick et al. 2013). Currently, each tissue bank decides how each graft type they distribute is named; tissue graft names can be proprietary, but most often the graft is simply named differently by tissue banks (i.e. an iliac crest wedge can also be named a tricortical wedge). In contrast, a common coding and nomenclature system, known as ISBT 128, exists for most other healthcare products of human origin, such as blood and blood products, and it is being developed for cellular therapy products, human milk banking, ocular tissue, and other tissue types. Secondly, tissue banks are only required to track tissue to the facility level, and may be unaware of whether tissue has been implanted, stored, or discarded. The FDA is responsible for regulating cells, tissues, and cellular and tissue-based products and has direct oversight of tissue banks that screen and/or test donors, and those that recover, process, store and/or distribute tissues; the FDA does not have jurisdiction over entities that use these tissues until an event becomes a concern for public health (CDC 2011). Unless healthcare facilities are mandated to report information regarding tissue use through standards issued by an accrediting organization for healthcare such as the Joint Commission, notification of tissue use to the supplier by end users is voluntary. Notification of tissue use by a healthcare facility is not required by current standards, and reporting of tissue implantation with ‘‘implant cards’’ is voluntary with variable rates of return (AATB 2010; Kuehnert et al.
Cell Tissue Bank
2007). Finally, in most healthcare facilities, tissue is managed in a decentralized process, depending on the type of graft; this is different from the centralized process used in the distribution of blood products or solid organs. Thus, most hospitals have a nonstandardized tracking system to the patient level, resulting in difficulty with locating physicians and delays in notification and testing of patients. This was evident in the recent HCV investigation in which a 2-week time frame was needed to notify physicians, and 1 month was needed to test the patients. A voluntary public health surveillance system to monitor in real-time adverse events associated with blood products, the Hemovigilance Module of the National Healthcare Safety Network, already exists; at this point, a limited number of institutions are currently using this system. However, there is no standardized real-time tracking system that can provide feedback to users of tissue if potential transmissions occurred that involved a common donor (DePaolo and Barbeau 2013). Other than the requirement for tissue banks to report recognized problems to FDA, there is no mandated national surveillance for providers to report adverse events if they suspect a transmission-related event; MedWatch-the FDA Safety Information and Adverse Event Reporting Program—is a reporting system voluntary for clinicians. Although not currently operational, the Transplantation Transmission Sentinel Network, a pilot reporting program developed by the CDC, demonstrated that enhanced infrastructure and standardization will be needed for success of such an effort on a national level (Strong et al. 2010). The issues of tissue tracking and standardized coding systems are not unique to the United States. The European Tissue Directive 2004/23/EC and their technical appendices discuss the problem of tracking and tissue traceability including the demand for a common basic nomenclature and a single coding system (The European Parliament and the Council of the European Union 2004). More recently, the ICCBBA in the United States has released a document for public comment regarding the need for uniform labeling of cellular therapy products (ICCBBA 2013), but challenges remain for implementation. Changes to improve patient safety for tissue recipients will require addressing gaps in the healthcare setting that cannot be easily fixed given the lack of infrastructure for tissue traceability in most
healthcare facilities. Three key changes that could improve timeliness in the event of a recall include: (1) common tissue nomenclature and coding that is specific to the donor; (2) tissue traceability requirements that are similar to ones used for blood products; (3) a surveillance system for adverse events that provides feedback at the provider level. Until these key components are implemented, preventable transplant-transmitted infections likely will continue to threaten patient safety. Acknowledgments The authors thank Susan Hocevar, MD, Division of Healthcare Quality Promotion, and Scott D Holmberg, MD, MPH, Division of Viral Hepatitis, Centers for Disease Control and Prevention for their assistance with this investigation. Conflict of interest No conflicts of interest have been declared for the authors on this manuscript.
References American Association of Tissue Banks (AATB) (2010) Annual survey of accredited tissue banks in the United States. AATB, McLean, VA Centers for Disease Control and Prevention (CDC) (2011) Transmission of hepatitis C virus through transplanted organs and tissues—Kentucky and Massachusetts, 2011. MMWR Morb Mortal Wkly Rep 60:1697–1700 DePaolo JS, Barbeau JM (2013) Enhanced tracking of tissue for transplantation. JAMA 309:443–444 ICCBBA (2013) http://www.iccbba.org. Accessed October 4, 2013 Kuehnert MJ, Yorita KL, Holman RC, Strong DM (2007) For the AABB Tissue task force. Human tissue oversight in hospitals: an AABB survey. Transfusion 47:194–200 Strong DM, Seem D, Taylor G, Parker J, Stewart D, Kuehnert MJ (2010) Development of a transplantation transmission sentinel network to improve safety and traceability of organ and tissues. Cell Tissue Bank 11:335–343 The European Parliament and the Council of the European Union (2004) Official Journal of the European Union. http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri= OJ:L:2004:102:0048:0058:en:PDF. Accessed October 4, 2013 Warwick RM, Chapman J, Pruett TL, Wang H (2013) Globally consistent coding systems for medical products of human origin. Bull World Health Organ. http://www.who.int/ bulletin/volumes/91/5/12-116988/en/index.html#.UYETS4 dhdS8.email. Accessed May 1, 2013 World Health Organization (2006) Second global consultation on regulatory requirements for human cells and tissues for transplantation: towards global harmonization through graduated standards. http://www.who.int/transplantation/ 2dHTTGHreport.pdf. Accessed February 26, 2013
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