[Application of qNMR in Standard Materials Used for the Crude Drugs].

Crude drugs and Kampo formulations derived from natural materials such as plants, animals, and minerals are multicomponent medicines that contain numerous chemical constituents. Quantitative determination of characteristic constituents for quality control is crucial for the standardization and quality assurance of natural medicines. Quantitative assays to determine marker compound contents are commonly performed using HPLC systems. In order to achieve accurate quantitative determination, it is essential to use standard materials with well-defined purities corresponding to the target analytes. Many marker compounds used as standard materials must be purified and isolated from natural products while ensuring sufficient purity. However, the composition of impurities in the standard material differs among different batches due to differences in the raw materials and their extraction, separation, and purification processes. Therefore, controlling the purity of standard materials derived from natural products is more complex than that of synthetic substances. Quantitative NMR (qNMR), which has become widely used as an absolute quantitative method for low-molecule organic compounds, makes it possible to solve these issues. qNMR has been introduced into the crude drug section of the Japanese Pharmacopoeia (JP) for evaluating the purity of standard materials used for the assay. This review outlines an example of quantitative determination using relative molar sensitivity (RMS) based on qNMR adopted in the JP and introduces the latest efforts toward the application of qNMR to standard materials used for crude drugs in this context.

[Route to the Adoption of Quantitative NMR in the Japanese Pharmacopoeia].

Quantitative NMR (qNMR) is employed to determine the purity of reagents used as standards for HPLC quantification in the Japanese Pharmacopoeia (JP) and has become recognized as a new absolute quantification method in various fields such as pharmaceuticals, foods, and food additives. This report outlines how and why qNMR has been adopted as an official method in the JP and introduces its progression from JP16 to JP18. The results of a survey of companies in the Japan Pharmaceutical Manufacturers' Association regarding how and when to use qNMR from development to manufacturing stages are introduced. The issues involved in the expansion of the use of qNMR in the field of chemical pharmaceuticals in 2017 are discussed and how these were resolved.

Ph. Eur. testing for histamine and depressor substances using guinea-pigs and cats: the end of an era. Strategy for removal of animal tests for histamine and depressor substances and their vestiges from the Ph. Eur.

For more than 50 years, in vivo assays have been used for testing pharmaceutical product safety due to their assumed ability to broadly detect potential unidentified contaminants. As part of these in vivo tests, the animal tests for depressor substances and histamine have been described in the European Pharmacopoeia since its first edition in 1977. Both tests measure the effect of histamine and histamine-like substances, using guinea-pigs and cats respectively. In 2024, the Histamine (2.6.10) general chapter is referenced in the Production section of four monographs and 10 monographs have variations of a sentence on designing the manufacturing process to eliminate or minimise substances lowering blood pressure in this same section, without referencing the chapter. The Depressor substances (2.6.11) chapter is referenced only in the Histamine (2.6.10) chapter as a next step if the histamine test is invalid. A historical search was performed and it has shown that the tests for histamine and for depressor substances were introduced by different groups of experts in an inconsistent way at different times, and for different reasons, leading to non-harmonised approaches across monographs. The control of histamine and other depressor substances has been the subject of numerous debates where their use was questioned. During these discussions, reports on positive cases or batches failing the test for histamine or depressor substances were anecdotal. In addition, in vivo tests can be considered non-specific, very variable, time-consuming, costly and ethically doubtful. More importantly, the majority of in vivo methods originate from a time when good manufacturing practice was not widely used and formal method validation requirements were not yet established. In view of the above, the removal of all references to animal tests for histamine or depressor substances from all texts still referring to them is proposed. Since the sentences in the Production section referring to the control of "substances lowering blood pressure", "vasoactive substances" or "hypotensive substances" appeared as remainders of the animal test without further guarantee of safety, it will also be proposed to remove all these sentences from the concerned monographs. Ultimately, the suppression of general chapters 2.6.10 and 2.6.11 from the Ph. Eur. is envisaged. Independently from the above, it is also envisaged to elaborate a new general chapter Histamine in active substances (2.5.47) to include physicochemical or immunochemical methods enabling the detection of histamine. This new text would aim at supporting manufacturers in their histamine control strategy following the inclusion of precaution statements in the general monograph on Products of fermentation (1468); these statements had been added in Ph. Eur. Supplements 9.6 and 10.4, following adverse events related to a GMP issue with gentamicin sulfate. This strategy has been endorsed by the European Pharmacopoeia Commission at its 177th Session in November 2023. The concerned monographs would be a subject of public consultation in Pharmeuropa 36.2 (April 2024).

