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Pharmaceutical manufacturers are globally forced to follow international guidelines on cleaning validation. Cleaning validation is related to the concept of the worst-case product; however, the worst-case product is a function of the manufacturer and the product portfolio. Consequently, manufacturers are faced repeatedly by cycles of worst-case product alteration, and repeated cycles of worst-case oriented analytical method development. Generally, this problem is hardly controlled due to the various products manufactured by the same facility. However, Analytical Quality by Design (AQbD) offers a possible solution through the development of robust and sensitive multicomponent analytical methods that span a wide spectrum of possible products. Cephalosporin antibiotics are a broadly manufactured class of antibiotics that can lead to anaphylaxis in extremely small quantities; therefore, an ultra-level of cleanness is required for facilities involved in such products. A group of the highest market share cephalosporin products was used to present the application of AQbD to introduce a reliable solution to cleaning validation that can be employed in pharmaceutical facilities. A multivariate optimization approach was utilized for the development of a sensitive multicomponent HPLC method; in addition to the proposal of a novel chemometric approach to troubleshoot the developed method. [ABSTRACT FROM AUTHOR] more...

Abstract Metal doping is an effective method to tune the optical and chemical properties of nanoparticles. Herein, a comparative study was conducted to assess the effect of metal dopant (Mg, Cu and Sn) on ZnO nanoparticles for visible LED photocatalysis. The photocatalysts were synthesized via a facile co-precipitation method. Doped ZnO nanoparticles were employed for photodegradation of citalopram; a commonly used antidepressant drug. The structural, morphological and optical properties of the nanoparticles were analyzed using high resolution transmission electron microscopy, X-ray diffraction, Brunauer-Emmett-Teller measurements and diffuse reflectance spectroscopy. A decrease in band gap energy was obtained for Mg (3.21 eV), Cu (3.15 eV) and Sn (3.05 eV) compared to undoped ZnO (3.34 eV). Results showed that the photocatalytic activity of ZnO nanoparticles towards citalopram degradation under visible light was enhanced by doping with Sn which showed superior photocatalytic performance compared to Cu. Whereas, Mg doped ZnO demonstrated the lowest photocatalytic activity. Full factorial design (24) was conducted to investigate the effect of dopant, pH, catalyst loading and initial citalopram concentration on the efficiency of the treatment process. The interaction between the metal dopant and pH had significant impact on photodegradation efficiency. At optimum conditions, 80% degradation of 25 µg mL−1 citalopram was obtained in 2 h using commercially available LED light using 0.5 mg mL−1 Sn doped ZnO. Kinetics of citalopram degradation was also investigated and was found to follow pseudo-first order kinetics. The optimized photocatalytic protocol was successfully applied for treatment of water samples obtained from production lines during the cleaning validation cycles of citalopram. Sn and Cu doped ZnO nanoparticles had great sustainability for wastewater treatment as it kept its catalytic behavior up to three cycles without significant decrease in photocatalytic activity. The integration of such an approach into the currently employed cleaning validation protocols would offer an economical advantage for pharmaceutical wastewater treatment. Graphical Abstract more...

The potential of adaptive tank cleaning devices to reduce resource consumption of cleaning processes is quantified on the example of a dairy tank under production conditions. As methodological approach, a cleaning validation process was applied to obtain information on the resource consumption of the existing cleaning procedure as reference. An improved cleaning procedure with increased mechanical cleaning action was designed. It exploits the capabilities of motor‐driven jet cleaners to perform helical, zigzag, spiral and meander‐shaped nozzle movements. The nozzle movements were applied according to the location of cleaning‐critical area and the fouling deposit distribution. The configuration was supported by cleaning simulations. Both cleaning procedure were quantitatively compared. The adapted cleaning process reduced the cleaning time by 32 per cent without compromising the cleanling success. The volumetric flow rate was 55 l/min instead of 130 l/min and the energy requirement for cleaning was lowered by approx. 227,260 kJ per cleaning cycle. Practical applications: Reducing cleaning times, water consumption, and strengthening food safety are essential challenges for food production. The methodical approach for conducting a cleaning validation provides necessary information to systematically address priorities of optimization: (1) reduction of cleaning time, (2) reduction of water consumption, (3) reduction of energy consumption. The optical detection of cleaning‐critical area, fouling deposit distribution and the temporal cleaning process opens the possibility of monitoring the hygiene status and strengthening food safety. The use of adaptive, motor‐driven tank cleaning devices enables the targeted adjustment of cleaning intensity. This enables the targeted cleaning of hard‐to‐clean and easy‐to‐clean tank areas and may reduce resource consumption and cleaning time. [ABSTRACT FROM AUTHOR] more...

