Material substance originating from a biological entity intended to be transplanted or infused into another (possibly the same) biological entity.

Comment

Promoting Biologically Derived Product Data Class to USCDI v4

For the past 3 years, the Center for Biologics Evaluation and Research (CBER) Biologics Effectiveness and SafeTy (BEST) Innovative Methods Initiative has been working on developing a FHIR-based solution to enhance the reporting and validation of adverse events associated with the use of biologics, often known as medical products of human origin (MPHO), in the US. The BEST team developed and balloted a FHIR IG (https://build.fhir.org/ig/HL7/fhir-icsr-ae-reporting/branches/main/index.html) to detail the process where adverse event (AE) individual case safety reports (ICSR) are generated from EHR data. The FHIR IG provides examples for vaccine AEs, using VAERS (Vaccine Adverse Event Reporting System), and Transfusion-related AEs (TRAEs), using FAERS (FDA  Adverse Event reporting system) reports. For a TRAE report, accurate documentation of exposure (product type and time of encounter) is extremely critical to establish causality of events. The BEST FHIR IG uses the Biologically Derived Product (BDP) (https://www.hl7.org/fhir/biologicallyderivedproduct.html) FHIR resource (to provide product identifying ISBT-128 codes) to ascertain the accurate exposure for a TRAE. Working with our foundational data partner over the past 3 years, the BEST team has been able to obtain and use ISBT-128 codes captured in their EHR.   CBER has submitted the BDP FHIR resource to the USCDI ONDEC, and it is currently at Level 2. The BDP data element submission has gained support from many stakeholders, including eHealth Exchange, Association for the Advancement of Blood & Biotherapies (AABB), American Society for Clinical Pathology (ASCP), America’s Blood Centers (ABC), International Council for Commonality in Blood Bank Automation (ICCBBA), and Terumo blood and cell technologies, as evidenced by their comments (https://www.healthit.gov/isa/uscdi-data-class/biologically-derived-product). To further the BDP data element to USCDI v4, CBER and the BEST team explored the availability of ISBT-128 data (typically resident in the hospital blood bank information system) with some collaborators. We approached 3 collaborating healthcare systems, 2 EPIC users and one CERNER user, and we were able to confirm the availability of ISBT-128 codes in their EHR systems. The evidence we collected (via emails, meetings, and redacted screenshots) confirms that the 2 EPIC users (each with a different blood bank Laboratory Information System (BB LIS)) receive and display ISBT-128 codes to their clinicians and patients. The CERNER user as well, using a third BB LIS, can capture and display the ISBT-128 codes in the EHR system.  Based on the discussions with our collaborators, the core data needed (ISBT-128) to generate an accurate TRAE report, among many important use cases, is available in the EHR. Therefore, it would be feasible to implement BDP in USCDI v4. Also, including BDP in v4 will allow CBER to continue improving capability to report adverse events associated with biologics, and as mentioned earlier, will create the on-ramp for establishing a nationwide system that enables traceability of transplanted cells, tissues, and organs to ensure the safety of the recipients.  

Additional Interoperable Blood Bank Information System

FDA CBER can confirm that we received additional evidence of a fourth instance of interoperable EPIC/Blood Bank Information Systems that exchange Biologically Derived Product information, specifically ISBT-128 codes, between the Blood Bank Laboratory Information System and the transfused patient’s EPIC medical record (EPIC).