Determination of procoagulant activity in human normal immunoglobulin preparations for therapeutic use by FXIa chromogenic assay: Evaluation of test kit sensitivity, reference standard performance and product formulation effects on the FXIa assay.

In 2010, the reporting of thrombotic adverse events for one subcutaneous and certain intravenous immunoglobulins (IGs) raised some concerns. In Europe, regulatory bodies rapidly revised compendial specifications for therapeutic IGs to ensure they do not exhibit thrombogenic (procoagulant) activity (PCA). At the global level, a working group (GWG) was launched with the aim of assessing PCA measurement methods and limits, considering results obtained by human IG manufacturers during in-process controls. The GWG created three dedicated subgroups to investigate the FXIa chromogenic assay, the non-activated partial thromboplastin time (NAPTT) test and the thrombin generation assay (TGA). The European Directorate for the Quality of Medicines & HealthCare (EDQM) was responsible for co-ordinating the subgroup in charge of evaluating the FXIa chromogenic assay in a study that assessed the sensitivity and robustness of two commercial chromogenic FXIa test kits. The impact of IG product formulation on FXIa recovery and the suitability of PCA-containing IG products as potential reference standards/controls were also assessed. IG materials representative of marketed products were provided to four laboratories for a study that was carried out in two steps: 1) two chromogenic FXIa test kit manufacturers assessed the performance and determined optimal test conditions by their respective methods, 2) two OMCLs studied both kits using an optimised study design. Regarding sensitivity, the study results identified suitable dose-response intervals and limits with both chromogenic FXIa test kits. This allowed the establishment of dilution ranges for optimal detection of FXIa/PCA in 5 % and 10 % IG products in the range of 1-6 mIU/mL. However, careful optimisation of the sample dilutions was required (notably to avoid potential matrix effects) and the choice of the mode of data acquisition (kinetic or end-point method) contributed to sensitivity in routine use. Importantly, the composition of IG products was of minor concern for FXIa determination with both test kits. Potential reference materials evaluated in the study behaved as expected and could be useful should a separate reference standard to the FXIa WHO IS be deemed necessary in future.

Collaborative study for the establishment of Ph. Eur. Biological Reference Preparation for Human tetanus immunoglobulin batch 2.

This publication describes the outcome of a project to develop a replacement European Pharmacopoeia (Ph. Eur.) Biological Reference Preparation (BRP) for Human tetanus immunoglobulin (TIg) as well as for the World Health Organization (WHO) International Standard (IS) for Tetanus Immunoglobulin, Human. Bulk TIg was kindly provided by a European manufacturer and was used to prepare the candidate standard. The candidate standard was freeze-dried and calibrated in an international collaborative study jointly co-ordinated by the Medicines & Healthcare products Regulatory Agency (MHRA) and the European Directorate for the Quality of Medicines & HealthCare (EDQM, Council of Europe). The results of this study show that there was good agreement between laboratories for the potency estimates obtained for the candidate standard relative to the current WHO IS/Ph. Eur. BRP. The study also demonstrated that the candidate standard is suitable for use in Ph. Eur. assays for potency testing of TIg products and there was good agreement in the potency estimates obtained using the different assay methods included in the study. Accelerated degradation studies performed at the MHRA over a period of 4 years suggest that the freeze-dried candidate standard will be very stable. The candidate standard was established as Ph. Eur. BRP for Human tetanus immunoglobulin, batch 2 with an assigned potency of 45 IU/ampoule. The same preparation was also adopted by the WHO Expert Committee on Biological Standardization (ECBS) to serve as the WHO 2nd IS for Tetanus Immunoglobulin, Human (13/240).

