Discriminative and quantitative analysis of norepinephrine and epinephrine by surface-enhanced Raman spectroscopy with gold nanoparticle suspensions.

Surface-enhanced Raman spectroscopy (SERS) is a powerful analytical technique capable of increasing the Raman signal of an analyte using specific nanostructures. The close contact between those nanostructures, usually a suspension of nanoparticles, and the molecule of interest produces an important exaltation of the intensity of the Raman signal. Even if the exaltation leads to an improvement of Raman spectroscopy sensitivity, the complexity of the SERS signal and the numbers of parameters to be controlled allow the use of SERS for detection rather than quantification. The aim of this study was to develop a robust discriminative and quantitative analysis in accordance with pharmaceutical standards. In this present work, we develop a discriminative and quantitative analysis based on the previous optimized parameters obtained by the design of experiments fixed for norepinephrine (NOR) and extended to epinephrine (EPI) which are two neurotransmitters with very similar structures. Studying the short evolution of the Raman signal intensity over time coupled with chemometric tools allowed the identification of outliers and their removal from the data set. The discriminant analysis showed an excellent separation of EPI and NOR. The comparative analysis of the data showed the superiority of the multivariate analysis after logarithmic transformation. The quantitative analysis allowed the development of robust quantification models from several gold nanoparticle batches with limits of quantification of 32 µg/mL for NOR and below 20 µg/mL for EPI even though no Raman signal is observable for such concentrations. This study improves SERS analysis over ultrasensitive detection for discrimination and quantification using a handheld Raman spectrometer.

Quality of economic evaluations of drug-coated balloons and drug-eluting stents in peripheral artery disease: a systematic review.

OBJECTIVE: We aimed to perform a systematic review of economic evaluations of drug-coated balloons (DCBs) and drug-eluting stents (DESs) in peripheral artery disease (PAD) and to assess the level of evidence of relevant studies. The purpose was not to present economic findings. METHODS: A systematic review was performed using four electronic databases to identify health economic evaluation studies reporting on the use of DCBs and DESs in PAD. The methodological and reporting quality of the studies was assessed using three different tools, the Drummond, Cooper, and CHEERS (Consolidated Health Economic Evaluation Reporting Standards) checklists. RESULTS: Six articles were included in this review of the 1,728 publications identified. Four studies were cost-effectiveness analyses and two cost-utility analyses. According to the Cooper hierarchy scale, the studies used good-quality data sources. The level of evidence used for clinical effect sizes, safety data, baseline clinical data, and costs was of high quality in general. In contrast, an evaluation of the reporting quality suggested that essential information was lacking. CONCLUSION: The present study demonstrates that clinical data used in economic evaluations of DCBs and DESs in PAD are from clinical studies of high quality in general. However, the quality of reporting represents a concern when interpreting the results provided by these economic studies.

Quality of economic evaluations of ventricular assist devices: A systematic review.

OBJECTIVE: Because of a lack of suitable heart donors, alternatives to transplantation are required. These alternatives can have high costs. The aim of this study was to perform a systematic review of cost-effectiveness studies of ventricular assist devices (VADs) and to assess the level of evidence of relevant studies. The purpose was not to present economic findings. METHODS: A systematic review was performed using four electronic databases to identify health economic evaluation studies dealing with VADs. The methodological quality and reporting quality of the studies was assessed using three different tools, the Drummond, Cooper, and CHEERS (Consolidated Health Economic Evaluation Reporting Standards) checklists. RESULTS: Of the 1,258 publications identified, thirteen articles were included in this review. Twelve studies were cost-utility analyses and one was a cost-effectiveness analysis. According to the Cooper hierarchy scale, the quality of the data used was heterogeneous. The level of evidence used for clinical effect sizes, safety data, and baseline clinical data was of poor quality. In contrast, cost data were of high quality in most studies. Quality of reporting varied between studies, with an average score of 17.4 (range 15-19) according to the CHEERS checklist. CONCLUSION: The current study shows that the quality of clinical data used in economic evaluations of VADs is rather poor in general. This is a concern that deserves greater attention in the process of health technology assessment of medical devices.

Evaluation of 3D printing costs in surgery: a systematic review.

