Description of Event or Problem · 1
MILD ULCERATION TO GASTRO-OESOPHAGEAL JUNCTION [GASTRIC ULCER]. CONCENTRATION OF THERASPHERES AT THE GASTRO-OESOPHAGEAL JUNCTION (MISADMINISTRATION) [DEVICE DEPLOYMENT ISSUE]. PERCENTAGE 20% OF THE ACTIVITY REMAINED IN THE ADMINISTRATION KIT [DEVICE ISSUE] MINIMAL UPTAKE IN THE LEFT LOBE OF THE LIVER [RADIATION UNDERDOSE]. CASE DESCRIPTION: INITIAL INFORMATION RECEIVED ON 21-APR-2017 AND ADDITIONAL INFORMATION RECEIVED ON 24-APR-2017: THIS SPONTANEOUS MEDICAL DEVICE REPORT WAS RECEIVED FROM A HEALTHCARE PROFESSIONAL VIA COMPANY REPRESENTATIVE CONCERNING A (B)(6) MALE PATIENT WEIGHING 84 KG INCLUDED IN EPOCH CLINICAL TRIAL. THE REPORTER ALSO SUBMITTED THIS CASE REPORT TO MHRA UNDER THE REFERENCE 2017/004/013/401/014. THE PATIENT'S MEDICAL HISTORY AND CONCOMITANT MEDICATIONS WERE NOT PROVIDED. ON (B)(6) 2017, THE PATIENT ATTENDED FOR RADIOEMBOLISATION OF THE LIVER WITH Y-90 THERASPHERES. A TECHNICAL PROBLEM WAS EXPERIENCED WITH THE ADMINISTRATION KIT USED TO DELIVER THE TREATMENT TO THE LEFT LOBE. ADMINISTRATION WAS ABANDONED FOR THE LEFT LOBE; ADMINISTRATION TO THE RIGHT LOBE USING ANOTHER KIT OF THE SAME BATCH PROCEEDED UNEVENTFULLY. ON (B)(6) 2017, THE PATIENT RE-ATTENDED FOR REPEAT RADIOEMBOLISATION WITH Y-90 THERASPHERES (LOT NUMBER 1799097, VIAL 58, CALIBRATION DATE:(B)(6) 2017, EXPIRATION DATE: (B)(6) 2017, 11.0 GBQ) TO THE LEFT LOBE OF THE LIVER FOR AN UNKNOWN INDICATION. THE MICROCATHETER WAS POSITIONED ACCORDING TO PATIENT'S PREVIOUS TC-99M MAA PRE-THERAPY WORKUP SCAN (WHICH WAS PERFORMED ON (B)(6) 2017). DURING ADMINISTRATION, SOME TECHNICAL PROBLEMS WERE AGAIN EXPERIENCED WITH THE ADMINISTRATION KIT, ALTHOUGH THE THERASPHERES WERE SUCCESSFULLY ADMINISTERED TO THE PATIENT. THE TUBING LOT NUMBER WAS X904, WAS MANUFACTURED ON 20-JAN-2016 AND THE EXPIRATION DATE WAS 20-JAN-2018. AGAIN, THE DOSE RATE DID NOT DROP AS QUICKLY AS EXPECTED AND SALINE DIVERTED TO THE PRESSURE RELIEF VIAL TO A GREATER DEGREE THAN EXPECTED, AND APPROXIMATELY 20% OF THE ACTIVITY REMAINED IN THE ADMINISTRATION KIT. THE COUNT RATE AT CONNECTION E WAS MEASURED TO BE 20000 CPS AT 1CM USING A RADHOUND DURING ADMINISTRATION AND THE ACTIVITY IN THE WASTE ADMIN KIT WAS CALCULATED TO BE 150 MBQ AFTER THE PROCEDURE. THE PATIENT ATTENDED FOR POST-THERAPY BREMSSTRAHLUNG IMAGING ON (B)(6) 2017, WHICH WAS REVIEWED ON (B)(6) 2017. THESE IMAGES SHOWED CONCENTRATION OF THERASPHERES IN THE GASTRO-OESOPHAGEAL JUNCTION (GOJ) (85%), WITH MINIMAL UPTAKE IN THE LEFT LOBE OF THE LIVER (15%). THE VOLUME OF GOJ UPTAKE WAS CALCULATED TO BE 100CM^3. 