Compounding Trade Association Issues Ketamine, Office Pay Best Practices APC Also Updated Position Statements on Constructive Transfer and Peptide Compounding.

The Alliance for Pharmacy Compounding recently released four resource documents aimed at shaping compounding best practices and regulatory compliance.

Sterile Basics of Compounding: Repackaging, Part 1.

This article on the topic of sterile and nonsterile repackaging is based on the content of United States Pharmacopeia 35-National Formulary 30 and how the respective official chapters of the publication relate to pharmacy compounding and practice. The article differentiates between commercial repackagers and pharmacists that repackage in their pharmacy for their patients. It also discusses the standards for packaging and the beyond-use dates that should be assigned.

Characterization of Prototype Gummy Formulations Provides Insight into Setting Quality Standards.

Gummy formulations are considered suitable alternatives to traditional oral dosage forms like tablets and capsules due to their merits that include chewability, softness/flexibility, improved drug release, administration without water, appealing organoleptic properties, better patient compliance, easy preparation and usefulness for persons of different ages (e.g. children). Though there is increasing interest in gummy formulations containing drugs, measurable parameters, and specification limits for evaluating their quality are scarce. Quality check forms an essential part of the pharmaceutical development process because drug products must be distributed as consistently stable, safe, and therapeutically effective entities. Consequently, some quality parameters that could contribute to the overall performance of typical gummy formulations were investigated employing six brands of non-medicinal gummies as specimens. Accordingly, key physicochemical and micromechanical characteristics namely adhesiveness (0.009 - 0.028 mJ), adhesive force (0.009 - 0.055 N), chewiness (2.780 - 6.753 N), cohesiveness (0.910 - 0.990), hardness (2.984 - 7.453 N), springiness (0.960 - 1.000), and resilience (0.388 - 0.572), matrix firmness - compression load (2.653 - 6.753 N) and work done (3.288 - 6.829 mJ), rupture (5.315 - 29.016 N), moisture content (< 5%), weight uniformity (< 2.5 g; < 7.5% deviation), and intraoral dissolution pH (≥ 3.5 ≤ 6.8) were quantified to identify measures that may potentially function as specification limits and serve as prospective reference points for evaluating the quality of gummy formulations. Findings from this work contribute to ongoing efforts to standardize the quality control strategies for gummy formulations, particularly those intended for oral drug delivery.

Consensus Statements on the Use of Novel Formulations of Isotretinoin: A Modified Delphi Process.

Oral isotretinoin remains a mainstay of treatment for severe, recalcitrant nodular acne. Novel formulations of isotretinoin have been developed over the past decade, including lidose isotretinoin and micronized isotretinoin. It is important to understand the differences between isotretinoin formulations to help guide clinical decision-making and selection of isotretinoin therapy. This study aims to provide evidence-based consensus statements regarding the use of novel formulations of isotretinoin for the treatment of moderate-to-severe acne. The Expert Consensus Group consisted of dermatologists with expertise in the treatment of acne. Voting members met in person to conduct a modified Delphi process; a maximum of 2 rounds of voting were conducted for each consensus statement. A total of 5 statements were generated regarding the use of novel formulations of isotretinoin, addressing the efficacy, tolerability, and side effects of novel isotretinoin formulations. All 5 statements achieved agreement with high consensus. The Expert Consensus Group agrees that individualized selection of isotretinoin therapy is important to maximize efficacy and minimize side effects. Compared to generic isotretinoin, micronized isotretinoin may require lower doses to achieve sufficient plasma concentrations. With the increased bioavailability of micronized formulation, there is no need to calculate cumulative dose; instead, the general recommendation with micronized isotretinoin is to treat for at least 5 months, or longer if needed to achieve clearance. Micronized isotretinoin can be taken in the fed or fasted state and has an acceptable safety profile. J Drugs Dermatol. 2024;23(6):429-432.     doi:10.36849/JDD.7971.

Basics of Sterile Compounding: Sterilization Methods in Sterile Product Manufacturing.

Sterilization methods to produce sterile preparations include heat, gas, radiation, and filtration. This article focuses on heat, gas, and radiation sterilization, plus a brief introduction to bright-light sterilization. Microbiology basics and microbial death kinetics, key to understanding why these sterilization methods work, will also be briefly discussed. Filtration sterilization will be covered in a separate article.