OBJECTIVES: The use of three-dimensional (3D) printing in surgery is expanding and there is a focus on comprehensively evaluating the clinical impact of this technology. However, although additional costs are one of the main limitations to its use, little is known about its economic impact. The purpose of this systematic review is to identify the costs associated with its use and highlight the first quantitative data available. METHODS: A systematic literature review was conducted in the PubMed and Embase databases and in the National Health Service Economic Evaluation Database (NHS EED) at the University of York. Studies that reported an assessment of the costs associated with the use of 3D printing for surgical application and published between 2009 and 2019, in English or French, were included. RESULTS: Nine studies were included in our review. Nine types of costs were identified, the three main ones being printing material costs (n = 6), staff costs (n = 3), and operating room costs (n = 3). The printing cost ranged from less than U.S. dollars (USD) 1 to USD 146 (in USD 2019 values) depending on the criteria used to calculate this cost. Three studies evaluated the potential savings generated by the use of 3D printing technology in surgery, based on operating time reduction. CONCLUSION: This literature review highlights the lack of reliable economic data on 3D printing technology. Nevertheless, this review makes it possible to identify expenditures or items that should be considered in order to carry out more robust studies.

The learning curve in transcatheter aortic valve implantation clinical studies: A systematic review.

BACKGROUND: Transcatheter aortic-valve implantation (TAVI) has become an essential alternative to surgical aortic-valve replacement in the treatment of symptomatic severe aortic stenosis, and this procedure requires technical expertise. The aim of this study was to identify prospective studies on TAVI from the past 10 years, and then to analyze the quality of information reported about the learning curve. MATERIALS AND METHODS: A systematic review of articles published between 2007 and 2017 was performed using PubMed and the EMBASE database. Prospective studies regarding TAVI were included. The quality of information reported about the learning curve was evaluated using the following criteria: mention of the learning curve, the description of a roll-in phase, the involvement of a proctor, and the number of patients suggested to maintain skills. RESULTS: A total of sixty-eight studies met the selection criteria and were suitable for analysis. The learning curve was addressed in approximately half of the articles (n = 37, 54 percent). However, the roll-in period was mentioned by only eight studies (12 percent) and with very few details. Furthermore, a proctorship was disclosed in three articles (4 percent) whereas twenty-five studies (37 percent) included authors that were proctors for manufacturers of TAVI. CONCLUSION: Many prospective studies on TAVI over the past 10 years mention learning curves as a core component of successful TAVI procedures. However, the quality of information reported about the learning curve is relatively poor, and uniform guidance on how to properly assess the learning curve is still missing.

A centralized automated-dispensing system in a French teaching hospital: return on investment and quality improvement.

OBJECTIVES: To evaluate the return on investment (ROI) and quality improvement after implementation of a centralized automated-dispensing system after 8 years of use. DESIGN: Prospective evaluation of ROI; before and after study to evaluate dispensing errors; user satisfaction questionnaire after 8 years of use. SETTING: The study was conducted at a French teaching hospital in the pharmacy department, which is equipped with decentralized automated medication cabinets in the wards. PARTICIPANTS: Pharmacy staff (technicians and residents). INTERVENTION(S): Implementation of a centralized automated-dispensing robot. MAIN OUTCOME MEASURE(S): The true ROI was prospectively and annually compared to estimated returns calculated after implementation and upgrade of the robot; dispensing errors determined by observation of global deliveries and the satisfaction of users based on a validated questionnaire were evaluated. RESULTS: Following the upgrade, we found little difference for the ROI (+1.86%). The payback period increased by almost 3 years. There was a significant reduction of dispensing errors, from 2.9% to 1.7% (P < 0.001). User satisfaction of the robot by the pharmacy staff was reported (score of 5.52 ± 1.20 out of 7). CONCLUSIONS: These systems are worthwhile investments and largely contribute to improving the quality and safety of the medication process.

HARMONIZING HEALTH TECHNOLOGY ASSESSMENT PRACTICES IN UNIVERSITY HOSPITALS: TO WHAT EXTENT IS THE MINI-HTA MODEL SUITABLE IN THE FRENCH CONTEXT?