Report of a collaborative study to establish the first Indian Pharmacopoeia reference standard for teriparatide.

A collaborative study was conducted to establish the first Indian Pharmacopoeia Reference Standard (IPRS) for teriparatide to be used in quality control testing of marketed products in compliance with the Indian Pharmacopoeia (IP) monograph. The study objective was to evaluate the candidate standard in terms of the WHO International Standard (IS) to assign its content in mg per vial terms. This study involved four laboratories from India and the candidate standard was calibrated against the WHO IS by each participant laboratory using high-performance liquid chromatography (HPLC) assay method per IP monograph. Direct calibration of the candidate standard resulted in an assigned content of 1.02 mg per vial. Based on the study results the candidate standard was judged suitable to serve as the first IPRS for teriparatide for identification and assay by HPLC.

Physicochemical quality assessment of various brands of paracetamol tablets sold in Freetown Municipality.

Paracetamol is a widely used over-the-counter drug for managing fever and pain, but its quality may vary among different brands, especially in low- and middle-income countries, where counterfeit and substandard medicines are prevalent. This study evaluated the physicochemical properties of fifteen brands of 500 mg paracetamol tablets sold in various pharmacies in Freetown, Sierra Leone using identification tests, friability tests, assay, dissolution tests, and mass variation. The results showed that three brands were not registered with the Pharmacy Board of Sierra Leone, and two brands did not meet the requirement for labelling (no manufacturing date). All the brands met the requirement for mass variation, friability tests and assays. The percentage assay of the different brands ranged from 96.17 %w/w to 101.97 %w/w. However, two brands did not meet the specification for dissolution, with P012 releasing about 21.23 % ± 5.76 of the drug within 45min. Most of the paracetamol brands evaluated met the physicochemical test specification. However, two brands failed the dissolution test, two brands did not meet the labelling requirement and three brands were identified as unregistered products with the National Medicines Regulatory Authority in Sierra Leone. This study underscores the necessity of enhancing monitoring and post-market surveillance of pharmaceuticals in Sierra Leone to ensure they comply with regulatory requirements.

Generic pharmaceuticals, regulatory aspects, bioequivalence investigation, and perception.

INTRODUCTION: The objective and significance of the topic is to draw attention toward regulatory aspects (and pharmacopoeias) for bioequivalence investigation, and perception for generic pharmaceuticals, especially their stereoselective bioequivalence evaluation for understanding the performance of the racemic generic products available in the market. AREAS COVERED: The areas covered include bioequivalence studies (and related USP and FDA requirements) on certain generic APIs for comparison, examples of concern related to inspection of pharmaceuticals for export/import. Literature methodology includes search through USP monographs, MDPI.com, msn.com, WHO Drug Information, certain specific web links, PubMed Central®, PubMed®, NLM's advanced biomedical information services, and several pdf published in relevant journals in the field for related authentic information. EXPERT OPINION: The USP, the USFDA, and the units alike internationally should enforce pharmaceutical companies to perform stereoselective investigations on generic APIs to show that their PK/PD parameters are (nearly) equal to the standards set by such units for allowing marketing of that API. This should be provided to professionals in the areas of patient care and every country should enforce such regulations at the time of export and import of generics.

Collaborative study for the establishment of Ph. Eur. Biological Reference Preparation for Human tetanus immunoglobulin batch 2.

