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Particle Sample Tube Lengths for Pharmaceutical Monitoring

日期：2024-02-21 15:48

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摘要：

AirborneParticleCounters (APC) are used for a variety of purposes inpharmaceuticalcleanrooms for such applications:

·Filter testing

·Cleanroomcertification andtesting

·Isolator certificationandtesting

·Cleanroom and cleandevicemonitoring in Pharmaceutical Manufacturing Facilities

The use ofAPCsrequires the use of tubing for the sampling of the air, as theAPCmay be located some distance from the actual air being sampled.Thetubing is connected to an isokinetic probe that allows forthesampling of air in both unidirectional andnon-unidirectionalcleanrooms or clean devices. Per various GMPs,the guidance valuefor this air velocity in these unidirectionalenvironments is 0.45meters/second 20%.Thetubing connects an isokinetic probe to the particlecounter.

Various factorsimpactthe efficiency of particle transport in tubing. Factors suchas theclean air velocity, tubing length, tubing material, thenumber ofbends, the radius of such bends and the tubing diameterneed to beconsidered in selecting and using such tubing.

Particle size,particlevelocity and tubing diameter are the key factors indeterminingparticle transport efficacies in tubing. Tubing materialis asecondary concern. Several common materials arelistedbelow.

Materials used forthistesting consisted of:

Bev-A-Line XX Co-extruded tubing consisting of PVC exterior and Hytrel interior. This material has been the particle transport material of choice for years, due to the smoothness of the interior walls (Hytrel).

Stainless Steel Extremely clean, durable and conductive, stainless steel is an excellent material for particle transport. However, stainless steel tubing is inflexible and expensive to install.

Polyurethane Smooth material is chemically resistant and is a lower cost than either Bev-A-Line XX or Stainless Steel.

Within the realmofpharmaceutical manufacturing, particle counting is performedusingseveral types of instruments, with different particle samplingflowrates:

·1.0 CFM (28.3 LPM) isthetraditional flow rate used for testing filters andcertifyingcleanrooms. Some portable and remote particle counterssample airat 1.0 CFM. Nominal transport tubing for this flow rateis ¼”ID.

·50 LPM is an alternateflowrate. One such reason for choosing a higher flow rate isbecause ofthe requirements of cleanroom certification testing atthe 5.0micron particle level. ISO 14644-1 requires a minimum samplevolumeof 1000 liters or 1.0 cubic meter. The one cubic meterminimumsample volume is also specified in EU Annex 1. Nominaltubing forthis flow rate is ½” ID.

Pharmaceutical CleanroomsandParticle Transport

Inpharmaceuticalapplications, 0.5 and 5.0 micron particles aremonitored as part ofGMP Regulations. It should be noted thatalthough 0.5 micronparticles have a high transport efficacy at 1.0CFM and 50 LPM flowrates, particles > 1.0 micron do nottransport well in tubingregardless of the flow rate and tubingdiameter. For applicationswhere 5.0 micron particle monitoring isregulated, keeping tubinglengths as short as possible isrecommended.

Looking attheassociated data in Figures 1 and 2, an approximate 20% lossofparticles 5.0 micron and greater is realized at 10 feet. Forthisreason, sample lengths greater than 10 feet should notbeconsidered because of the amount of error such sample lengthscouldimpose on the measurements.

An additional pointofreference is the latest version of “EU Guidelines toGoodManufacturing Practice, Medicinal Products for Human andVeterinaryUse: Annex 1 Manufacture of Sterile Medicinal Products”.Thisdocument prescribes the use of short sampling tubing.

Item 6 (in Annex1)States: “Portable particle counters with a short length ofsampletubing should be used for classification purposes because oftherelatively higher rate of precipitation of particles ≥5.0μminremote sampling systems with long lengths of tubing.Isokineticsample heads shall be used in unidirectionalairflowsystems.”

This reflects upontheuse of tubing for the cleanroom classification but not that oftheroutine or continuous monitoring during manufacturing.

The length oftubingfor routing monitoring is also called out in Annex 1, Item11,where it states: “Where remote sampling systems are used,thelength of tubing and the radii of any bends in the tubing mustbeconsidered in the context of particle losses in thetubing.”

As Annex 1 states,thelength of tubing as well as the radius of any bends need tobeconsidered with particle sampling systems. Of particularimportanceare Grade A and Grade B cleanrooms. The maximum allowablenumber of5.0 micron particles is 20 per cubic meter for Grade A,and 29 forGrade B at Rest. (2900 for Grade B in the operationalstate). Withsuch low numbers for Grade A and B limits, a greaterthan 20% lossin 5.0 micron and larger particles represents aconsiderable riskand should be carefully considered when designinga particlemonitoring system.

LighthouseWorldwideSolutions recommends that continuous particle monitoringincritical locations (Grade A) be carried out only withparticlesample tubing lengths of less than 10 feet or approximately3meters. For Grade B operations, similar practices should alsobeconsidered.

Figure 1illustratesthe effects of particle size on transport efficacy in a1.0 CFMflow rate particle-counting test.

Figure 2illustratesthe effects of particle size on transport with a 50 LPMflowrate.

OtherFactors:

As the sampletubingwill retain some particles over time, this accumulationofparticles can impact the results of continuous monitoring.Suddenrelease of particles (previously suspended on the tube walls)mayresult in an unusually high count outside the actualconditionsinside the cleanroom or clean air device. Sample tubecleaning orreplacement may be considered to limit these suddenunexpected highparticle counts.

Particle Sample Tube Lengths for Pharmaceutical Monitoring

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