Carbon Measurement Methods for Cleaning Validation: Comparing Direct Combustion with Rinse and Swab Sampling Methods. - Pharmaceutical Technology

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Carbon Measurement Methods for Cleaning Validation: Comparing Direct Combustion with Rinse and Swab Sampling Methods.
Cleaning validation provides assurance that the quantity of residual substances collected from equipment surfaces are within permissible limits, helping to ensure quality control and safety in pharmaceutical manufacturing facilities. Three different cleaning validation methods for measuring the carbon in residual samples of various pharmaceutical substances were compared.


Pharmaceutical Technology Europe
Volume 24, Issue 8

Swab-sampling with direct-combustion method


Figure 3: Total organic carbon (TOC) concentrations for (a) tranexamic acid, (b) isopropylantirine and (c) Gentashin ointment using swab sampling with direct combustion.
Swab sampling with direct combustion consists of wiping the inside surface of the production apparatus with a piece of quartz filter-paper swab material, and then conducting measurement using a direct-combustion carbon-measurement system. The swab material with adhering residue is measured directly (i.e., without first extracting with water) in a TOC analyser using a connected solid-sample combustion unit or module (SSM).


Table IV: Measurements using swab sampling with direct combustion.
To evaluate the rate of recovery of the different types of substances using this method, paper swab material (45-mm diameter Advantec quartz glass paper QR-100, heat treated at 600 C for 15 min) was used to wipe the sample adhering to the stainless steel pot and placed in the sample boat, which is then placed in the SSM (SSM-5000A, Shimadzu) connected to the TOC analyser (TOC-LCPH, Shimadzu). Three replicates of each sample were run. The SSM uses 400 mL/min oxygen as a carrier gas. The calibration curve is a 1-point calibration using 1% C glucose aqueous solution. The total carbon (TC) content on the swab was measured directly by the TOC analyser. Selected measurement data are shown in Figure 3.


Table V: Summary of measurement results.
Since the carbon content in each of the residue measurement samples is 200 g, the TC value would be 200 g if all of the sample were wiped off. For the blank, measurement was conducted in the same way by wiping the stainless pot, which had no sample applied. The measured blank value was subtracted from each TC value, and then divided by the theoretical value of 200 g using Equation 1 to determine the rate of recovery. The results are shown in Table IV. A high recovery rate of about 100% was obtained for all the substances, regardless of whether they were water soluble or water insoluble.

Conclusion

The measurement methods used here and their respective recovery rates are summarised in Table V. When using the rinse- and swab-sampling methods, some of the water-insoluble substances had high recovery rates while others had low recovery rates. It is thought that this may be due to differences in the affinity with which the substances adhere to the stainless steel pot. Accordingly, it is possible that residue evaluation using these methods would be difficult for substances with low recovery rates.

In contrast, high recovery rates were obtained for all the substances when using the swab sampling with direct-combustion method, regardless of whether the substances were water soluble or water insoluble. Therefore, this method is considered to be the most versatile measurement method for conducting cleaning validation, especially when multiple compounds are being manufactured in the same vat, if the compounds are unknown, or if there is a possibility the known compounds will decompose into other compounds.

Robert Clifford*, PhD, is industrial business unit manager at Shimadzu Scientific Instruments, 7102 Riverwood Drive, Columbia, MD 21046, tel. 800.447.1227,
. Minako Tanaka is a scientist at Shimadzu Applications Development Center, Kyoto, Japan,
.

*To whom all correspondence should be addressed.

Submitted: 17 Nov. 2011. Accepted: 12 March 2012.

References

1. R. Baffi et al., J. Parenter. Sci. Technol. 45 (1), 7–12 (1991).

2. K.M. Jenkins et al., PDA J. Pharm. Sci. Technol. 50 (1), 6–15 (1996).

3. M.A. Strege et al., BioPharm Intl. 9 (4), 42(1996).

4. A.J. Holmes et al., PDA J. Pharm. Sci. Technol. 51 (4), 149–152 (1997).


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