Effects of radio frequency identification-related radiation on in vitro biologics.

The recent developments on the use of e-pedigree to identify the chain of custody of drugs suggests the use of advanced track and trace technologies such as two-dimensional barcodes and radio frequency identification (RFID) tags. RFID technology is used mainly for valuable commodities such as pharmaceutical products while incorporating additional functionalities like monitoring environmental variables to ensure product safety and quality. In its guidance for the use of RFID technologies for drugs (Compliance Policy Guide Section 400.210), the Food and Drug Administration outlined multiple parameters that would apply to any study or application using RFID. However, drugs approved under a Biologics License Application or protein drugs covered by a New Drug Application were excluded mainly due to concerns about the effects of radio frequency radiation (thermal and/or non-thermal) on biologics. Even though the thermal effects of radio frequency on biologics are relatively well understood, there are few studies in the literature about the non-thermal effects of radio frequency with regards to the protein structure integrity. In this paper, we analyze the non-thermal effects of radio frequency radiation by exposing a wide variety of biologics including biopharmaceuticals with vaccines, hormones, and immunoglobulins, as well as cellular blood products such as red blood cells and whole blood-derived platelets as well as fresh frozen plasma. In order to represent the majority of the frequency spectrum used in RFID applications, five different frequencies (13.56 MHz, 433 MHz, 868 MHz, 915 MHz, and 2.4 GHz) are used to account for the most commonly used international frequency bands for RFID. With the help of specialized radio frequency signal-generating hardware, magnetic and electromagnetic fields are created around the exposed products with power levels greater than Federal Communications Commission-regulated limits. The in vitro test results on more than 100 biopharmaceutical products from eight major pharmaceutical companies as well, as different blood products, show no non-thermal effect by radio frequency radiation. LAY ABSTRACT: Forthcoming requirements, such as the California Board of Pharmacy Track and Trace initiative regarding the use of e-pedigree to identify the chain of custody of drugs, suggest the use of advanced track and trace technologies such as two-dimensional barcodes and radio frequency identification (RFID) tags. When used for pharmaceuticals, RFID technology can support additional functionalities like monitoring temperature to ensure product safety. In its guidance for the use of RFID technologies for drugs, the Food and Drug Administration outlined multiple parameters that would apply to pilot studies using RFID while excluding drugs approved under a Biologics License Application or protein drugs covered by a New Drug Application due to concerns about the effects of radio frequency radiation on biologics. Even though the effects of radio frequency on biologics due to temperature changes are relatively well understood, there are few studies in the literature about other effects of radio frequency that can occur without a noticeable change in temperature. In this paper, we expose a wide variety of biologics including biopharmaceuticals to radio frequency radiation at different frequencies, as well as cellular blood products and plasma to high frequency radiation. The in vitro test results show no detectable effect due to radio frequency radiation.

Absence of acute adverse in vitro effects on aged AS-1 red blood cells and thawed plasma after prolonged exposure to 13.56-MHz radio energy.

BACKGROUND: There is growing interest in radio frequency identification (RFID) technology for tracking blood products to improve productivity and safety in the transfusion medicine supply chain. We conducted a limited study to assess the temperature and biologic effects after extreme exposure to 13.56-MHz RF radiation on aged red blood cells (aRBCs) nearing their 42-day life and three types of thawed plasma (TP). STUDY DESIGN AND METHODS: Using a Food and Drug Administration-approved limit test protocol, test units of both aRBCs and three types of TP were subjected to high levels of RF energy for an extended duration to assess worst-case effects compared to minimally exposed control units. Three replications were performed for each product type. RESULTS: Hemolysis after 23 to 25 hours of RF energy exposure was less than 0.3% for all test and control aRBC units and well within the 1% or less acceptance criterion. Both biologic test and temperature increase results were within acceptance criteria and consistent with earlier tests on 6- to 9-day RBCs, with no detectable acceleration in cellular degradation of aRBCs. Nine different plasma coagulation factors were evaluated and, with one explainable exception, all showed less than 20% change in their measured test versus control values, meeting the acceptance criteria. The relative temperature increase between test and control units never exceeded the 1.5°C acceptance criterion for RBCs and 4°C for plasma. CONCLUSION: Use of 13.56-MHz RFID technology is unlikely to have any significant temperature or biologic effects on aRBC and plasma units under normal operating conditions.

Applying radio-frequency identification (RFID) technology in transfusion medicine.

ISO/IEC 18000-3 mode 1 standard 13.56 MHz RFID tags have been accepted by the International Society for Blood Transfusion (ISBT) and the United States Food and Drug Administration (FDA) as data carriers to integrate with and augment ISBT 128 barcode data carried on blood products. The use of 13.56 MHz RFID carrying ISBT 128 data structures allows the global deployment and use of RFID, supporting both international transfer of blood and international disaster relief. The deployment in process at the BloodCenter of Wisconsin and testing at the University of Iowa Health Center is the first FDA-permitted implementation of RFID throughout in all phases of blood banking, donation through transfusion. RFID technology and equipment selection will be discussed along with FDA-required RF safety testing; integration with the blood enterprise computing system and required RFID tag performance. Tag design and survivability is an issue due to blood bag centrifugation and irradiation. Deployment issues will be discussed. Use of RFID results in significant return on investment over the use of barcodes in the blood center operations through labor savings and error reduction.

Absence of acute adverse in-vitro effects on AS-1 RBCs and whole blood-derived platelets following prolonged exposure to 13.56 MHz radio energy.

BACKGROUND: There is growing interest in radio frequency identification (RFID) technology application for tracking blood products to achieve higher productivity and safety in the transfusion medicine supply chain. We have conducted a limited study to assess the temperature and biological effects of 13.56 MHz RF radiation on RBCs and whole blood-derived platelets (WBDP) under extreme exposure conditions. STUDY DESIGN AND METHODS: Using an FDA-approved protocol, test units of both RBC and WBDP were subjected to approximately 100 watts of RF energy for an extended duration (23-25 h) to assess worst-case effects. Three replications of the test were performed. RESULTS: Hemolysis after 23-25 hours of RF energy exposure was 0.09% and 0.05%, respectively, for TEST and CONTROL RBC units and well within the ≤1% limit in the FDA-approved acceptance criteria. For WBDP units, the mean pH of TEST and CONTROL units were 7.27 and 7.19, respectively, following 23-25 hours of RF energy exposure, and well above the ≥6.2 acceptance limit. Further, there was no detectable acceleration in cellular degradation of RBC and WBDP products. While there was minimal temperature rise, the relative temperature increase between TEST and CONTROL units never exceeded the 1.5°C acceptance criterion. CONCLUSIONS: 13.56 MHz-based RFID technology is unlikely to have any significant temperature or biological effects on RBC and WBDP units under the normal operating conditions (a maximum of 4 watts RF power exposure for about 20 nonconsecutive minutes for RFID tracking during the life of the blood product).