Pharmeuropa bio & scientific notes最新文献_第8页

Collaborative study for the recalibration of Ph. Eur. Heparin sodium BRP batch 3 for chromogenic potency assays. Ph. Eur重新校准的合作研究。肝素钠BRP第3批进行显色效价测定。

Pharmeuropa bio & scientific notes Pub Date : 2014-01-01

A Daas, G Rautmann, E Terao

{"title":"Collaborative study for the recalibration of Ph. Eur. Heparin sodium BRP batch 3 for chromogenic potency assays.","authors":"A Daas, G Rautmann, E Terao","doi":"","DOIUrl":"","url":null,"abstract":"Following the heparin adulteration crisis, the European Pharmacopoeia (Ph. Eur.) Group of Experts on Biologicals (Group 6) considered a revision of the general chapter 2.7.5. Assay of heparin with regard to the assay of the anticoagulant activity of heparin in order to replace the clotting method with more specific chromogenic methods for anti-IIa and anti-Xa activities. An international collaborative study was carried out in 3 phases under the aegis of the Biological Standardisation Programme (BSP) of the Council of Europe and the European Commission in order to recalibrate Heparin sodium Biological Reference Preparation (BRP) batch 3 for these new assays. Phase 1 confirmed the feasibility of the project, but also indicated that the composition of the buffers affects the assay results, thereby highlighting the importance of using common assay procedures. Phase 2 consisted of a collaborative study involving 15 laboratories to calibrate the anti-IIa and anti-Xa activities of Heparin sodium BRP batch 3. The collaborative study confirmed that Heparin sodium BRP batch 3 is suitable for use as a reference preparation in the proposed chromogenic assays for unfractionated heparin. It also showed that the currently defined acceptance limits (90 % to 111 %) can be maintained in the revised Ph. Eur. texts. Phase 3 of the study collected data on the impact of the new unitage on the release of products marketed in Europe. The data from 5 manufacturers, who each reported results from both the clotting and chromogenic assays for a total of 23 batches, indicated that the replacement of the pharmacopoeial method is unlikely to cause batch release issues. Based on the results of this study, the Ph. Eur. Commission assigned Heparin sodium BRP batch 3 with a potency of 1000 IU/vial for both anti-IIa and anti-Xa activities in the chromogenic assays.","PeriodicalId":39192,"journal":{"name":"Pharmeuropa bio & scientific notes","volume":"2014 ","pages":"103-17"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33031567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development and validation of a molecular size distribution method for polysaccharide vaccines. 多糖疫苗分子大小分布方法的开发和验证。

Pharmeuropa bio & scientific notes Pub Date : 2014-01-01

G Clément, J-F Dierick, C Lenfant, D Giffroy

{"title":"Development and validation of a molecular size distribution method for polysaccharide vaccines.","authors":"G Clément, J-F Dierick, C Lenfant, D Giffroy","doi":"","DOIUrl":"","url":null,"abstract":"Determination of the molecular size distribution of vaccine products by high performance size exclusion chromatography coupled to refractive index detection is important during the manufacturing process. Partial elution of high molecular weight compounds in the void volume of the chromatographic column is responsible for variation in the results obtained with a reference method using a TSK G5000PWXL chromatographic column. GlaxoSmithKline Vaccines has developed an alternative method relying on the selection of a different chromatographic column with a wider separation range and the generation of a dextran calibration curve to determine the optimal molecular weight cut-off values for all tested products. Validation of this method was performed according to The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The new method detected product degradation with the same sensitivity as that observed for the reference method. All validation parameters were within the pre-specified range. Precision (relative standard deviation (RSD) of mean values) was < 5 per cent (intra-assay) and < 10 per cent (inter-assay). Sample recovery was > 70 per cent for all polysaccharide conjugates and for the Haemophilus influenzae type B final container vaccine. All results obtained for robustness met the acceptance criteria defined in the validation protocol (≤ 2 times (RSD) or ≤ 2 per cent difference between the modified and the reference parameter value if RSD = 0 per cent). The new method was shown to be a suitable quality control method for the release and stability follow-up of polysaccharide-containing vaccines. The new method gave comparable results to the reference method, but with less intra- and inter-assay variability.","PeriodicalId":39192,"journal":{"name":"Pharmeuropa bio & scientific notes","volume":"2014 ","pages":"40-59"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33031562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