Metal doping is an effective method to tune the optical and chemical properties of nanoparticles. Herein, a comparative study was conducted to assess the effect of metal dopant (Mg, Cu and Sn) on ZnO nanoparticles for visible LED photocatalysis. The photocatalysts were synthesized via a facile co-precipitation method. Doped ZnO nanoparticles were employed for photodegradation of citalopram; a commonly used antidepressant drug. The structural, morphological and optical properties of the nanoparticles were analyzed using high resolution transmission electron microscopy, X-ray diffraction, Brunauer-Emmett-Teller measurements and diffuse reflectance spectroscopy. A decrease in band gap energy was obtained for Mg (3.21 eV), Cu (3.15 eV) and Sn (3.05 eV) compared to undoped ZnO (3.34 eV). Results showed that the photocatalytic activity of ZnO nanoparticles towards citalopram degradation under visible light was enhanced by doping with Sn which showed superior photocatalytic performance compared to Cu. Whereas, Mg doped ZnO demonstrated the lowest photocatalytic activity. Full factorial design (24) was conducted to investigate the effect of dopant, pH, catalyst loading and initial citalopram concentration on the efficiency of the treatment process. The interaction between the metal dopant and pH had significant impact on photodegradation efficiency. At optimum conditions, 80% degradation of 25 µg mL−1 citalopram was obtained in 2 h using commercially available LED light using 0.5 mg mL−1 Sn doped ZnO. Kinetics of citalopram degradation was also investigated and was found to follow pseudo-first order kinetics. The optimized photocatalytic protocol was successfully applied for treatment of water samples obtained from production lines during the cleaning validation cycles of citalopram. Sn and Cu doped ZnO nanoparticles had great sustainability for wastewater treatment as it kept its catalytic behavior up to three cycles without significant decrease in photocatalytic activity. The integration of such an approach into the currently employed cleaning validation protocols would offer an economical advantage for pharmaceutical wastewater treatment. [ABSTRACT FROM AUTHOR] more...

Eco-friendly stannic oxide nanoparticles functionalized with gallic acid (SnO2/GA NP) were synthesized and employed as a novel photocatalyst for the degradation of citalopram, a commonly prescribed antidepressant drug. SnO2/GA NP were characterized using high-resolution transmission electron microscopy, Fourier transform infrared spectroscopy, Brunauer–Emmett–Teller measurements and X-ray diffraction. A validated RP-HPLC assay was developed to monitor citalopram concentration in the presence of its degradation products. Full factorial design (24) was conducted to investigate the effect of irradiation time, pH, SnO2/GA NP loading and initial citalopram concentration on the efficiency of the photodegradation process. Citalopram initial concentration was found to be the most significant parameter followed by irradiation time and pH, respectively. At optimum conditions, 88.43 ± 0.7% degradation of citalopram (25.00 µg/mL) was obtained in 1 h using UV light (1.01 mW/cm2). Citalopram kinetics of degradation followed pseudo-first order rate with Kobs and t0.5 of − 0.037 min−1 and 18.73 min, respectively. The optimized protocol was successfully applied for treatment of water samples collected during different cleaning validation cycles of citalopram production lines. The reusability of SnO2/GA NP was studied for 3 cycles without significant loss in activity. This approach would provide a green and economic alternative for pharmaceutical wastewater treatment of organic pollutants. [ABSTRACT FROM AUTHOR] more...