Detection and reduction of errors in parenteral nutrition compounding through gravimetric and product control. / [Artículo traducido] Detección y reducción de errores en la elaboración de la nutrición parenteral mediante control gravimétrico y de producto.

OBJECTIVE: To analyze the errors in the preparation of parenteral nutrition in a Pharmacy Service, detected through an already consolidated gravimetric and product quality control, and compare them with those detected during the initial years of implementing this quality control. METHODS: All errors detected through quality control in the compounding of pediatric and adult parenteral nutrition between 2019 and 2021 were prospectively analyzed. This quality control consisted of 3 sequential processes: a visual check, a gravimetric control, and a product control. Errors were classified as gravimetric, when the nutrition had a deviation of more than 5% from the theoretical weight, or as product errors when a qualitative or quantitative error was detected upon reviewing the remainder of the components used. These errors were analyzed in terms of type and the component involved. A comparison was made with the errors detected during the implementation phase of this quality control from 2016 to 2018. RESULTS: A total of 41,809 parenteral nutritions were reviewed, and 345 errors were detected (0.83% of the preparations); of these, 59 errors were found in pediatric nutritions (0.68% of them), and 286 in adult nutritions (0.86% of them). Among these errors, 193 were of gravimetric nature, while 152 were detected through product control. The main components involved in product errors were electrolytes, primarily due to the addition of excessive volumes and the use of incorrect components. A significant absolute reduction of 0.71% (p < 0.05) in the total number of errors was observed when compared to the implementation phase. This reduction was consistent in both gravimetric errors (-0.59%) and product-related errors (-0.12%) (p < 0.05). CONCLUSIONS: Comprehensive quality control of parenteral nutrition preparation is an easily implementable tool that effectively detected and prevented significant errors. Furthermore, its widespread adoption contributed to a reduction in the overall error count.

[Overwiew of compounding oncology pharmacy in France in 2021]. / États des lieux de la pharmacotechnie oncologique en France en 2021.

The pharmacotechnical expert group of the French Society of Oncological Pharmacy presents the results of its national survey carried out in 2021 in the form of an inventory of pharmaceutical compounding units dedicated to oncology. Premises, equipment, controls, production flows and trends are described in this article, providing an overview of the sector at a time when the new Good Manufacturing Practices (GMP) are applicable. This overview will allow us to better address the needs and expectations of production pharmacists regarding the application of GMP and the development of their units.

In-lab synthesized turn-off fluorescence sensor for estimation of Gemigliptin and Rosuvastatin polypill appraised by Spider diagram, AGREE and whiteness metrics.

Gemigliptin-Rosuvastatin single-pill combination is a promising therapeutic tool in the effective control of hyperglycemia and hypercholesterolemia. Organic sensors with high quantum yields have profoundly significant applications in the pharmaceutical industry, such as routine quality control of marketed formulations. Herein, the fluorescence sensor, 2-Morpholino-4,6-dimethyl nicotinonitrile 3, (λex; 226 nm, λem; 406 nm), was synthesized with a fluorescence quantum yield of 56.86% and fully characterized in our laboratory. This sensor showed high efficiency for the determination of Gemigliptin (GEM) and Rosuvastatin (RSV) traces through their stoichiometric interactions and simultaneously fractionated by selective solvation. The interaction between the stated analytes and sensor 3 was a quenching effect. Various experimental parameters and the turn-off mechanism were addressed. The adopted approach fulfilled the ICH validation criteria and showed linear satisfactory ranges, 0.2-2 and 0.1-1 µg/mL for GEM and RSV, respectively with nano-limits of detection less than 30 ng/mL for both analytes. The synthesized sensor has been successfully applied for GEM and RSV co-assessment in their synthetic polypill with excellent % recoveries of 98.83 ± 0.86 and 100.19 ± 0.64, respectively. No statistically significant difference between the results of the proposed and reported spectrophotometric methods in terms of the F- and t-tests. Ecological and whiteness appraisals of the proposed study were conducted via three novel approaches: the Greenness Index via Spider Diagram, the Analytical Greenness Metric, and the Red-Green-Blue 12 model. The aforementioned metrics proved the superiority of the adopted approach over the previously published one regarding eco-friendliness and sustainability. Our devised fluorimetric turn-off sensing method showed high sensitivity, selectivity, feasibility, and rapidity with minimal cost and environmental burden over other sophisticated techniques, making it reliable in quality control labs.

