Cleaning Validation Research Articles

Cleaning Method Validation for Determination of Residues in Anti-Cancer Drug product for Injection by Using RP-HPLC Technique

Cleaning method validation is a part of good practices in pharmaceutical sector and need to seek the contamination present in production area. OBJECTIVE: An RP-HPLC method for the cleaning samples analysis for Anti-Cancer Drug product Melphalan Hydrochloride for Injection was develop and validated. The method was developed and validated for quantitation of Cleaning of residue left in the vessels of the production equipment’s. The analytical method used to determine the complete cleaning for Melphalan Hydrochloride for Injection by HPLC method. METHOD: The Cleaning validation was performed on Inertsil ODS,C18,(150mm×4.6mm,5μm) chromatographic column temperature at 40°C, and the detection wavelength was set at 260nm. Mobile Phase-A:10mL ammonium acetate, 88mL Purified water, 10mL acetic acid, 2mL Triethylamine, and Mobile Phase-B: 1mL Buffer, 10mL acetonitrile,190mL Purified water, and at a flow rate of 1.5 mL/min, and the injection volume was 10μL. RESULTS: The validation results of Melphalan Hydrochloride were linear over the concentration from 0.10 µg/mL to 0.75µg/mL (r = 1.00) and the recoveries from LOQ to 150% and precision ranged from 50% to 76% (RSD < 30%, n =9). CONCLUSION: This method has been validated successfully and all the results met the acceptance criteria. Hence method of Cleaning Validation is suitable for testing of residue sample of Melphalan Hydrochloride for Injection.

Improving Cleaning Validation Utilizing Adenosine Triphosphate Technology

Background: Thorough cleaning and disinfection of high-touch surface areas in hospital inpatient rooms remain vital parts of effective strategies in reducing hospital-acquired infections (HAIs). Currently, Methodist Specialty & Transplant Hospital (MHST) inconsistently utilizes fluorescent marking for terminal cleaning validation. Without quantitative results, it’s difficult to measure the effectiveness of cleaning. To ensure MHST is maintaining a safe and clean environment for patients & staff, MHST implemented a comprehensive cleaning verification program to include adenosine triphosphate (ATP) technology. We aimed to establish the program with baseline readings, and an overall weekly passing score of 95% for all tested inpatient rooms. Methods: To achieve sustained improvement, we needed to monitor, educate, and have periodic performance feedback to individuals and stakeholders. Key stakeholders (IP, EVS, Operations Leadership, Nursing Leadership representative) were identified, and a weekly meeting was established to discuss the planning and implementation of the ATP program. Some key actions included: standardization of brand of luminometer- device to measure ATP for microbial contamination; establishment of 16 high surface touch points to be tested; partnership with IT to create a database & dashboard for ATP results & data analysis; training of ATP device to all personnel who will be utilizing ATP device; establishment of a threshold for a “pass” clean (relative light unit [RLU] less than or equal to 45). Summary of Results: After baseline testing, the average weekly pass score met goal at 95 percent for all tested rooms. The bedside table located on the 2W floor was the location that failed the most (3 instances). Conclusions: Our program implementation project aimed to improve terminal cleaning validation utilizing ATP technology in inpatient rooms, was successfully implemented. Equipped with quantitative results, the MHST team, was able to verify cleaning quickly and efficiently without any confusion, as it may have been with the previous verification method of fluorescent marking. The partnership between Infection Prevention (IP) & Environmental Services (EVS) was crucial in the implementation of this process improvement- from participating in training together to understanding and sharing ATP pass/fail score data.

Ensuring Purity: A Comprehensive Guide to Cleaning Validation in Pharmaceuticals

Ensuring Purity: A Comprehensive Guide to Cleaning Validation in Pharmaceuticals

Clean-in-place (CIP) validation of oil-based cleaning and sanitization for Salmonella-contaminated tubing: Evaluation of Enterococcus faecium as a surrogate