[Display omitted] • Effective LLME for HPLC-UV determination of enrofloxacin in swabs. • New cotton disk-assisted dispersion of extractant in LLME. • Solidification of floating organic drop. • Dodecan-1-ol as extraction solvent for preconcentration of enrofloxacin. • First LLME procedure for cleaning validation in pharmaceutical manufacturing. In this work, a preconcentration approach, cotton disk-assisted liquid–liquid microextraction with solidification of floating organic drop, was developed. A molten extractant (dodecan-1-ol) was placed on the surface of a rotating cotton disc, embedded with a magnetic stirrer bar, for extractant crystallization and retention on the disc. Rotation of the disc in a sample solution on a hot-plate magnetic stirrer (at 65 °C) resulted in extractant melting, tearing and dispersion in sample phase. Dispersion of extractant was achieved without the use of dispersing solvent, as in classical dispersive liquid–liquid microextraction. Cooling of the extraction mixture (−5 °C) with simultaneous rotation of the disc promoted crystallization of extract drop. The solidified floating extract drop was then separated. The preconcentration approach was applied to chromatographic determination of enrofloxacin in swabs for cleaning validation in pharmaceutical manufacturing. The rotating cotton disc ensured efficient dispersion of the extractant in the aqueous sample phase, leading to high analyte recovery between 98 and 105 %. The linear range of analyte detection was 0.6 to 180 mg/L; and the limit of detection (3σ) was 0.2 mg/L. [ABSTRACT FROM AUTHOR] more...

Dietary supplements as pharmaceutical dosage forms, can be found commercially available in online pharmacies, drugstores and other establishments. They represent foods that supplement the normal diet and are concentrated sources of nutrients (vitamins, minerals, and other nutrients or physiological effects), marketed in dosage forms designed to be taken in prescribed amounts (capsules, tablets, drops, etc.). The purpose of this paper is to validate the cleaning process of the production line for the production of solid pharmaceutical forms. The aim of the research is to determine the effectiveness of the proposed measures by the validation of the cleaning process from the microbiologic perspective, as well as to define the time of the status of "clean" equipment, i.e. reliable and safe work on multifunctional equipment, a process in which there is no cross-contamination of one product with residues of another. The validation has clearly and unequivocally demonstrated that one production line for the production of solid pharmaceutical preparations may produce more products on the same line even if it also produces probiotic preparations which are normally considered believed to require a separate production facility. Continuous monitoring of the effectiveness of the validated cleaning procedure should be carried out at defined intervals after production of the selected product. more...

In this study, the HPLC and Total Organic Carbon (TOC) analysis methods have been developed and validated for the determination of the amount of Mometasone furoate and CIP100 residues on the surface of production equipment and to confirm the efficiency of the cleaning procedure. Mometasone furoate and CIP100 have been chosen based on the worst case assessment approach. The limit of mometasone furoate contamination that has been determined is 100 ug/swab and the specified limit of CIP100 contamination is 100 ug/swab which should not be exceeded during sequential cleaning of the equipment. Mometasone furoate shows good linearity in the range 0.1-1.0 ppm for the HPLC method and CIP100 2.0-10.0 ppm for TOC Analysis. The percentage of recovery from stainless steel plates using swab sampling techniques was found in the limits of 95.12% and 99.93% respectively in the HPLC and TOC methods. Both methods are simple, inexpensive, short analysis time and high sensitivity for quantitative determination of Mometasone furoate and CIP100 on the surface of manufacturing equipment well below the contamination limit. The validated method meets the requirements for demonstration of the validation of residual cleaning of mometasone furoate and CIP100 on the surface of production equipment more...

A cleaning validation for a family of compounds utilizing swab sampling and rinse solution procedures, and high performance liquid chromatography for separation and detection of the analytes was performed.Effective parameters on recovery including sampling method, swab characteristics, solvent, swabbing technique, and material substance of product contact surfaces within the manufacturing equipment for swab and rinse sampling method, quantitative cleaning verification method, and active pharmaceutical ingredient (API) level and nature have been studied. The limit of detection and the limit of quantitation for the HPLC method were determined to be 0.0198 μg/mL, and 0.0495 μg/mL of the analyte, respectively. The linearity on replicate injections of the standard prepared in the range of 0.78, 1.55, 3.1, and 6.2 μg/mL, and relative standard deviation (R.S.D.) found to be 1.2, 1.0, 0.9, and 0.6, respectively with correlation coefficient of R2 = 0.9999. Recovery coverage for each type of surface was acceptable, ranging from 63.88% for swab sampling of stainless steel to 97.85% for rinse sampling of PVC. The acceptance criteria for precision on replicate injections of the analyte prepared in three concentration levels covering the specified range of 50, 100, and 200% was successfully accomplished R.S.D. lower than 15% for recovery results.Thus, choosing the appropriate sampling method, swab type, and surface condition can affect and increase recovery rate determination efficiency. [ABSTRACT FROM AUTHOR] more...