676 MBQ OF THERASPHERE WERE ESTIMATED TO HAVE BEEN ADMINISTERED. THEREFORE, 575 MBQ AND APPROXIMATELY 280 GY OF Y-90 THERASPHERES WAS ESTIMATED IN THE GOJ. ON (B)(6) 2017, THE PATIENT DEVELOPED CHEST-ABDOMINAL DISCOMFORT, ATTENDED THE EMERGENCY ASSESSMENT UNIT AND WAS SEEN BY THE SURGICAL TEAM, WHO CARRIED OUT AN OESOPHAGOGASTRO DUODENOSCOPY (OGD), WHICH DEMONSTRATED MILD ULCERATION AT THE GOJ. THE PATIENT WAS DISCHARGED WITH GAVISCON (SODIUM BICARBONATE AND SODIUM ALGINATE) AND OMEPRAZOLE. A CT SCAN WAS PERFORMED ON (B)(6) 2017 WHICH DID NOT DEMONSTRATE ANY CHANGES TO THE GOJ. A REPEAT BREMSSTRAHLUNG SPECT/CT, ON THE SAME DATE, SHOWED NO SIGNIFICANT CHANGE IN THE DISTRIBUTION OF Y-90 THERASPHERES. THE REPORTER ASSESSED THE EVENT MILD ULCERATION TO GASTRO-OESOPHAGEAL JUNCTION TO BE SERIOUS AND DID NOT PROVIDE ANY SERIOUSNESS ASSESSMENT FOT THE OTHER EVENTS. THE REPORTER ASSESSED THE EVENTS MILD ULCERATION TO GASTRO-OESOPHAGEAL JUNCTION AND CONCENTRATION OF THERASPHERES AT THE GASTRO-OESOPHAGEAL JUNCTION (MISADMINISTRATION) AS RELATED TO THE ADMINISTRATION OF THE THERASPHERE. THE COMPANY ASSESSED THE EVENT MILD ULCERATION TO GASTRO-OESOPHAGEAL JUNCTION AS SERIOUS AND ALL THE OTHER EVENTS AS NON-SERIOUS. THE CASE IS LINKED TO CASE BTG01197 FOR THE FIRST ADMINISTRATION OF THERASPHERES TO THE SAME PATIENT. RISK ASSESSMENT: AN INVESTIGATION OF THE REPORTED EVENT WAS CONDUCTED AND COMPLETED ON 24-APR-2017, THE ROOT CAUSE ANALYSIS CONCLUDED: - NONE OF THE INFORMATION PROVIDED WOULD SUGGEST THAT THERE WAS A DEFECT OF THE THERASPHERE MICROSPHERES, DOSE VIAL, ADMIN SET OR ACCESSORY KIT, OR THE SYSTEM OF THESE PARTS, OR THE INSTRUCTIONS FOR USE OF THE DEVICE. THE LOWER-THAN-NORMAL DELIVERY EFFICIENCY MAY BE DUE TO FLOW RATE OR OBSTRUCTION IN THE FLOW PATH. THE LOW DELIVERY EFFICIENCY IS UNRELATED TO THE FACT THAT MICROSPHERES WENT TO NON-TARGET TISSUE. - WE ARE UNABLE TO CONFIRM OR DISPROVE THE REPORT THAT THE MICROSPHERES WENT TO THE GOJ, ALTHOUGH IMAGES PROVIDED APPEAR TO SHOW THE DEPOSITION IN THE NON-TARGET TISSUE, HOWEVER BECAUSE THIS IS A 2-D IMAGE WE ARE NOT ABLE TO DISTINGUISH WHETHER THE ACTIVITY IS IN THE LEFT LOBE, OR THE GOJ, BECAUSE THOSE LOCATIONS ARE OVERLAID IN THIS IMAGE. WE ARE UNABLE TO CONFIRM OR DISPROVE THE MECHANISM OF HOW THE MICROSPHERES WENT TO THE GOJ, ALTHOUGH THE MOST LIKELY CAUSES INCLUDE USE ERROR IN CATHETER PLACEMENT