The safety of low-moisture foods is of continual concern due to the survival and cross-tolerance of certain bacterial pathogens under dry conditions. This study screened for Salmonella surrogates using a controlled bacterial desiccation system for testing against formulated antimicrobial oils. The effect of inoculum preparation on the heat resistance of Salmonella in peanut butter was also addressed. Thereafter, a tubing system was utilized to validate a dry cleaning and sanitation procedure at the temperature range of peanut butter processing. Tubes were contaminated by re-circulating peanut butter inoculated with a test organism to 108−9 CFU/g. The contaminated system was flushed with fresh canola oil under laminar flow for cleaning, followed by holding with acidified oil or water-in-oil (W/O) emulsion to sanitize. A linear relation (R2, 0.89) was observed between the oil-flush (cleaning) duration and surface cell removal, and the prevailing surface cleanliness dictated the efficacy of sanitization. System decontamination was achieved at 60 °C through a two-step oil flush (3.6 min) and acidified W/O emulsion treatment (30 min). The test organisms, S. Enteritidis phage type 30 and Enterococcus faecium NRRL B-2354, were reduced by this procedure to levels undetectable by enrichment of tubes (n = 9). The E. faecium showed less susceptibility than S. Enteritidis under all the conditions tested, suggesting that it may be used as a Salmonella surrogate to validate such a process in the food-processing environment. Adaptation of the proposed oil-based system would allow a shifted cleaning and sanitation paradigm precluding the necessity of traditional wet cleaning and application of flammable alcohol-based sanitizers.

HPLC Method Development and Validation for Residue Analysis of Steroid

A High-Performance Liquid Chromatography technique was developed for Residue Analysis of Megestrol Acetate collected from pharmaceutical manufacturing equipment’s. The samples were collected by Texwipe swab, separated by using Primesil C18 150mm x 4.6 mm, 5µm (Part No.: PC181504650) stationary phase and 65:35 of Acetonitrile: water as mobile phase in isocratic mode of elution. The residues were extracted from the swab in ultrasonic bath and later determined at a wavelength of 280nm. The detection was done using PDA detector for improved sensitivity. The developed method was then validated depending on the parameters of Cleaning Validation suggested by FDA. The method was found to be linear in a concentration range of 0.03-15 μg/ml. RSD of six replicates (Precision) were found to be 1% and the Recovery was found to be >90%. This method can be used to determine trace residues by Megestrol Acetate API on the manufacturing equipment’s in order to avoid any cross contamination during batch manufacturing.

Test Soil and Material Affinity for Reusable Device Cleaning Validations.

While selecting the test variables for a cleaning validation for reusable medical devices, the manufacturer must provide a simulative and clinically representative challenge for the device. An appropriate challenge must be identified with care so as not to overchallenge the cleaning process by selecting the worst case for every variable, thus leading to an impossible validation or unrealistic processing requirements. To appropriately select the testing variables, an understanding of the challenge to the cleaning process is important. The relationship among device material, test soil, and application method was investigated by testing 140 variable combinations, including seven materials (stainless steel, polyoxymethylene, polyether ether ketone, nitinol, aluminum, titanium, and silicone), four test soils (defibrinated blood soil, coagulated blood, modified coagulated blood, and Miles soil), and five soil application methods (pipetting neat, pipetting spreader, painting, handling with soiled gloves, and immersion). Stainless steel was the only material that showed consistent soil application in a thickness (at ~6 μL/cm2) that fully covered the test surface without some element of pooling, cracking, flaking, or soil migration with all test soils and application methods. The data collected using solubility testing indicated that a complex relationship for material adherence may exist between device materials and test soil. Stainless steel was the most challenging material tested.

Review on Cleaning Validation

Each pharmaceutical industry's objective is to reliably and affordably produce goods with the necessary qualities and attributes. Method development is crucial for drug discovery, development, and evaluation in pharmaceutical formulations drug discovery, development, and evaluation in pharmaceutical formulations, method development is crucial. This review article's main goal was to examine how pharmaceutical manufacturing procedures are developed and validated from the beginning of formulation to the final commercial batch of product. The results must be trustworthy when analytical procedures are used to get high-quality results for pharmaceutical samples.A verification policy in the pharmaceutical business specifies how verification is carried out, and both the type of verification and the verification policy adhere to Good Manufacturing Practice (GMP) laws. The efficient running of pharmaceutical enterprises depends on validation. From raw ingredients to finished goods, stability and validation are performed at every stage. Accuracy, specificity, precision, limit of detection (LOD), limit of quantitation (LOQ), robustness, robustness, and system were the validation parameters for the method. In terms of conformity testing, it is explained. Both routine and stability assessments make use of all validation parameters.[1].