Detection and reduction of errors in parenteral nutrition compounding through gravimetric and product control.

OBJECTIVE: To analyze the errors in the preparation of parenteral nutrition in a Pharmacy Service, detected through an already consolidated gravimetric and product quality control, and compare them with those detected during the initial years of implementing this quality control. METHODS: All errors detected through quality control in the compounding of pediatric and adult parenteral nutritions between 2019 and 2021 were prospectively analyzed. This quality control consisted of 3 sequential processes: a visual check, a gravimetric control, and a product control. Errors were classified as gravimetric, when the nutrition had a deviation of more than 5% from the theoretical weight, or as product errors when a qualitative or quantitative error was detected upon reviewing the remainder of the components used. These errors were analyzed in terms of type and the component involved. A comparison was made with the errors detected during the implementation phase of this quality control from 2016 to 2018. RESULTS: A total of 41,809 parenteral nutritions were reviewed, and 345 errors were detected (0.83% of the preparations); of these, 59 errors were found in pediatric nutritions (0.68% of them), and 286 in adult nutritions (0.86% of them). Among these errors, 193 were of gravimetric nature, while 152 were detected through product control. The main components involved in product errors were electrolytes, primarily due to the addition of excessive volumes and the use of incorrect components. A significant absolute reduction of 0.71% (P < .05) in the total number of errors was observed when compared to the implementation phase. This reduction was consistent in both gravimetric errors (-0.59%) and product-related errors (-0.12%) (P < .05). CONCLUSIONS: Comprehensive quality control of parenteral nutrition preparation is an easily implementable tool that effectively detected and prevented significant errors. Furthermore, its widespread adoption contributed to a reduction in the overall error count.

Quality control evaluation of paediatric chocolate-based dosage forms: 3D printing vs mold-casting method.

Pharmaceutical compounding is a core activity in the preparation of patient-specific dosage forms. In the current study we aimed to investigate whether 3D printing could be employed for the preparation of pediatric-friendly personalized dosage forms that fulfil the acceptance criteria specified in the pharmacopoeias for conventional dosage forms. We then compared the 3D printed dosage forms with the same formulations prepared with mold-casting, a method frequently applied during pharmaceutical compounding. The molded dosage forms failed to pass most of the quality control tests, including the mass uniformity and content uniformity tests, as well as dose accuracy, contrary to the 3D printed, which not only passed all tests but also enabled precision overdose adjustment. Hence, 3D printing of chocolate-based dosage forms may effectively serve as an acceptable alternative method to mold casting in compounding patient-specific medication at the point-of-care.

Quality Control: Photodocumentation in Pharmacy Compounding.

In addition to the numerous physical, chemical, instrumental, and microbiological tests commonly utilized in the quality control of compounded medications, it also seems appropriate to incorporate visual testing and photodocumentation to provide additional assurance supporting the quality of compounded medications. This article provides a brief listing of what is needed, along with a description of simple procedures, to establish photodocumentation in a compounding pharmacy.

A pharmacokinetics study of proposed bevacizumab biosimilar MYL-1402O vs EU-bevacizumab and US-bevacizumab.

PURPOSE: Bevacizumab is a recombinant humanized monoclonal antibody that inhibits vascular endothelial growth factor-specific angiogenesis in some cancers. MYL-1402O is a proposed bevacizumab biosimilar. METHODS: The primary objective of this single-center, randomized, double-blind, three-arm, parallel-group, phase 1 study in healthy male volunteers was to evaluate bioequivalence of MYL-1402O to EU and US-reference bevacizumab, and EU-reference bevacizumab to US-reference bevacizumab. The primary pharmacokinetic parameter was area under the serum concentration-time curve from 0 extrapolated to infinity (AUC0-∞). Pharmacokinetic parameters were analyzed using general linear models of analysis of variance. Secondary endpoints included safety and tolerability. RESULTS: Of 111 enrolled subjects, 110 were included in the pharmacokinetic analysis (MYL-1402O, n = 37; EU-reference bevacizumab, n = 36; US-reference bevacizumab, n = 37). Bioequivalence was demonstrated between MYL-1402O and EU-reference bevacizumab, MYL-1402O and US-reference bevacizumab, and between EU- and US-reference bevacizumab where least squares mean ratios of AUC0-∞ were close to 1, and 90% CIs were within the equivalence range (0.80-1.25). Secondary pharmacokinetic parameters (AUC from 0 to time of last quantifiable concentration [AUC0-t], peak serum concentration [Cmax], time to Cmax, elimination rate constant, and elimination half-life) were also comparable, with 90% CIs for ratios of AUC0-t and Cmax within 80-125%. Treatment-emergent adverse events were similar across all three treatment groups and were consistent with clinical data for bevacizumab. CONCLUSION: MYL-1402O was well tolerated and demonstrated pharmacokinetic and safety profiles similar to EU-reference bevacizumab and US-reference bevacizumab in healthy male volunteers. No new significant safety issues emerged (ClinicalTrials.gov, NCT02469987; ClinicalTrialsRegister.eu EudraCT, 2014-005621-12; June 12, 2015).

