An Overview of Degradation Strategies for Amitriptyline.

Antidepressant drugs play a crucial role in the treatment of mental health disorders, but their efficacy and safety can be compromised by drug degradation. Recent reports point to several drugs found in concentrations ranging from the limit of detection (LOD) to hundreds of ng/L in wastewater plants around the globe; hence, antidepressants can be considered emerging pollutants with potential consequences for human health and wellbeing. Understanding and implementing effective degradation strategies are essential not only to ensure the stability and potency of these medications but also for their safe disposal in line with current environment remediation goals. This review provides an overview of degradation pathways for amitriptyline, a typical tricyclic antidepressant drug, by exploring chemical routes such as oxidation, hydrolysis, and photodegradation. Connex issues such as stability-enhancing approaches through formulation and packaging considerations, regulatory guidelines, and quality control measures are also briefly noted. Specific case studies of amitriptyline degradation pathways forecast the future perspectives and challenges in this field, helping researchers and pharmaceutical manufacturers to provide guidelines for the most effective degradation pathways employed for minimal environmental impact.

Non-destructive Raman Method Development for Quantifying Active Pharmaceutical Ingredient in an Oral Suspension Through Plastic Dosing Syringes.

For liquid drug products, e.g., solutions or suspensions for oral or parenteral dosing, stability needs to be demonstrated in primary packaging during storage and in dosing devices during in-use periods per quality guidelines from the International Conference on Harmonisation (ICH) and the European Agency for the Evaluation of Medicinal Products (EMEA). One aspect of stability testing for liquid drug products is in-use stability, which typically includes transferring the liquid samples into another container for further sample preparation with extraction diluent and necessary agitation. Samples are then analyzed with traditional chromatography methods, which are laborious, prone to human errors, and time-consuming, especially when this process needs to be repeated multiple times during storage and in-use periods. Being able to analyze the liquid samples non-destructively would significantly improve testing efficiency. We investigated different Raman techniques, including transmission Raman (TRS) and back scatter Raman with a non-contact optic (NCO) probe, as alternative non-destructive tools to the UHPLC method for API quantitation in in-use liquid samples pulled into plastic dosing syringes. The linearity of the chemometric methods for these two techniques was demonstrated by cross-validation sample sets at three levels over an API concentration range of 60 to 80 mg/mL. The accuracy of the chemometric models was demonstrated by the accurate prediction of the API concentrations in independent samples from four different pilot plant batches manufactured at different sites. Both techniques were successful in measuring a signal through a plastic oral dosing syringe, and predicting the suspension API concentration to within 4% of the UHPLC-measured value. For future work, there are opportunities to improve the methodology by exploring additional probes or to expand the range of applications by using different sample presentations (such as prefilled syringes) or formulation matrices for solutions and suspensions.

Physicochemical stability of bortezomib solutions for subcutaneous administration.

For the majority of cytotoxic drug preparations, such as bortezomib, the unit dose information is not available. In addition, there is a lack of information on the physicochemical stability of the pharmaceutical preparation after opening; this information is crucial for its administration to patients in successive visits, and the per-patient cost can be affected. The purpose of our proposed physicochemical stability study is to determine the shelf life of the reconstituted liquid product under refrigeration and clinical practice conditions. This evaluation was extended to both vials and ready-to-use syringes prefilled with the contents of the open vial. The stability test design includes the specified storage conditions and the critical physicochemical parameters of reconstituted injectable bortezomib. Furthermore, this approach includes the determination of impurities, the monitoring of the purity of the mean peak using a photodiode array, the control of the mass balance, the monitoring of subvisible particles using a laser diffraction analyser, and the setting of stability specifications. For the chemical stability study, the amount of bortezomib and its degradation products were determined using a stability-indicating HPLC method. The physical inspection of the samples was performed throughout the stability study, and their pH values were also monitored. Bortezomib (2.5 mg/mL) in 0.9% sodium chloride remained stable for 7 days when stored in both polypropylene syringes and vials at 5 ± 3 °C (refrigeration) and shielded from light. Additionally, it exhibits stability for 24 h under storage conditions simulating clinical use (20-30 °C and protected from light). The proposed protocol provides the stability in the vials once reconstituted and in prefilled refrigerated syringes; this protocol can be used to reduce waste and increase cost savings.