Level 2 Data Class: Biologically Derived Product

Level 2 Data Class: Biologically Derived Product Level 2 Data Element: Product Code Level 2 Data Element: Unique Identifier Level 2 Data Element: Source Identifier Level 2 Data Element: Division Level 2 Data Element: Processing Facility While IMO agrees that exchange of information regarding biological entities for transplants or blood products has importance, neither the technical specifications cited in the submission, nor the referenced terminologies are widely in use in ONC Certified HIT or implemented in clinical care.   The FHIR Resource to support the submission as a Level 2 Data Class, Biologically Derived Product BiologicallyDerivedProduct (R5 Draft Ballot) is not in use in production environments. The use of ISBT 128 Product Codes for Medical Products of Human Origin required by the resource could be a significant roadblock to implementation as this code system is not widely used in ONC Certified HIT to support clinical care.   IMO does not recommend that the proposal for Biologically Derived Product data class or data elements for inclusion in USCDI V3. While the use and exchange of ISBT 128 Product Codes for Medical Products of Human Origin between HIT has value in automation of NHSN reporting, this terminology is not required in regulation for ONC Certified HIT.  IMO supports the inclusion of ISBT 128 in future regulation for interoperability, and eventual inclusion in the USCDI.  

Response to IMO

We thank IMO for providing their thoughts on the Biologically Derived Product data class submission. While we agree that the FHIR Resource Biologically Derived Product in R5 Draft Ballot is not widely used (because R5 is not yet in Normative status), the R4 version of the resource has been agreed to be raised to FMM Level 2, indicating implementation across a number of implementers that are capturing and exchanging this data in FHIR. The BDP resource will then be on its way to FMM Level 3, following a formal round of balloting with comments from implementers. It is also important to note that the underlying data elements that are being proposed under the Biologically Derived Product data class have been mapped to ICCBBA ISBT data elements which are widely used in capturing and exchanging data around biologically derived products in the US and internationally. As noted in our submission, ISBT labeling is required for all blood and blood components, as well as various tissues and transplant products in the United States, in order to be accredited by accrediting organizations in the United States and many other countries. These accrediting organizations require their members to use ISBT 128 coding and labeling for cellular therapies and ocular tissue (AABB [https://www.aabb.org/news-resources/resources/cellular-therapies/isbt-128-for-cellular-therapy], the Foundation for the Accreditation of Cellular Therapy (FACT) [https://news.factwebsite.org/isbt-128-audit-tool-for-cellular-therapy-provides-additional-resource-for-verifying-labels/] and the Eye Bank Association of America (EBAA) [http://restoresight.org/wp-content/uploads/2016/01/ISBT-Webpage-Implementation-Guide-Use-of-ISBT-128-in-North-American-Eye-Banks-v130.pdf]). This results in these data elements being captured physically on all blood bags and blood components, as well as other biologically derived products. As such, ISBT-related data elements are captured in blood banking, laboratory information systems (LIS), and pathology software used across providers in the United States, and are being exchanged in HL7 formats today [reference: https://www.iccbba.org/uploads/8b/eb/8beb16a5f9e2c0c420a3e5f099f49b03/RT042-ISBT-128-Data-References-for-use-in-Electronic-Messages.pdf], as well as for reporting to NHSN and to FDA for hemovigilance and product safety purposes. We believe that inclusion of this data class in the next version of USCDI will encourage providers to capture these data elements in FHIR format, rather than in older HL7 formats, in an effort to move towards a modern FHIR API-based exchange of these very important data elements for patient access, as well as for coordination of care.

