United States Pharmacopeia Chapter Research Articles

An Alternative Microbiological Validation for an Online Water Bioburden Analyzer.

The Mettler-Toledo 7000RMS analyzer is a Bio-Fluorescent Particle Counter (BFPC) used to monitor real-time bioburden results from Purified Water (PW). Validation of the analyzer using 13 microorganisms and a low-intensity, fluorescent, polystyrene bead. During the execution of the validation, a laboratory water system that met Purified Water (PW) quality standards was connected to the 7000RMS, and a syringe pump was used to introduce various concentrations of microorganisms and fluorescent polystyrene beads to the analyzer. Samples were collected and tested via the traditional Membrane Filtration (MF) method and the Colony Forming Unit (CFU) plate count results were compared to the Auto-Fluorescent Unit (AFU) of the 7000RMS analyzer. The validation study was designed to follow the guidance in United States Pharmacopeia (USP) Chapter <1223 > (1), European Pharmacopeia (EP) Chapter 5.1.6 (2), PDA Technical Report 33 (3). Concepts and strategies were adapted from EP Chapter 2.6.12 Microbiological Examination of Non-sterile Products: Microbial Enumeration Tests, EP 10.2 (4), European Pharmacopeia Chapter 2.6.1 Sterility, EP 10.2 (5), USP Chapter <61> Microbiological Examination of Non-sterile Products: Microbial Enumeration Tests (6), USP Chapter <71> Sterility Tests (7), Japanese Pharmacopoeia (JP) General Information Chapter G8 Water: Quality Control of Water for Pharmaceutical Use (8). All pre-determined validation acceptance criteria for Accuracy, Specificity, Precision, Limit of Detection (LOD), Limit of Quantitation (LOQ), Linearity, and Range were met. Further, the 7000RMS demonstrated Performance Equivalence to the MF method per USP <1223> but characteristically lacked correlation to the CFU. This validation approach highlights the superior capabilities of the 7000RMS when compared against the traditional compendial MF testing method for PW.

Comparative Evaluation of Dissolution Performance in a USP 2 Setup and Alternative Stirrers and Vessel Designs: A Systematic Computational Investigation.

The dissolution testing method described in the United States Pharmacopeia (USP) Chapter ⟨711⟩ is widely used for assessing the release of active pharmaceutical ingredients from solid dosage forms. However, extensive use over the years has revealed certain issues, including high experimental intervariability observed in specific formulations and the settling of particles in the dead zone of the vessel. To address these concerns and gain a comprehensive understanding of the hydrodynamic conditions within the USP 2 apparatus, computational fluid dynamic simulations have been employed in this study. The base design employed in this study is the 900 mL USP 2 vessel along with a paddle stirrer at a 50 rpm rotational speed. Additionally, alternative stirrer designs, including the hydrofoil, pitched blade, and Rushton impeller, are investigated. A comparison is also made between a flat-bottom tank and the USP round-bottom vessel of the same volume and diameter. Furthermore, this work examines the impact of various parameters, such as clearance distance (distance between the bottom of the impeller and bottom of the vessel), number of impeller blades, impeller diameter, and impeller attachment angle. The volume-average shear rate (Stv), fluid velocity (Utv), and energy dissipation rates (ϵtv) represent the key properties evaluated in this study. Comparing the USP2 design and systems with the same stirrer but flat-bottom vessel reveals more homogeneous mixing compared to the USP2 design. Analyzing fluid flow streamlines in different designs demonstrates that hydrofoil stirrers generate more suspension or upward movement of fluid compared to paddle stirrers. Therefore, when impellers are of a similar size, hydrofoil designs generate higher fluid velocities in the coning area. Furthermore, the angle of blade attachment to the hub influences the fluid velocity in the coning area in a way that the 60° angle design generates more suspension than the 45° angle design. The findings indicate that the paddle stirrer design leads to a heterogeneous shear rate and velocity distributions within the vessel compared with the other designs, suggesting suboptimal performance. These insights provide valuable guidance for the development of improved in vitro dissolution testing devices, emphasizing the importance of optimized design considerations to minimize hydrodynamic variability, enhance dissolution characterization, and reduce variability in dissolution test results. Ultimately, such advancements hold potential for improving in vitro-in vivo correlations in drug development.