Fabrication and characterization of chitosan/anthocyanin intelligent packaging film fortified by cellulose nanocrystal for shrimp preservation and visual freshness monitoring.

In this study, a multi-functional packaging film was fabricated, utilizing the natural polysaccharide chitosan (CS) as the base material, integrating natural blueberry anthocyanin (AN) as pH-responsive indicator, and reinforced with cellulose nanocrystals (CNCs). The implications of addition levels of CNCs on the characteristics of the films were systematically investigated, resulting in that CS-AN-CNCs 9 % film exhibited optimal performance. Specifically, the film showed a substantial enhancement in maximum tensile strength from 15 MPa to 35 MPa; On the other hand, the swelling degree properties, the oxygen permeability and water vapor permeability decreased from 159.2 % to 92.0 %, from 51.7 g/(m2d) to 12.2 g/(m2d), from 31.6 × 10-12 g/(m·s·Pa) to 1.6 × 10-12 g/(m·s·Pa), respectively. Moreover, the CS-AN-CNCs 9 % film exhibited antioxidant, antibacterial, coupled with a color metrically responsive to pH variations, displaying great potential in indicating the shrimp freshness and delaying spoilage. Another notable advantage of the-prepared packaging material lies in its completely biodegradability, therefore meeting the requirement of environmental protection. Therefore, the prepared CS-AN-CNCs film as an intelligent packaging solution with potential applications in food preservation and freshness monitoring applications.

Easy-to-implement educational interventions to bring climate-smart actions to daily anesthesiologic practice: a cross-sectional before and after study.

BACKGROUND: Anesthesia contributes significantly to a hospital's carbon footprint. Climate-smart actions have the potential to reduce greenhouse gas emissions. Prerequisites for sustainable behavior of providers are knowledge and awareness. We aimed to assess the change in anesthesiologists' climate-friendly behavior before and after educational interventions in three areas that every anesthesiologist can address in their daily clinical routine: 1) energy use; 2) recycling opportunities; 3) consumption of volatile anesthetics. METHODS: We performed a cross-sectional before-and-after single center sub-study within the multicenter "Provider Education and Evaluation Project" at the Department of Anesthesiology, RWTH Aachen University hospital from May3 2021 to May 1 2022. Educational interventions consisted of stickers, posters and a presentation on climate-smart actions in anesthesiologists' work routine between the first and the second assessment. For each cross-sectional assessment, all central 28 ORs were observed for one week. During the before-and-after comparison we analyzed: 1) energy wasted in unoccupied ORs because of running computers and turned-on lights at 9 p.m.; 2) feasibility of recycling preoperative anesthesia plastic packaging by determining the difference between calculated weight of unseparated preoperative plastic waste in the first assessment and the weight of actual separated waste in the second assessment; 3) fresh gas flow in balanced anesthesia cases in steady state at 9 a.m., and purchased hypnotics converted to bottles/1000 general anesthesia cases in 2018-2022. RESULTS: We observed a reduction of wasted energy by 44% in unoccupied ORs. Usage of low fresh gas flow settings increased from 55% to 75%. The average of purchased desflurane in 2018-2020 decreased by 72% in 2022. We calculated 10.33 kg of preoperative plastic waste per week but were unable to implement waste separation for infrastructural and logistical reasons. CONCLUSIONS: We found that environment-friendly working behaviors increased after the implementation of educational interventions. The causality between the interventions and the observed improvements remains to be proven.

Research progress of protein complex systems and their application in food: A review.