This publication describes the outcome of a project to develop a replacement European Pharmacopoeia (Ph. Eur.) Biological Reference Preparation (BRP) for Human tetanus immunoglobulin (TIg) as well as for the World Health Organization (WHO) International Standard (IS) for Tetanus Immunoglobulin, Human. Bulk TIg was kindly provided by a European manufacturer and was used to prepare the candidate standard. The candidate standard was freeze-dried and calibrated in an international collaborative study jointly co-ordinated by the Medicines & Healthcare products Regulatory Agency (MHRA) and the European Directorate for the Quality of Medicines & HealthCare (EDQM, Council of Europe). The results of this study show that there was good agreement between laboratories for the potency estimates obtained for the candidate standard relative to the current WHO IS/Ph. Eur. BRP. The study also demonstrated that the candidate standard is suitable for use in Ph. Eur. assays for potency testing of TIg products and there was good agreement in the potency estimates obtained using the different assay methods included in the study. Accelerated degradation studies performed at the MHRA over a period of 4 years suggest that the freeze-dried candidate standard will be very stable. The candidate standard was established as Ph. Eur. BRP for Human tetanus immunoglobulin, batch 2 with an assigned potency of 45 IU/ampoule. The same preparation was also adopted by the WHO Expert Committee on Biological Standardization (ECBS) to serve as the WHO 2nd IS for Tetanus Immunoglobulin, Human (13/240).

Current veterinary regulations and way ahead.

This article aims to perform a comparative systematic review of regulations in veterinary medicine between the years 2016 to 2023. It explores the complex web of veterinary medicine regulations in various agencies and the nations, including USA (United States of America), EU (European Union), UK (United Kingdom), Japan, Australia, and India. Current article provides the comparative study on the veterinary regulations of different countries, including acts, directives, and drug approval processes. Such as, the specific legislation is needed to address zoonotic diseases. The strategic and regulated stockpiling of the veterinary drugs especially in chronic veterinary disease outbreak. It is essential to develop the dedicated Veterinary Pharmacopoeia for the regulated standardization of the raw materials as well as the formulations. Veterinary medical device is a field which is highly unregulated. There is a need to have regulations for the same. It is important to have dedicated veterinary pharmacovigilance centers which help in improving quality of medications to the livestock farms. After comparing the regulations of different countries. We observed that there is the absence of the zoonotic diseases and pharma stockpiling in every country. There is also an absence of the dedicated veterinary pharmacopoeia in every country. USA and Australia have the veterinary medical device regulation which is not there in other countries. Around the globe only Australia has the dedicated pharmacovigilance center. Including these recommendations into regulatory framework enhances the quality and safety of veterinary medicine. The current article adds a valuable resource for policymakers, veterinarians, and stakeholders in the field of animal health care.

Revealing active constituents within traditional Chinese Medicine used for treating bacterial pneumonia, with emphasis on the mechanism of baicalein against multi-drug resistant Klebsiella pneumoniae.

ETHNOPHARMACOLOGICAL RELEVANCE: The emergence of antibiotic-resistant bacteria has rendered it more challenging to treat bacterial pneumonia. Traditional Chinese medicine (TCM) has superior efficacy in the treatment of pneumonia, and it has the unique advantage of antibacterial resistance against multi-drug resistant (MDR) bacteria, but the medication rule and pharmacological mechanism of its antibacterial activity are not clear. AIM OF THE STUDY: This study aims to reveal Chinese medication patterns in treating bacterial pneumonia to select bioactive constituents in core herbs, predict their pharmacological mechanisms and further explore their antibacterial ability against clinically isolated MDR Klebsiella pneumoniae (KP) and their antibacterial mechanisms. MATERIALS AND METHODS: The high-frequency medicinal herbs to treat lung diseases were first screened from Pharmacopoeia of the People's Republic of China (ChP.), and then bioactive compounds in core herbs and targets for compounds and disease were collected. Potential targets, signaling pathways, and drugs' core components were determined by constructing protein-protein interaction network, enrichment analysis and "component-target-pathway-disease" network were mapped by Cytoscape 3.8.2, and the potential therapeutic value of selected core components was verified by comparing the disease targets in the GEO database with the herbal component targets in the ITCM database. The clinically isolated KP were screened by drug sensitivity tests with meropenem (MEM), polymyxin E (PE), and tigecycline and biofilm-forming assay; broth microdilution, chessboard methods and biofilm morphology and permeability experiments were employed to determine the antibacterial, bactericidal and biofilm inhibition ability of selected bioactive constituents alone and in combination with antibiotics; The mechanism of bioactive components on quorum sensing (QS) genes LuxS and LuxR was predicted by molecular docking and tested by RT-PCR. RESULTS: The 13 core Chinese medicines were obtained by mining ChP., and 615 potential targets of core herbal medicine were screened, and the PI3K-Akt signaling pathway might play crucial roles in the therapeutic process. In-vitro experiments revealed that the selected core compounds, including forsythoside B, baicalin, baicalein, and forsythin, all have antibacterial activity, in which baicalein had the strongest ability and a synergistic effect in combination with MEM or PE. Their synergy exhibited a stronger effect on biofilms of MDR KP, inhibiting biofilm formation, disrupting formed biofilms, and removing the residual structures of dead bacteria. Baicalein was predicted to have stable binding capacity to LuxS and LuxR genes by molecular docking, and RT-PCR results verified that the combination of baicalein with MEM or PE was effective in inhibiting the expression of QS genes (LuxS and LuxR) and consequently suppressing biofilm formation. CONCLUSION: The core Chinese herbal medicine in the ChP. to treat lung diseases has a multi-component, multi-target, and multi-pathway synergy to improve bacterial pneumonia. Experimental studies have confirmed that the bioactive compound baicalein was able to combat MDR KP alone and synergistic with MEM or PE, inhibited and disrupted biofilms via regulating LuxS and LuxR genes, and further disturbed quorum sensing system to promote the therapeutic efficacy, which provides a new pathway and rationale for treating MDR KP-induced bacterial pneumonia.

