DrugStability:Updateandfutureplans.

TimHillsNottinghamUniversityHospitalsNHSTrust

OnbehalfoftheBSACWorkingPartyonDrugStability

BSACDrugStabilityWorkstream

•  Updateofprogresssofar•  PK/PDconsiderations•  FlucloxacillinStabilityresults•  MeropenemStabilityresults•  Clinicalexperienceofbufferedcontinuousinfusions

2016andbefore•  NationalOPATsurvey

–  LackofavailabilityofinfusiondeviceswaslimitingOPATandeffectiveantimicrobialstewardshipinOPAT

•  Literaturereview121articlesvsNHSQCstandards“YellowCoveredDocument”–  Nostudyfullycompliant

JenkinsetalJAC2017

BSACDrugStabilityTestingProgramme

•  BSAC-supportedprogrammewithindustrypartners

•  Independentlyverified•  Open-accessdrug-stabilitydata•  Increasingtheopportunityandavailabilityfor

sterileproductionforuseinOPATservices•  Stabilitytenderawarded

–  Continuousinfusionflucloxacillin–  Continuousinfusionmeropenem

PK/PDconsideration

Pre-ScopingStudy

•  Assessingpotentiallystableconcentration/formulations

•  Lowerstandardofscrutiny

MainStudy(YCD)

•  Triplicatetesting•  Body-worn32oC•  Twoelastomericpumps•  Shelf-lifeassignmentrequires95-105%concentration(90-105%ifdegradationproductsfullyunderstood)

BSACDrugStabilityTestingProgramme

Pre-ScopingStudy

• 10and50mg/ml• Unbufferedèunstableat24hr• Sodiumcitratebuffer0.3%pHcirca.7

Flucloxacillin-Results

SodiumCitrate0.3%BufferedFlucloxacillin

•  Assignedshelflife13days2-8oCthen24hoursat32oCPoster:Hills,AllwoodetalBSACOPAT2017

Meropenem–6.25mg/ml

Poster:Hills,AllwoodetalBSACOPAT2017

Meropenem–25mg/ml

Poster:Hills,AllwoodetalBSACOPAT2017

CitrateBuffer

3Ca2+

Ca2+

- O-O-

O-Ca2+

Ca2+

6Na+

CitrateBuffer–potentialissues

Citrate-BufferedCIVbeta-lactams•  11patientepisodes

–  Fluclox.8g/24hr(n=4)–  Fluclox.12g/12hr(n=2)–  Pip/taz13.5g/24hr(n=5)

•  Arangeofinfectionsweretreated,–  Discitis/spinalsurgicalinfection(n=4),–  Lungabscess/empyema(n=2),–  Neurosurgicalinfection,prostheticjointinfection,diabetic

foot,osteomyelitis,Enterobacterialpneumonia,bronchiectasis(n=1each).

•  Extendedbloodstakenatleastonce

Monitoredbloodresults

•  NopatientrequiredCIVinterruption•  LowCa2+:1xderangedLFTs,1xLowVitaminD•  9from11“Cured”or“Improved”•  Nofailuresduetobuffer

OtherCIVissues•  Clampwasnotreleased–missedoneday•  Patientcutlinewhilstgardening•  Linebecame“stiff”èincompleteinfusion•  Drugnotrunningthrough?insufficientwarmuptimeor?patienttampering

•  Patientselectionimportant•  Currentleadtimes•  Localpreparation

BSACDrugStabilityTestingProgramme-2018

•  Publicationwithopenaccessfromhttp://www.bsac-dsp.com/

•  Agents– Piperacillin/tazobactam– ?Benzylpenicillin–  Industrypartners

Whichcontinuousinfusionpipercillin/tazobactamwould/doyouuseinyourservice?

Votingoptionsforslido1.13.5g/24hour2.18g/24hour3.Bothoftheabove4.Either5.Neither6.Don’tknow/notsure

2016andbefore

•  OPATsurveyresults•  LiteraturereviewvsYCDstandards•  AwardingofBSACtenderforLaboratorystabilitytestingin-linewithYCD

2017

•  Jan-LiteraturereviewpublishedJAC•  April-YCDupdate–32oC+/-1oCstandardforexternalbody-wornin-usestudies

•  Resultsforbody-wornCIVflucloxacillinandmeropenem•  Piperacillin/tazobactamagreedasnextcommissionedagentforstabilitytesting

2018

• Publicationinpeer-reviewedjournalsasopen-accesspublications,linksfromdrugstabilityprogrammewebsite

• Discussionswithindustryrefuturetesting

Acknowledgements•  BSACOPATStandardsCommittee-Devices/DrugStabilityWork-stream–  ConorJamieson(SandwellandWestBirminghamNHSTrust)

–  AndrewSeaton(Glasgow)– MarkGilchrist(Imperial)– MarkSantillo(ChairNHSPharmaceuticalQualityAssuranceCommitteeandQCSouthWest)

–  CarolyneHorner(BSACProgrammeManager)