Among the common natural biomolecules, the excellent properties of proteins have attracted extensive attention from researchers for functional applications, however, in native form proteins have many limitations in the performance of their functional attribute. However, with the deepening of research, it has been found that the combination of natural active substances such as polyphenols, polysaccharides, etc. with protein molecules will make the composite system have stronger functional properties, while the utilization of pH-driven method, ultrasonic treatment, heat treatment, etc. not only provides a guarantee for the overall protein-based composite system, but also gives more possibilities to the protein-composite system. Protein composite systems are emerging in the fields of novel active packaging, functional factor delivery systems and gel systems with high medical value. The products of these protein composite systems usually have high functional properties, mainly due to the interaction of the remaining natural active substances with protein molecules, which can be broadly categorized into covalent interactions and non-covalent interactions, and which, despite the differences in these interactions, together constitute the cornerstone for the stability of protein composite systems and for in-depth research.

Assessing biologic/toxicologic effects of extractables from plastic contact materials for advanced therapy manufacturing using cell painting assay and cytotoxicity screening.

Plastic components are essential in the pharmaceutical industry, encompassing container closure systems, laboratory handling equipment, and single-use systems. As part of their material qualification process, studies on interactions between plastic contact materials and process solutions or drug products are conducted. The assessment of single-use systems includes their potential impact on patient safety, product quality, and process performance. This is particularly crucial in cell and gene therapy applications since interactions with the plastic contact material may result in an adverse effect on the isolated therapeutic human cells. We utilized the cell painting assay (CPA), a non-targeted method, for profiling the morphological characteristics of U2OS human osteosarcoma cells in contact with chemicals related to plastic contact materials. Specifically, we conducted a comprehensive analysis of 45 common plastic extractables, and two extracts from single-use systems. Results of the CPA are compared with a standard cytotoxicity assay, an osteogenesis differentiation assay, and in silico toxicity predictions. The findings of this feasibility study demonstrate that the device extracts and most of the tested compounds do not evoke any measurable biological changes on the cells (induction ≤ 5%) among the 579 cell features measured at concentrations ≤ 50 µM. CPA can serve as an important assay to reveal unique information not accessible through quantitative structure-activity relationship analysis and vice versa. The results highlight the need for a combination of in vitro and in silico methods in a comprehensive assessment of single-use equipment utilized in advanced therapy medicinal products manufacturing.

Current State of Minitablet Product Design: A Review.

Interest in minitablets (MTs) has grown exponentially over the last 20 years and especially the last decade, as evidenced by the number of publications cited in Scopus and PubMed. MTs offer significant opportunities for personalized medicine, dose titration and flexible dosing, taste masking, and customizing drug delivery systems. Advances in specialized MT tooling, manufacturing, and characterization instrumentation have overcome many of the earlier development issues. Breakthrough MT swallowability, acceptability, and palatability research have challenged the long-standing idea that only liquids are acceptable dosage forms for infants and young children. MTs have been shown to be a highly acceptable dosage form for infants, small children, and geriatric patients who have difficulty swallowing. This review discusses the current state of MT applications, acceptability in pediatric and geriatric populations, medication adherence, manufacturing processes such as tableting and coating, running powder and tablet characterization, packaging and MT dispensing, and regulatory considerations.

Development of biodegradable packaging films from carboxymethyl cellulose and oxidised natural rubber latex.

The present study investigates the biopolymer packaging film developed from carboxymethyl cellulose (CMC) with varying concentrations of natural rubber latex (NR) and oxidised natural rubber latex (ONR) using the solvent casting method. The physicochemical properties of the CMC/NR and CMC/ONR film samples were characterised using FTIR, TG/DTA, DSC, SEM, and XRD analysis. The increased concentration of NR and ONR helped to enhance mechanical characteristics, superior UV resistance, enhanced resistance to oxygen and water vapour penetration, improved dimensional stability, and a reduction in the moisture retention ability of the film samples. The CMC sample film, incorporated with 1.5 g ONR, was found to have more than a 100 % increase in the tensile strength. The tensile value increased from 21.56 MPa to 48.36 MPa, with the highest young modulus of 0.73 GPa and elastic stability of 7.14 %. The incorporation of NR and ONR significantly reduced the super water absorbency nature of the CMC film, and the moisture content values reduced from 21.6 % to ≅ 0.15 % for ONR-incorporated film. Additionally, the CMC/NR and CMC/ONR films exhibited high optical transparency values and were found to be fast biodegradable, substantiating their potential use in various packaging applications. Application of these materials in perishable fruit packaging has shown significant enhancement in shelf life, highlighting their practical efficiency and potential for sustainable packaging solutions.

