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It was reported that a quadrox-id adult was contaminated with a black substance, which was found during priming.The affected product was not used for patient treatment.No harm to any person has been reported.The affected product was technical investigated in the getinge laboratory on 2022-10-04.During visual inspection the black substance could be confirmed.In order to determined the substance, the destructive manipulation of the oxygenator was necessary.The production records of the affected hmod 70000-usa #squadrox-id adult o.Filt with lot # 3000201531 were reviewed on 2022-10-13.According to the final test results, all quadrox-id with lot #3000201531 passed the test as per specifications.Production related influences can be excluded.A nc review was performed for the reported product and batch; in regards to manufacturer date of 2021-10-27 no non conformance were found associated with the reported failure.Further investigation steps were performed.Microbiological and sterilization investigations and evaluations: microbiological review: microbiological examination of the complaint sample was performed by external laboratories in order to characterize the microbial growth associated with the complaint sample.For the sample the microorganisms were characterized as fungi.Namely the species could be identified to be cladosporium halotolerans or cladosporium parahalotolerans.Cladosporium halotolerans is a well-known indoor fungi and well-known to be found also in hypersaline environments supporting the observed growth in priming solution.It is unlikely the organism would be derived from the product as the product is terminally sterilized.Sterilization review: adult oxygenators like, quadrox hmod 70000-usa are provided as sterile.The product is sterilized by ethylene oxide gas.The affected product lot in question was traced back to its respective sterilization process.The routine sterilization process is also monitored with biological indicators to demonstrate the efficacy of the sterilization run.The sterilization process was delivered within specification and biological indicator results from each of the sterilization processes tested negative for growth (sterile).There is no indication that the suspected contamination could be attributed to the sterilization process.-sterilization process and validation review: the sterilization process, identified as cycle 2 is an established sterilization cycle that has been qualified.The sterilization process has been validated per the industry standards.The process is formally reviewed annually and periodic requalification of the process have been executed to confirm the efficacy of the process.The sterilization process has been validated by an overkill sterilization method according to the sterilization standard.This approach is conservative in nature and is based on a reference organism in the form a biological indicator with both high population and high resistance to the sterilization process.Per the standard sterilization processes qualified in this manner are conservative in nature and often use a sterilization treatment in excess of what is necessary to achieve sterility.The latest annual review completed in may of 2022 reviewed the sterilization for year 2021.There were no changes made to the sterilization cycle.The annual review demonstrated a state of control with no history of repeated nonconforming events in regards to sterilization at sterigenics wiesbaden.Microbiological quality review: the microorganism characterization of the contaminated samples was noted as nonspecific fungi source and a mold species cladosporium halotolerans/parahalotolerans from the genus cladosporium.The microbiological characterization from the complaint sample does not suggest organisms that represent challenge to the sterilization the ethylene oxide sterilization process.The ethylene oxide sterilization process is validated with known a high population and known high resistance bacterial spore of bacillus atrophaeus.There is one known mold organism that can represent a challenge to the sterilization process, pyronema domesticum.P.Domesticum is associated with cotton material sourced from china, where the product of interest is produced from synthetic plastic materials.Microbial id testing of complaint (b)(4) resulted in the detection of cladosporium halotolerans/parahalotolerans, a common indoor fungus.A review of bioburden as well as environmental monitoring data for 2022 determined that within in total 4985 microbial id testings performed cladosporium has not been identified on any product.In clean room area of maquet cardiopulmonary gmbh in hechingen, the mold species cladosporium cladosporoides complex was found six times in a close time range starting august 2022 until october 2022.4 hits came from air sampling, 2 hits from surface sampling.Cladosporium halotolerans was never identified.According to sandle t.A (2011)*1 and barnett et al.(2007)*2 the most common fungi found in clean rooms are penicillium, aspergillus and trychopyton.Within hechingen site clean rooms the genus penicillium was identified in 9 cases and aspergillus in four (4) cases, while only one (1) trychopyton species was identified.Additionally, nine (9) microbial ids did not determine any species or genus and were determined to be mold.These identifications account for about 1.02% of all microbial ids performed, which is according to sandle t.A (2011)*1 typical for grade c cleanroom areas not considering other mold species present in the clean rooms.The samples were taken over the course of the year.Most of the ids were reported during clean room qualification activities.About 68% of all mold was detected there.In 2022 in total 54 ids were reported from yeast and mold accounting for 1.0% of all microbial id samples.There is also no obvious negative trend in course of the year detectable.Thus there is no information to suggest the source of the organism, related to the reported complaint, is associated with, or arises from, the product.Conclusion: the sterilization process has been validated, periodically reviewed, and periodically requalified to confirm the sterilization process is effective.The characterization of the organism growth is not representative of those that known to present a challenge to the sterilization process.There is no indication the suspected contamination is related to the design of the sterilization process.Packaging of the product" there are no known packaging issues at the quadrox-id that could lead to a compromised primary sterile barrier.Therefore it is unlikely that the primary sterile barrier of complaint (b)(4) has been compromised.Furthermore a medical assessment was performed with following outcome: a review of the correspondence, external test results, and the sequence of events suggest the ¿black substance¿ observed in the oxygenator is mold.Dna sequencing and species identification by emsl support the conclusion of mold infiltration by cladosporium halotolerans or cladosporium parahalotolerans.The cladosporium species is ubiquitous in the environment having been isolated in almost any environmental source and geographic location.The fungi is only infrequently associated with human or animal opportunistic infections.Ninety-two phenotypes of this species have been isolated with the most frequent sub species identified as cladosporium halotolerans (14%) as identified in the culture report (sandoval-denis, et al., 2015).An extensive investigation of manufacturing (production and sterilization) packaging, shipment and storage by getinge subject matter experts failed to uncover a root cause, or root causes, that may be associated with this event (maquet cardiopulmonary gmbh, 2022).The additional non-getinge components used in the extracorporeal circuit were not in the scope or purview of the getinge internal investigation team.The complaint documentation did not identify the secondary supplier.Contamination at any step in the manufacturing and supply chain by non-getinge components cannot therefore be ruled out as a possible vector.The un-packaging, set-up, priming, and storage of the extracorporeal circuit ¿sequence of events cluster¿ may include a possible vector for contamination that is very difficult to identify.However, assuming the circuit was received sterile from the manufacturer(s); the review can conclude that any breach in aseptic technique during set-up, priming, and storage (environmental control) during the 40 days sequence, may have led to contamination by a cladosporium fungus.The clinical practice of ¿pre-priming extracorporeal circuits¿, as described specifically, warrants further commentary.Extended pre-priming of extracorporeal circuits prior to therapy application is not promoted by getinge in training, company policies or in the instructions for use.Getinge has conservatively and explicitly cautioned against extend prepriming and storage, citing the risk of bacterial growth, accumulation of air bubbles, and the possibility of leakage.To conclude, the available information provided appears to support a contamination vector that occurred during set-up, pre- priming and/or extended storage prior to clinical application.Thus the reported failure "black substance in the oxygenator" was confirmed but was most probable not associated with or contributed by a product related malfunction.The exact root cause of the reported event could not be determined.As a immediate action a hhe (health hazard evaluation) was initiated.Within the course of the hhe further actions will be defined.The occurrence rate was calculated for the reported issue and it was determined that this is not a systemic issue.Therefore, no remedial action is required.The occurrence rate related to the reported issue is currently being monitored as part of maquet cardiopulmonary¿s trending program and additional investigations or corrections will be implemented in case of adverse 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