Permitted Daily Exposure Limits (PDEs) are set for Active Pharmaceutical Ingredients (APIs) to control cross-contamination when manufacturing medicinal products in shared facilities. With the lack of official PDE lists for pharmaceuticals, PDEs have to be set by each company separately. Although general rules and guidelines for the setting of PDEs exist, inter-company variations in the setting of PDEs occur and are considered acceptable within a certain range. To evaluate the robustness of the PDE approach between different pharmaceutical companies, data on PDE setting of five marketed APIs (amlodipine, hydrochlorothiazide, metformin, morphine, and omeprazole) were collected and compared. Findings show that the variability between PDE values is within acceptable ranges (below 10-fold) for all compounds, with the highest difference for morphine due to different Point of Departures (PODs) and Adjustment Factors (AFs). Factors of PDE variability identified and further discussed are: (1) availability of data, (2) selection of POD, (3) assignment of AFs, (4) route-to-route extrapolation, and (5) expert judgement and differences in company policies. We conclude that the investigated PDE methods and calculations are robust and scientifically defensible. Additionally, we provide further recommendations to harmonize PDE calculation approaches across the pharmaceutical industry. [Display omitted] • Study compares PDE values for five APIs among companies. • POD and AF selection impact PDE variability up to 10-fold. • Morphine shows highest PDE difference due to diverse data. • PDE calculation methods evaluated show robustness and defensibility. • Recommendations are presented for harmonizing PDE calculation approaches. [ABSTRACT FROM AUTHOR] more...

The main objective of the cleaning validation procedure is to verify the effectiveness of the cleaning procedure for removal and minimising the risk of cross-contamination, a topic that has become more important regarding the development of the medicines. Furthermore, if a product is found to be the worst among many of the products, one cleaning validation procedure of the worst-case product can cover the validation of the remaining ones, thus saving time and money. A novel, reproducible and efficient high-performance liquid chromatography (HPLC) method was optimised and validated for the detection of the following cephalosporin residues: cephalexin (CPH), cefaclor (CFC), cefixime (CFX), cefdinir (CFR) and ceftazidime (CFZ) in human spiked plasma and in production machines using rinse and swab sampling collected from surfaces and application to Cosa®CIP Detergent. Isocratic chromatographic system was performed at ambient temperature using mobile phase consisting of acetonitrile: 40% tetrabutylammonium hydroxide adjusted to pH 7.0 ± 0.1 with 10% phosphoric acid (72.5:27.5, v/v) on Ultrasphere ion pair column (250 mm × 4.6 mm, 5.0 μm particle size) at a flow rate 1.0 mL/min, injection volume 10 μL and UV detection at 265 nm. The chromatographic run time was less than 20 min for the mixture. Linear relationships were obtained over the concentration ranges 0.5–25 ng mL−1 for CPH, 1.5–30 ng mL−1 for CFC, 2–33 ng mL−1 for CFX, 3–35 ng mL−1 for CFR and 4–40 ng mL−1 for CFZ with correlation coefficients >0.998. Analytical and bioanalytical validation methods were carried out following terms of linearity, specificity, LOQ, LOD, accuracy and precision for determination of cephalosporin residues in production machines and in human spiked plasma according to FDA guidelines. [ABSTRACT FROM AUTHOR] more...