Support for Biologically Derived Product

Inclusion of the Biologically Derived Product element in USCDI, including the use of ISBT-128 standard codes, is vital for public health, regulatory, and research activities related to biological product effectiveness and safety, including hemovigilance surveillance supported by CDC’s National Healthcare Safety Network (NHSN). Current tracking of adverse events related to biologically derived products (e.g., blood transfusion-associated adverse events) is hindered by lack of accurate identifiers for transfusions amenable to fully electronic extraction from the electronic health record. The capability of identifying biologically derived products using this identifier would facilitate automated reporting for transfusions/transplants, reduce burden of reporting on providers, and significantly improve accuracy of hemovigilance and other patient safety activities. Ongoing surveillance for blood safety in the United States is conducted through the CDC’s National Healthcare Safety Network (NHSN) Hemovigilance (HV) module, which is part of the Biovigilance component of NHSN. The NHSN HV module captures several types of transfusion-associated adverse events as well as monthly totals of blood use, by component type, at participating facilities. This surveillance is used to track the incidence and prevalence of transfusion-associated adverse events with the goal of informing strategies to reduce such events and improve overall patient safety.  In addition, CDC performs investigations and other studies as needed that do not currently make use of automated capture of electronic health records but are potential candidates for such automation in the future. Lantana supports NHSN in hemovigilance surveillance and strongly recommends inclusion of a Biologically Derived Product in USCDI, including the use of ISBT-128 standard codes. A Biologically Derived Product data element would enable capture of individual blood components as well as adverse events for hemovigilance. Current tracking of adverse events in the NHSN HV module requires manual input of adverse events (including ISBT-128 codes for all implicated products), which can be burdensome and may not always yield complete information. Inclusion of a Biologically Derived Product element is vital for hemovigilance surveillance for multiple reasons, including reducing burden on providers by facilitating more automated reporting, improving overall participation in hemovigilance activities, and strengthening robustness and accuracy of reporting. Inclusion of the Biologically Derived Product data element now is important for future consideration regarding how the standard will need to be expanded to meet the needs of hemovigilance and overall surveillance of biologically derived products in the future. It is vital that the USCDI engages with stakeholders in hemovigilance and other areas of surveillance of biologically derived products to ensure the standards are harmonized with the community-consensus definitions of adverse events, and to facilitate automated capture of essential safety information. The Biologically Derived Product data element is relevant to all U.S. healthcare settings where blood transfusions, transplants, and other biological products are administered. Use Case: https://www.cdc.gov/nhsn/biovigilance/blood-safety/index.html In addition to the NHSN HV module, Lantana is leading work that relies on accurate information from electronic health records regarding identity of biologically derived products, https://www.lantanagroup.com/resources/blood-bank-ig/. This initiative is seeking to establish FHIR standards for blood product phenotyping. A biologically derived product element in USCDI is vital to support interoperability of data exchange to improve blood product inventory, facilitate safer transfusions, and contribute to more efficient adverse event reporting. Additionally, Lantana is engaged on work led by IBM and FDA on adverse event reporting related to transfusions, which could benefit from inclusion of the Biologically Derived Product data element in USCDI: https://build.fhir.org/ig/HL7/fhir-icsr-ae-reporting/branches/main/index.html.

Terumo Supports a Biologically Derived Product Unique Identifier

Terumo Blood and Cell Technologies is a medical technology company. Our products, software and services enable customers to collect and prepare blood and cells to help treat challenging diseases and conditions. Our associates around the world believe in the potential of blood and cells to do even more for patients than they do today.  Terumo Blood and Cell Technologies supports the addition of a Biologically Derived Product data element to the United States Core Data for Interoperability (USCDI). Addition of the Medical Product of Human Origin (MPHO) Unique Identifier to USCDI will enhance the industries’ ability to track blood utilization and will enable more efficient hemovigilance activities such as disease transmission tracing, transfusion reaction investigations and preventing the transfusion of an incompatible unit of blood. Including the existing ISBT-128 label information into the MPHO Unique Identifier will provide seamless traceability of a transfusion from the donor to the patient. This simple act can help improve the health outcomes for all transfused patients and especially sickle cell and other chronically transfused individuals.

ABC Supports a Biologically Derived Product Unique Identifier

America’s Blood Centers (ABC) represents 46 independent blood centers throughout the United States and a portion of Canada, who collect and distribute 60% of the U.S. blood supply.  ABC member centers support efforts to improve transfusion safety, including measures to increase traceability for blood, blood products and cellular therapies. Blood centers already label blood products with a plethora of identifying information about the contents of the product, the method of collection and production, and a unique product code to allow for tracing a product from the donor to the recipient.  However, no standard mechanism currently exists for entering transfusion/infusion related information into a patient’s electronic health record (EHR). ABC supports the addition of a Medical Product of Human Origin (MPHO) Unique Identifier that utilizes the existing information and codes already generated by blood centers as a part of the blood label.  Adding an MPHO to the U.S. Core Data for Interoperability (USCDI) data set will allow for easier data collection and tracing, without creating any additional work for blood collectors. Capturing existing ISBT-128 data elements (donation number, product code, and division number), into the MPHO Unique Identifier will provide critical traceability to the donor and collection/processing facility, providing a more efficient and accurate process for disease transmission look-back activities and transfusion reaction investigations. Interoperability will provide patients and health care providers access to previous transfusion records, which is critical in managing individuals with unexpected antibodies (e.g. sickle cell disease patients) or a history of adverse transfusion events. ABC supports the creation of a new standardized data element utilizing existing ISBT-128 blood labeling information to increase transfusion safety, improve patient outcomes and enhance data collection valuable to monitoring blood utilization. 