Multifunctional alginate films blended with polyphenol-rich extract from unconventional edible sources: Bioactive properties, UV-light protection, and food freshness monitoring.

The development of active and smart packaging from non-conventional food sources is an ecological trend to ensure safe food supply in the food chain. The study aimed to develop multifunctional films based on alginate blended with different concentrations of purple onion peel (POPE) and butterfly-pea flower extract (BFE). The addition of the extracts increased the opacity of the films by 80 %, indicating greater UV-light barrier ability. The tensile strength and elongation at break of the films increased by 70 % and 30 %, while water vapor permeability decreased by 15 %. The interaction between the extract and the alginate positively modified the structure of the films, increasing the melting temperature of the films (112-131 °C). Mixing both extracts in the matrix generated materials with antioxidant activity, antimicrobial capabilities, and sensitivity to freshness factors (gases, pH, and temperature) superior to films added with a single extract, suggesting better active and intelligent performances. The films protected the color of food products against the effects of UV-light, being strongly capable of colorimetrically checking the deterioration of protein-rich products. Therefore, alginate films blended with POPE and BFE have a promising potential for developing smart materials, preserving, and monitoring the food quality.

Subcutaneous immunoglobulin replacement therapy in patients with immunodeficiencies - impact of drug packaging and administration method on patient reported outcomes.

BACKGROUND: Here, the perspective of patients with primary and secondary immunodeficiency receiving subcutaneous immunoglobulin (SCIg) via introductory smaller size pre-filled syringes (PFS) or vials were compared. METHODS: An online survey was conducted in Canada by the Association des Patients Immunodéficients du Québec (APIQ) (10/2020-03/2021). Survey questions included: reasons for choosing SCIg packaging and administration methods, training experiences, infusion characteristics, and switching methods. The survey captured structured patient-reported outcomes: treatment satisfaction and its sub-domains, symptom state, general health perception, and physical and mental function. Respondents using PFS were compared with vial users, overall and stratified by their administration method (pump or manual push). RESULTS: Of the 132 total respondents, 66 respondents used vials, with 38 using a pump and 28 using manual push. PFS (5 and 10 mL sizes) were being used by 120 respondents, with 38 using a pump and 82 using manual push. PFS users were associated with a 17% lower median (interquartile range) SCIg dose (10 [8, 12] vs. 12 [9, 16] g/week, respectively), a significantly shorter infusion preparation time (15 [10, 20] vs. 15 [10, 30] mins, respectively), and a trend for shorter length of infusion (60 [35, 90] vs. 70 [48, 90] mins, respectively) compared with those on vials. Patient-reported treatment satisfaction scores were overall similar between vial and PFS users (including on the domains of effectiveness and convenience), except for a higher score for vials over PFS on the domain of global satisfaction (p=0.02). CONCLUSIONS: Consistent with prescribing that reflects a recognition of less wastage, PFS users were associated with a significantly lower SCIg dose compared with vial users. PFS users were also associated with shorter pre-infusion times, reflecting simpler administration mechanics compared with vial users. Higher global satisfaction with treatment among vial users compared with PFS users was consistent with users being limited to smaller PFS size options in Canada during the study period. Patient experience on PFS is expected to improve with the introduction of larger PFS sizes. Overall, treatment satisfaction for SCIg remains consistently high with the introduction of PFS packaging compared with vials.

