Post-marketing sampling and testing programs for licensed medicinal products: a narrative review

Abstract The globalization of the pharmaceutical market has enabled access to a considerable number of new medicinal products. Consequently, the circulation of substandard medicinal products has also increased. To minimize this problem, post-marketing quality sampling and testing programs are performed to monitor and confirm that the medicinal products available in the market meet appropriate quality requirements. In this review, the post-approval sampling and testing procedures of six regulatory authorities were compared with the goal of strengthening these market surveillance systems. Similarities were observed between the procedures adopted by different regulatory authorities. However, the agencies were not always transparent about the results of these monitoring procedures. A probable mismatch between the registration procedures and the quality requirements listed in official compendiums was observed, which resulted in dissonance and contradiction between the specifications approved by the regulatory authorities and those required in the pharmacopeias. Therefore, strengthening harmonization projects related to these activities can help minimize such difficulties.

Evaluation of pharmacological properties, phytochemistry, and medicinal uses of Baccharoides guineensis

The leaves, roots, and/or tubers of Baccharoides guineensis are used as traditional medicines in West Africa. Thisstudy is aimed to evaluate the pharmacological properties, photochemistry, and medicinal uses of B. guineensis. Theresults of this study are based on data derived from online databases such as Scopus, Google Scholar, PubMed,ScienceDirect, and MEDLINE and pre-electronic sources such as scientific publications, theses, books, dissertations,book chapters, and journal articles. This study revealed that the leaves, roots, and/or tubers of B. guineensis are widelyused as anthelmintic, snakebite antidote, and ethnoveterinary medicine and as traditional medicine for toothache,gastrointestinal problems, jaundice, malaria, female, and male infertility. Phytochemical compounds identified fromthe species include anthraquinones, ceramide, fatty acids, flavonoids, glycerol esters, sesquiterpene lactones, steroids,stigmatanes, sucrose esters, and triterpenoids. The pharmacological research revealed that B. guineensis extracts andphytochemical compounds isolated from the species have antioxidant, anthelmintic, antiangiogenic, antibacterial,antiplasmodial, antiproliferative, antitrypanosidal, clonogenic, and antifungal activities. The future research on B.guineensis should focus on the possible biochemical mechanisms of both the crude extracts and phytochemicalcompounds including the toxicological, in vivo, and clinical studies to corroborate the traditional medicinal applicationsof the species.

Comparative Study of Microbial Limit Test and Criteria of TCM Decoction Pieces among United States Pharma- copeia，European Pharmacopeia ，Japanese Pharmacopeia and Chinese Pharmacopeia / 中国药房

OBJECTIVE：To compare the difference of microbiological limit test and criteria of TCM decoction pieces among 43 edition of United States Pharmacopeia （USP43），10.0 edition of European Pharmacopeia （EP10.0），17 edition of Japanese Pharmacopeia （JP17）and 2020 edition of Chinese Pharmacopeia （ChP2020），and to provide refernce for the revision and improvement of microbiological standards for TCM decoction pieces in China. METHODS ：The differences in the microbial enumeration tests method （including sampling and sample preparation ，selection of bacteria and culture medium ，count of microorganisms and heat-resistant bacteria ，etc.），tests for specified microorganisms （including sample pretreatment ，enrichment， separation and identification ，etc.）and microbial related limit criteria were compared among USP 43，EP10.0，JP17 and ChP 2020. RESULTS & CONCLUSIONS ：In terms of microbiological examination of TCM decoction pieces ，USP43，EP10.0，JP17 had their own independent provisions. Chp 2020 added“general rule 1108”. In terms of inspection items ，in addition to the total aerobic bacteria count and total combined yeasts and molds count ，ChP2020 and EP 10.0 provided three methods for the inspection of control bacteria （bile-resistant Gram-negative bacteria ， Escherichia coli ， Salmonella）. On the basis ， JP17 supplemented Staphylococcus aureus test；However，USP43 added Clostridium test method and put forward the concept of objectionable microorganisms risk assessment ；ChP2020 also added a new method for counting heat-resistant bacteria. In terms of microbial limit criteria，USP43 was the most detailed in the classification of TCM decoction pieces ，which was more strict than EP 10.0 and JP 17； ChP2020 had not set up a unified limit for the inspection of control bacteria of TCM decoction pieces. ChP 2020 revised the “microbial limit standard for TCM extracts and TCM decoction pieces ”，but it was not perfect compared with the Pharmacopoeia of the United States ，Europe and Japan. It is suggested that according to the current situation of microbial contamination and control of TCM decoction pieces ，the microbial limit test and criteria of TCM related products in Pharmacopoeia should be gradually improved ，and the microbial limit level of corresponding products should be reasonably refined.