FDA CBER Biologically Derived Product Submission Clarifications

FDA’s Center for Biologics Evaluation and Research appreciates the comments shared by numerous stakeholders related to the Biologically Derived Product submission. As of April 2021, there are three aspects worth noting:
  1. Resubmission: A revised version of the Biologically Derived Product submission was resubmitted in January 2021 following an update to the ONDEC guidance. This version has not yet been updated on the ONC USCDI website as of April 2021. See attachment for details.
  2. Product Information Elements: Based on other stakeholder comments, the submission could be further modified to incorporate division number and derived or concatenated identifiers (i.e., Medical Products of Human Origin).
  3. Policy: Based on other stakeholder comments, the submission could be further modified to clarify that inclusion of Biologically Derived Product in USCDI would not require the use of a particular identification standard if it is not currently being exchanged by an organization. The current submission references code systems/identifiers (i.e., ISBT-128, RxNorm, and NDC) that are widely used and support a majority of use cases.
As demonstrated above, the ONDEC process has enabled a valuable platform for stakeholders to discuss specifics related to the Biologically Derived Product domain. Continued discussion will be critical to ensure this submission is sufficiently robust to meet criteria for inclusion in USCDI.

FDA CBER ONDEC BioDerProd Resubmission 2021-01.docx

Support for “Biologically Derived Product” Data Element

AABB is an international, not-for-profit association representing institutions and individuals involved in transfusion medicine and cellular therapies. The association is committed to “improving lives by making transfusion medicine and biotherapies safe, available and effective worldwide.” AABB works toward this vision by developing and delivering standards, accreditation, and educational programs that focus on optimizing patient and donor care and safety. AABB individual membership includes physicians, nurses, scientists, researchers, administrators, medical technologists, and other health care providers. AABB supports the addition of a Biologically Derived Product data element to the United States Core Data for Interoperability (USCDI) and believes that using the ISBT-128 standard will enhance the nation’s understanding of blood availability and utilization, advance hemovigilance capabilities and improve health outcomes.   A Biologically Derived Product data element would enable providers to uniformly capture the utilization of individual blood components as well as adverse events for hemovigilance. As noted in the FDA’s use case description, the absence of interoperability in this area was particularly problematic during the rollout of COVID-19 convalescent plasma (CCP) and limited the ability of regulators and researchers to perform safety and effectiveness surveillance. The data could be used to assess whether the current supply of specific blood components is adequate to satisfy patient needs and to monitor safety and effectiveness. Additionally, a Biologically Derived Product data element has the potential to inform policies and guide clinical practices early in the course of treatment (e.g., capturing blood group genotyping in chronically transfused patients or patients initiating novel monoclonal therapies known to cause complication in transfusion workups). It would also serve as a tool to help identify non-infectious complications, such as transfusion-associated circulatory overload (TACO), the transfusion-related acute lung injury (TRALI), and transfusion of an incompatible unit of blood. Importantly, interoperability in this area would facilitate the ability of providers to have access to a patient’s transfusion history, regardless of where a previous transfusion occurred. This can help prevent incompatible transfusions, support red blood cell antigen matching, and ultimately improve health outcomes for chronically transfused individuals, such as patients with sickle cell disease. AABB believes that adding a Biologically Derived Product data element to the USCDI is key to strengthening the nation’s blood system, advancing patient safety, and improving health outcomes.

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