Impaction Technology and ISO 14698

Transcription

1 T E C H N I C A L P A P E R Impactin Technlgy and ISO Selectin f Prtable and Autmated Air Sampler Systems t meet cgmp by Jasn Kelly 01. Rev /24/2017

2 Impactin Technlgy and ISO Selectin f Prtable and Autmated Air Sampler systems t meet cgmp. PIC/s Annex 1 was recently updated in Jan 2017 and under the Clean Rm and Clean Air Device Mnitring sectin the recmmended limits fr micrbial mnitring f clean areas during peratin have remained intact since A ne cubic meter sample vlume is still required using an air sampling instrument fr active air sampling. Fig.1 PICs Annex 1 Table fr Micrbial Cntaminatin recmmended limits Even thugh these requirements frm a GMP pint f view have remained the same since 2003 there are still many Cmpanies receiving FDA 483 s fr lack f micrbial mnitring using Air Samplers. This is alarming as CFU results dictate the release/hld decisins f prduct batches and are a reflectin f prduct quality. FDA Warning Letter Example (2016) Air and surface sampling within all classified areas is nt adequate based n the fllwing; 1. Viable particulate sampling was nt cnducted inside yur Ante rm, Gwning rm, Buffer rm and laminar flw hd during certificatin f these abve classified areas. FDA Warning Letter Example (2014) Aseptic prcessing areas are deficient regarding the system fr mnitring envirnmental cnditins. Specifically, yur firm s prcedures fr mnitring ISO5 hds are nt suitable t ensure the quality f air. Fr example; A. During perids f prductin, yur firm des nt cnduct viable air mnitring daily.

3 There are many mre with the same theme and with that in mind it is the authrs pinin that this technical article shuld be dedicated t understanding active air sampling technlgy t help decisin makers make infrmed decisins when reviewing the many makes and mdels currently available n the market. What is Air Sampling Impactin Technlgy? Aersl Impactin Air Samplers are designed t have a sharp cutff curve [1] and is the prcess in which particles are remved frm an air stream by frcing the gases t make a sharp bend. Particles abve a certain size pssess s much mmentum that they cannt fllw the air stream and strike a cllectin surface such as a media plate which is available fr later analysis f cmpsitin after an incubatin perid. It is imprtant t understand that nt all Air Samplers have the same physical abilities in particle impactin capture. We all understand that a Particle Cunter used widely in Envirnmental Mnitring prgrams has a set reslutin based n the smallest particle size it can physically detect. The same hlds true fr Air Samplers as they have a limitatin n the size f particles that will impact n the media. Fr Air Samplers this reslutin is based n many physical factrs that we will cver in this article. Let s first lk clser at ISO Why is ISO s imprtant? ISO Part 1 - Cleanrms and assciated cntrlled envirnments Bi-cntaminatin cntrl - Part 1: General principles and methds was first released in One significant part f ISO Part 1 is in the selectin f an apprpriate air sampling instrument utlined in Annex A. In Jan 2013 it was vted that this standard including Part 2 were further revised. This is a key indicatr as t the imprtance f this standard t GMP and an indicatin that it firmly stands as an imprtant GMP guidance dcument. The main changes t ISO under discussin are: A new classificatin system fr viable cunts, split int surface and air cleanliness Guidance fr assessing cleanrms at start-up r after mdificatins fr bi-burden, in a similar way that cleanrms are currently assessed fr particle cunts Guidance n viable mnitring methds Recmmendatins fr data analysis

