GELFOAM
Report
- Report Number
- 1810189-2023-00014
- Event Type
- Death
- Date Received
- April 25, 2023
- Report Date
- April 12, 2023
- Manufacturer
- PFIZER, INC.
- Product Code
- LMF
- PMA / PMN Number
- 18-286
- Adverse Event
- Yes
- Product Problem
- Yes
- Report Source
- Manufacturer report
- Reporter Location
- KS
- Reporter Occupation
- OTHER
- Health Professional
- N
Narratives
QA REVIEW & RATIONALE: THE HAZARD ANALYSIS WITHIN THE RISK MANAGEMENT FILE HAS BEEN REVIEWED USING THE COMPLIANT NARRATIVE AND ASSOCIATED DOCUMENTATION FOR HAZARDS/HAZARDOUS SITUATIONS, AND THEIR ASSOCIATED SEVERITIES. THE REVIEW DETERMINED THAT THE HAZARD/HAZARDOUS SITUATION WAS INTRAVASCULAR APPLICATION (EMBOLIZATION PROCEDURE) (INX100314477V7.0) AND THE WORST-CASE SEVERITY WAS S4. UPON FURTHER REVIEW BY THE DCHU, THE SEVERITY OF THE REPORTED COMPLAINT WAS DETERMINED TO BE S5. REGULATORY REPORTABILITY IS ASSESSED BY THE DCHU. NO ADDITIONAL INFORMATION HAS BEEN PROVIDED REQUIRING ESCALATION. THE DETAILS OF THE REPORTED COMPLAINT HAVE BEEN FORWARDED TO THE MEDICAL DEVICE COMBINATION PRODUCT (MDCP) TEAM FOR EVALUATION. THE COMPLAINT, ITS PRIORITY, AND ITS CLASSIFICATION HAVE BEEN REVIEWED AND DETERMINED TO BE APPROPRIATE. THE COMPLAINT AND ITS CLASSIFICATION HAVE BEEN REVIEWED AND IT WAS DETERMINED THAT OUR CONTAINMENT ACTION IS A NOTIFICATION TO MANAGEMENT. A FULL INVESTIGATION WILL BE PERFORMED. THIS IS A COMPLAINT FOR 'PERFORMANCE NOT AS INDICATED IN LABEL' FOR AN UNKNOWN BATCH OF GELFOAM. THE INVESTIGATION WILL INCLUDE A REVIEW OF COMPLAINTS WITH KNOWN BATCH NUMBERS DETERMINED TO BE WITHIN SCOPE. SUMMARY OF INVESTIGATION: A PERFORMANCE NOT AS INDICATED IN LABEL COMPLAINT WAS RECEIVED FOR AN UNKNOWN LOT OF GELFOAM. REVIEW OF COMPLAINTS FOR GELFOAM SPONGE AND POWDER RECEIVED WITHIN 36 MONTHS (THE EXPIRY INTERVAL OF THE PRODUCT) PRIOR TO RECEIPT OF THE REPORTED COMPLAINT. NO PREVIOUS COMPLAINTS WITH A KNOWN BATCH NUMBER WERE IDENTIFIED. EXISTING PROCESS CONTROLS, SUCH AS USE OF A SPECIFIC VALIDATED FORMULATION RECIPE AND AUTOMATIC RECORDING OF ALL WEIGHTS AND IDENTITIES OF RAW MATERIALS, DOCUMENTATION AND VERIFICATION OF CRITICAL FORMULATION, PROCESSING, AND STERILIZATION STEPS, AND FINAL RELEASE TESTING OF EACH BATCH TO ASSURE THAT IT MEETS ALL INTERNAL TARGETS AND REGISTERED SPECIFICATIONS PRIOR TO RELEASE FOR DISTRIBUTION WERE REVIEWED AS A PART OF THIS INVESTIGATION. NO TRENDS WERE NOTED THAT WOULD REQUIRE ADDITIONAL INVESTIGATION. NO RETURNED COMPLAINT SAMPLE WAS RECEIVED. ROOT CAUSE ANALYSIS/IDENTIF: PFIZER KALAMAZOO QUALITY OPERATIONS COULD NOT DETERMINE A ROOT CAUSE FOR THE REPORTED DEFECT TO BE RELATED TO THE KALAMAZOO PRODUCTION PROCESS. A REVIEW OF PREVIOUSLY COMPLETED INVESTIGATION REPORTS DETERMINED TO BE WITHIN SCOPE DID NOT RESULT IN IDENTIFICATION OF A BATCH NUMBER, OR A ROOT CAUSE FOR THE REPORTED COMPLAINT. EXAMINATION OF A RETURNED COMPLAINT SAMPLE MAY HAVE AIDED IN IDENTIFICATION OF A ROOT CAUSE; HOWEVER, NONE WERE RECEIVED. IT IS UNKNOWN HOW THE REPORTED COMPLAINT SAMPLE WAS HANDLED, STORED, OR USED AFTER LEAVING THE PFIZER KALAMAZOO SITE. IMPACT ANALYSIS: THE WORST-CASE SEVERITY DETERMINED THROUGH A REVIEW OF THE DEVICE RISK FILE FOR THE PRODUCT WAS S5. REGULATORY REPORTABILITY IS ASSESSED BY THE DCHU. ADDITIONALLY, THE DETAILS OF THE COMPLAINT HAVE BEEN FORWARDED TO THE MDCP TEAM FOR REVIEW. THE REGISTERED USE OF THIS PRODUCT IS FOR TREATMENT AND THE NATURE OF THIS COMPLAINT INDICATES THAT IT IS DIRECTLY RELATED TO THE DEVICE. HOWEVER, THERE IS NO INDICATION THAT THE DEVICES FAILED TO MEET REGISTERED SPECIFICATIONS. BASED UPON THE RESULTS OF THIS INVESTIGATION, THE FINAL DETERMINED SCOPE AND THE INABILITY TO DETERMINE A ROOT CAUSE FOR THE REPORTED COMPLAINT, PGS-QO KALAMAZOO CONCLUDES THAT THE QUALITY OF THE PRODUCT ON THE MARKET REMAINS ACCEPTABLE. THERE IS NO IMPACT TO THE QUALITY OF THE LOT. SPECIAL OR COMMON CAUSE: COMMON CAUSE ROOT CAUSE IS ALWAYS PRESENT TO SOME DEGREE IN THE PROCESS. SPECIAL CAUSE ROOT CAUSE IS SOMETHING DIFFERENT HAPPENING AT A CERTAIN TIME OR PLACE IN THE PROCESS. IMPROVE /CONTROL CORRECTIVE / PREVENTIVE ACTION: INVESTIGATION OF THE COMPLAINT DID NOT DETERMINE THE REPORTED ISSUE TO BE PROCESS RELATED; THEREFORE, A CORRECTION, OR CORRECTIVE OR PREVENTATIVE ACTION, IS NOT REQUIRED FOR THIS CASE. THE DETAILS OF THE REPORTED COMPLAINT HAVE BEEN FORWARDED TO THE KALAMAZOO MDCP TEAM FOR REVIEW. A REVIEW OF PREVIOUSLY COMPLETED INVESTIGATION REPORTS DETERMINED TO BE WITHIN SCOPE DID NOT RESULT IN IDENTIFICATION OF CORRECTIONS, OR CORRECTIVE OR PREVENTATIVE ACTIONS FOR THE REPORTED COMPLAINT. ALL REVIEWED RECORDS, TRENDS, AND IN-PROCESS CONTROLS WERE ACCEPTABLE, AND HAVE MET THE ESTABLISHED REQUIREMENTS. CONCLUSION: THE COMPLAINT FOR 'THE COMPLAINT FOR 'PERFORMANCE NOT AS INDICATED IN LABEL' FOR AN UNKNOWN BATCH OF GELFOAM SPONGE WAS INVESTIGATED. THE INVESTIGATION INCLUDED REVIEWING APRRS FOR THE PRODUCT AND A MEDICAL DEVICE TREND REVIEW. THE FINAL SCOPE WAS