Quality parameters for the medicinal plant Drosera rotundifolia L.: A new approach with established techniques.

Monographs of the European Pharmacopoeia (Ph. Eur.) are the basis for quality control of medicinal plants and therefore important to ensure the consistency, quality, safety, and efficacy of phytopharmaceuticals. The traditional medicinal plant sundew (Drosera sp.) has disappeared from therapy due to nature conservation, but can now be cultivated sustainably on rewetted peatland. However, currently there is no valid Ph. Eur. monograph for the quality control of Droserae herba. In this study, sundew material from different species and sources was investigated with the aim of developing quality control methods based on the Ph. Eur. and defining a uniform quality standard for Droserae herba. It was possible to distinguish between sundew species of different quality, using macroscopic, microscopic, and chromatographic methods. Special emphasis was laid on the content of flavonoids and naphthoquinones as important quality parameters as their content differed between the sundew species. The differences in content and toxicity result in the recommendation that only round-leaved sundew (Drosera rotundifolia L.) should be used as a medicinal plant for the production of phytopharmaceuticals in the future.

Classification Changes of Origin Plants of Traditional Chinese Medicine Based on APG Ⅳ System / 中国实验方剂学杂志

ObjectiveThe angiosperm phylogeny group （APG） Ⅳ system is currently the latest angiosperm classification system. The APG system based on DNA sequence can more naturally reflect the phylogeny and evolution of plants， which has been widely recognized and applied in scientific research and teaching of plants in other countries. Through the comparison between the changes in the APG Ⅳ system and the traditional plant classification system， the changes in the taxonomic status of the original plants of traditional Chinese medicine （TCM） in the 2020 edition of Chinese Pharmacopoeia were reviewed. MethodBy referring to the literature in China and abroad， the changes in the taxonomic status of the original plants of TCM recorded in Chinese Pharmacopoeia were sorted out according to the basic groups of angiosperms in the APG Ⅳ system， including the basal group of ANA， the magnoliid and chloranthales， the basal groups of monocots and eudicots， the superrosids， and the superasterids. ResultThere are about 72 species of TCM in the 2020 edition of Chinese Pharmacopoeia. A total of 76 species of the original plants change in family grade according to the APG Ⅳ system. There are 22 species of TCM belonging to the dicotyledon class， involving 26 species of the original plants. It should be placed in front of the differentiation of monocotyledons and eudicotyledons according to the APG Ⅳ system. ConclusionThis paper largely clarifies the change in the taxonomic status of the original plants of TCM in Chinese Pharmacopoeia according to the APG Ⅳ system， which is helpful to the reviewing literature in China and abroad for the original plants of TCM and facilitates the international academic exchange for TCM. It provides a reference for the revision of textbooks such as Botany and Medicinal Botany in Chinese colleges and universities and will lay the foundation for updating the content of Chinese Pharmacopoeia in the future.