National Collaborative Study to Establish the 1st National Standards of Heparin Molecular Weight Calibrant and Heparin for System Suitability of Molecular Weight Determinations / 中国药学杂志

OBJECTIVE: Molecular weight determinations of heparin sodium and heparin calcium were added in Chinese Pharmacopoeia (2015).To establish the 1st national standards of heparin molecular weight calibrant and heparin for system suitability of molecular weight determinations were needed to establish. METHODS: An national collaborative study involving twelve laboratories had taken place, organized by National Institutes for Food and Drug Control(NIFDC)to provide supporting data for the establishment of the 1st batches of heparin molecular weight calibrant and heparin for system suitability of molecular weight determinations standard. The method of heparin molecular weight determinations in Chinese Pharmacopoeia (2015) was used in the national collaborative study. The USP heparin sodium molecular weight calibrant RS (F0L483) was used as molecular weight calibrant. The USP heparin sodium identification RS(G1L413) was used as the standard of system suitability. The candidate national standards of heparin molecular weight calibrant (140819-201501) and the candidate heparin for system suitability of molecular weight determination standard(140818-201501) were tested in the study. RESULTS: To be calculated the cumulative percent of peak area at the 20 molecular points from 5 000-42 000 of the candidate national standard of heparin molecular weight calibrant (140819-201501). Based on the statistical analysis, the candidate gave low intra-and inter-laboratories variations. In laboratories, standard deviations (SD) of two laboratories ranged from 1% to 2%,others were less than 1%.Between laboratories, SD were all less than 1%,relative standard deviation(RSD) was all less than 10%. The intra-lab SD of the test to determine the molecular weight of the candidate heparin for system suitability of molecular weight determinations standard(140818-201501) was less than 180,except Lab 2. The inter-lab SD was 180. The RSD was 1.1%. CONCLUSION: After the examination of the expert committee on pharmaceutical standardization, the candidate (140819-201501) is approved as the first national standard of heparin molecular weight calibrant, provides the broad standard table. The candidate(140818-201501) is approved as the first national standard of heparin for system suitability of molecular weight determinations, with an assigned molecular weight (Mw) of 16 200. The two national standards can be used in the test of heparin molecular weight determinations in Chinese Pharmacopeia(2015).

Establishment of the First National Reference Material for Low Molecular Weight Heparin / 中国药学杂志