4 With these significant revisins under discussin the scpe f Air Samplers increases significantly and s it is very imprtant make infrmed decisins n the selectin f the right mdel fr yur applicatin smething that ISO Annex A has required since Many eager salesmen will tell yu that faster air sampling is the best ptin since it saves yu time. But the key questin t ask and t verify shuld be; is that mdel sufficient fr my prcess? Tw main prperties f an Air Sampler effect the instruments ability t capture and assist in incubatin f the captured particles n a media plate. Physical Efficiency [2] is the ability f the Air Sampler t cllect varius sizes f particles. This efficiency is the same whether the particle is a micr-rganism, carries a micrrganism, r is an inanimate particle. Physical efficiency is based n many factrs and the sample head gemetry and Air Sampler internal design including the media height, even envirnmental cnditins influence physical efficiency. Bilgical Efficiency [2] is the efficiency in cllecting micrbe-carrying particles. Bilgical efficiency will be lwer than physical efficiency fr a number f reasns, such as the survival f the micr-rganisms during cllectin and the ability f the cllectin medium t supprt their grwth. Accrding t ISO Annex A.3.2, there are many factrs t cnsider when chsing an Air Sampler. The sampling rate, duratin f sample, and type f sampling device can strngly influence the viability f the micr-rganisms that are cllected. Because f the number and variety f micrbial air sampling systems cmmercially available, the selectin fr a particular applicatin shuld cnsider, as a minimum, the fllwing factrs: [2] type and size f viable particles t be sampled sensitivity f the viable particles t the sampling prcedure expected cncentratin f viable particles ability t detect high r lw levels f bi-cntaminatin apprpriate culture media time and duratin f sampling ambient cnditins in the envirnment being sampled disturbance f unidirectinal airflw by sampling apparatus One f the mst fundamental selectin CRITERIA in an Air Sampler is the reslutin f the Air Sampler which can be equated t what is knwn as the d50 cutff pint.

5 We all knw with a particle cunter in pharmaceutical applicatins it must cunt 0.5um and 5.0um particles as a minimum s we make sure whatever particle cunter mdel is selected it meets that requirement. Fr an Air Sampler and its ability t capture particle sizes f interest especially when we cnsider single rd bacteria diameters are ptentially as lw as 0.3um in diameter its becmes such a critical factr t select an air sampler with the right d50 (Reslutin) and ability t cllect the smallest particle size physically pssible, s yu are cnfident in the results btained and further mre cnfident in prduct batch released. The d50 is based n particles greater than a certain aerdynamic size cllected n the media plate (nrmally 90mm diameter plates are used) and particles less than that size passing thrugh the Air Sampler. Fig.2 belw prvides a gd verview f particles entering an impactr (Sample Head f Air Sampler) and the fluid dynamics as well as the flight path f varius sizes f particles fllwing the jet stream as it fllws the airflw path. Fig.2 Flight path and jet streamlines f an Impactr head and media plate

6 With fluid dynamics and Air Sampler impactin technlgy an indicatr f cllectin efficiency is the Stkes Number. The Stkes number (StK) [1] is a dimensinless number characterizing the behavir f particles suspended in a fluid flw. The stkes number is defined as the rati f the characteristic time f a particle t a characteristic time f flw r f an bstacle and is based n the fllwing frmulae; = is the relaxatin time f the particle (the time cnstant in the expnential decay f the particle velcity due t drag). = is the fluid velcity f the flw well away frm the bstacle. = is the characteristic dimensin f the bstacle (typically its diameter). Mst well designed impactrs can be assumed t be ideal and their efficiency curves characterised by a single number StK50, the Stkes number that gives 50% cllectin efficiency [1]. StK50 is the lcatin f the ideal cutff curve that best fits the actual cutff curve.

7 A particle with a lw Stkes number fllws fluid streamlines, while a particle with a large Stkes number is dminated by its inertia and cntinues alng its initial trajectry. The d50 is the 50% cutff particle size where 50% are likely t be impacted and 50% are likely t pass thrugh the Air Sampler. Hence the d50 can be seen as the reslutin f the Air Sampler the smallest particle size that can be physically be captured by the Air Sampler. Fr thse readers ut there with a physics backgrund yu will als understand that the Reynlds Number cmes int play. Quick reminder the Reynlds number is the rati f inertial frces t viscus frces within a fluid which is subject t relative internal mvement due t different fluid velcities. The physical design and flw rate f the Air Sampler greatly influence the Reynlds number. Fr impactin technlgy Air Samplers with a Reynlds number between 500 and 3000 are best suited [1]. (This science is als applied t iskinetic sampling f particles using iskinetic prbes). Fig.3 Prtable Air Sampler Overview and Jetstream flw between sample head and media plate

8 Be aware ut in the market Air Samplers have varying d50 s sme as high as 10um that means anything belw 10um is nt impacted n the media. Try t explain that t an Auditr wh has firm ISO and bacteria size knwledge. T put all this int simple terms the sample head must be capable f effectively capturing particles in the air and maintaining uni-flw (laminar) cnditins between the sample head and the media where the particles impact. Smaller particles are subject t airflw and larger particles maintain their flight path due t higher inertia. The d50 is the pint where 50% ff the smallest size particles impact n the media, in ther wrds it s really the reslutin f the impactr as the ther 50% f these smaller particles will fllw the airflw and nt impact n the media. The same hlds true fr remte sampling heads used in autmated systems used in cntinuus mnitring where a remte vacuum surce is cntrlled using mass flw meters fr vlume cntrl. Fig.4 belw gives mre detail n the impactin technlgy and the cllectin efficiency f a remte air sampler. Fig.4 Remte Prtable Air Sampler Overview and Jetstream flw between sample head and media plate

