The University of Kentucky's Drug Quality Task Force (DQTF) conducted a study to perform consumer-level quality assurance screening of vasopressin injections used in their healthcare pharmacies. The primary objective was to identify potential quality defects by examining intralot and interlot variability using Raman spectrometry and statistical analyses. Raman spectra were collected noninvasively and nondestructively from vasopressin vials (n=51) using a Thermo Scientific Smartraman DXR3 Analyzer.
View Article and Find Full Text PDFChlorothiazide sodium for injection, USP, is a diuretic and antihypertensive medication in the form of a white or practically white, sterile, lyophilized powder. Each vial contains 500 mg of chlorothiazide sodium, equivalent to 500 mg of chlorothiazide, and 250 mg of mannitol as an inactive ingredient. The pH is adjusted with sodium hydroxide.
View Article and Find Full Text PDFThis study employed Fourier Transform near-infrared spectrometry to assess the quality of vecuronium bromide, a neuromuscular blocking agent. Spectral data from two lots of vecuronium were collected and analyzed using the BEST metric, principal component analysis (PCA) and other statistical techniques. The results showed that there was variability between the two lots and within each lot.
View Article and Find Full Text PDFPurpose: The University of Kentucky Drug Quality Study team briefly reviews the growing concerns over pharmaceutical manufacturing quality in the globalized environment, reviews the historical approach by the US Food and Drug Administration (FDA) that prioritizes process over product in enforcing quality with manufacturers, reviews the science of process analytical technology (PAT) such as near-infrared (NIR) spectroscopy, illustrates the use of PAT methods for assessing uniformity and quality in injectable pharmaceuticals, and demonstrates the application of NIR spectroscopy in a health-system pharmacy setting while maintaining current good practice quality guidelines and regulations (cGxP).
Summary: Given that the current approach to monitoring quality in pharmaceutical manufacturing was developed in the late 1960s at a time when manufacturing was mostly domestic, the current approach prioritizes process over product, and the global footprint of manufacturing is straining federal resources to fulfill their task of monitoring quality, an approach to augment the quality monitoring process has been developed. PAT methodologies are supported by FDA for monitoring quality and offer a fast, low-cost, nondestructive solution.
SOLU-CORTEF Sterile Powder is a type of anti-inflammatory glucocorticoid that contains hydrocortisone sodium succinate as its active ingredient. It can be administered intravenously or intramuscularly, and comes in several packages including 100 mg plain vials without diluent. The diluent, which is part of the ACT-O-VIAL system, contains only Water for Injection and no preservatives.
View Article and Find Full Text PDFThe U.S. Food and Drug Administration (FDA) is a worldwide leader among analogous regulatory organizations in other countries.
View Article and Find Full Text PDFDantrolene sodium is a direct-acting skeletal muscle relaxant. Dantrolene sodium for injection is indicated, along with suitable supportive measures, for the management of sudden, severe hypermetabolism of skeletal muscle typical of malignant hyperthermia crises in patients of any age. The formulation scanned in this work was designed to be injected intravenously.
View Article and Find Full Text PDFThyrotropin alfa is a heterodimeric glycoprotein containing human thyroid stimulating hormone (TSH). It is used as an adjunctive diagnostic tool for serum thyroglobulin (Tg) testing with or without radioiodine imaging in the follow-up of patients with well-differentiated thyroid cancer who have previously undergone thyroidectomy. Inter-lot variability in the Fourier transform near-infrared spectra of 30 samples obtained from four separate lots of Thyrogen was detected in the Drug Quality Study (DQS).
View Article and Find Full Text PDFJ Mech Behav Biomed Mater
August 2023
Soft tissue is susceptible to injury from single high-magnitude static loads and from repetitive low-magnitude fatigue loads. While many constitutive formulations have been developed and validated to model static failure in soft tissue, a modeling framework is not well-established for fatigue failure. Here we determined the feasibility of using a visco-hyperelastic damage model with discontinuous damage (strain energy-based damage criterion) to simulate low- and high-cycle fatigue failure in soft fibrous tissue.
View Article and Find Full Text PDFCarfilzomib is a prescription injectable drug approved for use by the FDA as an antineoplastic agent, part of a drug class of medications known as proteasome inhibitors, and used to stop and slow the growth and progression of cancer cells within the body. The drug is approved as an agent to treat multiple myeloma. It is provided as a single-use vial that contains 60 mg of carfilzomib as a sterile, white to off-white lyophilized cake or powder.
View Article and Find Full Text PDFMeniscal tears are a common, painful, and debilitating knee injury with limited treatment options. Computational models that predict meniscal tears may help advance injury prevention and repair, but first these models must be validated using experimental data. Here we simulated meniscal tears with finite element analysis using continuum damage mechanics (CDM) in a transversely isotropic hyperelastic material.
View Article and Find Full Text PDFThis assessment of subcluster detection in analytical chemistry offers a nonparametric approach to address the challenges of identifying specific substances (molecules or mixtures) in large hyperspaces. The paper introduces the concept of subcluster detection, which involves identifying specific substances within a larger cluster of similar samples. The BEST (Bootstrap Error-adjusted Single-sample Technique) metric is introduced as a more accurate and precise method for discriminating between similar samples compared to the MD (Mahalanobis distance) metric.