OBJECTIVE: In June 2017, the National Pharmacopoeia Committee published on the internet the draft of national standards for dalteparin sodiumenoxaparin sodium and nadroparin calcium. As the new monographs to be added to the Chinese Pharmacopoeia in 2020. To establish the first batch national standards of low molecular weight calirantdalteparin sodiumenoxaparin sodium and nadroparin calcium for system suitability. METHODS: A national collaborative study involving thirteen laboratories had taken place, organized by National Institutes for Food and Drug Control(NIFDC)to provide supporting data for the establishment of the 1st national standards of low molecular weight heparin for molecular weight calibrantdalteparin sodium enoxaparin sodium and nadroparin calcium for system suitability of molecular weight determinations. The molecular weight determination methods in draft standards were used in the national collaborative study. The 2nd international standard low molecular weight heparin for molecular weight calibration(05/112) were used as molecular weight calibrant. The candidate national standards of low molecular weight heparin for molecular weight calibration (140820-201801) and the candidate dalteparin sodium(140811-201801) enoxaparin sodium(140810-201801) nadroparin calcium(140812-201801)for system suitability of molecular weight determination were tested in the study. RESULTS: The cumulative percent of peak area at the 18 molecular points from 600-18 000 of the candidate national standard of low molecular weight heparin for molecular weight calibration (140820-201801) were calculated. Based on the statistical analysis, the candidate gave low intra- and inter-laboratories variations.Of all 13 laboratories, standard deviations (SD) of two laboratories ranged from 1% to 2%,the others were less than 1%.Between laboratories, SD were all less than 1%,relative standard deviation(RSD) were all less than 5% except two points of the small molecular. The intra-lab SD of the test to determine the molecular weight of the candidate dalteparin sodium(140811-201801) enoxaparin sodium(140810-201801) nadroparin calcium(140812-201801)for system suitability of molecular weight determination was between 4 and 110,RSD was less than 2.5%. The inter-lab SD were less than 30, RSD was less than 1.0%. CONCLUSION: After the examination of the expert committee on pharmaceutical standardization, the candidate (140820-201801) was approved as the first national standard of low molecular weight heparin for molecular weight calibration, the broad standard table is also provided the broad standard table. The candidate(140811-201801) is approved as the first national standard of dalteparin sodium for system suitability of molecular weight determination, with an assigned molecular weight (Mw) of 6 268. The candidate(140810-201801) is approved as the first national standard of enoxaparin sodium for system suitability of molecular weight determination, with an assigned molecular weight (Mw) of 4 435. The candidate(140812-201801) was approved as the first national standard of nadroparin calcium for system suitability of molecular weight determination, with an assigned molecular weight (Mw) of 4 832.

Professor Meng Moody and His Dedication to the Four Chinese Pharmacopeias before and after the Founding of P.R. China / 中国药学杂志

Prof. Meng Moody and his professional career, especially his experience in Peking Union Medical College Hospital over 1925 to 1931 was briefly reviewed. He took the Interim Director of the Pharmacy Department in 1926 and 1930, respectively, while John Cameron left for vacation. Regarding to his dedications to Chinese Pharmacopeia in 1930's and after the founding of P. R. China, respectively, he played major role there.

Development and Revision of Dosage Forms General Chapters of Chinese Pharmacopeia 2020 Edition Volume / 中国药学杂志

OBJECTIVE: To guide pharmaceutical manufacturing to pay full attention to and implement the quality control and overall requirements of preparation production based on the analysis of the revision work and major changes of the Dosage Forms General Chapters of the 2020 edition of the Chinese Pharmacopoeia. METHODSE: This article mainly introduces the compilation progress of the Dosage Forms General Chapters of the 2020 edition of the Chinese Pharmacopoeia. RESULTS: The analysis is helpful to improve the integrity, advancement and readability of the Dosage Forms General Chapters of the 2020 edition of the Chinese Pharmacopoeia. CONCLUSION: The improvement of the Dosage Forms General Chapters of the 2020 edition of the Chinese Pharmacopoeia will play an important role in improving the overall level of Chinese pharmacopoeia standards, strengthening drug quality control and improving drug quality.

Sérum anidro fluido como veículo para formulações de drug delivery: resultados do teste de esterilidade para crescimento bacteriano e fúngico / Anhydrous fluid serum as vehicle for drug delivery formulations: sterility test results for bacterial and fungal growth