9 Lking at ISO 5 Classificatin tables in fig.1 we see that very tight limits are set fr viable particles effectively expecting an average f zer CFU s ver a 1000L f air sampled. It is critical that the device prtable r remte air sampler used t sample with has been carefully selected. Summary With s many makes and mdels f Air Samplers n the market it is wrth lking deeply int the specificatins f each befre cmmitting t purchase. ISO Part 1 Annex A part A recmmends the Air Sampler impact velcity being high enugh t allw the entrapment f viable particles dwn t apprximately 1um and being lw enugh t ensure viability f viable particles as well has having a filtered exhaust. Fllwing cgmp and ISO the recmmended selectin criteria belw shuld be used as a guidance in selecting an apprpriate Prtable Air sampler r Autmated Air Sampling system and remember faster flw rate mdels d nt indicate better cllectin efficiencies the key factr is the d50 and the criteria fr active air sampling in sterile applicatins is fr cntinuus mnitring during that prcess. Media can dry ut faster under higher flw rates which requires mre media plate changes. Air Sampler Attributes Physical size small ftprint Material f cnstructin f enclsure and sample head Stainless Steel preferable Ability t wipe dwn easily n crevices, buttns switches r particle traps Media plate hlder easy adjustable hlder mechanism media dish diameters vary +/- 1mm t 3mm HEPA filtered exhaust - captures viable particles that have nt impacted Tuchscreen Interface - reduces cntact and ptential particle generatin Battery Operated fr better prtability n prtable units Remte sample ptins ffer mre flexibility Gas cnnectr ptins fr testing gases t ISO 8573 requirements Lcal r field calibratin ptins frm supplier Easily autclave parts Capture particles dwn t 1um t meet ISO requirements Validated fr cllectin efficiency by third party

10 References; [1] Aersl Technlgy Prperties, Behavir and Measurement f Airbrne Particles Secnd Editin (1999) William C Hinds, published by Jhn Wiley & Sns. [2] ISO Cleanrms and assciated cntrlled envirnments Bi-cntaminatin cntrl Part 1 General Principals and Methds, Annex B Guidance n validating air samplers, First Editin [3] PICs GMP Guide t Gd Manufacturing Practice fr Medicinal Prducts Annexes PE (Annexes) 1 Jan 2017 Annex 1: Manufacture f sterile medicinal prducts. [4] Applied and Envirnmental Micrbilgy (1996) Evaluatin f Three Prtable Samplers fr Mnitring Airbrne Fungi. (Sarish K. Metha, S.K. Mishra and Duane L. Piersn) [5] Aersl Research and Expsure Assessment Labratry, Department f Envirnmental Health, University f Cincinnati. (1998) Klaus Willeke, Ph.D Prfessr and Directr. Particle Cut Size Evaluatin f Air-O-Cell Sampler reprt. [6] Investigatin f Cut-Off Sizes and Cllectin Efficiencies f Prtable Micrbial Samplers. Masheng Ya and Gediminas Mainelis (2006) published in Aersl Science and Technlgy, 40: , [7] Cllectin Efficiencies and design f micrbial air samplers, Jurnal f Aersl Science, W. Whyte, C. Green and A. Albisu, Department f Mechanical Engineering, University f Glasgw. (2007). [8] FDA published 483 Warning letters.

11 Bigraphy Jasn Kelly Directr f Systems Lighthuse Wrldwide Slutins 20 Years Upper Management psitins in Envirnmental Mnitring Systems Service, Design, Installatin, Validatin and nging supprt. Has wrked n many Prjects fr tp Life-Science cmpanies assisting in prcurement, delivery and cmpliance t ensure regulatry acceptance. Wrked acrss the Wrld n many prjects in the UK, Ireland, Eurpe, Australia and nw resides in Oregn USA. He can be cntacted by n jasnk@glighthuse.cm r n LinkedIn and always welcmes queries and questins n Mnitring Systems cnnected t particle cunters r envirnmental sensrs.