Identification and quantification of medical device extractables and leachables via non-target analysis (NTA); Analytical uncertainty.

Leachables are substances that are leached from a medical device during its clinical use and are important due to the patient health-related effects they may have. Thus, medical devices are profiled for leachables (and/or extractables as probable leachables) to assess their potential impact on patient health and safety. This profiling is accomplished by screening extracts or leachates of the medical device for released organic substances via non-targeted analysis (NTA) employing chromatographic methods coupled with mass spectrometric detection. Chromatographic mass spectral response factors (RFs) for extractables and leachables vary significantly from compound to compound, complicating the quantitation of these compounds and the application of assessment strategies such as the Analytical Evaluation Threshold (AET). The analytical uncertainty resulting from response factor variation can be expressed in terms of an uncertainty factor (UF), which estimates the magnitude of response factor variation. This manuscript discusses the concept and impact of analytical uncertainty and provides best practice recommendations for the calculation and use of the uncertainty factor, UF.

An action research study of quality improvement in instrument packaging procedures for the central sterile supply department.

This study aimed to reduce instrument packaging defects in the Central Sterile Supply Department (CSSD) using action research. Data of the instrument packs packaged by the packaging personnel at the CSSD of the authors' institution during March to May 2023 were collected and analyzed. After identifying the problems, 2 rounds of cyclic process of "plan-action-observe-reflect" were implemented to standardize the packaging procedures and develop and improve the applicable check of standard operating procedures for the CSSD. After strictly implementing the packaging operation standards and checklists, the number of packaging defect cases dropped from 274 to 41. A significant difference was identified between the number of packaging personnel who achieved a "pass" in the assessment of 3 items for maintenance. Also, 1 item for assembly had significant differences compared with the baseline number after the first cycle (P ≤ 0.001). A significant difference was identified between the number of packaging personnel who achieved a "pass" in the assessment of 20 items for 6 components after the second cycle compared with that after the first cycle (P ≤ 0.05). Through action research methodology, strict implementation of standardized packaging procedures in the CSSD can reduce packaging defects, thereby decreasing clinical complaints and ensuring patient safety.

Development of a generic sample preparation method using dispersive liquid-liquid microextraction for the monitoring of leachable compounds in hospital pharmacy-prepared prefilled drug products.

Performant sample preparation is mandatory in any leachable study to clean and preconcentrate analytes within the sample to offer the best possible extraction recovery as well the best precision for any given substance. The aim consists in developing a sample preparation method for hospital pharmacy-prepared drug products such as long-term storage prefilled syringes, vials and IV bags for the screening of leachable compounds. The Quality Control Laboratory of the Pharmacy of the Lausanne University Hospital (Switzerland) has developed a time- and cost-effective, highly sensitive, robust, and fast method using liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) for the analysis of 205 plastic additives. An innovative setup, based on postcolumn infusion (PCI) using 2% ammonium hydroxide in methanol was used to boost the signal intensity of the analytes in MS detection. A database for extractable and leachable trace assessment (DELTA) was built to assist in the screening process of 205 plastic packaging-related compounds. The development of the sample preparation was based on 33 plastic additive candidates in different hospital pharmacy compounding solutions, and their extraction recovery rates as well as their relative standard deviation were taken into consideration. In conclusion, the developed DLLME was assigned with ultrasound assistance and triple extraction, which brought about extraction recovery rates between 67% and 92%, a good RSD <10%, and a preconcentration factor of 50×. Therefore, DLLME could be considered suitable for the semiquantitative screening of leachable additives in simple hospital pharmacy-prepared prefilled drug products.

Container-content interactions with radiopharmaceuticals: Seeing is believing.