Introdução: A entrega tópica de medicamentos é essencial na Dermatologia. Devido à dificuldade de permeação do estrato córneo, as técnicas de drug delivery vêm recebendo destaque. O uso de formulações não específicas para este fim nos faz atentar para possíveis efeitos adversos e para a segurança microbiológica destas formulações. Objetivo: Avaliar crescimento bacteriano e fúngico no sérum anidro fluido por meio do teste de esterilidade simples. Materiais e métodos: O teste de esterilidade simples foi realizado em um sérum anidro contendo ativos lipofílicos e hidrofílicos. Este teste foi realizado três meses após a manufatura do produto. Resultados: A formulação estudada foi aprovada no teste de esterilidade simples realizado três meses após a manufatura do produto, mesmo sem uso de conservantes na formulação. A formulação em estudo foi aprovada no teste de esterilidade possivelmente devido ao fato de o veículo sérum ser de origem mineral e anidra, características que não favorecem a proliferação de micro-organismos. Conclusões: Embora somente o veículo contando ativos específicos tenha sido testado, os resultados deste estudo são promissores e demonstram a necessidade de estudos futuros que englobem de forma mais ampla o assunto.

Introduction: Topical delivery of drugs is essential in Dermatology. Due to the difficulty of permeation of the stratum corneum, drug delivery techniques have been highlighted. The use of non-specific formulations for this purpose makes raises the concern of possible adverse events and the microbiological safety of these formulations. Objective: To assess bacterial and fungal growth in anhydrous fluid serum through simple sterility test. Materials and methods: The simple sterility test was performed on an anhydrous serum containing lipophilic and hydrophilic active substances. This test was performed three months after the manufacture of the product. Results: The formulation studied was approved in the simple sterility test conducted three months after the manufacture of the product, even without the use of preservatives in the formulation. Discussion: The assessed formulation was approved in the sterility test possibly due to the fact that the serum vehicle has mineral and anhydrous origin, characteristics that do not favor the proliferation of microorganisms. Conclusions: Although only the vehicle counting specific assets has been tested, the results of this study are promising and demonstrate the need for future studies broadly encompassing this subject.

Analysis of the Inclusion of Set Prescription Preparation Containing Coptis chinensis and Its Processed Product in 2015 Edition of Chinese Pharmacopeia ·Guidelines for Clinical Drug Use / 中国药房

OBJECTIVE： To provide reference for standardizing rational use of set prescription preparation containing Coptis chinensis and its processed product. METHODS： By retrieving 2015 edition of Chinese Pharmacopeia·Guidelines for Clinical Drug Use（volume of TCM set prescription）， the inclusion of set prescription preparation containing C. chinensis and its processed product were summarized and analyzed. RESULTS&CONCLUSIONS： There were 127 set prescription preparations containing C. chinensis and its processed product included in 2015 edition of Chinese Pharmacopeia·Guidelines for Clinical Drug Use（volume of TCM set prescription）， among which， there were 83， 5， 2， 8， 4， 11， 6， 5 and 3 set prescription preparations for internal medicine， surgery， gynecology， pediatrics， dermatology， ophthalmology， pharyngology， stomatology， orthopedics and traumatology， respectively. There were 120 set prescription preparations containing C. chinensis（94.49％）， 2， 4 and 1 set prescription preparations containing prepared C. chinensis with vino， prepared C. chinensis with ginger and prepared C. chinensis with Euodia rutaecarpa， respectively. There were 39， 59 and 29 kinds of set prescription preparations with C. chinensis as main symptoms medicine， assists medicine and complication medicine， which were mainly for clearing heat， drying dampness， purging fire and detoxifying（104 kinds， 81.89％）. Main types included Shexiang niuhuang pills， Gegen cenlian tablets， Kaiwei jianpi pills， etc. By comparing the efficacy of C. chinensis and its processed product， it was found that the names of processed products were not standardized， the labeling of C. chinensis and its processed products were not uniform and the application was not standardized； the related contents still needed to be further improved. It is necessary to strengthen the research on the pharmacodynamic basis and processing standard of C. chinensis and carry out the investigation and correction of relevant publications in order to help improve the rational drug use level of set prescription preparations containing C. chinensis and its processed products.