DETERMINED TO BE ALL BATCHES OF GELFOAM MANUFACTURED BY PFIZER KALAMAZOO WITHIN THE 36 MONTHS (THE EXPIRY INTERVAL OF THE PRODUCT) PRIOR TO THE RECEIPT DATE OF THE COMPLAINT. A COMPLAINT SAMPLE WAS NOT RETURNED. NO RELATED QUALITY ISSUES WERE IDENTIFIED DURING THE INVESTIGATION. NO ROOT CAUSE OR CAPA WERE IDENTIFIED AS THE COMPLAINT WAS NOT CONFIRMED. NO RELATED QUALITY DEFECTS WERE IDENTIFIED THROUGH INVESTIGATION. THERE IS NO IMPACT ON MEDICAL DEVICE QUALITY, REGULATORY, VALIDATION, OR STABILITY.' FOR AN UNKNOWN BATCH OF GELFOAM SPONGE WAS INVESTIGATED. THE FINAL SCOPE WAS DETERMINED TO BE ALL BATCHES OF GELFOAM MANUFACTURED BY PFIZER KALAMAZOO WITHIN THE 36 MONTHS (THE EXPIRY INTERVAL OF THE PRODUCT) PRIOR TO THE RECEIPT DATE OF THE COMPLAINT. A COMPLAINT SAMPLE WAS NOT RETURNED. NO RELATED QUALITY ISSUES WERE IDENTIFIED DURING THE INVESTIGATION. NO ROOT CAUSE OR CAPA WERE IDENTIFIED AS THE COMPLAINT WAS NOT CONFIRMED. NO RELATED QUALITY DEFECTS WERE IDENTIFIED THROUGH INVESTIGATION. THERE IS NO IMPACT ON MEDICAL DEVICE QUALITY, REGULATORY, VALIDATION, OR STABILITY. DOCUMENT REVIEW SUMMARY: DEVIATIONS: A REVIEW OF DEVIATIONS, LABORATORY INVESTIGATION REPORTS (LIR), AND CHANGE MANAGEMENT RECORDS COULD NOT BE PERFORMED FOR THE REPORTED COMPLAINT, AS THE BATCH IS UNKNOWN. MANUFACTURING/PACKAGING RECORDS: COMPLETE - ACCEPTABLE A REVIEW OF MANUFACTURING AND PACKAGING RECORDS COULD NOT BE PERFORMED FOR THE COMPLAINT, AS THE COMPLAINT IS FOR AN UNKNOWN BATCH. ADDITIONALLY, A REVIEW OF BATCH RECORDS FROM THE PREVIOUSLY INVESTIGATED COMPLAINTS DETERMINED TO BE IN SCOPE COULD NOT BE PERFORMED, AS THERE WERE NO COMPLAINTS WITH A KNOWN BATCH. GELFOAM POWDER IS MANUFACTURED FROM SOLID SPONGE BRICKS. THE BULK MANUFACTURED SOLUTION IS FORCED THROUGH A FILTER WITH NITROGEN TO EXTRUDE THE LARGE, SOLID SPONGE BRICKS. THE BRICKS ARE DRIED, TRIMMED AND SPLIT. THE SPLIT BRICKS ARE THEN MILLED TO FORM POWDER. THE POWDER IS COLLECTED IN HIGH DENSITY POLYETHYLENE BAGS AND THEN SEALED INTO BULK CONTAINERS. THE GELFOAM POWDER IS THEN FILLED INTO INNER ENVELOPES USING A POWDER FILLING DEVICE. EACH ENVELOPE IS FILLED WITH A TARGET OF 1.2 GRAMS PER ENVELOPE AND A MINIMUM OF 1.0 GRAM PER ENVELOPE. TWO WEIGHT CHECKS OF EACH POWDER FILLING DEVICE ARE CONDUCTED AT 30-MINUTE INTERVALS TO ASSURE THAT THE DEVICE IS DISPENSING THE PROPER AMOUNT OF POWDER. THE FINAL PRODUCT YIELD IS CALCULATED AGAINST LIMITS FOR THE PRODUCT. THE INNER ENVELOPES ARE FOLDED OVER TWICE AND INSERTED INTO SLEEVES. THE FILLED SLEEVES ARE PLACED INTO TRAYS. THE SLEEVES (PEEL POUCHES) ARE SEALED, AND HEAT STERILIZED. SEALED AND STERILIZED GELFOAM PEEL POUCHES ARE 100% VISUALLY INSPECTED BY TRAINED PACKAGING OPERATORS PRIOR TO FINAL PACKAGING. THE PURPOSE OF THIS INSPECTION IS TO ENSURE THAT THE ENVELOPES HAVE THE PROPER APPEARANCE, SEAL AND PRINT, AND ALL NOTED DEFECTIVE PRODUCT IS REMOVED FROM THE LOT PRIOR TO FINAL PACKAGING AND NO OPEN SIDE SEALS WERE OBSERVED. THE STERILIZED PEEL POUCHES ARE PACKAGED INTO EACH FINAL GOODS CARTON. FOR GELFOAM SPONGE, THE BILL OF MATERIALS LISTS THE SPECIFIC PRODUCT COMPONENTS AND WEIGHTS REQUIRED FOR THE FORMULATION OF EACH BATCH. ALL MANUFACTURING MIXING SPEEDS, TIMES, AND TEMPERATURES HAVE SPECIFICATION CRITERIA. ALL EXTRUSION PARAMETERS HAVE REQUIRED SPECIFICATIONS. AFTER THE PRODUCT IS EXTRUDED INTO BRICKS, THE BRICKS ARE INSPECTED PRIOR TO BEING SLICED INTO INDIVIDUAL SPONGES. AFTER THE BRICKS ARE SLICED INTO SPONGES, A VISUAL INSPECTION IS PERFORMED FOR CONSISTENCY, UNIFORMITY, SHAPE, AND SIZE AT THE BEGINNING, MIDDLE, AND END OF SHIFTS AND EVERY FOUR HOURS IN BETWEEN. ALL DEFECTIVE SPONGES ARE IDENTIFIED AND REMOVED. THE GELFOAM IS PLACED INTO INNER ENVELOPES AND TRANSFERRED TO THE DOYEN PACKAGING EQUIPMENT TO PACKAGE THE ENVELOPES INTO PEEL POUCHES. THE DOYEN TAKES SIX ENVELOPES PER ROTATION BY SUCTION AND LOADS THEM ONTO A CONVEYER BELT AGAINST AN ALIGNMENT TAB. TWO OPERATORS SIT AT THE DOYEN TO CORRECT ALIGNMENT ISSUES PRIOR TO SEALING. THE FRONT AND BACK PAPERS, WHICH MAKE UP THE OUTER PEEL POUCH, ENCLOSE EACH INDIVIDUAL INNER ENVELOPE ENTIRELY WITH A FOUR-SIDED, HEAT-ACTIVATED ADHESIVE SEAL. THE TOP, BOTTOM, AND SIDES OF THE OUTER PEEL POUCHES ARE SEALED BY THREE DIFFERENT PARTS OF THE DOYEN WHICH EACH HAVE SEPARATE TEMPERATURE CONTROLS. EACH TEMPERATURE CONTROL IS VERIFIED AND DOCUMENTED IN THE BATCH RECORD. THE PEEL POUCHES ARE SEALED, AND HEAT STERILIZED. SEALED AND STERILIZED GELFOAM PEEL POUCHES ARE 100% VISUALLY INSPECTED BY TRAINED PACKAGING OPERATORS PRIOR TO FINAL PACKAGING. THE PURPOSE OF THIS INSPECTION IS TO ENSURE THAT THE PEEL POUCHES HAVE THE PROPER APPEARANCE, SEAL AND PRINT. A SEAL INTEGRITY TEST (SIT) IS UTILIZED THROUGHOUT THE FINAL PACKAGING TO ENSURE THE SIDE SEALS OF THE PEEL POUCHES ARE ACCEPTABLE. THE STERILIZED PEEL POUCHES ARE PACKAGED INTO EACH FINAL GOODS CARTON. AUDITS ARE PERFORMED ON THE FINISHED PACKAGED UNITS AT REGULAR INTERVALS THROUGHOUT THE FINAL PACKAGING PROCESS.