An Analytical Target Profile for the Development of an In Vitro Release Test Method and Apparatus Selection in the Case of Semisolid Topical Formulations.

This study focuses on how to define an Analytical Target Profile (ATP) which is intended for use in practice and on facilitating the selection of in vitro release test (IVRT) technology for diclofenac sodium topical hydrogel and cream. The implementation involves incorporating the new draft guidelines of the International Council for Harmonisation (ICH Q14) and USP (United States Pharmacopeia) Chapter 1220. Four IVRT apparatuses were compared (USP Apparatus II with immersion cell, USP Apparatus IV with semisolid adapter, static vertical diffusion cell, and a new, in-house-developed flow-through diffusion cell) with the help of the ATP. Performance characteristics such as accuracy, precision, cumulative amount released at the end of the IVRT experiment, and robustness were investigated. We found that the best apparatus for developing IVRT quality control (QC) tests in both cases was USP II with an immersion cell. All four different IVRT apparatuses were compared with each other and with the data found in the literature.

A new ultrasound-assisted microextraction for elemental impurities determination in tablets by ICP-MS according to USP chapters 232 and 233

Along with the United States Pharmacopeia (USP) chapters 232 and 233 regarding elemental impurities in pharmaceutical products, new challenges have been imposed in terms of sample preparation procedures prior to inductively coupled plasma mass spectrometry analysis, considering the matrix complexities. As so, a new microextraction procedure assisted by ultrasound using a cup-horn sonoreactor, minimal reactants, and sample was proposed and validated according to USP. The procedure was optimized with samples of milled tablets and 3 different acid mixtures (HNO3, 3HNO3:1HCl, and 9HNO3:1HF) and it was compared with microwave-assisted acid digestion. In the validation step, recoveries ranging from 85 to 120 % and RSD below 10 % were obtained for 22 analytes (except Ag and Pt) with satisfactory linearity and good sensitivity. The method was then applied for 37 samples of antidepressants, which presented trace levels of As, Ba, Cd, Co, Cr, Cu, Ni, Pb, Pd, Sn, and V.

Greening microwave-assisted digestion method using hydrogen peroxide for determination of elemental impurities by ICP-OES in antihypertensive active pharmaceutical ingredients

Microwave-assisted wet digestion (MAWD) using only H2O2 was proposed for oxidizing active pharmaceutical ingredients (APIs) for hypertension treatment and subsequent determination by inductively coupled plasma optical emission spectrometry (ICP-OES). Diltiazem hydrochloride (DIL) presented the most refractory characteristic for oxidation using MAWD-H2O2. This proposed MAWD-H2O2 method was validated for specificity, accuracy, and precision according to United States Pharmacopeia (USP) Chapter 233 guidelines. Regarding specificity, the most sensitive emission lines were utilized to analyze all elemental impurities in the digests, and no significant spectral interferences were observed. Sample masses of 500 mg for all APIs and a digestion temperature of 250 °C provided digests with residual carbon (RC) below 2400 mg L−1 of C. Additionally, the residual acidity of the MAWD-H2O2 digests was lower than the acidity presented by the HNO3 digests. The highest and lowest residual carbon content (RCC) for digests were observed for DIL and captopril (CAP), respectively, using MAWD-H2O2. When comparing the RCC for MAWD-H2O2 and MAWD-HNO3 digests for APIs containing aromatic rings, it was evident that H2O2 offered equivalent conditions for digesting these compounds. Accuracy tests showed recovery values of 91–110% for all elemental impurities, as recommended by USP chapter 233. Validation experiments for precision presented relative standard deviation (RSD) values below 6.4% and 10% under repeatability and intermediate precision conditions, respectively. The limits of quantification (LOQs) provided by MAWD-H2O2 are at most half of those recommended by of USP and International Council for Harmonisation of Technical Requirements (ICH). In conclusion, MAWD-H2O2 can be considered an alternative method for API digestion, aligning with green analytical chemistry principles, as it does not employ toxic reagents, minimizes waste, and the main products of H2O2 oxidation are water and oxygen. Considering the analytical Eco-Scale, the MAWD-H2O2 method scored 81, classifying it as an excellent green analysis.