Evaluation of Phase Identification Methods Using Powder X-ray Different Analysis in Various Pharmaceutical Compendiums / 中国药学杂志

OBJECTIVE: To investigate the impacts of particle size and preferred orientation on relative peak intensity, number of peaks and order of peak intensity in powder X-ray diffraction (PXRD) analysis of organic and inorganic pharmaceutical crystalline materials and evaluate the phase identification methods in various pharmaceutical compendiums. METHODS: The PXRD patterns of organic and inorganic materials with different particle sizes obtained by sieving or grinding were acquired and the number of diffraction peaks, peak position and intensity of diffraction peaks were compared across different samples. RESULTS: Due to preferred orientation effects, the diffraction patterns of samples with different particle sizes were apparently different, including the number of peaks, relative peak intensity and the order of the peak intensity. CONCLUSION: Scientists may get different conclusions from the results of same tests performed according to the related guiding principles of current Chinese Pharmacopeia and USP39, EP8.0, JP16 X IV pharmacopoeia for identifying the crystalline forms. The phase identification by PXRD method in current Chinese Pharmacopeia neglects the effects of preferred orientation on diffraction peaks and relative peak intensity. This guideline needs to be updated to better reflect the scientific observation in industry and align with other well accepted compendiums such as USP, EP and JP.

Application of Residual Solvents Determination Method in Chinese Pharmacopoeia 2015 Edition / 中国药学杂志

OBJECTIVE: To introduce the application of the residual solvents determination methods in general chapter 0861 of Chinese pharmacopoeia 2015 edition. METHODS: Determination of the residual solvents of cefathiamidine was chosen as an example to indicate that how to use the residual solvents determination methods in general chapter 0861 of Chinese pharmacopoeia 2015 edition when the methods for the determination of residual solvent in monograph of cefathiamidine did not work. RESULTS: The residual solvents in cefathiamidine from different manufactures were determined accurately using methods in general chapter 0861 of Chinese pharmacopoeia 2015 edition. CONCLUSION: The residual solvents determination methods in general chapter 0861 of Chinese pharmacopoeia 2015 can be used to screening and confirm the unknown peaks by the two opposite polar column systems, which can help to establish the residual solvents method.

A abordagem historiográfica dos séculos XIX e XX sobre a atuação de médicos e boticários jesuítas na América platina no século XVIII / The historiographical approach taken in the nineteenth and twentieth centuries to the work of Jesuit doctors and apothecaries in the a Plata region in the eighteenth century

Analisam-se as posições de Pedro Arata, Moisés Santiago Bertoni, Carlos Leonhardt e Guillermo Furlong no debate sobre o papel da Companhia de Jesus na introdução e no desenvolvimento das ciências na América platina. Escritas entre 1890 e fins de 1950, as obras desses autores tanto analisam o conhecimento médico, farmacêutico e botânico dos missionários jesuítas nos séculos XVII e XVIII quanto avaliam a contribuição da Companhia para o pensamento científico nos países de colonização ibérica. Suas posições antecipam o debate historiográfico sobre o reacionarismo da ordem jesuíta e as reflexões sobre a contribuição dos saberes indígenas sobre a farmacopeia americana para o conhecimento que os missionários levaram aos continentes em que atuaram.

The positions of Pedro Arata, Moisés Santiago Bertoni, Carlos Leonhardt and Guillermo Furlong in the debate about the role of the Society of Jesus in the introduction and development of science in the La Plata region are investigated. Written between 1890 and the late 1950s, these authors’ works not only analyze the medical, pharmaceutical and botanical knowledge of the Jesuit missionaries in the 1600s and 1700s, but also evaluate their contribution to scientific thinking in the countries colonized by Spain and Portugal. Their positions foretaste the historiographical debate about the reactionary nature of the Jesuit order and reflections about the contribution made by indigenous knowledge of American pharmacopeia to the knowledge the missionaries took to the continents where they were active.

Several Thoughts and Suggestions on International Quality Standard System Construction of Traditional Chinese Medicine / 世界科学技术-中医药现代化

Monographs of Chinese medicine into the United States Pharmacopeia and the European Pharmacopoeia is the prerequisite and foundation for the aim of Chinese medicine standards leading the international standard-set-ting. By comparative analysis of the key issues of quality standards among Chinese, American and European Phar-macopoeia, thoughts and suggestions are proposed on how to implement the construction of international quality stan-dard of traditional Chinese medicine. Meanwhile, under the pressure of the present international environment, the pa-per can also provide some reference and advices which can help to break down the difficult situation for the process of internationalization of traditional Chinese medicine.

