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•Saffron cultivation as “niche crop” for food purposes was started in Ukraine.•Standard operating procedure to assure saffron quality and traceability proposed.•Crocins, picrocrocin ...and safranal contents corresponds to the highest quality category.•Saffron meets the European Pharmacopoeia requirements as a homeopathic remedy.•Saffron is a promising raw material for creating drugs and dietary supplements.
Saffron (Crocus sativus L.) is one of the most expensive spices in the world. At the international trading and pharmaceutical market, an establishment of saffron quality in accordance with the International Standardization Organization (ISO) specifications, the European Medicines Agency, Food and Drug Administration, and European Pharmacopeia is obligatory. The medicinal properties of saffron can be used in the pharmaceutical, food and cosmetic industries if the quality of raw materials is clearly controlled on all levels of production. In 2015, the scale cultivation of saffron in the Kherson region (Ukraine) for food purposes was started. Therefore, it was decided to develop the standard operating procedure of saffron cultivation in accordance with the Good Agricultural and Collection Practices (GACP) rules to ensure the traceability of the plant material origin. For this purpose, saffron was grown in seven different experimental zones with a disparity of altitudes, soils and climates of Ukraine. Each saffron sample harvested in 2016/2018 was processed to determine the moisture content, total ash and amount of picrocrocin, crocins, and safranal using ultraviolet-visible spectroscopy according to the ISO 3632. The best yield was 40 g/100 m2 in Cherson region. To obtain a stable crop and quality, the cultivation and harvest processing of saffron should be carried out in accordance with the proposed GACP standards. In addition, the quality of raw materials complies with the standards of European Pharmacopoeia and Deutscher Arzneimittel Codex as a medicinal plant material. Our analysis showed that Ukraine has a good ecological conditions and indicators for saffron cultivation as a food spice and pharmaceutical drugs.
The Biological Standardization Project BSP090 has been successfully concluded in 2021. As a result, two standard methods for quantification of the major allergens Bet v 1 and Phl p 5 will be ...implemented in the European Pharmacopoeia (Ph. Eur.). The General Chapter describing the protocol of the respective Bet v 1‐specific ELISA has already been adopted by the Ph. Eur. Commission and will become an official part of the Ph. Eur. in the beginning of 2023. As this will be the first allergen‐specific standard method in the EU, this paper intends to summarize the preceding process and outline the measures necessary to comply with the new regulatory requirement.
Diagnostic allergens are defined as medicinal products in the EU. Marketing authorization by national authorities is necessary; however, diagnostic allergens are not homogeneously regulated in ...different EU member states. Allergen manufacturers argue with increasing costs forcing them to continuously reduce the diagnostic allergen portfolios offered to allergists. In contrast, EAACI and national European Allergy Societies see the need for the availability of a wide range of high‐quality diagnostic allergens for in vivo diagnosis of IgE‐mediated allergies not only covering predominant but also less frequent allergen sources. In a recent EAACI task force survey, the current practice of allergy diagnosis was shown to rely on skin tests as first option in almost 2/3 of all types of allergic diseases and in 90% regarding respiratory allergies.
With the need to ensure the availability of high‐quality diagnostic allergens in the EU, an action plan has been set up by EAACI to analyse the current regulatory demands in EU member states and to define possible solutions stated in this document: (a) simplification of authorization for diagnostic allergens; (b) specific regulation of special types of diagnostic allergens; (c) new models beyond the current model of homologous groups; (d) simplification of pharmacovigilance reporting; (e) reduction of regulation fees for diagnostic allergens; (f) reimbursement for diagnostic allergens.
Joining forces of allergists, manufacturers and authorities are of high importance to ensure remaining relevant allergens in the EU markets to facilitate a sustainable and comprehensive service for the diagnosis and treatment of allergic diseases.
Traditional Chinese medicine (TCM) are becoming more and more popular all over the world. However, quality issues of TCM may lead to medical incidents in practice and therefore quality control is ...essential to TCM. In this review, the state of TCM in European Pharmacopoeia are compared with that in Chinese Pharmacopoeia, and herbal drugs that are not considered as TCM and not elaborated by TCM working party at European Directorate for the Quality of Medicines & Health Care (EDQM) but present in both European Pharmacopoeia and Chinese Pharmacopoeias are also discussed. Different aspects in quality control of TCM including origins, identification, tests and assays, as well as sample preparation, marker selection and TCM processing are covered to address the importance of establishing comprehensive quality standard of TCM. Furthermore, advanced analytical techniques for quality control and standard establishment of TCM are also reviewed.
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.
Medicinal cannabis and respective products have been available in EU member states as single-patient prescriptions without regular marketing authorizations for a couple of years. The Netherlands was ...the first member state to realize this; in the meantime other member states have followed. Today, aside from the Netherlands, Germany is the most important market for such products. The regulatory framework for the approval of medicinal cannabis and its distribution to patients in the EU member states is, however, not harmonized at all, and there are distinct national regulations. Regarding the quality of such products, the general requirements for herbal medicinal products as defined in the European Pharmacopoeia, national pharmacopoeias, and the EMA guidance documents in place beside GMP requirements in the EU are applicable. However, for a couple of aspects, every EU member state follows its own interpretation of these requirements. To facilitate free distribution of such products between EU member states in future and to harmonize requirements for quality and GMP, an EU-wide approach is needed. As a first step, this should be realized by implementing monographs for cannabis medicinal products in the European Pharmacopoeia.