Collaborative study for the establishment of replacement batches of Ph. Eur. Heparin Low-Molecular-Mass for Calibration CRS.

An international collaborative study was run within the framework of the Biological Standardisation Programme (BSP) of the Council of Europe and the Commission of the European Union to establish replacement batches for European Pharmacopoeia (Ph. Eur.) Heparin Low-Molecular-Mass (LMM) for calibration Chemical Reference Substance batch 3 (CRS3) used for the characterisation of LMM heparins by high performance size-exclusion chromatography. Two candidate batches (A, cCRS4 and B, cCRS5) were filled using the same material as the existing official calibrants, adopted with either an assigned number-average molecular mass (Mna) or a broad standard table (BST). Fifteen laboratories evaluated the suitability of these candidate batches for use as calibrants with the pharmacopoeial dual refractive index/ultraviolet (RI/UV) detector calibration method, as well as with a modified mobile phase and the BST calibration method. Seven preparations of LMM heparin were tested. The results confirmed that the proposed batches are suitable for use with the same characteristic Mna as CRS3 and with the BST established for the World Health Organization (WHO) 2nd International Standard (IS). The BST calibration method gave comparable results to the RI/UV method, while showing better reproducibility, being easier to perform and requiring no calibrant with UV absorbance. The modified mobile phase had no impact on the calculated values while improving separation between the calibrant and salt peaks. The two candidate batches were adopted as Ph. Eur. Heparin LMM for calibration CRS batches 4 and 5, respectively, with the assigned Mna value of 3800 and a BST. In anticipation of the depletion of the calibrant required for use with the RI/UV method, and taking into account the unlikely procurement of a new lot of suitable starting material, it was recommended to include the BST method in Ph. Eur. monograph 0828, Heparins, low-molecular-mass. In order to improve peak separation, it was also recommended to include the use of ammonium acetate solution as mobile phase in the monograph, both for the Ph. Eur. RI/UV and the proposed BST calibration methods. Further to this study, Ph. Eur. monograph 0828 was revised to replace the RI/UV method by the BST method. This contributed to the harmonisation of methods across regions, thereby facilitating a concerted global action for the development and establishment of the next batches of calibrants for the quality control of LMM heparins.

East meets west: using ethnobotany in ethnic urban markets of Barcelona metropolitan area (Catalonia) as a tool for biocultural exchange.

BACKGROUND: Ethnobotanical studies in metropolitan areas and urban ethnic markets have grown considerably in recent years as large cities have demonstrated to be significantly rich in biocultural diversity and in driving its evolution, as human populations migrate from one region to another. Urban spaces also represent important places of rich multicultural and multilingual interaction and exchange, where ethnobotany can act as a bridge between research and action. The purpose of this study is to present a case study on how to use ethnobotany in multicultural urban settings by studying people-plant interactions and the larger implications and applications to promote biocultural learning in these areas. METHODS: We inventoried the botanical composition of fresh and dry products sold in most food stores owned by Chinese immigrants in Fondo, a neighbourhood of Barcelona's metropolitan area, in Santa Coloma de Gramenet municipality (Barcelonès county, Catalonia, Iberian Peninsula), pharmacologically validating the obtained list with the Chinese Pharmacopoeia. We also participated in multiple dissemination activities and materials (non-academic and academic), along with exchanges with the broader community in relation to this research. RESULTS: In total, 103 plants were identified at the species level, pertaining to 88 genera and 46 botanical families. Including the infraspecific level, a total of 113 plant taxa were inventoried. One algal and six fungal species were also recorded, but not included in the analyses. Brassicaceae (12.4%) and Fabaceae (10.6%) were the most predominant families inventoried, followed by Cucurbitaceae (7.1%) and Poaceae (7.1%). Over three-quarters of all the taxa have an Asian origin (76.11%), indicating a high conservation of the use of Asian taxa. Over one-third (36.89%) of the plant parts pertain to species contained in the Chinese Pharmacopoeia, showing the relevance of medicinal plants in local stores and the preponderance of Eastern Asian food-medicine continuums. To promote ethnobotanical education programmes, over 50 dissemination activities and educational materials were produced from this study and shared with the local urban community in different fora. CONCLUSIONS: Further research in these and similar settings can provide significant ethnographic information to better understand anthropological processes and phenomena underlying migration and transculturation that can be used in an umbrella of applications, from adequate nomenclature and labelling of foreign products in local languages to multicultural integration and social cohesion programmes along with educational activities on biocultural topics.