EVENT VERBATIM [PREFERRED TERM] EMBOLIZATION WAS PERFORMED USING GELFOAM [OFF LABEL USE], EMBOLIZATION WAS PERFORMED USING GELFOAM [DEVICE USE ISSUE], SIZE OF THE HEMATOMA IN THE RIGHT UPPER ARM GRADUALLY INCREASED/AFTER REPEATED EMBOLIZATION, THE PATIENT DEVELOPED SHOCK AND DIED OF UNCONTROLLED [THERAPEUTIC PRODUCT INEFFECTIVE FOR UNAPPROVED INDICATION], , NARRATIVE: THIS IS A LITERATURE REPORT FOR THE FOLLOWING LITERATURE SOURCE: "LIFE-THREATENING BRACHIAL ARTERY HEMORRHAGE AND A LETHAL OUTCOME IN PATIENTS WITH NEUROFIBROMATOSIS TYPE 1: TWO CASE REPORTS AND A REVIEW OF THE LITERATURE", JOURNAL OF INTERNATIONAL MEDICAL RESEARCH, 2021; VOL:49(6), PGS:1-8, DOI:10.1177/03000605211025344. A 32-YEAR-OLD MALE PATIENT RECEIVED ABSORBABLE GELATIN (GELFOAM), FOR HAEMOSTASIS; BUTYL 2-CYANOACRYLATE (BUTYL 2-CYANOACRYLATE), (BATCH/LOT NUMBER: UNKNOWN) FOR HAEMOSTASIS; IODIZED OIL (IODIZED OIL), (BATCH/LOT NUMBER: UNKNOWN) FOR HAEMOSTASIS. THE PATIENT'S RELEVANT MEDICAL HISTORY INCLUDED: "NEUROFIBROMATOSIS" (UNSPECIFIED IF ONGOING), NOTES: NF TYPE 1; "SEVERE SWELLING AND PAIN IN HIS RIGHT UPPER ARM CAUSED BY BUMPING INTO A CHAIR" (UNSPECIFIED IF ONGOING), NOTES: SEVERE SWELLING AND PAIN IN HIS RIGHT UPPER ARM CAUSED BY BUMPING INTO A CHAIR 1 HR BEFORE ADMISSION; "SEVERE SWELLING AND PAIN IN HIS RIGHT UPPER ARM" (UNSPECIFIED IF ONGOING); "PAIN IN HIS RIGHT UPPER ARM" (UNSPECIFIED IF ONGOING); "HUGE HEMATOMA WITH ACTIVE BLEEDING" (UNSPECIFIED IF ONGOING). THE PATIENT'S CONCOMITANT MEDICATIONS WERE NOT REPORTED. THE FOLLOWING INFORMATION WAS REPORTED: OFF LABEL USE (DEATH, HOSPITALIZATION, LIFE THREATENING), DEVICE USE ISSUE (DEATH, HOSPITALIZATION, LIFE THREATENING), OUTCOME "FATAL" AND ALL DESCRIBED AS "EMBOLIZATION WAS PERFORMED USING GELFOAM"; THERAPEUTIC PRODUCT INEFFECTIVE FOR UNAPPROVED INDICATION (DEATH, HOSPITALIZATION, LIFE THREATENING), OUTCOME "FATAL", DESCRIBED AS "SIZE OF THE HEMATOMA IN THE RIGHT UPPER ARM GRADUALLY INCREASED/AFTER REPEATED EMBOLIZATION, THE PATIENT DEVELOPED SHOCK AND DIED OF UNCONTROLLED". THE PATIENT WITH NEUROFIBROMATOSIS TYPE 1 (NF1) PRESENTED TO OUR HOSPITAL WITH SEVERE SWELLING AND PAIN IN HIS RIGHT UPPER ARM CAUSED BY BUMPING INTO A CHAIR 1 HOUR BEFORE ADMISSION. HE HAD A BLOOD PRESSURE OF 80/40 MMHG AND A HEART RATE OF 104 BEATS/MINUTE ON ARRIVAL TO THE HOSPITAL. A CT SCAN SHOWED A HUGE HEMATOMA WITH ACTIVE BLEEDING IN THE RIGHT UPPER ARM, AND A PSEUDOANEURYSM ARISING FROM THE RIGHT BRONCHIAL ARTERY WAS IDENTIFIED ON A VOLUME RENDERING IMAGE. THE SURGICAL TEAM ON-CALL DECIDED TO PROCEED WITH SURGICAL RESECTION AND LIGATION OF THE INVOLVED VESSEL AS THE FIRST-LINE TREATMENT. UNFORTUNATELY, THE PATIENT'S CONDITION DETERIORATED THAT NIGHT WITH INCREASING SWELLING AND PAIN IN THE RIGHT UPPER ARM, AND EMERGENT ANGIOGRAPHY WAS RECOMMENDED. SELECTIVE SUBCLAVIAN ARTERY ANGIOGRAPHY SHOWED EXTRAVASATION OF THE CONTRAST MEDIUM AT MULTIPLE LOCATIONS AND A PSEUDOANEURYSM AROSE FROM THE BRANCHES OF THE BRACHIAL ARTERY. ADDITIONALLY, ALL OF THE FEEDING VESSELS WERE TORTUOUS AND HYPERTROPHIED. EMBOLIZATION WAS PERFORMED VIA A MICROCATHETER, USING A MIXTURE OF N-BUTYL CYANOACRYLATE AND IODIZED OIL, MICROCOILS, AND GELFOAM. POSTEMBOLIZATION ANGIOGRAPHY SHOWED SUCCESSFUL OCCLUSION OF THE ACTIVE BLEEDING. HOWEVER, THE SIZE OF THE HEMATOMA IN THE RIGHT UPPER ARM GRADUALLY INCREASED 4 DAYS AFTER EMBOLIZATION, AND THE PATIENT BECAME HEMODYNAMICALLY UNSTABLE. THEREFORE, UPPER EXTREMITY AMPUTATION WAS PERFORMED. ANGIOGRAPHY WAS REPEATED BECAUSE OF SWELLING OF THE RIGHT SHOULDER 1 DAY AFTER SURGERY, AND SUBCLAVIAN ANGIOGRAPHY SHOWED NEW AND MULTIPLE ACTIVE BLEEDING SITES ARISING FROM THE BRANCH OF THE AXILLARY ARTERY. COMPLETE TOTAL EMBOLIZATION OF THE AXILLARY ARTERY WAS PERFORMED USING A MIXTURE OF N-BUTYL CYANOACRYLATE AND IODIZED OIL. SUBSEQUENT ANGIOGRAPHY SHOWED SUCCESSFUL COMPLETE OBLITERATION OF THE AXILLARY ARTERY. DESPITE AGGRESSIVE TREATMENT, ON THE SEVENTH DAY AFTER REPEATED EMBOLIZATION, THE PATIENT DEVELOPED SHOCK AND DIED OF UNCONTROLLED BLEEDING. THE ACTION TAKEN FOR ABSORBABLE GELATIN, BUTYL 2-CYANOACRYLATE AND IODIZED OIL WAS UNKNOWN. THE PATIENT DATE OF DEATH WAS UNKNOWN. REPORTED CAUSE OF DEATH: "DEVELOPED SHOCK", "UNCONTROLLED BLEEDING". IT WAS NOT REPORTED IF AN AUTOPSY WAS PERFORMED. NO FOLLOW-UP ATTEMPTS ARE POSSIBLE. NO FURTHER INFORMATION IS EXPECTED. AMENDMENT: THIS FOLLOW-UP REPORT IS BEING SUBMITTED TO AMEND PREVIOUS INFORMATION: ADDED EVENT OF OFF LABEL USE IN UNAPPROVED INDICATION. THE REPORTABLE EVENTS ARE ALSO DEVICE MALFUNCTION. FOLLOW-UP (27MAY2023): THIS IS A FOLLOW-UP REPORT FROM PRODUCT QUALITY GROUP PROVIDING INVESTIGATION RESULTS. PRODUCT QUALITY GROUP PROVIDED INVESTIGATIONAL RESULTS ON [27MAY2023] FOR [ABSORBABLE GELATIN]: UDI: (B)(4). QA REVIEW & RATIONALE: THE HAZARD ANALYSIS WITHIN THE RISK MANAGEMENT FILE HAS BEEN REVIEWED USING THE COMPLIANT NARRATIVE AND ASSOCIATED DOCUMENTATION FOR HAZARDS/HAZARDOUS SITUATIONS, AND THEIR ASSOCIATED SEVERITIES. THE REVIEW DETERMINED THAT THE HAZARD/HAZARDOUS SITUATION WAS INTRAVASCULAR APPLICATION (EMBOLIZATION PROCEDURE) (INX100314477V7.0) AND THE WORST-CASE SEVERITY WAS S4. UPON FURTHER REVIEW BY THE DCHU, THE SEVERITY OF THE REPORTED COMPLAINT WAS DETERMINED TO BE S5. REGULATORY REPORTABILITY IS ASSESSED BY THE DCHU. NO ADDITIONAL INFORMATION HAS BEEN PROVIDED REQUIRING ESCALATION. THE DETAILS OF THE REPORTED COMPLAINT HAVE BEEN FORWARDED TO THE MEDICAL DEVICE COMBINATION PRODUCT (MDCP) TEAM FOR EVALUATION. THE COMPLAINT, ITS PRIORITY, AND ITS CLASSIFICATION HAVE BEEN REVIEWED AND DETERMINED TO BE APPROPRIATE. THE COMPLAINT AND ITS CLASSIFICATION HAVE BEEN REVIEWED AND IT WAS DETERMINED THAT OUR CONTAINMENT ACTION IS A NOTIFICATION TO MANAGEMENT. A FULL INVESTIGATION WILL BE PERFORMED. THIS IS A COMPLAINT FOR 'PERFORMANCE NOT AS INDICATED IN LABEL' FOR AN UNKNOWN BATCH OF GELFOAM. THE INVESTIGATION WILL INCLUDE A REVIEW OF COMPLAINTS WITH KNOWN BATCH NUMBERS DETERMINED TO BE WITHIN SCOPE. SUMMARY OF INVESTIGATION: A PERFORMANCE NOT AS INDICATED IN LABEL COMPLAINT WAS RECEIVED FOR AN UNKNOWN LOT OF GELFOAM. REVIEW OF COMPLAINTS FOR GELFOAM SPONGE AND POWDER RECEIVED WITHIN 36 MONTHS (THE EXPIRY INTERVAL OF THE PRODUCT) PRIOR TO RECEIPT OF THE REPORTED COMPLAINT. NO PREVIOUS COMPLAINTS WITH A KNOWN BATCH NUMBER WERE IDENTIFIED. EXISTING PROCESS CONTROLS, SUCH AS USE OF A SPECIFIC VALIDATED FORMULATION RECIPE AND AUTOMATIC RECORDING OF ALL WEIGHTS AND IDENTITIES OF RAW MATERIALS, DOCUMENTATION AND VERIFICATION OF CRITICAL FORMULATION, PROCESSING, AND STERILIZATION STEPS, AND FINAL RELEASE TESTING OF EACH BATCH TO ASSURE THAT IT MEETS ALL INTERNAL TARGETS AND REGISTERED SPECIFICATIONS PRIOR TO RELEASE FOR DISTRIBUTION WERE REVIEWED AS A PART OF THIS INVESTIGATION. NO TRENDS WERE NOTED THAT WOULD REQUIRE ADDITIONAL INVESTIGATION. NO RETURNED COMPLAINT SAMPLE WAS RECEIVED. ROOT CAUSE ANALYSIS/IDENTIF: PFIZER KALAMAZOO QUALITY OPERATIONS COULD NOT DETERMINE A ROOT CAUSE FOR THE REPORTED DEFECT TO BE RELATED TO THE KALAMAZOO PRODUCTION PROCESS. A REVIEW OF PREVIOUSLY COMPLETED INVESTIGATION REPORTS DETERMINED TO BE WITHIN SCOPE DID NOT RESULT IN IDENTIFICATION OF A BATCH NUMBER, OR A ROOT CAUSE FOR THE REPORTED COMPLAINT. EXAMINATION OF A RETURNED COMPLAINT SAMPLE MAY HAVE AIDED IN IDENTIFICATION OF A ROOT CAUSE; HOWEVER, NONE WERE RECEIVED. IT IS UNKNOWN HOW THE REPORTED COMPLAINT SAMPLE WAS HANDLED, STORED, OR USED AFTER LEAVING THE PFIZER KALAMAZOO SITE. IMPACT ANALYSIS: THE WORST-CASE SEVERITY DETERMINED THROUGH A REVIEW OF THE DEVICE RISK FILE FOR THE PRODUCT WAS S5. REGULATORY REPORTABILITY IS ASSESSED BY THE DCHU. ADDITIONALLY, THE DETAILS OF THE COMPLAINT HAVE BEEN FORWARDED TO THE MDCP TEAM FOR REVIEW. THE REGISTERED USE OF THIS PRODUCT IS FOR TREATMENT AND THE NATURE OF THIS COMPLAINT INDICATES THAT IT IS DIRECTLY RELATED TO THE DEVICE. HOWEVER, THERE IS NO INDICATION THAT THE DEVICES FAILED TO MEET REGISTERED SPECIFICATIONS. BASED UPON THE RESULTS OF THIS INVESTIGATION, THE FINAL DETERMINED SCOPE AND THE INABILITY TO DETERMINE A ROOT CAUSE FOR THE REPORTED COMPLAINT, PGS-QO KALAMAZOO CONCLUDES THAT THE QUALITY OF THE PRODUCT ON THE MARKET REMAINS ACCEPTABLE. THERE IS NO IMPACT TO THE QUALITY OF THE LOT. SPECIAL OR COMMON CAUSE: COMMON CAUSE ROOT CAUSE IS ALWAYS PRESENT TO SOME DEGREE IN THE PROCESS. SPECIAL CAUSE ROOT CAUSE IS SOMETHING DIFFERENT HAPPENING AT A CERTAIN TIME OR PLACE IN THE PROCESS. IMPROVE /CONTROL CORRECTIVE / PREVENTIVE ACTION: INVESTIGATION OF THE COMPLAINT DID NOT DETERMINE THE REPORTED ISSUE TO BE PROCESS RELATED; THEREFORE, A CORRECTION, OR CORRECTIVE OR PREVENTATIVE ACTION, IS NOT REQUIRED FOR THIS CASE. THE DETAILS OF THE REPORTED COMPLAINT HAVE BEEN FORWARDED TO THE KALAMAZOO MDCP TEAM FOR REVIEW. A REVIEW OF PREVIOUSLY COMPLETED INVESTIGATION REPORTS DETERMINED TO BE WITHIN SCOPE DID NOT RESULT IN