Y-site simulation compatibility study of 10% calcium salts with various injectable solutions during toxicological resuscitation

PurposeTo determine the physical compatibility of 10% calcium chloride and 10% calcium gluconate in combination with injectable solutions, administered in the paediatric and adult intensive care unit setting during toxicological...

Physical compatibility of medications with concentrated neonatal and pediatric parenteral nutrition: A simulated Y-site drug compatibility study.

The physical intravenous Y-site compatibility of 15 different medications with highly concentrated neonatal and pediatric parenteral nutrition (PN) compounds is described, using existing and novel methods. PN formulations were developed based on common prescribing practices in a 400+-bed freestanding children's hospital. Medications at commonly used pediatric concentrations were mixed in a 1:1 ratio with both pediatric and neonatal PN formulations and incubated at room temperature for 4 h to simulate Y-site administration. Samples were then analyzed using the light obscuration (LO) technique, as recommended by United States Pharmacopeia (USP) chapter 788, in addition to novel flow imaging (FI) microscopy and backgrounded membrane imaging (BMI). Physical compatibility was determined using USP 788 particle count limits for all techniques. Most combinations were found to be compatible per USP 788 thresholds. Pediatric PN was incompatible by at least two methods with cisatracurium 2 mg/ml, sildenafil 0.8 mg/ml, furosemide 10 mg/ml, and ketamine 10 mg/ml. Neonatal PN was incompatible by at least two methods with cisatracurium 2 mg/ml and furosemide 10 mg/ml. Overall, results for 20 of the 30 combinations (66%) agreed across all three methods. FI and BMI results agreed for 22 of 30 combinations. LO agreed with FI in 25 of 30 combinations, and BMI and LO results agreed in 23 of 30 combinations. Most combinations tested were found to be compatible across all methods. Novel methods of FI and BMI seem useful to further evaluate LO findings and improve accuracy of particle counts when assessing PN-medication combinations.

Visual compatibility and particle counter evaluations of syringes of intramuscular psychotropic coadministered solutions

BackgroundPatients in the acute phase of agitation can require the administration of multiple drugs by intramuscular injection in order to temporarily stabilise their condition. Administration of multiple psychotropic medications in...

Disintegration testing augmented by computer Vision technology

Oral solid dosage forms, specifically immediate release tablets, are prevalent in the pharmaceutical industry. Disintegration testing is often the first step of commercialization and large-scale production of these dosage forms. Current disintegration testing in the pharmaceutical industry, according to United States Pharmacopeia (USP) chapter 〈701〉, only gives information about the duration of the tablet disintegration process. This information is subjective, variable, and prone to human error due to manual or physical data collection methods via the human eye or contact disks. To lessen the data integrity risk associated with this process, efforts have been made to automate the analysis of the disintegration process using digital lens and other imaging technologies. This would provide a non-invasive method to quantitatively determine disintegration time through computer algorithms. The main challenges associated with developing such a system involve visualization of tablet pieces through cloudy and turbid liquid. The Computer Vision for Disintegration (CVD) system has been developed to be used along with traditional pharmaceutical disintegration testing devices to monitor tablet pieces and distinguish them from the surrounding liquid. The software written for CVD utilizes data captured by cameras or other lenses then uses mobile SSD and CNN, with an OpenCV and FRCNN machine learning model, to analyze and interpret the data. This technology is capable of consistently identifying tablets with ≥ 99.6% accuracy. Not only is the data produced by CVD more reliable, but it opens the possibility of a deeper understanding of disintegration rates and mechanisms in addition to duration.