[CAR-T cells gene therapy medicines: Regulatory status and pharmaceutical circuits in Europe and France]. / Les médicaments de thérapie génique CAR-T cells : statuts réglementaires et circuits pharmaceutiques en Europe et en France.

CAR-T cells belong to a new class of biological medicines, referred to as Advanced Therapy Medicinal Products (ATMPs). Despite the cellular component, according to the regulatory definition, CAR-T cells are gene therapy medicines, a sub-category of ATMPs, since their therapeutic effect is the result of their genetic modification. The specificity and the complexity of these innovative drugs have required a complete reorganization of the hospital and pharmaceutical circuits, from the cell collection to the drug administration to the patient. Indeed, increased interaction and collaboration between different healthcare professionals is essential in order to guarantee the quality and safety of these innovative medicines.

Challenges in Formulating Sunscreen Products.

Developing efficient sunscreen products with an acceptable sensory feel after application on skin, that meet current regulatory market and consumer requirements, is a major challenge, exacerbated by new restrictions limiting the use of certain ingredients previously considered crucial. This paper outlines a development strategy for -formulating sunscreens along a generic professional development pathway. Each galenic system will be different and must be customized. Development starts with benchmarking, followed by UVA/UVB filter platform selection and in silico calculation/optimization of photoprotection performance for the desired SPF, UVA-PF, and other requested endpoints. Next comes the selection of the emulsifier system and other key formulation ingredients, such as oil components, triplet quenchers, and antioxidants, with sensory, rheological, and film formation functions. Preliminary cost estimation is then performed to -complete the conceptual process before the start of the practical galenic development. The successful development of modern sunscreen products is based on -comprehensive expertise in chemistry, galenic methodology, regulation, and patenting, as well as specific -market and consumer requirements. The selection of the UV filters is the first key decision and constrains later choices. Other properties, such as water resistance and preservation or active ingredients, may need to be considered. The 4 basic requirements of efficacy, safety, registration, and patent freedom become checklist items to ensure that after development, a sunscreen product has a chance of success.

Digital twin of low dosage continuous powder blending - Artificial neural networks and residence time distribution models.

In this paper we present a thorough description of the digital twin development for a continuous pharmaceutical powder blending process in accordance with the Process Analytical Technologies (PAT) and Quality by Design (QbD) guidelines. A low-dosage system of caffeine active pharmaceutical ingredient (API) and dextrose excipient was examined via continuous blending experiments. Near infrared (NIR) spectroscopy-based process analytics were applied; quantitative evaluation of spectra was achieved using multivariate data analysis. The blending system was represented with mechanistic residence time distribution (RTD) models and two types of recurrent artificial neural networks (ANN), experimental datasets were used for model training or fitting and validation. Detailed comparison of the two modelling approaches, the optimization of the model-based digital twin, and efficiency of the soft sensor-based process monitoring is presented through several validating simulations. Both RTD models and nonlinear autoregressive neural networks demonstrated excellent predictive power for the low dosage blending process. RTD models can prove to be more advantageous in industrial development as they are less resource-intensive to develop and prediction accuracy on low concentration levels lacks dependency from the precision of chemometric calibration. Reduced material costs and limited development timeframe render the digital twin an efficient tool in technological development.

A Review of the Main Considerations for Formulation Development in Preclinical Toxicology Studies.