Development and Validation of Analytical Method of Novel Cleaning Validation for Immunomodulating Agent by New RP-HPLC

The analytical method was developed to evaluate the effectiveness of the procedure to clean the remains of the active pharmaceutical ingredients (APIs) from the equipment surface after manufacture of the final product. For this validation, High Performance Liquid Chromatographic (HPLC) method has been chosen. The HPLC chromatographic separations were achieved using C18 (150×4.6 mm), 5µm, column, employing buffer solution and organic solvent in the ratio of 70:30 (v:v) as mobile phase with the flow rate 1.0 ml/min. The column temperature was maintained at 25 °C and a detector wavelength of 225 nm was employed. Method validation study was conducted on eight separate surfaces. In this paper, stainless steel surface, one of the eight surfaces, was chosen since it is the most widely used surface during the manufacture of the finished product including immunomodulating agent. Validation study was studied between the linearity levels of 2.7% (LOQ% level) and 300%. The method was successfully validated by establishing specificity, linearity, precision (system precision, repeatability, and intermediate precision), accuracy, robustness, solution stability and limit of detection (LOD) & limit of quantification (LOQ) for immunomodulating agent raw material.

Handheld FTIR outperforms total organic carbon swab in pharmaceutical cleaning validation.

Cleaning Validation is a crucial process in pharmaceutical manufacturing, as it verifies that cross-contamination levels are below acceptable limits. The use of Mid-Infrared (IR) spectroscopy has long been proposed as a rapid method enabling real-time release, but only with the recent emergence of a handheld Fourier-Transform IR (FTIR) does a feasible solution exist for practical implementation in pharmaceutical manufacturing plants. This paper address the model development challenges for multi-product plants without complete traceability of production equipment and produced product. This is done by developing a partial least squares discriminant analysis model determining if the sample is clean or not clean compared to a residual acceptance limit, based on total organic carbon (TOC) measurements. The model is built and tested on artificial samples printed with a chemical printer for multiple products with different spectral peaks based on 91 samples in the calibration set and tested on 30 samples in the validation set. Furthermore, the model also incorporates spectra from surfaces with different surface roughness. The evaluation of the model is based on sensitivity, specificity and class error. The model outperforms or performs equally well as TOC swab with sampling error, dependent on the sampling error distribution for the TOC swab.

A Brief Review On Cleaning Validation-Regulatory Guidelines For Pharmaceuticals

Cleaning validation is a process used by pharmaceutical manufacturers to ensure that their equipment and facilities are thoroughly cleaned and free of any residual contaminants that could potentially compromise the quality of their products. This process is guided by regulatory guidelines set forth by FDA and European Medicines Agency (EMA) are two examples of such agencies.
 Cleaning validation protocols are typically required by these guidelines, which outline cleaning procedures, acceptance criteria for evaluating the effectiveness, as well as testing and documenting the results. The protocol should also include a risk assessment to determine which equipment and areas of the facility are most critical to the product's quality and safety.
 Manufacturers are also expected to periodically review and update their cleaning validation protocols as necessary, and to keep detailed records of all cleaning validation activities. A manufacturer's cleaning validation protocol and the presence of contaminants may also be verified by FDA or EMA inspections. To ensure consistently high quality, pharmaceutical manufacturers must control cross-contamination. There must be a comprehensive cleaning regime in place to demonstrate that the methods employed in a facility consistently control the carryover of product (including intermediates and impurities), cleaning agents, and extraneous material into subsequent products. An effective cleaning regime provides documented evidence that these aspects are consistently controlled within a facility. As a pharmaceutical manufacturer, it is your responsibility to ensure that your cleaning process complies with cGMP regulations, first and foremost.