USP releases new chapter &lt;797&gt; proposals

The United States Pharmacopeia (USP) has finally released its updated Chapter <797> revisions. These revisions were written over the past 22 months while USP considered appeals filed by stakeholders. The 2019 version is mostly intact in the revision, but there are some changes to beyond-use dates (BUD) for certain institutions. In addition, USP clarifies when to identify microorganisms found during various sampling activities. “There’s very little difference in what was in the 2019 and the 2021 proposed revision,” said Patricia Kienle, RPh, MPA, BCSCP, director of accreditation and medication safety at Cardinal Health and a member of the USP compounding expert committee. (Her comments are her opinions and not the opinions of USP.) “If people were ready for the 2019 version, they’re fine with the 2021 proposed revision. There won’t be any cataclysmic change from what they were expecting from the 2019 version.” This should be reassuring news to hospitals that have been diligently working toward compliance with the 2019 version. Compounded sterile products (CSPs) were assigned one of two categories in the 2019 version. Category 1 CSPs were defined as being prepared in an unclassified segregated compounding area. These products were assigned the shortest BUDs: 12 hours or less at room temp, or 24 hours or less refrigerated. Category 2 CSPs were defined as being prepared in a compliant compounding cleanroom suite and were allowed longer dating. The new revision defines a third category, applicable to those who want to extend BUDs beyond that allowed for Category 2. Using stability-indicating analytical methods, which are based on USP Chapter <1225>, “Validation of Compendial Procedures,” institutions can assign a BUD of up to 180 days. Additional stricter garbing and cleaning procedures are also required for Category 3 CSPs. Hospital pharmacies that perform sterile compounding will see some changes in how specific they need to be when identifying microorganisms collected during surface or air sampling. Pharmacists can view the updated revisions for all of the nitty-gritty details on sampling changes (apha.us/USPrevs). “If sites have not geared up for monthly surface sampling, it is unlikely that the certifier will be able to do this,” said Kienle. “The pharmacy needs to be prepared for doing this more often if they have not already done so. Incubator space is needed, [as well as] the right media, a microbiologist will need to be referred to if an excursion is noted.” Institutions that have been preparing for the 2019 revisions will likely need to abide by additional requirements. State boards of pharmacy often have other requirements with CSPs. Any institution considering making changes to become compliant with the updated revisions should also check with their state board of pharmacy’s requirements. With these new revisions, it is possible that state boards of pharmacy may amend their existing CSP-related requirements. Pharmacists should pay close attention to what their state board of pharmacy is doing so they are not caught off-guard when the new chapter becomes enforceable. The USP compounding expert committee is allowing comments on the new revisions to be submitted until March 17, 2022. Afterward, they will review the comments and determine if additional changes need to be made to the revisions. There is no timeline defined for how long they may consider comments. Regardless, there will be a 6-month implementation window defined by USP whenever the new revisions are officially published. Upon completion of this 6-month window, the chapter will likely become enforceable in many states. If an institution has not made changes to the CSP compounding strategy after the 2019 revisions were proposed, work will be needed to get up to speed. If the institution has adequately prepared for the 2019 revisions, these new revisions will require some review and changes, but should not be overwhelming. Pharmacists should spend time reviewing these proposed revisions (and then the final versions once they are published), identify gaps at their institution, and plan accordingly.