BACKGROUND: The number of new medical devices for individual use that are launched annually exceeds the assessment capacity of the French national health technology assessment (HTA) agency. This has resulted in hospitals, and particularly university hospitals (UHs), developing hospital-based HTA initiatives to support their decisions for purchasing innovative devices. However, the methodologies used in such hospitals have no common basis. The aim of this study was to assess a mini-HTA model as a potential solution to harmonize HTA methodology in French UHs. METHODS: A systematic review was conducted on Medline, Embase, Health Technology Assessment database, and Google Scholar to identify published articles reporting the use of mini-HTA tools and decision support-like models. A survey was also carried out in eighteen French UHs to identify in-house decision support tools. Finally, topics evaluated in the Danish mini-HTA model and in French UHs were compared using Jaccard similarity coefficients. RESULTS: Our findings showed differences between topics evaluated in French UHs and those assessed in decision support models from the literature. Only five topics among the thirteen most evaluated in French UHs were similar to those assessed in the Danish mini-HTA model. The organizational and ethical/social impacts were rarely explored among the surveyed models used in French UHs when introducing new medical devices. CONCLUSIONS: Before its widespread and harmonized use in French UHs, the mini-HTA model would first require adaptations to the French context.

Combining multi-criteria decision analysis and mini-health technology assessment: A funding decision-support tool for medical devices in a university hospital setting.

BACKGROUND: At the hospital level, decisions about purchasing new and oftentimes expensive medical devices must take into account multiple criteria simultaneously. Multi-criteria decision analysis (MCDA) is increasingly used for health technology assessment (HTA). One of the most successful hospital-based HTA approaches is mini-HTA, of which a notable example is the Matrix4value model. OBJECTIVES: To develop a funding decision-support tool combining MCDA and mini-HTA, based on Matrix4value, suitable for medical devices for individual patient use in French university hospitals - known as the IDA tool, short for 'innovative device assessment'. METHODS: Criteria for assessing medical devices were identified from a literature review and a survey of 18 French university hospitals. Weights for the criteria, representing their relative importance, were derived from a survey of 25 members of a medical devices committee using an elicitation technique involving pairwise comparisons. As a test of its usefulness, the IDA tool was applied to two new drug-eluting beads (DEBs) for transcatheter arterial chemoembolization. RESULTS: The IDA tool comprises five criteria and weights for each of two over-arching categories: risk and value. The tool revealed that the two new DEBs conferred no additional value relative to DEBs currently available. CONCLUSIONS: Feedback from participating decision-makers about the IDA tool was very positive. The tool could help to promote a more structured and transparent approach to HTA decision-making in French university hospitals.

Innovative medical devices and hospital decision making: a study comparing the views of hospital pharmacists and physicians.

Objectives Many university hospitals have developed local health technology assessment processes to guide informed decisions about new medical devices. However, little is known about stakeholders' perceptions and assessment of innovative devices. Herein, we investigated the perceptions regarding innovative medical devices of their chief users (physicians and surgeons), as well as those of hospital pharmacists, because they are responsible for the purchase and management of sterile medical devices. We noted the evaluation criteria used to assess and select new medical devices and suggestions for improving local health technology assessment processes indicated by the interviewees. Methods We randomly selected 18 physicians and surgeons (nine each) and 18 hospital pharmacists from 18 French university hospitals. Semistructured interviews were conducted between October 2012 and August 2013. Responses were coded separately by two researchers. Results Physicians and surgeons frequently described innovative medical devices as 'new', 'safe' and 'effective', whereas hospital pharmacists focused more on economic considerations and considered real innovative devices to be those for which no equivalent could be found on the market. No significant difference in evaluation criteria was found between these groups of professionals. Finally, hospital pharmacists considered the management of conflicts of interests in local health technology assessment processes to be an issue, whereas physicians and surgeons did not. Conclusions The present study highlights differences in perceptions related to professional affiliation. The findings suggest several ways in which current practices for local health technology assessment in French university hospitals could be improved and studied. What is known about the topic? Hospitals are faced with ever-growing demands for innovative and costly medical devices. To help hospital management deal with technology acquisition issues, hospital-based health technology assessment has been developed to support decisions. However, little is known about the different perceptions of innovative medical devices among practitioners and how different perceptions may affect decision making. What does this paper add? This paper compares and understands the perceptions of two groups of health professionals concerning innovative devices in the university hospital environment. What are the implications for practitioners? Such a comparison of viewpoints could facilitate improvements in current practices and decision-making processes in local health technology assessment for these medical products.