OR FAILURE TO ADEQUATELY MAP THE VASCULATURE PRIOR TO TREATMENT. IT SHOULD BE NOTED THAT THERE WAS DIFFICULTY DELIVERING THE MICROSPHERES TO THE LEFT LOBE OF THE LIVER ON 2 SEPARATE OCCASIONS USING 2 DIFFERENT DELIVERY SETS WHICH SUGGESTS THAT PATIENT FACTORS MAY BE A CONTRIBUTING FACTOR FOR THIS EVENT. RISKS OF INCOMPLETE TREATMENT AND RADIATION EXPOSURE TO NON-TARGET TISSUES ARE KNOWN RISKS FOR THE PRODUCT AND ARE DOCUMENTED IN OUR RISK MANAGEMENT REPORT OTT-OT-08.002. FURTHERMORE THE REPORT REFERS: - SECTION 14.6 OVERALL RESIDUAL RISK ASSESSMENT: ALL INDIVIDUAL RISKS THAT HAVE BEEN CATEGORIZED AS ALAP (AS LOW AS POSSIBLE) BY THE RISK ACCEPTABILITY CRITERIA PROVIDED IN THE THERASPHERE RISK MANAGEMENT PLAN HAVE BEEN DEEMED TO HAVE BENEFITS THAT OUTWEIGH THE RISKS. THE OVERALL ASSESSMENT WHICH ASSESSES THE OVERALL RESIDUAL RISK OF ALL RISK ITEMS INCLUDING ACCEPTABLE AND ALAP CATEGORIES COMES TO THE SAME CONCLUSION. A REVIEW OF EVENTS OF NON-TARGET RADIATION - REVIEW PERIOD: 21 APR 2015 - 31 MAR 2017 CONFIRMED THE REPORTING RATE REMAINS LOW AT 0.049% (10/20500) AND IS WELL WITHIN THE ACCEPTABLE REPORTING RATE OF <1% FOR THIS EVENT WITH CRITICAL OUTCOME, PER THE RMR (RISK MANAGEMENT REPORT). THE REPORTED EVENT DOES NOT REQUIRE A CHANGE TO THE PROBABILITY OR SEVERITY OF HARM. NUMBER OF DEVICES YOU SUPPLIED IN THE UK, EU AND WORLD-WIDE (SELECT AND SPECIFY THE MOST SUITABLE TIME PERIOD FOR THESE DATA, E.G. WITHIN LAST 12 MONTHS, OR SINCE FIRST SOLD): DOSES SUPPLIED (FOC AND COMMERCIAL - NOT INCLUDING CLINICAL) 2014 2015 2016, WORLD WIDE (INC EU) 6564 8574 10678, EU (INC GB) 1311 1911 2385, GB 50 94 152. DATE WHEN DEVICE WAS FIRST SUPPLIED IN THE UK: JULY 11, 2013. NO FOLLOW-UP INFORMATION IS EXPECTED. THE CASE IS FINAL. CASE COMMENT: GASTRIC ULCER WAS CONSIDERED ANTICIPATED ACCORDING TO THERASPHERE CURRENT REFERENCE SAFETY INFORMATION WHEREAS DEVICE DEPLOYMENT ISSUE, DEVICE ISSUE AND RADIATION UNDERDOSE WERE UNANTICIPATED. IN LINE WITH THE ASSESSMENT MADE BY THE REPORTER, THE COMPANY CONSIDERED THAT GASTRIC ULCER AND DEVICE DEPLOYMENT ISSUE WERE RELATED TO THE USE OF THERASPHERE. DEVICE ISSUE AND RADIATION UNDERDOSE ARE NOT AN ADVERSE EVENT PER SE BUT SPECIAL SCENARIOS AND THEREFORE NOT ASSESSABLE. THIS SINGLE CASE REPORT DOES NOT MODIFY THE RISK BENEFIT BALANCE OF THERASPHERE. THE COMPANY IS CONTINUOUSLY MONITORING ALL RESPECTIVE REPORTS RECEIVED AND, BASED ON CUMULATIVE EXPERIENCE, WILL RE-EVALUATE THE AVAILABLE EVIDENCE ON AN ONGOING BASIS.