This perspective article addresses the critical issue of container-content interactions in the administration of intravenous medications, with a focus on radiopharmaceuticals used in nuclear medicine. Medication administration errors pose a significant challenge to patient safety. The "five rights" framework-ensuring the right patient, drug, time, dose, and route-serves as a cornerstone for safe drug administration. In the context of radiopharmaceuticals, notable for their use in nuclear medicine, adherence to these principles is paramount due to their unique properties and role in diagnostic and therapeutic procedures. The article explores the impact of container materials, particularly in syringes, on radiopharmaceutical stability and administration accuracy. It delves into the complexities of sorption phenomena, highlighting studies demonstrating its occurrence and potential consequences, including variations in administered doses and compromised diagnostic or therapeutic outcomes. Noteworthy factors influencing sorption include the type of radiopharmaceutical, container composition, molecular properties, and dilution. Findings revealing residual activity in syringes and identifying specific components, such as lubricants, silicon gaskets, and plungers, contributing to adsorption are presented. Migration of metal contaminants from container to content is discussed, emphasizing the potential impact on radiochemical yield and stability. There is a need for comprehensive studies to characterize drug-container interactions and poses crucial questions about the true benefit patients derive from prescribed activities. It challenges current practices, suggesting a need for tailored activity levels, container validation protocols, and rigorous testing of hospital preparations. Ultimately, this perspective paper calls for a deeper understanding of these interactions, urging regulatory consideration and standardization to ensure optimal drug administration and patient outcomes.

Outer packaging labelling of medicines in Southern African Development Community (SADC) countries: comparative analysis of requirements and transition terms for harmonisation.

INTRODUCTION: The COVID-19 pandemic highlighted an urgent need for harmonised requirements for the regulation of medicines. To fully implement harmonised medicines regulations across Africa, common technical standards of medicine regulations are needed. One such technical standard is the labelling of medicines on outer packaging. In this study, we compared outer packaging labelling requirements and transition terms for harmonization for countries in the Southern African Development Community (SADC) region. METHODS: Data on legislation and/or regulatory guidelines for medicine outer packaging labelling from National Medicines Regulatory Authorities (NMRAs) were obtained for countries in the SADC region (n = 16) by February 2023. A detailed comparative content analysis was conducted to determine alignment with the requirements of the Southern African Development Community (SADC) harmonised labelling guidelines to assess readiness levels of each country to transition to the SADC harmonised labelling guideline for outer packaging of medicines. RESULTS: Content analysis showed at least 11 out of 16 countries require national legal reform to transition to the SADC harmonised labelling guideline. In all cases where countries specified labelling requirements for outer packaging of medicines, these were stipulated in national medicines legislation. CONCLUSION: Even though there is a high level of alignment across the countries in terms of national labelling requirements, most countries in the SADC region would still require national legislative reform to transition to regional harmonised labelling requirements and then ultimately to continental requirements of the African Medicines Agency (AMA).

Cell and Gene Therapies: Challenges in Designing Extractables and Leachables Studies and Conducting Safety Assessments.

Over the past decade, Cell and Gene Therapies (C>) have been an emerging therapeutic area with more than twenty C> drug products approved and over 1000 registered trials. The remarkable progress in these modalities brings new challenges for scientists who evaluate manufacturing and storage materials, including risk assessments for extractables and leachables (E&L). Establishing a business process to qualify materials for these applications is an important risk mitigation strategy in support of these assessments. Process validation verifying process performance and product quality requirements using qualified materials also ensures that leachables from the materials do not result in an impact to process and product. The authors provide an overview of available guidelines and publications relevant to E&L risk assessments that can be used to support ex vivo C> products, highlighting gaps and standardization needs in the areas of biocompatibility and extractables conditions. Finally, the authors present leachable testing strategies, relevant to the specific manufacturing and storage conditions of C> products, and safety assessment considerations for organic and inorganic chemical entities.

Advanced technologies in biodegradable packaging using intelligent sensing to fight food waste.