IDENTIFICATION OF CORRECTIONS, OR CORRECTIVE OR PREVENTATIVE ACTIONS FOR THE REPORTED COMPLAINT. ALL REVIEWED RECORDS, TRENDS, AND IN-PROCESS CONTROLS WERE ACCEPTABLE, AND HAVE MET THE ESTABLISHED REQUIREMENTS. CONCLUSION: THE COMPLAINT FOR 'THE COMPLAINT FOR 'PERFORMANCE NOT AS INDICATED IN LABEL' FOR AN UNKNOWN BATCH OF GELFOAM SPONGE WAS INVESTIGATED. THE INVESTIGATION INCLUDED REVIEWING APRRS FOR THE PRODUCT AND A MEDICAL DEVICE TREND REVIEW. THE FINAL SCOPE WAS DETERMINED TO BE ALL BATCHES OF GELFOAM MANUFACTURED BY PFIZER KALAMAZOO WITHIN THE 36 MONTHS (THE EXPIRY INTERVAL OF THE PRODUCT) PRIOR TO THE RECEIPT DATE OF THE COMPLAINT. A COMPLAINT SAMPLE WAS NOT RETURNED. NO RELATED QUALITY ISSUES WERE IDENTIFIED DURING THE INVESTIGATION. NO ROOT CAUSE OR CAPA WERE IDENTIFIED AS THE COMPLAINT WAS NOT CONFIRMED. NO RELATED QUALITY DEFECTS WERE IDENTIFIED THROUGH INVESTIGATION. THERE IS NO IMPACT ON MEDICAL DEVICE QUALITY, REGULATORY, VALIDATION, OR STABILITY.' FOR AN UNKNOWN BATCH OF GELFOAM SPONGE WAS INVESTIGATED. THE FINAL SCOPE WAS DETERMINED TO BE ALL BATCHES OF GELFOAM MANUFACTURED BY PFIZER KALAMAZOO WITHIN THE 36 MONTHS (THE EXPIRY INTERVAL OF THE PRODUCT) PRIOR TO THE RECEIPT DATE OF THE COMPLAINT. A COMPLAINT SAMPLE WAS NOT RETURNED. NO RELATED QUALITY ISSUES WERE IDENTIFIED DURING THE INVESTIGATION. NO ROOT CAUSE OR CAPA WERE IDENTIFIED AS THE COMPLAINT WAS NOT CONFIRMED. NO RELATED QUALITY DEFECTS WERE IDENTIFIED THROUGH INVESTIGATION. THERE IS NO IMPACT ON MEDICAL DEVICE QUALITY, REGULATORY, VALIDATION, OR STABILITY. DOCUMENT REVIEW SUMMARY: DEVIATIONS: A REVIEW OF DEVIATIONS, LABORATORY INVESTIGATION REPORTS (LIR), AND CHANGE MANAGEMENT RECORDS COULD NOT BE PERFORMED FOR THE REPORTED COMPLAINT, AS THE BATCH IS UNKNOWN. MANUFACTURING/PACKAGING RECORDS: COMPLETE - ACCEPTABLE A REVIEW OF MANUFACTURING AND PACKAGING RECORDS COULD NOT BE PERFORMED FOR THE COMPLAINT, AS THE COMPLAINT IS FOR AN UNKNOWN BATCH. ADDITIONALLY, A REVIEW OF BATCH RECORDS FROM THE PREVIOUSLY INVESTIGATED COMPLAINTS DETERMINED TO BE IN SCOPE COULD NOT BE PERFORMED, AS THERE WERE NO COMPLAINTS WITH A KNOWN BATCH. GELFOAM POWDER IS MANUFACTURED FROM SOLID SPONGE BRICKS. THE BULK MANUFACTURED SOLUTION IS FORCED THROUGH A FILTER WITH NITROGEN TO EXTRUDE THE LARGE, SOLID SPONGE BRICKS. THE BRICKS ARE DRIED, TRIMMED AND SPLIT. THE SPLIT BRICKS ARE THEN MILLED TO FORM POWDER. THE POWDER IS COLLECTED IN HIGH DENSITY POLYETHYLENE BAGS AND THEN SEALED INTO BULK CONTAINERS. THE GELFOAM POWDER IS THEN FILLED INTO INNER ENVELOPES USING A POWDER FILLING DEVICE. EACH ENVELOPE IS FILLED WITH A TARGET OF 1.2 GRAMS PER ENVELOPE AND A MINIMUM OF 1.0 GRAM PER ENVELOPE. TWO WEIGHT CHECKS OF EACH POWDER FILLING DEVICE ARE CONDUCTED AT 30-MINUTE INTERVALS TO ASSURE THAT THE DEVICE IS DISPENSING THE PROPER AMOUNT OF POWDER. THE FINAL PRODUCT YIELD IS CALCULATED AGAINST LIMITS FOR THE PRODUCT. THE INNER ENVELOPES ARE FOLDED OVER TWICE AND INSERTED INTO SLEEVES. THE FILLED SLEEVES ARE PLACED INTO TRAYS. THE SLEEVES (PEEL POUCHES) ARE SEALED, AND HEAT STERILIZED. SEALED AND STERILIZED GELFOAM PEEL POUCHES ARE 100% VISUALLY INSPECTED BY TRAINED PACKAGING OPERATORS PRIOR TO FINAL PACKAGING. THE PURPOSE OF THIS INSPECTION IS TO ENSURE THAT THE ENVELOPES HAVE THE PROPER APPEARANCE, SEAL AND PRINT, AND ALL NOTED DEFECTIVE PRODUCT IS REMOVED FROM THE LOT PRIOR TO FINAL PACKAGING AND NO OPEN SIDE SEALS WERE OBSERVED. THE STERILIZED PEEL POUCHES ARE PACKAGED INTO EACH FINAL GOODS CARTON. FOR GELFOAM SPONGE, THE BILL OF MATERIALS LISTS THE SPECIFIC PRODUCT COMPONENTS AND WEIGHTS REQUIRED FOR THE FORMULATION OF EACH BATCH. ALL MANUFACTURING MIXING SPEEDS, TIMES, AND TEMPERATURES HAVE SPECIFICATION CRITERIA. ALL EXTRUSION PARAMETERS HAVE REQUIRED SPECIFICATIONS. AFTER THE PRODUCT IS EXTRUDED INTO BRICKS, THE BRICKS ARE INSPECTED PRIOR TO BEING SLICED INTO INDIVIDUAL SPONGES. AFTER THE BRICKS ARE SLICED INTO SPONGES, A VISUAL INSPECTION IS PERFORMED FOR CONSISTENCY, UNIFORMITY, SHAPE, AND SIZE AT THE BEGINNING, MIDDLE, AND END OF SHIFTS AND EVERY FOUR HOURS IN BETWEEN. ALL DEFECTIVE SPONGES ARE IDENTIFIED AND REMOVED. THE GELFOAM IS PLACED INTO INNER ENVELOPES AND TRANSFERRED TO THE DOYEN PACKAGING EQUIPMENT TO PACKAGE THE ENVELOPES INTO PEEL POUCHES. THE DOYEN TAKES SIX ENVELOPES PER ROTATION BY SUCTION AND LOADS THEM ONTO A CONVEYER BELT AGAINST AN ALIGNMENT TAB. TWO OPERATORS SIT AT THE DOYEN TO CORRECT ALIGNMENT