This report has been identified as b.Braun melsungen ag internal report#: (b)(4).Device history record (dhr): reviewed the dhr for batch: 18e29ge34r, which was a reworked batch for 18e29ge341 with holdback at final control inspection due to slow flow rate.Rework was performed on that batch.After reworked, the batch was tested as per test specification and passed all tests, thus the batch was released.Summary and assessment: we detected after 60 minutes the received pump is blocked.Because the sample is blocked a too fast flow (as described by the customer) could not be determined at the received sample.We have informed our manufacturing department accordingly and received the statement as follows: dissection was performed on the received sample to verify the blockage point.After the glass tube was cut off, the solution started to flow out.Therefore, it is indeed the crystallized residue at glass tube that blocked the flow.The flow restrictor was blocked by the crystallized drug residue, flow rate testing was not able to be performed on the received sample due to the blockage at the glass tube lumen.The flow restrictor of the received sample were removed and the inner diameter of the tubing (microbore tube) was measured under smartscope.The tube id is within the specification.Then, a new flow restrictor was assembled to the received sample and sent for flow rate test.The flow rate result was within specification ± 15% deviation from nominal flow rate.The blockage observed during bmi investigation was contributed by the crystalized drug residue in the glass tube lumen of the flow restrictor.Flow rate was within specification after the received pump assembled to a new flow restrictor.The crystallization of drug will affect the flow rate of the sample.The crystallization of drug will cause blockage or partial blockage on the path of solution.Hence, the flow of the solution will become slower.There is some drugs (e.G.5fu) which tend to crystallize at some special condition.The risk of crystallization is given by the drug itself.Some function of pump (filter, microbore, glass tube) may affected when forming high amount of crystallize particle from drug.The blockage issue due to cytotoxic drug has been addressed in capa.However, there are some possibilities that can cause the sample to empty the solution earlier, which is before the nominal time.Factor 1 temperature: the temperature of the surrounding will affect the flow rate of the sample.For every increase of 1°c, the flow rate of the sample will increase by approximately 3%.For example, if the flow restrictor of the product reaches the temperature of 37°c, the flow rate of the sample will increase by approximate 18%, which mean the flow rate will increase from 2 ml/hr to approximately 2.36 ml/hr.Factor 2 external pressure: external pressure such as squeezing or laying on the pump will increase the flow rate which cause the pump to empty earlier, before the nominal time.Simulation of external pressure had been conducted.The flow rate of the product can increase when external force is applied on the pump.However, this external force is against the intended use according to ifu.Factor 3 folded blow mold: folded blow mold will also act as the external pressure to elastomeric membrane and increased the flow rate of the sample.Summary of root cause analysis: complaint on flow rate could not be confirmed due to the blockage at the glass tube.However, the flow rate test on the received sample after replacing of new flow restrictor showed the flow rate result within the specification.The id of the microbore tube of the original flow restrictor from received sample showed the id measurement within specification.Flow contribution by the flow restrictor from received sample was not able to be confirmed.
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