Capillary electrophoresis for rapid identification of monoclonal antibodies for routine application in hospital.

mAbs are widely used in cancer therapy. Their compounding, performed just before their administration to patients, is executed in a production unit of the hospital. Identification of these drugs, individually prepared in bags for infusion before patient administration, is of paramount importance to detect potential mistakes during compounding stage. A fast and reliable analytical method based on CZE combined to a cationic capillary coating (hexadimethrine bromide) was developed for identification of the most widely used compounded therapeutic for cancer therapy (bevacizumab, cetuximab, rituximab, and trastuzumab). Considering the high structural and physico-chemical similarities of these mAbs, an extensive optimization of the BGE composition has been performed. The addition of perchlorate ions and polysorbate in the BGE greatly increased the resolution. To validate the method, an internal standard was used and the relative migration times (RTm) were estimated. Very satisfactory RSDs of the RTm for rituximab (0.76%), cetuximab (0.46%), bevacizumab (0.31%), and trastuzumab (0.60%) were obtained. The intraday and interday RSD of the method were less than 0.32 and 1.3%, respectively for RTm. Significant differences between theses RTms have been demonstrated allowing mAbs identification. Finally, accurate mAbs identification has been demonstrated by a blind test.

INTRODUCTION OF INNOVATIVE MEDICAL DEVICES AT FRENCH UNIVERSITY HOSPITALS: AN OVERVIEW OF HOSPITAL-BASED HEALTH TECHNOLOGY ASSESSMENT INITIATIVES.

OBJECTIVES: Local health technology assessment (HTA) to determine whether new health technologies should be adopted is now a common practice in many healthcare organizations worldwide. However, little is known about hospital-based HTA activities in France. The objective of this study was to explore hospital-based HTA activities in French university hospitals and to provide a picture of organizational approaches to the assessment of new and innovative medical devices. METHODS: Eighteen semi-structured interviews with hospital pharmacists were conducted from October 2012 to April 2013. Six topics were discussed in depth: (i) the nature of the institution concerned; (ii) activities relating to innovative medical devices; (iii) the technology assessment and decision-making process; (iv) the methodology for technology assessment; (v) factors likely to influence decisions and (vi) suggestions for improving the current process. The interview data were coded, collated and analyzed statistically. RESULTS: Three major types of hospital-based HTA processes were identified: medical device committees, innovation committees, and "pharmacy & management" processes. HTA units had been set up to support medical device and innovation committees for technology assessment. Slow decision making was the main limitation to both these committee-based approaches. As an alternative, "pharmacy & management" processes emerged as a means of rapidly obtaining a formal assessment. CONCLUSIONS: This study provides an overview of hospital-based HTA initiatives in France. We hope that it will help to promote hospital-based HTA activities in France and discussions about ways to improve and harmonize practices, through the development of national guidelines and/or a French mini-HTA tool, for example.

Use of a risk assessment method to improve the safety of negative pressure wound therapy.

To conduct a risk analysis of the negative pressure wound therapy (NPWT) care process and to improve the safety of NPWT, a working group of nurses, hospital pharmacists, physicians and hospital managers performed a risk analysis for the process of NPWT care. The failure modes, effects and criticality analysis (FMECA) method was used for this analysis. Failure modes and their consequences were defined and classified as a function of their criticality to identify priority actions for improvement. By contrast to classical FMECA, the criticality index (CI) of each consequence was calculated by multiplying occurrence, severity and detection scores. We identified 13 failure modes, leading to 20 different consequences. The CI of consequences was initially 712, falling to 357 after corrective measures were implemented. The major improvements proposed included the establishment of 6-monthly training cycles for nurses, physicians and surgeons and the introduction of computerised prescription for NPWT. The FMECA method also made it possible to prioritise actions as a function of the criticality ranking of consequences and was easily understood and used by the working group. This study is, to our knowledge, the first to use the FMECA method to improve the safety of NPWT.

Hospital-based health technology assessment for innovative medical devices in university hospitals and the role of hospital pharmacists: learning from international experience.

OBJECTIVES: Several models of hospital-based health technology assessment (HTA) have been developed worldwide, for the introduction of innovative medical devices and support evidence-based decision making in hospitals. Two such models, the HTA unit and mini-HTA models, are widespread in university hospitals and involve various stakeholders. The purpose of this work was to highlight the potential role of hospital pharmacists in hospital-based HTA activities. METHODS: We searched for articles, reviews, and letters relating to hospital-based HTA, as defined by the Hospital-Based Health Technology Assessment Worldwide Survey published by the Health Technology Assessment International (HTAi) Society, in the Health Technology Assessment database, MEDLINE, EMBASE, and hospital pharmacy journals. RESULTS: The number of university hospitals performing hospital-based HTA has increased since the 2008 Hospital-Based Health Technology Assessment Worldwide Survey. Our own experience and international findings show that hospital pharmacists already contribute to hospital-based HTA activities and have developed study interpretation skills and a knowledge of medical devices. CONCLUSIONS: Promoting multidisciplinary approaches is one of the key success factors in hospital-based HTA. Hospital pharmacists occupy a position between hospital managers, clinicians, health economists, biomedical engineers, and patients and can provide a new perspective. In the future, hospital pharmacists are likely to become increasingly involved in hospital-based HTA activities.