View Article and Find Full Text PDFULTIVA® (remifentanil hydrochloride) is a sterile, nonpyrogenic, preservative-free, white to off-white lyophilized powder for intravenous (IV) administration after reconstitution and dilution. Each vial contains 1, 2, or 5 mg of remifentanil base; 15 mg glycine; and hydrochloric acid to buffer the solutions to a nominal pH of 3 after reconstitution. ULTIVA® is a μ-opioid agonist with rapid onset and peak effect, and short duration of action.
View Article and Find Full Text PDFPemetrexed is a folate analog metabolic inhibitor used in treatment of locally advanced or metastatic nonsquamous non-small cell lung cancer and for mesothelioma. Intra-lot and inter-lot variability in the spectra of ALIMTA® was detected in the Drug Quality Study (DQS) using Fourier transform near-infrared spectrometry (FTNIR). One vial of 12 (8%) sampled from lot S20I013A appeared 3.
View Article and Find Full Text PDFSince the US Food and Drug Administration (FDA) began monitoring the quality of pharmaceutical manufacturing by enforcing current good manufacturing practices roughly 60 years ago, forces related to the global economy have changed, rendering the task of monitoring quality more difficult. Alternative strategies by groups like Valisure, LLC, and the University of Kentucky Drug Quality Study to monitor the quality of the currently circulated US drug supply through end-product testing and screening have resulted in several concerning findings. Given the successful approaches of identifying quality defects in pharmaceuticals by non-regulatory bodies, and considering the changing landscape and pressures on manufacturing, the FDA, large buying groups, and the US Department of Defense should consider these alternative strategies as a means to augment current regulatory activities.
View Article and Find Full Text PDFPiperacillin and Tazobactam Injection is a combination product consisting of a penicillin-class antibacterial, piperacillin, and a beta-lactamase inhibitor, tazobactam, indicated for the treatment of patients with moderate to severe infections caused by susceptible isolates of bacteria. In the past decade some quality problems have been noted by the US Food and Drug Administration (FDA) with the Apotex Corp. manufacturing.
View Article and Find Full Text PDFIntra-lot and inter-lot variability in the spectra of levothyroxine was detected in the Drug Quality Study (DQS) using Fourier transform near-infrared spectrometry (FTNIR). Two vials of 12 vials sampled from Athenex lot AFN102 appeared 10.1 and 9.
View Article and Find Full Text PDFThe measles, mumps, and rubella (MMR) vaccine is a vaccine used to prevent measles, mumps, and rubella (German measles). The vaccine is mandated for children to attend public school in nearly all US states. However, measles cases have been increasing in the past decade, and quality problems have recently been noted by the US Food and Drug Administration (FDA) with the vaccine manufacturer.
View Article and Find Full Text PDFIntra-lot and inter-lot variability in the spectra of micafungin was detected in the Drug Quality Study (DQS) using Fourier transform near-infrared spectrometry (FTNIR). Two vials of 6 vials sampled from Fresenius Kabi lot ACP106 appeared 7.9 and 14.
View Article and Find Full Text PDFJ Mech Behav Biomed Mater
March 2022
The knee menisci are prone to mechanical fatigue injury from the cyclic tensile stresses that are generated during daily joint loading. Here we characterize the tensile fatigue behavior of human medial meniscus and investigate the effect of aging on fatigue strength. Test specimens were excised from the medial meniscus of young (under 40 years) and older (over 65 years) fresh-frozen cadaver knees.
View Article and Find Full Text PDFIntra-lot and inter-lot variability in dacarbazine was detected in the Drug Quality Study (DQS) using Fourier transform near-infrared spectrometry (FTNIR). One vial of six vials sampled from Fresenius Kabi Lot 6125612 appeared 7.8 SDs from the center of the rest of the vials on the DQS FTNIR screening assay.
View Article and Find Full Text PDFIntra-lot and inter-lot variability in cosyntropin was detected in the DQS using Fourier transform near-infrared spectrometry. One vial of 12 sampled from Sandoz Lot0200062 appeared 6.9 SDs from the center of the rest of the vials, and another was 4.
View Article and Find Full Text PDFFree-standing, composite hydrogels containing the visible-light responsive metal-free semiconductor graphitic carbon nitride (-CN) as an integral component have been fabricated by direct casting techniques. At 0.67% -CN loading, intermolecular interactions between the semiconductor particles and the PVA polymer chains enhance both the mechanical and photophysical properties of the resulting hydrogels.
View Article and Find Full Text PDFIntra-lot and inter-lot variability in ceftaroline fosamil was detected in the DQS using Fourier transform near-infrared spectrometry. One vial of 18 sampled from Lot0013E06 appeared 9.0 SDs from the center of the rest of the vials.
View Article and Find Full Text PDFTensile testing is an essential experiment to assess the mechanical integrity of musculoskeletal soft tissues, yet standard test methods have not been developed to ensure the quality and reproducibility of these experiments. The ASTM International standards organization has created tensile test standards for common industry materials that specify geometric dimensions of test specimens (coupons) that promote valid failures within the gage section (midsubstance), away from the grips. This study examined whether ASTM test standards for plastics, elastomers, and fiber-reinforced composites are suitable for tensile testing of bovine meniscus along the circumferential fiber direction.
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