Implementation and sequencing of a compounded sterile preparation validation testing protocol for second- and third-year pharmacy students

Background and purposeIncorporation of aseptic technique validation testing in a pharmacy curriculum consistent with United States Pharmacopeia Chapter 797 Standards is not well described. Validation testing is optimally placed prior to assignment to health-system introductory and advanced pharmacy practice experiences. Educational activity and settingEnvironmental and engineering controls consistent with a segregated compounding area were implemented. Medium risk media fill and gloved fingertip test (GFT) testing were incorporated to achieve initial and subsequent training in the second and third curricular years, respectively. FindingsFor the graduating classes of 2018 through 2020, 234 students completed validation testing and knowledge assessment. Failure of the media fill test was uncommon. Failure of the initial GFT testing occurred in 16.1% to 22.1% of second-year students and 3.2% to 5.8% of third-year students. No significant differences were seen between three consecutive student classes. SummaryIncorporation of validation testing was successful, with consistent results. Procedures and results provide guidance with respect to student class size, available facility/equipment needs, implementation of validation protocols, and associated resources. Each student is provided with documentation of annual training and validation testing consistent with existing standards for health-system pharmacy practice.

Dispersive liquid-liquid microextraction based on deep eutectic solvent for elemental impurities determination in oral and parenteral drugs by inductively coupled plasma optical emission spectrometry

A simple, fast, sensitive and green pretreatment method for determination of Cd, Co, Hg, Ni, Pb and V in oral and parenteral drug samples using inductively coupled plasma optical emission spectrometry (ICP OES) has been developed. According to United States Pharmacopoeia (USP), those metals must be reported in all pharmaceutical products for quality control evaluation (i.e., elemental impurities from classes 1 and 2A of USP Chapter 232). To improve the analytical capabilities of ICP OES, a dispersive liquid-liquid microextraction (DLLME) has performed using a safe, cheap and biodegradable deep eutectic solvent (DES) as extractant solvent (a mixture of 2:1 M ratio of DL-menthol and decanoic acid). Seven parameters affecting the microextraction efficiency have carefully optimized by multivariate analysis. Under optimized conditions, the DES-based DLLME-ICP OES procedure improved limit of quantitation (LOQ) values on range from 12 to 85-fold and afforded an enrichment factor on average 60-times higher than those obtained to direct ICP OES analysis. Consequently, LOQ values for Cd, Co, Hg, Ni, Pb and V have been on average 10-times lower than target limits recommended for drugs from parenteral route of administration. Trueness has evaluated by addition and recovery experiments following USP recommendations for three oral drug samples in liquid dosage form and three parenteral drugs. Recovery and RSD values have been within the range of 90–109% and 1–6%, respectively. All analytes were below the respectives LOQ values, hence, lower than the limits proposed by USP Chapter 232.

Tubing determination in an hematology oncology clinic.

United States Pharmacopeia (USP) Chapter <800> for hazardous drug (HD) handling in healthcare settings requires HD be primed intravenously with a non-HD solution prior to dispensing. This review details our clinic's algorithm for determining tubing needs for medications used in an hematology oncology clinic. Factors to consider are volume, irritant and vesicant properties, and compatibility with hydration solution.

Process validation, current good manufacturing practice production, dosimetry, and toxicity studies of the carbonic anhydrase IX imaging agent [111 In]In-XYIMSR-01 for phase I regulatory approval.

[111 In]In-XYIMSR-01 is a promising single-photon emission computed tomography (SPECT) imaging agent for identification of tumors that overexpress carbonic anhydrase IX. To translate [111 In]In-XYIMSR-01 to phase I trials, we performed animal toxicity and dosimetry studies, determined the maximum dose for human use, and completed the chemistry, manufacturing, and controls component of a standard regulatory application. The production process, quality control testing, stability studies, and specifications for sterile drug product release were based on United States Pharmacopeia chapters <823> and <825>, FDA 21 CFR Part 212. Toxicity was evaluated by using nonradioactive [113/115 In]In-XYIMSR-01 according to 21 CFR Part 58 guidelines. Organ Level INternal Dose Assessment/EXponential Modeling (OLINDA/EXM) was used to calculate the maximum single dose for human studies. Three process validation runs at starting radioactivities of ~800 MBq were completed with a minimum concentration of 407 MBq/ml and radiochemical purity of ≥99% at the end of synthesis. A single intravenous dose of 55 μg/ml of [113/115 In]In-XYIMSR-01 was well tolerated in male and female Sprague-Dawley rats. The calculated maximum single dose for human injection from dosimetry studies was 390.35 MBq of [111 In]In-XYIMSR-01. We have completed toxicity and dosimetry studies as well as validated a manufacturing process to test [111 In]In-XYIMSR-01 in a phase I clinical trial.