Evaluation of drug administration errors in a teaching hospital.

BACKGROUND: Medication errors can occur at any of the three steps of the medication use process: prescribing, dispensing and administration. We aimed to determine the incidence, type and clinical importance of drug administration errors and to identify risk factors. METHODS: Prospective study based on disguised observation technique in four wards in a teaching hospital in Paris, France (800 beds). A pharmacist accompanied nurses and witnessed the preparation and administration of drugs to all patients during the three drug rounds on each of six days per ward. Main outcomes were number, type and clinical importance of errors and associated risk factors. Drug administration error rate was calculated with and without wrong time errors. Relationship between the occurrence of errors and potential risk factors were investigated using logistic regression models with random effects. RESULTS: Twenty-eight nurses caring for 108 patients were observed. Among 1501 opportunities for error, 415 administrations (430 errors) with one or more errors were detected (27.6%). There were 312 wrong time errors, ten simultaneously with another type of error, resulting in an error rate without wrong time error of 7.5% (113/1501). The most frequently administered drugs were the cardiovascular drugs (425/1501, 28.3%). The highest risks of error in a drug administration were for dermatological drugs. No potentially life-threatening errors were witnessed and 6% of errors were classified as having a serious or significant impact on patients (mainly omission). In multivariate analysis, the occurrence of errors was associated with drug administration route, drug classification (ATC) and the number of patient under the nurse's care. CONCLUSION: Medication administration errors are frequent. The identification of its determinants helps to undertake designed interventions.

Optimization of experimental conditions by surface enhanced Raman Scattering (SERS) spectroscopy with gold nanoparticles suspensions.

Surface Enhanced Raman Scattering (SERS) spectroscopy is a rapid and innovative analysis technique involving metallic nanoparticles (NPs). The interaction between NPs and norepinephrine gives an exaltation of the Raman signal under certain experimental conditions. The control of the signal exaltation, crucial for sensitive analyses, remains one of the main limitations of this technique. The aim of this work is to optimize the exaltation conditions for an optimal SERS signal at two concentrations of norepinephrine (NOR) and spherical gold NPs in suspension. This first work will fix the optimal experimental conditions essential for the development of robust discriminant and quantitative analysis of catecholamine. Two complete 3-factors 3-levels experiment designs were performed at 20 µg.mL-1 and 100 µg.mL-1 norepinephrine concentrations, each experiment being repeated 3 times. The optimization factors were the process of synthesis (variation of the quantity of gold and citrate used for the three synthesis SA, SB and SC) and HCl (0.3 M, 0.5 M, 0.7 M) as well as the volume ratio of NPs and norepinephrine (0.5, 2, 3.5) for SERS acquisition. Spectral acquisitions were performed with a handheld Raman spectrometer with an excitation source at 785 nm. For each sample, 31 acquisitions were realized during 3 s every 8 s. The optimization parameter was the intensity of the characteristic band of norepinephrine at 1280 cm-1. A total of 5,042 spectra were acquired and the pre-treatment selected for all spectra was asymmetric least square combined to a smoothing of Savistsky Golay (ALS - SG). The optimal contact time between norepinephrine and NPs depends on the experimental conditions and was determined for each experiment according to the mean intensity between the three replicates. After interpretation of the experimental designs, the optimal conditions retained were the quantity of gold corresponding to SA and the HCl concentration 0.7 M for the two concentrations of norepinephrine. Indeed, the optimal volume ratio depend on the NOR concentration.

Chronology of prescribing error during the hospital stay and prediction of pharmacist's alerts overriding: a prospective analysis.