A direct reversed-phase high-performance liquid chromatographic (HPLC) method was developed for determining the content of the enantiomeric impurity of the chiral statin rosuvastatin calcium salt ...(RSV) in commercial tablets. The baseline enantioseparation was achieved using the Lux Cellulose-2 column and a binary linear gradient of acetonitrile and trifluoroacetic acid 0.05% in an aqueous solution. The flow rate of the mobile phases and column temperature were set at 1.0 mL min− 1 and 40 °C, respectively. In comparison with the isocratic HPLC method reported in the European Pharmacopoeia (EP) monograph for RSV, the gradient elution method offered improved chemo-and enantio-selectivity and reduced analysis times. The limits of quantitation and detection of the enantiomeric impurity were found to be 0.15 and 0.05 µg mL−1.
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•Rosuvastatin is a chiral statin employed in enantiopure form as a hypolipidemic drug.•A RP HPLC method was developed for evaluating the ee of rosuvastatin in tablets.•The baseline enantioseparation was achieved using the Lux Cellulose-2 column.•As eluent, a binary linear gradient of acetonitrile and TFA 0.05% was employed.•The presence of other related substances did not interfere with the ee assessment.
The essential oil of Pimpinella anisum L. (Apiaceae) seeds from Lesvos Island (Greece), famous as flavor for the production of the aperitif “ouzo”, has been analyzed by GC-MS for the first time. ...Additionally, three samples of the Greek market originated from North and Central Greece (Thessaly, Viotia) and Turkey, were also analyzed and all of them were compared to the quality limits given in European Pharmacopoeia for medicinal purposes. The effect of hydrodistillation time found to be very important as the results showed differentiations of the oil yield and the chemical content. The most abundant identified metabolites were trans-anethole, γ-himachalene, estragole and pseudoisoeugenyl 2-methylbutyrate. It is noteworthy, that Lesvos anise oil showed the best quality according to European Pharmacopoeia's standards, while it had the highest yield and the richest chemical composition (28 identified compounds) among all studied samples, contributing to the well known quality of “ouzo” from Plomari. Furthermore, two major secondary metabolites from Lesvos' anise oil: trans-anethole and a mixture of himachalenes have been isolated and structurally determined. Moreover, the safe use of anise oil is discussed due to potential toxic effects of estragole.
•The first record on the essential oil of Pimpinella anisum seeds from Lesvos island (Greece), famous for ouzo production.•Comparison of the chemical composition of four different origin samples.•In 1hr hydro-distillation of Lesvos anise seeds gives the best oil yield percentage (80 ml/kg).•Lesvos anise oil showed the best quality according to European Pharmacopoeia.•Safety properties on the use of anise oil, due to its content on estragole in the EU.
Patch testing is the only clinically applicable diagnostic method for Type IV allergy. The availability of Type IV patch test (PT) allergens in Europe, however, is currently scarce. This severely ...compromises adequate diagnostics of contact allergy, leading to serious consequences for the affected patients. Against this background, the European Society of Contact Dermatitis (ESCD) has created a task force (TF) (i) to explore the current availability of PT substances in different member states, (ii) to highlight some of the unique characteristics of Type IV vs. other allergens and (iii) to suggest ways forward to promote and ensure availability of high‐quality patch testing substances for the diagnosis of Type IV allergies throughout Europe. The suggestions of the TF on how to improve the availability of PT allergens are supported by the ESCD, the European Academy of Allergy and Clinical Immunology, and the European Academy of Dermatology and Venereology and intend to provide potential means to resolve the present medical crisis.
A simple and stability-indicating reverse phase high-performance liquid chromatographic (RP-HPLC) method for the determination of rivaroxaban (RIX) and its related substances was developed. Fifteen ...impurities of RIX, including three unreported isomers, were identified, synthesized, purified, and confirmed using MS, 1H NMR, 13C NMR, and HSQC spectral methods. This new method offered baseline separation for all monitored impurities, and was fast and reliable when compared to the European Pharmacopoeia method. Optimum separation for RIX and its related impurities was achieved on an octyldecyl silica column (YMC Core C18, 4.6 ×100 mm, 2.7 µm) by using a gradient HPLC method in 38 min. The final method was validated with respect to precision, LOD and LOQ, linearity, accuracy, and robustness. This developed method was suitable for routine quality control and drug analysis of RIX active substance.
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•An RP-HPLC method for simultaneous determination of rivaroxaban (RIX) and its fifteen impurities was developed.•The method was validated with respect to precision, LOD and LOQ, linearity, accuracy, and robustness.•Fifteen related (including three unreported) impurities of RIX were identified, synthesized, purified, and characterized.
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