MAUDE Adverse Event Report: BIOMERIEUX INC. BACT/ALERT I AST; BACT/ALERT® I AST

Catalog Number 259786

Device Problem Incorrect, Inadequate or Imprecise Result or Readings (1535)

Patient Problem No Patient Involvement (2645)

Event Type  malfunction  

Event Description

An industry customer in (b)(6) notified biomérieux of potential false negative results in association with the bact/alert® i ast culture bottle (ref.259786, lot 0001054776) while performing an internal growth promotion test.The customer inoculated the bact/alert® i ast blood culture bottles with staphylococcus aureus and observed no growth after seven (7) days of incubation.The staphylococcus aureus strain was also plated onto tryptic soy agar and was positive for growth.Biomérieux customer service has requested information about the growth promotion study regarding the technique used and if the study is part of new reagent validation.At the time of this assessment the customer has not yet provided this information.As there is no patient associated with quality control strain, there is no adverse event related to any patient's state of health.Biomérieux has initiated an internal investigation.Note: the bact/alert® i ast culture bottle (ref.259786) is for industry use only, the clinical application bottle equivalent is product reference 259789.

Manufacturer Narrative

**context** complaint investigation was conducted in response to an industry customer complaint.The primary customer notified biomérieux on 14jan2020 (contact date) that bact/alert® iast lot 1053945 (p/n 249786,expiry date 14jun2020) showed an increase in time to detection (ttd) for the growth of staphylococcus aureus (s.Aureus) during their validated sterility testing.Previous iast lots would show positive growth within 4-5 days; however, lot 1053945 showed growth at 6-7 days, 8 days, or no growth at the 9-day incubation period.The customer used s.Aureus strain from a bioball® multishot 550 lot b5160 (ref 56009, expiry date 20mar2021) using re-hydration fluid ref 56021.Sixteen (16) other industry customer complaints are referenced to this investigation for a total of seventeen (17) case complaints from a total of ten (10) different customers on eight (8) different bact/alert iast culture bottle lots.Ten (10) complaints were determined not reportable as per biomérieux standard operating procedure.All of these complaints have been evaluated during investigation inv-1205.All customers associated with this investigation performed their own procedures for quality control lot qualifications, method suitability test and/or validation processes.Customers reported delayed growth or no growth of s.Aureus with bioball nctc 10788/ atcc® 6538¿ strain during quality control/qualification testing of bact/alert iast culture bottle lots.Internal testing: capa 1703190 was initiated on 17feb2020 due to a nonconformance trend of three bact/alert iast lots that showed out-of-specification results during the initial release testing for growth performance using staphylococcus aureus (s.Aureus) atcc 6538 strain.Initial time to detection (ttd) results were longer (means shift upward trend) than the qc release specification.Upon further investigational testing, all three lots passed the growth performance specification meeting the acceptable release criteria.Around the same time as the initiation of capa 1703190, several industry customer complaints were recorded for delayed (longer) ttd and/or no growth of s.Aureus atcc 6538 strain and/or bioball nctc 10788 strain (atcc 6538 strain equivalent) after inoculation and incubation of bact/alert iast culture bottles.These complaints are associated with inv-1205 and are referenced to capa 1703190.Root cause analysis was performed to evaluate cause and effect relationships in order to identify the primary root cause of delayed ttd.Based on the investigational findings, the root cause was determined to be lot-to-lot variability of a raw material used in the manufacturing of iast culture bottle lots.Growth performance differences (longer ttd) in iast culture bottles with s.Aureus strain atcc 6538 were observed with different raw material lots.Further evaluation of these complaints, revealed that a couple of customers obtained delayed ttd; however, the majority of the customers obtained no growth results of s.Aureus with bioball 6538 strain and bact/alert iast culture bottles.Therefore, a separate scientific study was performed by technical services to evaluate potential root cause for these complaint issues: comparison of bioball and atcc cultures of staphylococcus aureus in iast bottles.Scientific study: as per capa 1703190, lot-to-lot variation of the raw material identified contributed to iast lots either performing well or poorly for the growth of s.Aureus.The test method for this study incorporated the parameters of temperature, inoculum levels, organism strains, and different bioball lots/concentrations.Results were obtained and evaluated.All bottles flagged positive in less than 50 hours, within the 3 day criteria defined by pharmacopeias (e.G.