BACKGROUND: Drug prescribing errors are frequent in the hospital setting and pharmacists play an important role in detection of these errors. The objectives of this study are (1) to describe the drug prescribing errors rate during the patient's stay, (2) to find which characteristics for a prescribing error are the most predictive of their reproduction the next day despite pharmacist's alert (i.e. override the alert). METHODS: We prospectively collected all medication order lines and prescribing errors during 18 days in 7 medical wards' using computerized physician order entry. We described and modelled the errors rate according to the chronology of hospital stay. We performed a classification and regression tree analysis to find which characteristics of alerts were predictive of their overriding (i.e. prescribing error repeated). RESULTS: 12 533 order lines were reviewed, 117 errors (errors rate 0.9%) were observed and 51% of these errors occurred on the first day of the hospital stay. The risk of a prescribing error decreased over time. 52% of the alerts were overridden (i.e error uncorrected by prescribers on the following day. Drug omissions were the most frequently taken into account by prescribers. The classification and regression tree analysis showed that overriding pharmacist's alerts is first related to the ward of the prescriber and then to either Anatomical Therapeutic Chemical class of the drug or the type of error. CONCLUSIONS: Since 51% of prescribing errors occurred on the first day of stay, pharmacist should concentrate his analysis of drug prescriptions on this day. The difference of overriding behavior between wards and according drug Anatomical Therapeutic Chemical class or type of error could also guide the validation tasks and programming of electronic alerts.

Substitution of corticosteroid with everolimus after lung transplantation: a pediatric case report.

We report the case of a 12 year-old lung transplant recipient, in whom compressive epidural lipomatosis secondary to corticosteroid prompted us to replace prednisone with everolimus. Discontinuing corticosteroid treatment after lung transplantation is associated with a risk of graft rejection despite concomitant immunosuppressive therapy with tacrolimus and mycophenolate mofetil. During a follow-up of 18 months with everolimus instead of prednisone, we did not observe graft rejection. In parallel, all symptoms related to epidural compression disappeared within a month.

The application of hazard analysis and critical control points and risk management in the preparation of anti-cancer drugs.

OBJECTIVE: To apply the Hazard analysis and Critical Control Points method to the preparation of anti-cancer drugs. To identify critical control points in our cancer chemotherapy process and to propose control measures and corrective actions to manage these processes. SETTING: The Hazard Analysis and Critical Control Points application began in January 2004 in our centralized chemotherapy compounding unit. From October 2004 to August 2005, monitoring of the process nonconformities was performed to assess the method. METHODS: According to the Hazard Analysis and Critical Control Points method, a multidisciplinary team was formed to describe and assess the cancer chemotherapy process. This team listed all of the critical points and calculated their risk indexes according to their frequency of occurrence, their severity and their detectability. The team defined monitoring, control measures and corrective actions for each identified risk. Finally, over a 10-month period, pharmacists reported each non-conformity of the process in a follow-up document. RESULTS: Our team described 11 steps in the cancer chemotherapy process. The team identified 39 critical control points, including 11 of higher importance with a high-risk index. Over 10 months, 16,647 preparations were performed; 1225 nonconformities were reported during this same period. CONCLUSIONS: The Hazard Analysis and Critical Control Points method is relevant when it is used to target a specific process such as the preparation of anti-cancer drugs. This method helped us to focus on the production steps, which can have a critical influence on product quality, and led us to improve our process.

Forced Degradation of Monoclonal Antibodies After Compounding: Impact on Routine Hospital Quality Control.

Compounded therapeutic mAbs used in a hospital require quality control (QC). In our hospital, analytical QC process intended to mAbs identification and quantification is based on flow injection analysis associated with second-derivative UV spectroscopy and matching method algorithm. We studied the influence of degraded mAbs after compounding on this validated QC. Three forced stress conditions including mechanical, thermal, and freeze-thawing stresses were studied to yield degraded mAbs from 2 model compounds, that is, bevacizumab (IgG1) and nivolumab (IgG4). Different degraded mAbs were generated and were analyzed in terms of turbidity, the percentage of aggregation, size distribution, and changes in tertiary structure. Stresses showed to be mAb-dependent in terms of aggregation. Tertiary structural changes were observed in most of the stressed samples by principal component analysis of the UV second-derivative data. The structural and physicochemical modifications conducted to mismatch depending on the nature of the stress. The mismatch ranged from 17% to 72% for the mAbs, except for freeze-thawed bevacizumab for which a perfect match (100%) was reached. The quantification with an unfulfilled relative error of the concentration (i.e., > ±15%) was detected only for mechanically stressed mAbs. In conclusion, the study revealed that the influence of the mAbs and the type of stress impact on the QC of compounded mAbs.