ISSUES PRIOR TO SEALING. THE FRONT AND BACK PAPERS, WHICH MAKE UP THE OUTER PEEL POUCH, ENCLOSE EACH INDIVIDUAL INNER ENVELOPE ENTIRELY WITH A FOUR-SIDED, HEAT-ACTIVATED ADHESIVE SEAL. THE TOP, BOTTOM, AND SIDES OF THE OUTER PEEL POUCHES ARE SEALED BY THREE DIFFERENT PARTS OF THE DOYEN WHICH EACH HAVE SEPARATE TEMPERATURE CONTROLS. EACH TEMPERATURE CONTROL IS VERIFIED AND DOCUMENTED IN THE BATCH RECORD. THE PEEL POUCHES ARE SEALED, AND HEAT STERILIZED. SEALED AND STERILIZED GELFOAM PEEL POUCHES ARE 100% VISUALLY INSPECTED BY TRAINED PACKAGING OPERATORS PRIOR TO FINAL PACKAGING. THE PURPOSE OF THIS INSPECTION IS TO ENSURE THAT THE PEEL POUCHES HAVE THE PROPER APPEARANCE, SEAL AND PRINT. A SEAL INTEGRITY TEST (SIT) IS UTILIZED THROUGHOUT THE FINAL PACKAGING TO ENSURE THE SIDE SEALS OF THE PEEL POUCHES ARE ACCEPTABLE. THE STERILIZED PEEL POUCHES ARE PACKAGED INTO EACH FINAL GOODS CARTON. AUDITS ARE PERFORMED ON THE FINISHED PACKAGED UNITS AT REGULAR INTERVALS THROUGHOUT THE FINAL PACKAGING PROCESS. PROCESS CONTROL EVALUATION: EXISTING PROCESS CONTROLS, SUCH AS USE OF A SPECIFIC VALIDATED FORMULATION RECIPE AND AUTOMATIC RECORDING OF ALL WEIGHTS AND IDENTITIES OF RAW MATERIALS, DOCUMENTATION AND VERIFICATION OF CRITICAL FORMULATION, PROCESSING, AND STERILIZATION STEPS, AND FINAL RELEASE TESTING OF EACH BATCH TO ASSURE THAT IT MEETS ALL INTERNAL TARGETS AND REGISTERED SPECIFICATIONS PRIOR TO RELEASE FOR DISTRIBUTION WERE REVIEWED AS A PART OF THIS INVESTIGATION. THE REVIEW DETERMINED THAT THE PROCESS CONTROLS WERE APPROPRIATE AND ACCEPTABLE; THEREFORE THE MEDICAL DEVICE QOP WAS NOT NOTIFIED. APRR REVIEW: A REVIEW OF APRR FOR THE PRODUCTS AND TIMEFRAME IN SCOPE DID NOT FIND ANY ISSUE RELATING TO THE REPORTED COMPLAINT. QO BATCH HISTORY REPORT: A REVIEW OF RELEASE TESTING RESULTS COULD NOT BE PERFORMED AS THE REPORTED COMPLAINT BATCH IS UNKNOWN. OTHER TREND ASSMT. & RATIONALE: MEDICAL DEVICE TREND ANALYSIS: THE COMPLAINT HISTORY FOR PRODUCTS WITH THE PRODUCT CATEGORY DEFINED AS ABSORBABLE MATERIAL, 'DELIVERY SYSTEM' AND 'TOPICAL' HAS BEEN REVIEWED. THE FOLLOWING PARAMETERS WERE USED: -PRODUCT CATEGORY: ABSORBABLE MATERIAL, DELIVERY SYSTEM, TOPICAL -TIME PERIOD: (B)(6) 2020 - (B)(6) 2023 -COMPLAINT CLASS: PRODUCT USE ATTRIBUTES -INVESTIGATING SITE: PFIZER KDP USE OF THE PRODUCT CATEGORY OF 'ABSORBABLE MATERIAL' WAS REQUIRED TO CAPTURE HISTORICAL COMPLAINTS INVESTIGATED PRIOR TO MIGRATION INTO THE CURRENT COMPLAINT SYSTEM. THE PRODUCT CATEGORY OF 'DELIVERY SYSTEM' WAS USED TO CAPTURE COMPLAINTS RECEIVED WITHIN THE CURRENT DATABASE. THE RESULTS OF THE ABOVE QUERY WERE EVALUATED BY DATE CONTACTED AND BY THE CLASSIFICATION OF PRODUCT USE ATTRIBUTES. THERE WERE TWO MONTHS ((B)(6) 2020 AND (B)(6) 2021) THAT INCLUDED A HIGHER-THAN-NORMAL NUMBER OF COMPLAINTS (4 AND 7, RESPECTIVELY). A REVIEW OF THE PREVIOUSLY COMPLETED COMPLAINT INVESTIGATIONS DETERMINED THAT THE REPORTED DEFECTS WERE NOT CONFIRMED, OR PROCESS RELATED. ADDITIONALLY, THE RESULTS FROM THE QUERY WERE EVALUATED BY THE SUB-CLASSES OF 'PERFORMANCE NOT AS INDICATED IN LABEL' AND LACK OF EFFECT. THERE WERE TWO MONTHS ((B)(6) 2020) THAT INCLUDED A HIGHER-THAN-NORMAL NUMBER OF COMPLAINTS (4 DURING EACH MONTH). A REVIEW OF THE COMPLAINTS RECEIVED DURING (B)(6) 2020 DETERMINED THEY WERE DUE TO A REMEDIATION EFFORT BY PFIZER US SAFETY. A REVIEW OF THE FOUR PREVIOUSLY COMPLETED COMPLAINT INVESTIGATIONS FROM (B)(6) 2020 DETERMINED THAT THE REPORTED DEFECT WAS NOT CONFIRMED, OR PROCESS RELATED. NO TREND WAS OBSERVED THAT WOULD REQUIRE FURTHER INVESTIGATION. MEDICAL DEVICE COMPONENT TREND: A REVIEW OF TRENDS FOR MEDICAL DEVICE CONSTITUENTS FOR THE REPORTED PRODUCT COULD NOT BE PERFORMED AS THE BATCH NUMBER IS UNKNOWN., COMMENT: BASED ON AVAILABLE INFORMATION, A POSSIBLE CONTRIBUTORY ROLE OF THE SUBJECT PRODUCT ABSORBABLE GELATIN (GELFOAM) CANNOT BE EXCLUDED FOR THE EVENTS THERAPEUTIC PRODUCT INEFFECTIVE FOR UNAPPROVED INDICATION AND OFF LABEL USE. THIS CASE WILL BE REASSESSED UPON RECEIPT OF FOLLOW-UP INFORMATION. THE IMPACT OF THIS REPORT ON THE BENEFIT/RISK PROFILE OF THE PFIZER PRODUCT IS EVALUATED AS PART OF PFIZER PROCEDURES FOR SAFETY EVALUATION, INCLUDING THE REVIEW AND ANALYSIS OF AGGREGATE DATA FOR ADVERSE EVENTS. ANY SAFETY CONCERN IDENTIFIED AS PART OF THIS REVIEW, AS WELL AS ANY APPROPRIATE ACTION IN RESPONSE, WILL BE PROMPTLY NOTIFIED TO REGULATORY AUTHORITIES, ETHICS COMMITTEES AND INVESTIGATORS, AS APPROPRIATE.