Laboratory Glassware Cleaning Validation by Liquid Chromatographic Quantitation of Betamethasone Valerate Residues

Use of clean glassware ensures reliability of analyses that are carried out in laboratories. Glassware should be free of contaminants and residues from previous tests. It is therefore necessary to demonstrate the efficiency of glassware cleaning procedure through validation. This study aims to evaluate the cleaning efficiency of laboratory glassware by quantitation of betamethasone valerate residues in cleaned glassware. Betamethasone ointment was selected through a risk ranking process as the worst to clean product. Glassware used in analysis of this drug product was cleaned manually and residues evaluated using high performance liquid chromatography. The analysis method was validated at concentration levels of 1 - 8 µg/ml for specificity, accuracy, precision, linearity, limit of detection and limit of quantitation. The method demonstrated residue recovery of 97%. Repeatability and inter-mediate precision expressed as relative standard deviation were 1.2% and 1.4%, respectively. The calibration curve was linear over a concentration range from 2.04 to 6.13 µg/ml with a correlation coefficient of 0.9997. The detection limit and quantitation limit were 0.11 µg/ml and 0.34 µg/ml, respectively. No residue was detected in glassware that was sampled for the cleaning validation. The results indicate that the manual cleaning method is effective as the level of betamethasone residues in cleaned glassware was below detection limit and thus will not interfere with analysis of the subsequent analyte.

Cleaning Validation in Pharmaceutical Industry

In pharmaceutical industries there is possibilities of contamination, cross contamination, microbial contamination, adulteration of drug with other active ingredient or contamination with other material like raw material, dust, lubricant, intermediates and air born particle.1 Cleaning validation validate the effectiveness of cleaning procedure for removal of excipient, product residue, degradation product and cleaning agent. Cleaning validation improves the potency and reliability of cleaning in given pharmaceutical production and equipment. The cleaning validation is essential part of the quality assurance. As a result, validating cleaning procedures is critical in the pharmaceutical sector to ensure the safety, efficacy, and quality of drug batches. The purpose of this review is to provide information about cleaning validation in pharmaceutical industry to provide better customer care and quality of product. This article will discuss the relevance of cleaning validation in the pharmaceutical sector, and it will do so in accordance with regulatory guidelines.2,3

Design of Analytical Method Validation Protocol Evaluating Environmental Monitoring of AND Contamination on Surfaces Based on Cleaning Validation Procedures: A Multi Component RP-UHPLC Method.

Environmental monitoring of anti-neoplastic drug (AND) residues in workplaces is crucial to limit exposure to workers who handle with them. Although wipe sampling is the most appropriate methodology to evaluate the risk, conflicting results are also reported due to the lack of standardized and validated procedures. In this study, procedures for surface contamination of ANDs in workplaces are presented, with a focus on sampling, sample preparation and instrumentation. The analytical method validation parameters are designed to comply with requirements of The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Q7 Good Manufacturing Practice (GMP) for active pharmaceutical ingredients. Additionally, the study provides a simple, specific, rapid and multi-component analytical method to evaluate seven ANDs that are Gefitinib, Imatinib, Dasatinib, Axitinib, Erlotinib, Nilotinib and Sorafenib at very low concentration levels, simultaneously. Quantitative, precise and reproducible results obtained from the study show that environmental monitoring procedure and analytical method validation protocol presented in the study can be used to reduce and monitor occupational exposure risk to ANDs in wokplaces.

A Review on Pharmaceutical Cleaning Validation

The goal of this review is to establish the significance of cleaning validation in the pharmaceutical industry. Pharmaceutical product and active pharmaceutical ingredients (APIs) can be contaminated by other pharmaceutical products or APIs, by cleaning agents, by microorganisms or by other materials e.g. air borne particles, dust, lubricants, raw materials, intermediates, etc. Cleaning procedure is the process of assuring that cleaning procedures effectively remove the potentially dangerous substances from equipments. This can be minimized by proper cleaning of equipment, apparatus as well as the processing area. So it is necessary to validate the cleaning procedures to ensure safety, efficacy, quality of the subsequent batches of drug product and regulatory requirements in Pharmaceutical product manufacture. It briefly provides an overview on mechanism of contamination, cleaning mechanisms, cleaning agents, procedure of cleaning, and sampling techniques.