International collaborative study for the calibration of the Ph. Eur. somatropin chemical reference substance batches 3 and 4 (BSP108). 校准Ph. Eur的国际合作研究。生长激素化学对照品批次3和4 (BSP108)。

Pharmeuropa bio & scientific notes Pub Date : 2013-01-01

M Girard, G Rautmann, B Lorbetskie, M-A Joly, A Daas, E Terao

{"title":"International collaborative study for the calibration of the Ph. Eur. somatropin chemical reference substance batches 3 and 4 (BSP108).","authors":"M Girard, G Rautmann, B Lorbetskie, M-A Joly, A Daas, E Terao","doi":"","DOIUrl":"","url":null,"abstract":"An international collaborative study was carried out for the establishment of replacement batches for the European Pharmacopoeia (Ph. Eur.) Somatropin Chemical Reference Substance (CRS) batch 2. The study was organised within the framework of the Biological Standardisation Programme (BSP) of the Council of Europe and the European Commission. Seventeen laboratories from Europe, North America, South America and Australia took part in the collaborative study. The study aimed at calibrating the somatropin content of 2 candidate preparations and demonstrating their suitability to serve as a reference substance in the tests for identification, for related proteins, for dimers and related substances of higher molecular mass (HMM), for charged variants distribution and for the assay of somatropin, as prescribed by the current Ph. Eur. monographs 0950 Somatropin bulk solution, 0951 Somatropin and 0952 Somatropin for injection. Based on the results summarised herein the Ph. Eur. Commission adopted in January 2012 candidate preparation b (cCRS-b, Sample D) as somatropin CRS batch 3 with an assigned content of 3.86 mg of somatropin monomer per vial, and candidate preparation a (cCRS-a, Sample C) as somatropin CRS batch 4 with an assigned content of 2.59 mg of somatropin monomer per vial.","PeriodicalId":39192,"journal":{"name":"Pharmeuropa bio & scientific notes","volume":"2013 ","pages":"1-39"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31213950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The occurrence of bromide in herbal drugs: is there a need for a Ph. Eur. limit? 草药中溴化物的出现:是否需要博士学位?限制?

Pharmeuropa bio & scientific notes Pub Date : 2013-01-01

H Albert, J Busch, B Klier, M Klötzel, M Kühn, B Steinhoff

{"title":"The occurrence of bromide in herbal drugs: is there a need for a Ph. Eur. limit?","authors":"H Albert, J Busch, B Klier, M Klötzel, M Kühn, B Steinhoff","doi":"","DOIUrl":"","url":null,"abstract":"This contribution provides an overview on the current legal requirements regarding limits for bromide and presents data on the actual bromide burden of commonly used herbal drugs. Evaluation of an extensive data base shows that results exceeding the limit of 50 mg/kg are found in specific plants which take up bromide to a high extent from the environment. Thus, positive findings of bromide in herbal drugs do not necessarily serve as a proof for methyl bromide treatment. Taking into account the ADI recommended by EMA and WHO, there are no toxicological concerns with regard to the intake of herbal teas, extracts or comminuted herbal drugs at therapeutic doses. Furthermore, the use of methyl bromide and other fumigants must be documented within the batch documentation. If stated in the batch documentation that no fumigation was carried out, it is not necessary to perform the test on bromide. In cases of a particular suspect and if toxicological concerns exist, additional testing can be performed in accordance with the limits set by Regulation (EC) No. 396/2005. For the above reasons, information obtained by performing the test on bromide is not significant for the assessment of quality. Therefore, it seems no longer necessary to maintain bromide in Ph. Eur. general chapter 2.8.13. Pesticide residues and it is recommended to delete it from Table 2.8.13.-1.","PeriodicalId":39192,"journal":{"name":"Pharmeuropa bio & scientific notes","volume":"2013 ","pages":"40-63"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31246766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Validation of a new ELISA method for in vitro potency testing of hepatitis A vaccines. a型肝炎疫苗体外效价检测新方法的验证。

