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The two main sampling techniques available for cleaning validation are rinse and swab sampling. FDA prefers swab sampling to rinse sampling (4, 5). In many pharmaceutical manufacturing sites, a hood is used to sample and aliquot multiple active pharmaceutical ingredi- ents (APIs) on site.
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Sampling in cleaning validation in pharmaceutical industry has been a topic of ever-increasing interest and scrutiny in recent Food and Drug Administration (FDA) inspections. The Validation of procedures used to clean the equipment employed during the various steps of manufacturing process is a clear requirement of (cGMP). Such as, FDA inspectors now expect to see functioning cleaning validation program with appropriate documentation in place their inspections.
Let us have a step-by-step explanation of sampling techniques and requirement, as well as specific analytical procedures to be used in the analysis of those samples. It should specific which laboratories are to be involved in the testing and any precautions to be taken throughout the validation exercise.
A visual check should be incorporated into the cleaning assessment. The samling technique chosen to evaluate the effectiveness of the cleaning procedure should be swabbing with a swab, the fluid rinse of samples, or a combination of both methods. The Following sampling methods provide various levels of assurance concerning cleaning.
Visual Inspection:
The visual inspection is always performed at the end of a complete cleaning cycle. The visual inspection is an active and qualitative observation of product contact surfaces to confirm the absence of residue and the next batch production can start.
Rinse Water Sampling and analysis:
According to 2004 FDA “Guide to Inspections Validation of Cleaning Processes:” “Two advantages of using rinse samples are that a larger surface area may be sampled, and inaccessible systems or ones that can not be routinely disassembled can be sampled and evaluated.”
- Analysis can be quantitative, using pH, conductivity, particle count, microbial count, Total Organic Carbon (TOC) determination, spectrophotometry, bioassays, or limulus amebocyte lysate for pyrogens.
- Recovery factor is uncertain; it involves dilution.
Surface sampling and analysis
- Removes adherent materials.
- Analysis can be quantitative.
- The Precise definition of the area sampled is required.
Method Selection:
Whenever possible, each piece of equipment should be dismantled into its individual components after cleaning and each part should be individually tested for cleanliness. In this manner, any inadequacies in the cleaning process will be more readily identified and localized.
It may not be practical or desirable to dismantle large or Clean-IN-Place (CIP) equipment. Regardless, validation sampling and testing should commence as soon as possible after the cleaning process is complete to reduce the chance of contamination by outside sources. Equipment that has just been cleaned should be covered immediately by appropriate means to protect it from any contamination.
Swabbing:
involves using a wipe or swab that is moistened with high purity water (WFI – water for injection) that is typically wiped over a defined area in a systematic multi-pass way always going from clean to dirty areas to avoid recontamination – i.e. 10 side by side strokes vertically, 10 horizontally and 10 each with the flip side of the swab in each diagonal direction. For TOC analysis very clean low background swabs or wipes and sample vials such should be used.
Rinse Water Sampling:
involves taking a sample of an equilibrated post-final rinse that has been re-circulated over all surfaces. Rinse samples should be correlated to a direct measuring technique such as swabbing.
Solvents:
Aqueous or organic solvents used in the cleaning procedure should be sufficient to remove residues, and at the same time, should be minimized to reduce the risk of reaction with or damage to the equipment, or the over-dilution of the residue and the resultant loss of analytical sensitivity.
Samples should be collected in clean or sterile containers are suitable for this intended use. All validation samples must be properly labeled with complete information regarding the source of the sample,
Sampler’s name, sampling date, reference number, product name, and part of equipment from which the sample has been collected.
A sample of rinse or swabbing solvent should be always be included with the actual test samples to serve as a reagent blank for any chemical or microbiological determination when required.
All types of samples, physical chemical, or microbiological, should be collected according to a written procedure and using techniques, reagents, equipment, and containers appropriate to the type of testing to be performed. Only trained personnel should perform the collection of these samples.
The environmental effectiveness of cleaning procedure should be assessed by the surface sampling of non-product contact surfaces (e.g.: floors, walls, air dusts, exterior equipment surfaces, etc.).
Samples should be collected and analyzed for potential contamination.
Some Most Important Question And Answer Given Below Related to Sampling of Cleaning Validation:
- What are the sampling methods for cleaning validation?
Swabbing and rinsing are the two most common techniques used for sampling of cleaned surfaces (FDA, 1993). Swabbing is a direct surface sampling method, while rinsing is an indirect method.
- What is direct sampling for cleaning validation?
Direct sampling for cleaning validation is also known as the swab method, where a sterile material is systematically rubbed across a surface to be analyzed for the presence of residue.
- What is rinse sampling in cleaning validation?
Rinse samples can be used to determine the carryover of residues over a large surface area and cover all main process items including transfer pipework. In the cases where swab sampling is not practical, it is acceptable to analyse only rinse samples; however this should be justified as part of the validation study.
- What is the sampling inspection method?
samples are taken from a target lot (inspection lot) for examination in order to determine the acceptability of the lot according to that lot’s quality standards. Thanks to the small number of items to be inspected compared to 100% inspection, manufacturers can save on inspection costs and time.