Magnetic separation processes are known as integrated bioanalytical protein purification method since decades and are well described. However, use of magnetic separation processes in a regulated industrial production environment has been prevented by the lack of suitable process equipment and prejudice against the productivity of the process and its qualification for cleaning‐in‐place operation. With the aim of overcoming this prejudice, a comprehensive process development approach is presented, based on a GMP‐compliant magnetic separator, including an optimization of the batch adsorption process, implementation into a technical‐scale, and the development and validation of cleaning routines for the device. By the implementation of a two‐step counter‐current binding process, it was possible to raise the yields of the magnetic separation process even for very low concentrated targets in a vast surplus of competing proteins, like the hormone equine chorionic gonadotropin in serum, from 74% to over 95%. For the validation of the cleaning process, a direct surface swabbing method combined with a total organic carbon analysis was established for the determination of two model contaminants. The cleanability of the process equipment was proven for both model contaminants by reliably meeting the 10 ppm criteria. [ABSTRACT FROM AUTHOR] more...

Cleaning validation for pharmaceutical production equipment is a documented proof of the efficient cleaning, and one of prerequisites of good manufacturing practice in medicine production. Successful validation confirms the efficiency of the procedures of cleaning, washing, and disinfecting of the manufacturing equipment, and records results of the chemical and microbiological analyses, which are a prerequisite for a safe final dietary product. The main goal of this study was to improve the cleaning process of the production equipment by using cleaning validation procedures on the solid form production line (capsules) in the Abela Pharm d.o.o. The validation principles that are used in manufacturing of medicines can be applied to determine more efficient cleaning methods that will ensure longer periods of the status clean in the production of dietary supplements. The outcome is a practical analysis of the production equipment in view of regulatory demands, confirming that the cleaning validation measures ensure prevention of unwanted microbial growth or removal of contamination from the production equipment in order to preserve the activity, efficacy, and safety of the final dietary product. more...

Abstract A toxicological evaluation to determine the product specific permitted daily exposure (PDE) value is an accepted method to determine a safe limit for the carry-over of product residues in multipurpose manufacturing facilities. The PDE calculation for intravitreal (IVT) injection of small and large molecular weight (MW) drugs follows the guiding principles set for systemic administration. However, there are specific differences with respect to the volume administered with IVT administration, pharmacokinetic and pharmacodynamics (PK-PD) parameters and potential for toxicity. In this publication, we have proposed a method to derive PDE IVT in the presence of IVT dose. In the absence of an IVT dose we have a proposed default extrapolationof the systemic PDE for intravenous (IV) administration to the PDE IVT dose by applying a factor of 500 based on comparison of the volume of vitreous humour with the plasma volume, as well as provided examples for PK-PD and toxicity considerations. Highlights • A factor of 500 can be used to extrapolate intravitreal PDE IVT from the intravenous PDE IV. • A PDE IVT is a conservative dose that would cover potential for toxic effects in the eye. • PDE IVT can be applied to small and large molecular weight (MW) compounds. [ABSTRACT FROM AUTHOR] more...

In pharmaceutical industry there are some possibilities of contamination and cross contamination because of improper cleaning of equipment, apparatus, processing area or the starting material, this can lead to severe hazards, therefore in pharmaceutical industry we can't afford any contamination as well as cross contamination. This can be minimized by proper cleaning of equipment, apparatus as well as the processing area. TheIndustry wants to achieve these main goals with the help of GMP. This review focused on the different types of cleaning process adapted by pharmaceutical industry, how the process of cleaning validation is done. In the cleaning validation different critical parameter, factor, material and critical process are monitored and validated so that the cleaning consistency can be achieved and documented accordingly. [ABSTRACT FROM AUTHOR] more...

Due to newly introduced EU GMP (Good Manufacturing Practice) guideline for Medicinal Products for Human and Veterinary use, product specific permitted daily exposure (PDE) for toxicological evaluation in multi-purpose facilities are required within a documented process for risk assessment. European Medicines Agency (EMA) guidance on setting PDE limits so far focused on systemic administration routes such as intravenous (IV), oral or inhalation. This article provides guidance on setting PDE values for risk management purposes in multi-purpose facilities for active pharmaceutical ingredients (APIs) applied as topical otic drugs to the outer ear canal. The therewith determined PDE otic, is used for the calculation of maximum safe carry-over (MSC) in manufacturing scenarios where a topical otic product is manufactured followed by another topical otic product. [ABSTRACT FROM PUBLISHER] more...