<71> and eu 2.6.1); therefore all bottles showed growth with atcc 6538/bioball, between the temperature range of 32.5°c and 36.5°c.The temperature range of 32.5°c +/- 1°c is the recommended temperature range for bact/alert industry bottles.The outcome of the internal study indicated that all bact/alert iast bottles resulted in positive growth in under less than 50 hours regardless of s.Aureus strain, inoculation target, or incubation temperature.This study did not confirm the customer¿s complaints of delayed growth more than three (3) days or no organism growth.Six bioball batch numbers used: b5655 b5492 b6118 b5808 b5384 b5565 bact/alert iast lots used: 0001055504, 0001055716, 0001056132, 0001056284, 0001056588, 0001056814.**conclusion ** based on the evaluation of data and the information provided by the customer, there were two most probable root cause for delayed growth or no organism growth (s.Aureus) in bact/alert iast bottles pertaining to complaint inv-1205: - materals: bact/alert iast culture bottles provide suitable conditions for aerobic microorganism growth (e.G.S.Aureus).Aql inspections performed on bottle defects that could potentially occur due to the manufacturing processes of bact/alert iast culture bottles did not support the delayed growth or no growth results obtained by the customers during their qualification testing.Bioball (after rehydration as per ifu) provides a suspension of viable organisms that can be used as standardized suspension for serial dilutions and provide adequate volumes for inoculation into culture bottles.Capa 1703190 determined that a raw material lot-to-lot variation caused increased ttd in qc testing of iast lots; however, ttd was still within qc specifications.Internal testing as per technical services scientific study showed positive growth in under less than 50 hours, within the three (3) day criteria defined by pharmacopeias (e.G.<71> and eu 2.6.1) regardless of s.Aureus strain, inoculation target, or incubation temperature (32.5°c to 36.5°c).Inconsistencies existed within the materials used by customers for testing: not rehydrating the bioball as per the ifu, various manipulations of the rehydrated bioball jeopardizing the sustainability of viable organisms prior to inoculation, and using inadequate volume of the organism concentration for the inoculation into the iast culture bottles.Therefore, no growth was the common result throughout the testing performed by the customers.- method: the ifu provides adequate directions within the document and provides references to additional documents for quality control information to promote organism growth in bact/alert culture bottles.No revisions to the ifu are needed.The ifu for bioball provides specific directions to rehydrate and use the organism strain in their plated quantitative quality control sample testing.Industry customers are required to validate the suitability of the method for each sample type and volume in the bact/alert iast culture bottles according to their own governing regulatory requirements.Throughout the complaints associated with this investigation, there were inconsistencies with rehydration of the bioball as per ifu, following recommendations of using prepared standard suspensions of organism and serial dilutions for a inoculation volume of <100 cfu/ml.Due to these inconsistencies, it is difficult to maintain viability of the organism for inoculation into iast bottles and promote growth.There is a need for a guidance protocol for industry users to describe a growth performance method for qualification of bact/alert culture bottles with organisms incubated at temperatures that are in alignment with pharmacopeia sterility test standards.As per the biomérieux communication csn 5120-1, a quality control protocol to standardize instructions preparing a suspension for the inoculation into iast culture bottles and bottle incubation at recommended temperatures will increase the chance of obtaining organism growth within acceptable ttd using industry bact/alert culture bottles (e.G.Iast).Queries of manufacturing data and review of manufacturing records for the bact/alert iast lots did not reveal any adverse trends relating to growth performance (delayed growth or no growth with s.Aureus atcc strain) issues.Moreover, there is no evidence of any bottle malfunction with the bact/alert iast culture bottle lots.Monitoring and detection methods for potential bottle contamination are part of the manufacturing and quality control processes for bact/alert culture bottles.The investigator reviewed the instructions for use [ifu] and determined it provides adequate direction to prevent growth performance issues (e.G.Delayed growth or no growth) with organisms used for qualification purposes.

• Brand Name: BACT/ALERT I AST
• Type of Device: BACT/ALERT® I AST
• Manufacturer (Section D): BIOMERIEUX INC.; 100 rodolphe street; durham NC 27712
• MDR Report Key: 10148695
• MDR Text Key: 195364154
• Report Number: 3002769706-2020-00009
• Device Sequence Number: 1
• Product Code: MDB
• Combination Product (y/n): N
• PMA/PMN Number: K020931
• Number of Events Reported: 1
• Summary Report (Y/N): N
• Report Source: Manufacturer
• Source Type: foreign,health professional,u
• Type of Report: Initial,Followup
• Report Date: 07/07/2021

1 Device was Involved in the Event

1 Patient was Involved in the Event

• Date FDA Received: 06/12/2020
• Is this an Adverse Event Report?: No
• Is this a Product Problem Report?: Yes
• Device Operator: Health Professional
• Device Expiration Date: 11/12/2020
• Device Catalogue Number: 259786
• Device Lot Number: 0001054776
• Was Device Available for Evaluation?: No
• Date Manufacturer Received: 06/10/2021
• Is This a Reprocessed and Reused Single-Use Device?: No
• Patient Sequence Number: 1