Assessment of Purity Parameters of Generic and Brand Name Losartan Potassium

Background: Generic products must be bioequivalent to the innovator brand product. Nevertheless, in addition to meeting bioequivalence standards, attention must be paid to the content of the active substance and contaminants in generic drugs. Objective: This study compared the pharmaceutical quality of four generic losartan potassium formulations with the brand-name product: Cozaar®. Methods: The United States Pharmacopeia (USP) losartan potassium standard was used as reference material. The products tested (all 50 mg formulations) included four generic tablet formulations and the innovator brand product Cozaar®. Active substance content, organic impurities, and elemental impurities were assessed following the USP monograph for losartan potassium tablets and USP Chapter &lt;233&gt; on Elemental Impurities. Results: The results showed that three of the four generic products had low content of the active ingredient. The values ranged from 86.4 to 93.8%, being acceptable not below 95% of the labeled amount. Organic impurities were not detected in any of the products, and of the 13 elemental impurities tested, only four elements were detected. The elemental impurities Cr, Ni, Cu, and As were, however, in amounts within the limits established by the USP monograph. The only concern on the generic drugs analyzed was the low content of the active ingredient in 75% of the products. Conclusion: Since losartan is a drug of continuous use, lower content of the active ingredient may go unnoticed by the users of the generic product and entailed clinical consequences during long-term therapy.

Dispersive Liquid–Liquid Microextraction of Cd, Hg and Pb from Medicines Prior to ICP Oes Determination According to the United States Pharmacopeia

A simple, sensitive and matrix effect free analytical method for simultaneous determination of Cd, Hg and Pb in drug samples (i.e., commercial dosage tablets) by inductively coupled plasma optical emission spectrometry (ICP OES) has been developed. According to the United States Pharmacopoeia (USP) Chapter 232, those metals are considered elemental impurities from class 1 and they must be assessed in pharmaceutical production as well as in quality control evaluation. In order to increase the sensitivity of the analysis, a dispersive liquid-liquid microextraction (DLLME) was performed and seven factors affecting analyte extraction were optimized by multivariate analysis. The microvolume of analyte enriched phase was directly introduced into the plasma using a multinebulizer, providing a high enrichment factor. When compared to conventional ICP OES analysis, DLLME improves limits of quantitation (LOQ) values on average 40-fold for all analytes. Consequently, LOQ values were significantly lower than their permissible daily exposures for oral drugs. Accuracy was evaluated by addition and recovery experiments following USP recommendations in eight commercial drug samples. Recovery and RSD values were within the range of 90-108% and 1-9%, respectively.

Development of a sterile compounding training and competency program at a large academic medical center.

This article is one of the 5 articles describing steps taken to enhance sterile compounding compliance at a large, multisite academic medical center. This article focuses on the development of a comprehensive personnel training and assessment program for sterile compounding. Increased regulatory oversight and the release of new United States Pharmacopeia chapters motivated the reenvisioning of the medical center's sterile compounding personnel training and assessment program. The main challenges facing any entity undertaking sterile compounding include identification of compounding staff, development of policies and procedures, and baseline and ongoing training including observational competency assessments and record keeping. These challenges are exacerbated by high work volumes and variation in compounding practices encountered within a large multisite institution. Our organization developed a team of specialized pharmacists and pharmacy technicians to implement and enforce changes promoting the safe production and use of compounded sterile products and meet rising regulatory requirements. This team worked within various operational areas to customize purchased policies and procedures and group compounding staff based on training needs. The team performs ongoing personnel monitoring and training of new compounders in a shared training space. Challenges encountered and future considerations for program enhancement are described. Implementation of standards and enforcement of staff behaviors in a large academic medical center is perhaps best completed by a team of highly trained experts working in collaboration with supervisors and using a dedicated training and testing space, as evidenced by the success of the described program in overecoming past challenges.