Limits for the carry-over of product residues should be based on toxicological evaluation such as described in the “Guideline on setting health based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities”. The toxicological evaluation should be performed also for locally administered drugs to ensure patient safety. Currently, there is no guidance on setting PDE for ocular drug substances in particular. The purpose of this investigation was to identify and describe a method for calculating a PDE value for topical ocular drugs (PDEocular). As an alternative method, extrapolation of a PDE for systemically administered drugs to a PDEocularis presented. These methods may be applied in cross-contamination risk assessments for manufacturing of topical ocular drugs. Similarly, the methods apply to systemically administered drugs, if their production precedes manufacturing of a topical ocular drug. We have examined pharmacokinetic (PK) properties of topical ocular drugs and compared them to the PK parameters of systemically administered drugs. Furthermore, we examined possible adverse effects of the carry-over in topical ocular drugs at therapeutic doses. [ABSTRACT FROM PUBLISHER] more...

This report aims to determine the permitted daily exposure (PDE) of flutamide, an androgen receptor blocker, as directed by guideline EMA/CHMP/CVPM/SWP/169430/2012 that came into effect on June 2015. A literature review was conducted to identify toxicity studies of flutamide. Hazards and sensitive endpoints were determined. Based on the no adverse effect levels (NOAELs) and lowest observed adverse effect levels (LOAELs) reported from both reproductive, developmental, and 28-day toxicity studies the PDE was calculated. Most of the toxicity studies converge toward a NOAEL of 1 mg/kg/d that translates to a PDE of 0.1 mg/d. However, taking into consideration the worst case scenarios for additional safety a PDE of 0.025 mg/d (25 μg/d) was calculated based on a reported NOAEL of 0.25 mg/kg/d. A PDE of 0.05 mg/d (50 μg/d) was also calculated from reproductive/developmental toxicity studies, which is in close agreement with the PDE from the 28-day toxicity studies. Considering the lowest PDE of 0.025 mg/d, residual flutamide at this dose is unlikely to pose any risk to humans. Nonmonotonic dose response (NMDR) effects of flutamide were not supported by literature. Oral route of administration was considered. [ABSTRACT FROM AUTHOR] more...

The elderly constitute a significant, potentially sensitive, subpopulation within the general population, which must be taken into account when performing risk assessments including determining an acceptable daily exposure (ADE) for the purpose of a cleaning validation. Known differences in the pharmacokinetics of drugs between young adults (who are typically the subjects recruited into clinical trials) and the elderly are potential contributors affecting the interindividual uncertainty factor (UFH) component of the ADE calculation. The UFH values were calculated for 206 drugs for young adult and elderly groups separately and combined (with the elderly assumed to be a sensitive subpopulation) from published studies where the pharmacokinetics of the young adult and elderly groups were directly compared. Based on the analysis presented here, it is recommended to use a default UFH value of 10 for worker populations (which are assumed to be approximately equivalent to the young adult groups) where no supporting pharmacokinetic data exist, while it is recommended to use a default UFH value of 15 for the general population, to take the elderly into consideration when calculating ADE values. The underlying reasons for the large differences between the exposures in the young adult and elderly subjects for the 10 compounds which show the greatest separation are different in almost every case, involving the OCT2 transporter, glucuronidation, hydrolysis, CYP1A2, CYP2A6, CYP2C19, CYP2D6, CYP3A4 or CYP3A5. Therefore, there is no consistent underlying mechanism which appears responsible for the largest differences in pharmacokinetic parameters between young adult and elderly subjects. [ABSTRACT FROM AUTHOR] more...

Prevention of cross contamination with active pharmaceutical ingredient is crucial and requires special attention in pharmaceutical industry. Current method validation describes residual determination of olmesartan medoxomil (OLME) on stainless steel surface using swab sampling with a sensitive HPLC-DAD analysis. The acceptance limit was decided as 2 μg swab pro 100 cm2. Cotton swabs impregnated with extraction solution were used to determine residual drug content. Recoveries were 95.81%, 93.06%, and 96%. 24% with RSD below 1.5% at three concentration levels. Residual concentration was found to be linear in the range of 0.557–5.62 μg/mL, when estimated using Phenomenex Luna C18 (25 cm × 5 μm × 4.6 mm i.d.) column at 1.0 mL/min flow rate at 258 nm. The mobile phase consisted of a mixture of acetonitrile: methanol: phosphate buffer pH 3.5: tetrahydrofuran (28:13:58:1 v/v/v/v). The LOD and LOQ for OLME were found to be 0.07 and 0.22 μg/mL, respectively. The validated method was found to be simple, selective and sensitive for demonstration of cleaning validation of OLME residues on the stainless steel surface. more...

