Cleaning validation of ofloxacin on pharmaceutical manufacturing equipment and validation of desired HPLC method

M Saeed Arayne, Najma Sultana, S Shahnawaz Sajid, S Shahid Ali
PDA Journal of Pharmaceutical Science and Technology 2008, 62 (5): 353-61
Inadequate cleaning of a pharmaceutical manufacturing plant or inadequate purging of the individual pieces of equipment used in multi-product manufacturing or equipment not dedicated to individual products may lead to contamination of the next batch of pharmaceutics manufactured using the same equipment. Challenges for cleaning validation are encountered especially when developing sensitive analytical methods capable of detecting traces of active pharmaceutical ingredients that are likely to remain on the surface of the pharmaceutical equipment after cleaning. A method's inability to detect some residuals could mean that either the method is not sensitive enough to the residue in question or the sampling procedure is inadequate. A sensitive and reproducible reversed-phase, high-performance liquid chromatographic method was developed for the determination of ofloxacin in swab samples. The method for determining ofloxacin residues on manufacturing equipment surfaces was validated in regard to precision, linearity, accuracy, specificity, limit of quantification, and percent recovery from the equipment surface, as well as the stability of a potential contaminant in a cleaning validation process. The active compound was selectively quantified in a sample matrix and swab material in amounts as low as 0.55 ng/mL. The swabbing procedure using cotton swabs was validated. A mean recovery from stainless steel plate of close to 85% was obtained. Chromatography was carried out on a pre-packed Merck (Dermstadt, Germany) Lichrospher model 100 Rp-18 (5.0 microm, 250 mm X 4.0 mm) column using a mixture of sodium lauryl sulfate (0.024% aqueous solution), acetonitrile, and glacial acetic acid (500:480:20,v/v) as the mobile phase at a flow rate of 1.5 mL/min with a column temperature of 35 degrees C and 294 nm detection. The assay was linear over the concentration range of 2 ng/mL to 2000 ng/mL (R approximately 0.99998). The method was validated for accuracy and precision. The stability of ofloxacin in the swab samples was also assessed. In regard to the 10-ppm acceptance criteria in the succeeding batch, the calculated limit was 437 microg/cm2 while according to the 0.1% dosing approach the calculated value was 116 microg/cm2. The calculated recovery values from swab samples were below these acceptable limits during three consecutive cleaning trials. This confirms that the desired level of cleanliness is achieved using the current cleaning procedures, which were consequently validated.

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