The main considerations for the development of a formulation for preclinical safety assessment testing are explored. Intravenous, inhalation, oral and dermal dosing are given focus and although different dose routes do present their own individual challenges there are common themes that emerge. In each case it is necessary to maximise exposure to achieve high doses to satisfy regulatory requirements for safety assessment testing. This often involves producing formulations that are at the limits of solubility and maximum volumes possible for administration to different test species by the chosen route. It is concluded that for all routes it is important to thoroughly explore the stability of the test item in the proposed formulation matrix well ahead of dosing any animals, giving careful consideration to which excipients are used and what their underlying toxicity profile may be for the relevant preclinical species. In addition, determining the maximum achievable concentrations and weighing that against the maximum volumes that can be given by the chosen route in all the test species at an early stage will also give a read on whether it would be theoretically possible to achieve suitably high enough doses to support clinical work. Not doing so can cause delays in the development programme and may have ethical repercussions.

Preparation and preliminary quality evaluation of aspirin/L-glutamate compound pellets.

L-glutamate is an important component of protein. It can prevent gastrointestinal damage caused by NSAIDs. We constructed two-phase enteric-coated granules of aspirin and L-glutamate compound by extrusion spheronization method and fluidized bed coating. The subliminal effective dose of L-glutamate is 100 mg/kg tested by model of gastric ulcer of rats induced by aspirin and drug administration. HPLC-UV and UV-Vis methods were adopted to determine content and cumulative release of aspirin and L-glutamate as quality analysis method indexes. The prescription and process optimization were carried out with yield, sphericity and dissolution. The two-phase compound granules have good sphericity of 0.93 ± 0.05 (aspirin pellets) and 0.94 ± 0.02 (L-glutamate pellets), content of salicylic acid (0.24 ± 0.03)%, dissolution of aspirin (2.36 ± 0.11)%. Quality evaluation and preliminary stability meet the commercial requirements. The stored environment of compound preparation should be sealed in a cool and dark place.

Time to review how injectable medicines are prepared and administered in European hospitals.

It has been known, for decades, that the use of injectable medicines in European hospitals has been associated with frequent medication errors, some of which cause preventable severe harms and deaths. There  have been national and European inquiries and reports concerning  improving patient safety by recommending greater use of pharmacy  aseptic preparation services and provision of ready-to administer  injectables, which have not been widely implemented.In England experience of treating patients with COVID-19 infections has  brought into focus other benefits of significantly extending pharmacy aseptic preparation services. These benefits include saving  nursing time, having systems in place which have resilience and capacity,  reducing variation in practice, improving clinical staff and patient  experience, and enabling more injectable medicines to be administered to  patients at home. It has also been recognised that more action is required  to standardise policies and procedures for injectable medicines and  mplement the use of smart infusion devices with dose error reduction  software, to help minimise drug administration errors.Hospital pharmacists have a key role in developing these services to bring  European hospitals more in line with those provided by hospital pharmacies in North America.

Desde hace décadas se conoce que el uso de los medicamentos  nyectables en los hospitales europeos se encuentra asociado a numerosos  errores de medicación, algunos de los cuales provocan daños graves y  muertes prevenibles. Se han publicado investigaciones e informes  nacionales y europeos sobre la mejora de la seguridad del paciente que  recomiendan una mayor utilización de las unidades de preparación  aséptica de los servicios de farmacia y la provisión de los medicamentos  inyectables listos para su administración, recomendaciones que apenas se  han implementado.En Inglaterra, la experiencia de tratar a los pacientes con infección por  COVID-19 ha puesto de manifiesto otros beneficios que conlleva la ampliación de las unidades de preparación aséptica de los servicios de farmacia. Estos beneficios incluyen ahorrar tiempo de enfermería,  disponer de sistemas con mayor resiliencia y capacidad, reducir la  variabilidad en la práctica, mejorar la satisfacción del personal clínico y del paciente, y facilitar la administración de más medicamentos inyectables a  los pacientes en sus domicilios. También se ha reconocido que se precisan  actuaciones dirigidas a estandarizar las directrices y procedimientos de  utilización de los medicamentos inyectables e implementar el uso de  dispositivos de infusión inteligentes con software de reducción de errores  de dosis, con el fin de minimizar los errores en la administración de estos  medicamentos. Los farmacéuticos de hospital tienen un papel clave en el desarrollo de  stas actividades para que los servicios que prestan las farmacias  hospitalarias europeas estén más en consonancia con los que se  proporcionan en Norteamérica.