Cleaning validation procedures are carried out in order to assure that residues of cleaning agents are within acceptable limits after the cleaning process. Cleaning agents often consist of a mixture of various surfactants which are in a highly diluted state after the water rinsing procedure has been completed. This makes it difficult to find appropriate analytical methods that are sensitive enough to detect the cleaning agents. In addition, it is advantageous for the analytical methods to be simple to perform and to give results quickly.In this study, three different non-specific analytical methods are compared: visual detection of foam, pH and conductivity measurements. The analyses were performed on different dilutions of the cleaning agents Bactericidal Hydroclean and Tickopur R33. The results demonstrated that the most appropriate method for these detergents are conductivity measurements, by which it is possible to detect concentrations of cleaning agents down to 10 µg/ml. In this case, pH is an inadequate method (non-linear) and visual detection of foam is a semi-quantitative method. All these methods are easy to perform, gives a quick re-sults, and requires no expensive instrumentation. more...

The aim of this work was the single-laboratory validation of a quantitative method for the determination of amoxicillin residues in support of cleaning control and validation. Linearity was demonstrated between 2.5 and 17.5 μg/mL, without matrix effects. Mean recoveries ranged from 84.00 to 103.74% and the relative standard deviation under repetitivity and within-reproducibility conditions were from 0.58 to 4.20% and from 0.79 to 4.39%, respectively. The theoretical limits of detection and quantification were 0.133 and 0.442 μg/mL, respectively. The studied method was suitable for cleaning control purpose within good manufacturing practices. more...

In the pharmaceutical industry, an important step consists in the removal of possible drug residues from the involved equipments and areas. The cleaning procedures must be validated and methods to determine trace amounts of drugs have, therefore, to be considered with special attention. An HPLC–UV method for the determination of digoxin residues on stainless steel surfaces was developed and validated in order to control a cleaning procedure. Cotton swabs, moistened with methanol were used to remove any residues of drugs from stainless steel surfaces, and give recoveries of 85.9, 85.2 and 78.7 % for three concentration levels. The precision of the results, reported as the relative standard deviation (RSD), were below 6.3 %. The method was validated over a concentration range of 0.05–12.5 µg mL-1. Low quantities of drug residues were determined by HPLC–UV using a Symmetry C18 column (150´4.6) mm, 5 µm) at 20 °C with an acetonitrile–water (28:72, v/v) mobile phase at a flow rate of 1.1 mL min-1, an injection volume of 100 µL and were detected at 220 nm. A simple, selective and sensitive HPLC–UV assay for the determination of digoxin residues on stainless steel was developed, validated and applied. more...

In the pharmaceutical industry, an important step consists in the removal of possible drug residues from the involved equipments and areas. The cleaning procedures must be validated and methods to determine trace amounts of drugs have, therefore, to be considered with special attention. An HPLC–UV method for the determination of digoxin residues on stainless steel surfaces was developed and validated in order to control a cleaning procedure. Cotton swabs, moistened with methanol were used to remove any residues of drugs from stainless steel surfaces, and give recoveries of 85.9, 85.2 and 78.7 % for three concentration levels. The precision of the results, reported as the relative standard deviation (RSD), were below 6.3 %. The method was validated over a concentration range of 0.05–12.5 µg mL-1. Low quantities of drug residues were determined by HPLC–UV using a Symmetry C18 column (150´4.6) mm, 5 µm) at 20 °C with an acetonitrile–water (28:72, v/v) mobile phase at a flow rate of 1.1 mL min-1, an injection volume of 100 µL and were detected at 220 nm. A simple, selective and sensitive HPLC–UV assay for the determination of digoxin residues on stainless steel was developed, validated and applied. more...