QUANTITATIVE DETERMINATION OF TERBINAFINE RESIDUES ON THE PHARMACEUTICAL MANUFACTURING EQUIPMENT SURFACES

Background: Cleaning validation is a critical analytical responsibility required by GMP (Good Manufacturing Practice), which confirms the effectiveness of the cleaning standard procedure in the pharmaceutical manufacturing process for all the produced drug products contacting the shared pharmaceutical manufacturing equipment. The need to carry out cleaning validation is especially important when the drug product is the “worst-case” for the cleaning procedure regarding solubility, therapeutic potency, toxicity, and surface adherence of active pharmaceutical ingredients (API). Estimation of API residues requires a selective and sensitive method capable of quantitative determination of API traces remaining over the surface of manufacturing equipment after the cleaning procedure. Aim: The present study demonstrates the suitability and the applicability of the proposed method obtained with a combination of a sensitive, selective, and specific analytical HPLC and effective swab wipe sampling procedures for quantitative estimation of terbinafine residues in samples collected from pharmaceutical manufacturing equipment surfaces and the efficiency of the developed standard procedure for cleaning of the shared manufacturing equipment in support of cleaning validation. Methods: The swab sampling procedure was developed to obtain a suitable recovery (>80 %). The surface (sampling area – 25 cm2) was wiped with one swab moistened with methanol. The analytical procedure was developed using the HPLC system “Agilent 1260 Infinity II” and BDS Hypersil C18 250×4.6 mm, 5 ?m column with an isocratic elution of mobile phase. Results and Discussion: The developed combined method was validated concerning chromatographic system suitability test, specificity, linearity range, accuracy, precision, the limit of detection (LOD), and quantitation (LOQ). The stability of terbinafine HCl solutions in methanol, the swab material, and membrane filter compatibility was also studied. The calibration curve was linear (R2=0.99999) over a concentration range 0.00003-0.025 mg/mL; LOD – 0.000015 mg/mL, and LOQ – 0.00003 mg/mL; The determined concentrations of terbinafine residues in test solutions were not more than 0.00090 mg/mL which are below the limit of cross-contamination of the next drug product. Conclusions: The performed analytical study using the developed method with a combination of an analytical HPLC and swab sampling procedures for estimation of terbinafine residues on surfaces of the pharmaceutical equipment used during the manufacture of Terbinafine HCl 250 mg uncoated tablets demonstrates the validity of the cleaning procedure. Other quality control laboratories can apply the proposed method to carry out cleaning validation on various drug formulations of terbinafine HCl.

Controlling cross‐contamination by food allergens

Controlling cross‐contamination by food allergens

Connecting Across Competencies: Leveraging Best Practices for Processing.

The AAMI working group ST/WG 93 is finalizing a standard (AAMI ST98) for the cleaning validation of reusable medical devices based on guidance from the technical information report AAMI TIR30:2011/(R)2016. A number of analytical best practices are being considered for this new standard. Test method suitability for processing cleaning validations historically has been established using one positive control and performing an extraction efficiency. The new cleaning validation standard is proposed to require a change from only one replicate test sample to three when performing method suitability. This change will affect manufacturers; therefore, the value of and consideration for performing these additional replicates requires explanation. This article discusses how variation of validation parameters can affect the accuracy and precision during method suitability testing. Multiple replicates are needed to understand the variability of method extraction and impact on cleaning validations of reusable medical devices.

Cleaning validation in analytical development: Current challenges and future prospectives

Cleaning validation in analytical development: Current challenges and future prospectives - IJPCA- Print ISSN No: - 2394-2789 Online ISSN No:- 2394-2797 Article DOI No:- 10.18231/j.ijpca.2020.018, International Journal of Pharmaceutical Chemistry and Analysis-Int J Pharm Chem Anal

An Overview of Risk Management and Risk-based Cleaning Validation

Risk in general means exposure to harm or a factor that can contribute towards bringing harm to a system. Almost every operation in the pharmaceutical industry is susceptible to risks. There is a need to overcome risks and them to prevent unwanted changes in product quality and safety. This prevention can be done by carrying out quality risk management (QRM) that facilitates the proper of risks, risk analysis, risk assessment to control and reduce risks. ICH Q9 guidelines explain quality risk management and its applications in the pharmaceutical industry. Cleaning validation is performed to verify and evaluate the efficacy of cleaning procedures used to clean the equipment after production and to prevent cross-contamination between products that are manufactured in the production facility. current study on reviews of quality risk management and cleaning validation policies. By incorporating QRM in the quality policy, companies can look to improve the modern Approach towards facing risks related to the issues that affect the product quality, safety and compliance concerning the cleaning of equipment used in manufacturing and supporting operations in the industries.

Roundtable Discussion: The Challenge of Developing Effective Sterilization and Reprocessing Instructions for Use.

Roundtable Discussion: The Challenge of Developing Effective Sterilization and Reprocessing Instructions for Use.