The limitation of conventional packaging in demonstrating accurate and real-time food expiration dates leads to food waste and foodborne diseases. Real-time food quality monitoring via intelligent packaging could be an effective solution to reduce food waste and foodborne illnesses. This review focuses on recent technological advances incorporated into food packaging for monitoring food spoilage, with a major focus on paper-based sensors and their combination with smartphone. This review paper offers a comprehensive exploration of advanced macromolecular technologies in biodegradable packaging, a general overview of paper-based probes and their incorporation into food packaging coupled with intelligent sensing mechanisms for monitoring food freshness. Given the escalating global concerns surrounding food waste, our manuscript serves as a pivotal resource, consolidating current research findings and highlighting the transformative potential of these innovative packaging solutions. We also highlight the current intelligent paper-based food freshness sensors and their various advantages and limitations. Examples of implementation of paper-based sensors/probes for food storage and their accuracy are presented. Finally, we examined how intelligent packaging can be an alternative to reduce food waste. Several technologies discussed here have good potential to be used in food packaging for real-time food monitoring, especially when combined with smartphone diagnosis.

Pilot study: External surface contamination of gemcitabine and 5-fluorouracil on drug packaging.

INTRODUCTION: Antineoplastic drugs (ADs) are commonly used pharmaceuticals for anticancer treatments. It has previously been shown that the external surface of drug vials frequently is contaminated with ADs. More than a decade ago methods to prevent occupational exposure were introduced by using plastic coverage of the glass vials or packing vials in a secondary plastic container. The aim of the pilot study was to determine contamination levels of ADs on different parts of AD packaging of two different commercially available drug vials on the Swedish market and to investigate the occurrence of cross contamination of ADs. METHODS: Packagings of gemcitabine (GEM) and 5-fluorouracil (5-FU) were tested by wipe sampling. Five ADs; GEM, 5-FU, cyclophosphamide (CP), ifosfamide and etoposide were quantified using liquid chromatography mass spectrometry. RESULTS: AD contaminations were detected in 69% and 60% of the GEM and 5-FU packaging samples. Highest levels, up to approximately 5 µg/sample, were observed on the glass vials. The protective shrink-wrap of 5-FU vials and the plastic container of GEM were contaminated with low levels of 5-FU and GEM, respectively, and furthermore the 5-FU vials with shrink-wrap were cross-contaminated with GEM. Cross-contamination of CP and GEM was detected on 5-FU vials with plastic shrink-wrap removed. CONCLUSIONS: External contamination of ADs are still present at primary drug packagings on the Swedish market. Protection of AD vials by plastic shrink-wrap or a secondary plastic container does not remove the external contamination levels completely. The presence of cross contamination of ADs on drug packagings was also observed.

Extended physicochemical stability of cetuximab in opened vials and infusion bags when stored at 4°C and 25°C.

INTRODUCTION: This study aimed to determine the stability of cetuximab: (1) under "in-use" conditions after dilution to 1 mg/mL in 0.9% sodium chloride in polyolefin bags and (2) as an undiluted solution (5 mg/mL) repackaged in polypropylene bags or kept in the vial after opening. METHODS: Ready-to-use 500 mg/100 mL vials of cetuximab solution were diluted to 1 mg/mL in 100 mL bags of 0.9% sodium chloride or repackaged as a 5 mg/mL solution into empty 100 mL bags. Bags and vials were stored at 4°C for 90 days and 25°C for 3 days. A syringe sample of 7 mL was taken from each bag for the initial determinations. The sampled bags were weighed to determine their initial weight and placed under the planned storage conditions. The physicochemical stability of cetuximab was estimated using validated methods. RESULTS: No changes in turbidity, no protein loss, and no changes in cetuximab tertiary structure were observed after 30 days of storage or when subjected to a temperature excursion of 3 days at 25°C and when stored at 4°C for up to 90 days, regardless of the concentrations and batches. The colligative parameters did not change under any of the tested conditions. No evidence of microbial growth was found in bags after 90 days of storage at 4°C. CONCLUSION: These results support the extended in-use shelf-life of cetuximab vials and bags, which can be cost-effective for healthcare providers.