Allergen-specific immunotherapy and evidence: A European regulatory perspective.

Allergen immunotherapy (AIT) has been performed for 112 years. In this article we summarize regulatory standards and challenges based on scientific evidence on AIT. Most crucial and timely aspects concerning AIT are addressed from the regulatory perspective of the authors as employees of a national competent authority in Europe: (1) product specificity; (2) clinical efficacy; (3) treatment for adults and children (needs for extrapolation); (4) allergen exposure chambers; (5) biomarkers; (6) standardization; (7) real-world evidence; (8) independent official batch release (benefit and challenges); (9) harmonization on the EU level. The Paul-Ehrlich-Institut (PEI), the Federal Institute for Vaccines and Biomedicines, in Langen near Frankfurt/Main in Germany, examines and evaluates the benefits and risks of AIT products within the course of clinical development, marketing authorization, and subsequently throughout their entire life cycle to ensure high-quality, safe, and effective AIT products.

Validation and application of a SEC-HPLC method for the determination of total protein in therapeutic immunoglobulins as an alternative to the European Pharmacopoeia methods.

Several analytical procedures are described in the European Pharmacopoeia (Ph. Eur.) to determine total protein content. However, the method for the determination of protein content in therapeutic immunoglobulins prescribed in the Ph. Eur. monographs is the Kjeldahl method. The Kjeldahl method is time-consuming and requires the use of large amounts of hazardous reagents, which also results in the production of a large amount of hazardous chemical waste. The purpose of this work was to validate an alternative chromatographic method that requires no hazardous reagents and saves time, using the same instrumental conditions specified in the Ph. Eur. for the human immunoglobulin size-exclusion high-performance liquid chromatography (SEC-HPLC) molecular-size distribution assay. The chromatographic separation was achieved with a TSKgel G3000SW (600 × 7.5 mm, 10 µm) column, using an isocratic elution, with detection at 280 nm wavelength. The mobile phase consisted of an aqueous solution of 0.03 M disodium hydrogen phosphate dehydrate, 0.01 M sodium dihydrogen phosphate monohydrate, 0.2 M sodium chloride and 1 mM sodium azide. The protein content of the test samples was determined referring to a standard with a known protein concentration (i.e. Human immunoglobulin (molecular size) Biological Reference Preparation). The method was validated evaluating the characteristics precision and trueness according to the ICH Q2 guideline, and the goodness of linear fit for the signal response was assessed (given for information only). In addition, the equivalence of methods was evaluated with two one-sided t-tests (TOST) analysis with the Kjeldahl method mentioned in Ph. Eur. monographs on therapeutic immunoglobulins, and with Bland-Altman analysis of SEC-HPLC and manufacturers' data (Kjeldahl and biuret methods). The uncertainty of measurement was also calculated in order to evaluate the accuracy and quality of the results, thus facilitating a reliable compliance/non-compliance decision. Based on the outcome, the method is proposed as a suitable and convenient alternative for the determination of protein content in human immunoglobulins.

Therapeutics to Treat Psychiatric and Neurological Disorders: A Promising Perspective from Algerian Traditional Medicine.