SIZE OF THE HEMATOMA IN THE RIGHT UPPER ARM GRADUALLY INCREASED/AFTER REPEATED EMBOLIZATION, THE PATIENT DEVELOPED SHOCK AND DIED OF UNCONTROLLED [THERAPEUTIC PRODUCT INEFFECTIVE]. NARRATIVE: THIS IS A LITERATURE REPORT FOR THE FOLLOWING LITERATURE SOURCE: "LIFE-THREATENING BRACHIAL ARTERY HEMORRHAGE AND A LETHAL OUTCOME IN PATIENTS WITH NEUROFIBROMATOSIS TYPE 1: TWO CASE REPORTS AND A REVIEW OF THE LITERATURE", JOURNAL OF INTERNATIONAL MEDICAL RESEARCH, 2021; VOL:49(6), PGS:1-8, DOI:10.1177/03000605211025344. A 32-YEAR-OLD MALE PATIENT RECEIVED ABSORBABLE GELATIN (GELFOAM), FOR HAEMOSTASIS; BUTYL 2-CYANOACRYLATE (BUTYL 2-CYANOACRYLATE), (BATCH/LOT NUMBER: UNKNOWN) FOR HAEMOSTASIS; IODIZED OIL (IODIZED OIL), (BATCH/LOT NUMBER: UNKNOWN) FOR HAEMOSTASIS. THE PATIENT'S RELEVANT MEDICAL HISTORY INCLUDED: "NEUROFIBROMATOSIS" (UNSPECIFIED IF ONGOING), NOTES: NF TYPE 1; "SEVERE SWELLING AND PAIN IN HIS RIGHT UPPER ARM CAUSED BY BUMPING INTO A CHAIR" (UNSPECIFIED IF ONGOING), NOTES: SEVERE SWELLING AND PAIN IN HIS RIGHT UPPER ARM CAUSED BY BUMPING INTO A CHAIR 1 HR BEFORE ADMISSION; "SEVERE SWELLING AND PAIN IN HIS RIGHT UPPER ARM" (UNSPECIFIED IF ONGOING); "PAIN IN HIS RIGHT UPPER ARM" (UNSPECIFIED IF ONGOING); "HUGE HEMATOMA WITH ACTIVE BLEEDING" (UNSPECIFIED IF ONGOING). THE PATIENT'S CONCOMITANT MEDICATIONS WERE NOT REPORTED. THE FOLLOWING INFORMATION WAS REPORTED: THERAPEUTIC PRODUCT INEFFECTIVE (DEATH, HOSPITALIZATION, LIFE THREATENING), OUTCOME "FATAL", DESCRIBED AS "SIZE OF THE HEMATOMA IN THE RIGHT UPPER ARM GRADUALLY INCREASED/AFTER REPEATED EMBOLIZATION, THE PATIENT DEVELOPED SHOCK AND DIED OF UNCONTROLLED". CLINICAL COURSE: CASE 2: A 32-YEAR-OLD MAN WITH NEUROFIBROMATOSIS TYPE 1 (NF1) PRESENTED TO OUR HOSPITAL WITH SEVERE SWELLING AND PAIN IN HIS RIGHT UPPER ARM CAUSED BY BUMPING INTO A CHAIR 1 HOUR BEFORE ADMISSION. HE HAD A BLOOD PRESSURE OF 80/40 MMHG AND A HEART RATE OF 104 BEATS/MINUTE ON ARRIVAL TO THE HOSPITAL. A CT SCAN SHOWED A HUGE HEMATOMA WITH ACTIVE BLEEDING IN THE RIGHT UPPER ARM, AND A PSEUDOANEURYSM ARISING FROM THE RIGHT BRONCHIAL ARTERY WAS IDENTIFIED ON A VOLUME RENDERING IMAGE. THE SURGICAL TEAM ON-CALL DECIDED TO PROCEED WITH SURGICAL RESECTION AND LIGATION OF THE INVOLVED VESSEL AS THE FIRST-LINE TREATMENT. UNFORTUNATELY, THE PATIENT'S CONDITION DETERIORATED THAT NIGHT WITH INCREASING SWELLING AND PAIN IN THE RIGHT UPPER ARM, AND EMERGENT ANGIOGRAPHY WAS RECOMMENDED. SELECTIVE SUBCLAVIAN ARTERY ANGIOGRAPHY SHOWED EXTRAVASATION OF THE CONTRAST MEDIUM AT MULTIPLE LOCATIONS AND A PSEUDOANEURYSM AROSE FROM THE BRANCHES OF THE BRACHIAL ARTERY. ADDITIONALLY, ALL OF THE FEEDING VESSELS WERE TORTUOUS AND HYPERTROPHIED. EMBOLIZATION WAS PERFORMED VIA A MICROCATHETER, USING A MIXTURE OF N-BUTYL CYANOACRYLATE AND IODIZED OIL, MICROCOILS, AND GELFOAM. POSTEMBOLIZATION ANGIOGRAPHY SHOWED SUCCESSFUL OCCLUSION OF THE ACTIVE BLEEDING. HOWEVER, THE SIZE OF THE HEMATOMA IN THE RIGHT UPPER ARM GRADUALLY INCREASED 4 DAYS AFTER EMBOLIZATION, AND THE PATIENT BECAME HEMODYNAMICALLY UNSTABLE. THEREFORE, UPPER EXTREMITY AMPUTATION WAS PERFORMED. ANGIOGRAPHY WAS REPEATED BECAUSE OF SWELLING OF THE RIGHT SHOULDER 1 DAY AFTER SURGERY, AND SUBCLAVIAN ANGIOGRAPHY SHOWED NEW AND MULTIPLE ACTIVE BLEEDING SITES ARISING FROM THE BRANCH OF THE AXILLARY ARTERY. COMPLETE TOTAL EMBOLIZATION OF THE AXILLARY ARTERY WAS PERFORMED USING A MIXTURE OF N-BUTYL CYANOACRYLATE AND IODIZED OIL. SUBSEQUENT ANGIOGRAPHY SHOWED SUCCESSFUL COMPLETE OBLITERATION OF THE AXILLARY ARTERY. DESPITE AGGRESSIVE TREATMENT, ON THE SEVENTH DAY AFTER REPEATED EMBOLIZATION, THE PATIENT DEVELOPED SHOCK AND DIED OF UNCONTROLLED BLEEDING. NO FOLLOW-UP ATTEMPTS ARE POSSIBLE. NO FURTHER INFORMATION IS EXPECTED. COMMENT: BASED ON AVAILABLE INFORMATION, A POSSIBLE CONTRIBUTORY ROLE OF THE SUBJECT PRODUCT CANNOT BE EXCLUDED FOR SUSPECTED LOE WITH FATAL OUTCOME. THERE IS LIMITED INFORMATION PROVIDED IN THIS REPORT. THIS CASE WILL BE REASSESSED UPON RECEIPT OF FOLLOW-UP INFORMATION. THE IMPACT OF THIS REPORT ON THE BENEFIT/RISK PROFILE OF THE PFIZER PRODUCT IS EVALUATED AS PART OF PFIZER PROCEDURES FOR SAFETY EVALUATION, INCLUDING THE REVIEW AND ANALYSIS OF AGGREGATE DATA FOR ADVERSE EVENTS. ANY SAFETY CONCERN IDENTIFIED AS PART OF THIS REVIEW, AS WELL AS ANY APPROPRIATE ACTION IN RESPONSE, WILL BE PROMPTLY NOTIFIED TO REGULATORY AUTHORITIES, ETHICS COMMITTEES AND INVESTIGATORS, AS APPROPRIATE.