Selecting an Automated Parenteral Nutrition Compounder Device at a Tertiary Care Institute in Saudi Arabia.

Background: With advances in hospital automation, selecting an automated compounding device (ACD) for compounding parenteral nutrition (PN) may be challenging. A well-designed comparative review that considers safety and technical standards could assist in the selection process. United States Pharmacopeia chapter <797> and The American Society of Hospital Pharmacists (ASHP) has provided guidance on the safety and accuracy of ACDs. Objective: Utilizing a checklist of technical and performance specifications investigators sought to assess the adequacy of compounders available in the Kingdom of Saudi Arabia. Method: Investigators compared the NutriMiX KS-240 and the Exactamix EM 2400. A literature review of practice standards, safety, technical, and performance specifications was conducted. These were developed into a checklist of 46 technical and performance specifications. Investigators evaluated each ACD using the checklist. Results: It was found that 43 (93.48%) of the technical and performance specifications, required by the hospital, were met by the NutriMix KS-240, while 39 (84.78%) were met by Exactamix EM 2400. Conclusion: This review found that although ACDs comply with the majority of standards and specifications, software integration with the hospital information system may be a limiting factor in selecting an ACD. The investigators concluded that the NutriMiX KS- 240 matches the technical and performance specifications for automated compounders required by our institution.

A compounding compliance team at an academic medical center.

Highly publicized safety issues arising from poor sterile compounding practices in facilities around the United States have garnered substantial attention in recent years. This attention has led to increased scrutiny of health systems by regulatory bodies, new regulatory requirements, and changes to existing regulations or their interpretation. Health systems are often resource constrained, and the added work resulting from this scrutiny challenges pharmacy departments in meeting regulatory requirements and United States Pharmacopeia chapter 797 standards for sterile compounding. This article describes the creation of a dedicated compounding compliance team (CCT) and the team's responsibilities in support of pharmacy operations in achieving compliance with those standards. Visits to our organization by several regulatory bodies resulted in findings that required substantial work in order to achieve compliance with sterile compounding standards. Given the number and complexity of findings and the need for timely resolution, it was felt that specialized staff were needed to understand, evaluate, and correct identified deficiencies and help the already overburdened staff and leadership comply with existing standards. A CCT was formed, and work was simultaneously initiated on ensuring proper credentialing and training of all compounding staff, development of standard operating procedures, improvements in facilities, environmental monitoring, equipment certifications, practice auditing, and documentation. Key activities of the team included strategic planning, building relationships, communicating with stakeholders, self-education, and record keeping. Key partners included environmental services, facilities, and infection prevention and control personnel and departmental staff and leaders. The formation and collaborative work of a CCT at an academic medical center was successful in changing the culture of the organization and achieving compliance during visits from several regulatory agencies.

Customized antimicrobial efficacy tests offer superior evaluation of growth inhibitor efficacy for liquid microbial products

Antimicrobial effectiveness tests are common methods used to assess the risk of microbial contamination in pharmaceuticals and cosmetics. These assays may be inappropriate for endospore-based microbial products which often carry a similar – if not greater – risk of microbial contamination. In the present study, we compared the antimicrobial efficacy assessment provided by United States Pharmacopeia Chapter <51> Antimicrobial Effectiveness Testing with a modified test which utilized a customized bacterial challenge. The customized challenge inoculum comprised an assemblage of 12 bacterial strains (both pathogens and spoilage organisms) isolated from the product's end-use geography. Results suggest that some microbial inhibitor systems which pass industry standard antimicrobial effectiveness tests may fail when challenged with a customized bacterial assemblage. In order to provide the best possible assessment of microbial inhibitor systems for liquid Bacillus products, we suggest that new antimicrobial effectiveness tests be developed for this product class which include the addition of field-relevant contaminants in addition to the industry standard pathogen challenge.