Screening of North African Medicinal Plant Extracts for Cytotoxic Activity Against Tumor Cell Lines.

Aims: The aim of this study was to evaluate the in vitro cytotoxic activity and cellular effects of organic extracts and fractions of four plants; Inula viscosa, Ormenis eiriolepis (Asteraceae), Retama monosperma (Fabaceae) and Marrubium vulgare (Lamiaceae), all of them used in Moroccan traditional medicine. Methodology: The four plants were extracted using organic solvents and screened on a panel of human cancer cell lines including cell types from both solid and haematological cancer origin as well as non-transformed murine fibroblasts. Cell viability assays were performed with sixteen plant extracts. Sensitive cell lines were then exposed to increasing concentrations of the most efficient extracts in order to calculate IC50 values. Microscopy, flow cytometry and caspase activity assays were then performed in LN229, SW620 and PC-3 cell lines upon treatment to investigate the cell morphology, cell cycle distribution and cell death. Results: cell viability assays reveals that at least one extract from each plant was able to exert cytotoxic activity against the majority of cell lines tested, the IC50 values of the active extracts were in most cases ≤ 30 μg/ml. the study of the cellular effects of the most active extracts on LN229, SW620 and PC-3 cell lines shows their ability to promote cell cycle arrest and cell death. The data obtained herein support strongly the use of these plants by traditional healers for the treatment of cancer patients and could have some scientific support indicating the presence of bioactive compounds. Conclusion: The reported biological activity of these four medicinal plants used in traditional Moroccan medicine provides a starting point for forthcoming studies to determine the molecular basis of their activity and to identify the chemical compounds within the most active extracts responsible for their antitumoral effects.

Analysis to inadvisable combination of Chinese material medica recordered in Chinese Pharmacopoeia 2005 edition and 2010 edition / 国际中医中药杂志

To investigate and analyze inadvisable combination of Chinese materia medica recorded in China Pharmacopeia 2005 edition and 2010 edition, and to provide convenience for physicians and pharmacists in clinical practice.

On the Feasibility of General Regulations for the Processing of Crude Drugs in the Supplement of China Pharmacopeia / 中国药房

OBJECTIVE: To discuss the feasibility of the General Regulations for the Processing of Crude Drugs in the supplement in China Pharmacopeia. METHODS: The problems existing in the General Regulations for the Processing of Crude Drugs in the supplement in China Pharmacopeia were analyzed, aimed at which, some constructive suggestions were presented. RESULTS & CONCLUSION: It's urgent to improve the feasibility of the General Regulations for the Processing of Crude Drugs in the supplement in China Pharmacopeia and standardize the production of Chinese cut crude drugs.

Categories of Medicinal Materials and Cut Crude Drugs with Toxin and Precautions in Edition 2005 of China Pharmacopeia / 中国药房

OBJECTIVE: To better implement Edition 2005 of China Pharmacopeia in order to ensure the safety and rationalization of drug use.METHODS:551 categories of medicinal materials and cut crude drugs in Edition 2005 of China Pharmacopeia(Volume One) was classified on the basis of descriptions of their toxin and precautions.RESULTS:10 categories were classified as extremely poisonous,37 toxic,25 slightly toxic,479 nontoxic.5 categories were classified as contraindication in pregnancy,28 prohibited in pregnancy,38 cautiously used in pregnancy.1 category was classified as prohibited for children.So_me varieties of “Eighteen incompatible medicaments” and “Nineteen medicaments of mutual antagonism” were not mentioned.CONCLUSION:Although there is only small part of categories with toxin and precautions,much attention should be paid to.The use of these materials or drugs should strictly abide by Edition 2005 of China Pharmacopeia.