EVENT VERBATIM: EMBOLIZATION WAS PERFORMED USING GELFOAM [OFF LABEL USE], SIZE OF THE HEMATOMA IN THE RIGHT UPPER ARM GRADUALLY INCREASED/AFTER REPEATED EMBOLIZATION, THE PATIENT DEVELOPED SHOCK AND DIED OF UNCONTROLLED [THERAPEUTIC PRODUCT INEFFECTIVE FOR UNAPPROVED INDICATION], NARRATIVE: THIS IS A LITERATURE REPORT FOR THE FOLLOWING LITERATURE SOURCE: "LIFE-THREATENING BRACHIAL ARTERY HEMORRHAGE AND A LETHAL OUTCOME IN PATIENTS WITH NEUROFIBROMATOSIS TYPE 1: TWO CASE REPORTS AND A REVIEW OF THE LITERATURE", JOURNAL OF INTERNATIONAL MEDICAL RESEARCH, 2021; VOL:49(6), PGS:1-8, DOI:10.1177/03000605211025344. A 32-YEAR-OLD MALE PATIENT RECEIVED ABSORBABLE GELATIN (GELFOAM), FOR HAEMOSTASIS; BUTYL 2-CYANOACRYLATE (BUTYL 2-CYANOACRYLATE), (BATCH/LOT NUMBER: UNKNOWN) FOR HAEMOSTASIS; IODIZED OIL (IODIZED OIL), (BATCH/LOT NUMBER: UNKNOWN) FOR HAEMOSTASIS. THE PATIENT'S RELEVANT MEDICAL HISTORY INCLUDED: "NEUROFIBROMATOSIS" (UNSPECIFIED IF ONGOING), NOTES: NF TYPE 1; "SEVERE SWELLING AND PAIN IN HIS RIGHT UPPER ARM CAUSED BY BUMPING INTO A CHAIR" (UNSPECIFIED IF ONGOING), NOTES: SEVERE SWELLING AND PAIN IN HIS RIGHT UPPER ARM CAUSED BY BUMPING INTO A CHAIR 1 HR BEFORE ADMISSION; "SEVERE SWELLING AND PAIN IN HIS RIGHT UPPER ARM" (UNSPECIFIED IF ONGOING); "PAIN IN HIS RIGHT UPPER ARM" (UNSPECIFIED IF ONGOING); "HUGE HEMATOMA WITH ACTIVE BLEEDING" (UNSPECIFIED IF ONGOING). THE PATIENT'S CONCOMITANT MEDICATIONS WERE NOT REPORTED. THE FOLLOWING INFORMATION WAS REPORTED: OFF LABEL USE (DEATH, HOSPITALIZATION, LIFE THREATENING), OUTCOME "FATAL", DESCRIBED AS "EMBOLIZATION WAS PERFORMED USING GELFOAM"; THERAPEUTIC PRODUCT INEFFECTIVE FOR UNAPPROVED INDICATION (DEATH, HOSPITALIZATION, LIFE THREATENING), OUTCOME "FATAL", DESCRIBED AS "SIZE OF THE HEMATOMA IN THE RIGHT UPPER ARM GRADUALLY INCREASED/AFTER REPEATED EMBOLIZATION, THE PATIENT DEVELOPED SHOCK AND DIED OF UNCONTROLLED". CLINICAL COURSE: CASE 2: A 32-YEAR-OLD MAN WITH NEUROFIBROMATOSIS TYPE 1 (NF1) PRESENTED TO OUR HOSPITAL WITH SEVERE SWELLING AND PAIN IN HIS RIGHT UPPER ARM CAUSED BY BUMPING INTO A CHAIR 1 HOUR BEFORE ADMISSION. HE HAD A BLOOD PRESSURE OF 80/40 MMHG AND A HEART RATE OF 104 BEATS/MINUTE ON ARRIVAL TO THE HOSPITAL. A CT SCAN SHOWED A HUGE HEMATOMA WITH ACTIVE BLEEDING IN THE RIGHT UPPER ARM, AND A PSEUDOANEURYSM ARISING FROM THE RIGHT BRONCHIAL ARTERY WAS IDENTIFIED ON A VOLUME RENDERING IMAGE. THE SURGICAL TEAM ON-CALL DECIDED TO PROCEED WITH SURGICAL RESECTION AND LIGATION OF THE INVOLVED VESSEL AS THE FIRST-LINE TREATMENT. UNFORTUNATELY, THE PATIENT'S CONDITION DETERIORATED THAT NIGHT WITH INCREASING SWELLING AND PAIN IN THE RIGHT UPPER ARM, AND EMERGENT ANGIOGRAPHY WAS RECOMMENDED. SELECTIVE SUBCLAVIAN ARTERY ANGIOGRAPHY SHOWED EXTRAVASATION OF THE CONTRAST MEDIUM AT MULTIPLE LOCATIONS AND A PSEUDOANEURYSM AROSE FROM THE BRANCHES OF THE BRACHIAL ARTERY. ADDITIONALLY, ALL OF THE FEEDING VESSELS WERE TORTUOUS AND HYPERTROPHIED. EMBOLIZATION WAS PERFORMED VIA A MICROCATHETER, USING A MIXTURE OF N-BUTYL CYANOACRYLATE AND IODIZED OIL, MICROCOILS, AND GELFOAM. POSTEMBOLIZATION ANGIOGRAPHY SHOWED SUCCESSFUL OCCLUSION OF THE ACTIVE BLEEDING. HOWEVER, THE SIZE OF THE HEMATOMA IN THE RIGHT UPPER ARM GRADUALLY INCREASED 4 DAYS AFTER EMBOLIZATION, AND THE PATIENT BECAME HEMODYNAMICALLY UNSTABLE. THEREFORE, UPPER EXTREMITY AMPUTATION WAS PERFORMED. ANGIOGRAPHY WAS REPEATED BECAUSE OF SWELLING OF THE RIGHT SHOULDER 1 DAY AFTER SURGERY, AND SUBCLAVIAN ANGIOGRAPHY SHOWED NEW AND MULTIPLE ACTIVE BLEEDING SITES ARISING FROM THE BRANCH OF THE AXILLARY ARTERY. COMPLETE TOTAL EMBOLIZATION OF THE AXILLARY ARTERY WAS PERFORMED USING A MIXTURE OF N-BUTYL CYANOACRYLATE AND IODIZED OIL. SUBSEQUENT ANGIOGRAPHY SHOWED SUCCESSFUL COMPLETE OBLITERATION OF THE AXILLARY ARTERY. DESPITE AGGRESSIVE TREATMENT, ON THE SEVENTH DAY AFTER REPEATED EMBOLIZATION, THE PATIENT DEVELOPED SHOCK AND DIED OF UNCONTROLLED BLEEDING. NO FOLLOW-UP ATTEMPTS ARE POSSIBLE. NO FURTHER INFORMATION IS EXPECTED. AMENDMENT: THIS FOLLOW-UP REPORT IS BEING SUBMITTED TO AMEND PREVIOUS INFORMATION: ADDED EVENT OF OFF LABEL USE IN UNAPPROVED INDICATION. THE REPORTABLE EVENTS ARE ALSO DEVICE MALFUNCTION., COMMENT: BASED ON AVAILABLE INFORMATION, A POSSIBLE CONTRIBUTORY ROLE OF THE SUBJECT PRODUCT ABSORBABLE GELATIN (GELFOAM) CANNOT BE EXCLUDED FOR THE EVENTS THERAPEUTIC PRODUCT INEFFECTIVE FOR UNAPPROVED INDICATION AND OFF LABEL USE. THIS CASE WILL BE REASSESSED UPON RECEIPT OF FOLLOW-UP INFORMATION. THE IMPACT OF THIS REPORT ON THE BENEFIT/RISK PROFILE OF THE PFIZER PRODUCT IS EVALUATED AS PART OF PFIZER PROCEDURES FOR SAFETY EVALUATION, INCLUDING THE REVIEW AND ANALYSIS OF AGGREGATE DATA FOR ADVERSE EVENTS. ANY SAFETY CONCERN IDENTIFIED AS PART OF THIS REVIEW, AS WELL AS ANY APPROPRIATE ACTION IN RESPONSE, WILL BE PROMPTLY NOTIFIED TO REGULATORY AUTHORITIES, ETHICS COMMITTEES AND INVESTIGATORS, AS APPROPRIATE.
Devices
| Seq | Brand | Generic | Product Code | Manufacturer | Model | Lot | UDI-DI |
|---|---|---|---|---|---|---|---|
| 1163486 | GELFOAM | SPONGE, STERILE; CLASS III | LMF | PFIZER, INC. |
Patients
| Seq | Age | Sex | Outcome | Treatment |
|---|---|---|---|---|
| 1 | 32 YR | Male | Death| L| H |