Ancient people sought out drugs in nature to prevent, cure, and treat their diseases, including mental illnesses. Plants were their primary source for meeting their healthcare needs. In Algeria, folk medicine remains a fundamental part of the local intangible knowledge. This study aims to conduct a comprehensive ethnomedicinal investigation and documentation of medicinal plants and the different plant formulations traditionally used in Algeria for the treatment of pain, psychiatric, and neurological disorders. It also intends to improve the current knowledge of Algerian folk medicine. Several scientific databases were used to accomplish this work. Based on this investigation, we identified 82 plant species belonging to 69 genera and spanning 38 distinct botanical families used as remedies to treat various psychological and neurological conditions. Their traditional uses and methods of preparation, along with their phytochemical composition, main bioactive constituents, and toxicity were noted. Therefore, this review provides a new resource of information on Algerian medicinal plants used in the treatment and management of neurological and psychological diseases, which can be useful not only for the documentation and conservation of traditional knowledge, but also for conducting future phytochemical and pharmacological studies.

Product development and quality of pharmacy compounded chenodeoxycholic acid capsules for Dutch cerebrotendinous xanthomatosis patients.

Introduction: In 2017 the drug chenodeoxycholic acid (CDCA) became unavailable to Dutch patients with the rare inborn error of metabolism cerebrotendinous xanthomatosis (CTX). This was a direct result of a steep price increase after CDCA was authorized in the EU as an orphan drug. As a result, Dutch health insurance companies were unable to reimburse this drug and the availability of CDCA to patients with CTX was directly at risk creating an unmet medical need. CTX is characterized by juvenile cataract, tendon xanthomas, infantile-onset diarrhea, psychomotor retardation and progressive cerebellar ataxia. Treatment with CDCA, when initiated before neurological symptoms are present, can prevent the onset of neurological complications. Methods: To assure continuation of patient treatment with a high quality product, the hospital pharmacy of the Amsterdam UMC developed CDCA capsules as a pharmacy preparation. A simple and robust formulation was developed for capsules in a broad dose range of 35-250 mg, ensuring that both pediatric and adult patients can receive an exact dose tailored to their specific needs. Capsules are prepared manually on a small scale for the individual patient. To assure the quality of the product, product validation and stability studies were performed. Results: The results show that the product complies with all specifications based on the requirements of the European Pharmacopoeia. The capsules contain the declared amount of CDCA, no degradation product or other (microbiological) impurities are formed during the production process and the capsules show a quick dissolution profile. Stability studies indicate that it is a stable product and no impurities increase or arise over time. These results show that these pharmacy preparations are of high quality and comply to Good Manufacturing Practice (GMP) requirements. Discussion: Through our research, we have demonstrated that pharmacy compounding can be a viable alternative in situations where immediate access to essential medication is crucial or when certain drugs are temporarily inaccessible. The purpose of this paper is to offer comprehensive guidance to other pharmacies to improve the availability of currently inaccessible drugs through the practice of pharmacy compounding, thereby facilitating improved patient care.

Ensuring the quality of medicines in India: An update on the development, modernization, and harmonization of drug standards in the Indian Pharmacopoeia.

India has a sparkling pharmaceutical sector that holds a distinguished place by producing and supplying high-quality and affordable medicines across the globe. Ensuring the quality and safety of the marketed medicinal products is one of the most important components of the drug regulatory framework and assessment of the quality of medicines is usually achieved by referring to the public standards of the official Pharmacopoeia. In India, the Indian Pharmacopoeia (IP) is published at regular intervals to fulfill the requirements of the Drugs and Cosmetics Act, 1940 to ensure the quality of medicines being manufactured and/or marketed in India. The present article aims to provide an overview of the history of the IP, its standards-setting process, and the current status of monographs in the 9th edition of the IP 2022. Special focus is placed on the newly added and upgraded general chapters and monographs within the IP 2022. There are a total of 223 general chapters and 3152 drug monographs available under various categories in the IP 2022. This study also highlights a total of 92 new drug monograph additions and 412 monograph revisions in the IP 2022. It is anticipated that the standards laid down in the IP 2022 will play an imperative role in delivering quality medicines to patients within and outside India.