Pharmeuropa bio & scientific notes Pub Date : 2013-01-01

S Morgeaux, P Variot, A Daas, A Costanzo

{"title":"Validation of a new ELISA method for in vitro potency testing of hepatitis A vaccines.","authors":"S Morgeaux, P Variot, A Daas, A Costanzo","doi":"","DOIUrl":"","url":null,"abstract":"The goal of the project was to standardise a new in vitro method in replacement of the existing standard method for the determination of hepatitis A virus antigen content in hepatitis A vaccines (HAV) marketed in Europe. This became necessary due to issues with the method used previously, requiring the use of commercial test kits. The selected candidate method, not based on commercial kits, had already been used for many years by an Official Medicines Control Laboratory (OMCL) for routine testing and batch release of HAV. After a pre-qualification phase (Phase 1) that showed the suitability of the commercially available critical ELISA reagents for the determination of antigen content in marketed HAV present on the European market, an international collaborative study (Phase 2) was carried out in order to fully validate the method. Eleven laboratories took part in the collaborative study. They performed assays with the candidate standard method and, in parallel, for comparison purposes, with their own in-house validated methods where these were available. The study demonstrated that the new assay provides a more reliable and reproducible method when compared to the existing standard method. A good correlation of the candidate standard method with the in vivo immunogenicity assay in mice was shown previously for both potent and sub-potent (stressed) vaccines. Thus, the new standard method validated during the collaborative study may be implemented readily by manufacturers and OMCLs for routine batch release but also for in-process control or consistency testing. The new method was approved in October 2012 by Group of Experts 15 of the European Pharmacopoeia (Ph. Eur.) as the standard method for in vitro potency testing of HAV. The relevant texts will be revised accordingly. Critical reagents such as coating reagent and detection antibodies have been adopted by the Ph. Eur. Commission and are available from the EDQM as Ph. Eur. Biological Reference Reagents (BRRs). ","PeriodicalId":39192,"journal":{"name":"Pharmeuropa bio & scientific notes","volume":"2013 ","pages":"64-92"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32048763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Collaborative study for the establishment of the 3rd international standard for neomycin. 合作研究新霉素第三项国际标准的制定。

Pharmeuropa bio & scientific notes Pub Date : 2013-01-01

G Rautmann, A Daas, K-H Buchheit

引用次数: 0

Evaluation of the risk of aflatoxin contamination in fresh medicinal plants. 新鲜药用植物中黄曲霉毒素污染风险评价。

Pharmeuropa bio & scientific notes Pub Date : 2012-04-01

J Busch, I Allmann, H Hölz, M Klötzel, M Kühn, T Mackiw, U Riegert, B Steinhoff

引用次数: 0

Regulatory requirements for therapeutic proteins: the relationship between the conformation and biological activity of filgrastim. 治疗性蛋白的调节要求:非格司汀的构象与生物活性之间的关系。

Pharmeuropa bio & scientific notes Pub Date : 2012-04-01

A F Bristow, C Bird, B Bolgiano, R Thorpe

{"title":"Regulatory requirements for therapeutic proteins: the relationship between the conformation and biological activity of filgrastim.","authors":"A F Bristow, C Bird, B Bolgiano, R Thorpe","doi":"","DOIUrl":"","url":null,"abstract":"Higher order structure, including conformation, is considered a critical quality parameter of therapeutic proteins, and is mandatory information in development of first use and bio-similar therapeutic protein drugs, the assumption being that the biological activity of a protein is directly dependent on its adoption of a 'correct' conformation. Studies on the relationship between conformation and activity depend on the ability to induce conformational changes in proteins, and conventional approaches such as thermal or chemical denaturation are incompatible with bioactivity measurements. To explore the relationship between bio-activity and conformational studies, we have studied variants of the therapeutic protein filgrastim (rec met huGCSF) which have been mutated by the replacement of helical alanine residues with glycine, to destabilise the conformation of the molecule. In the GCSF A-G mutant series studied, single conformation-destabilising amino-acid substitutions significantly reduced the biological activity. These effects were not, however correlated with changes in secondary structure measurable by far-UV Circular Dichroism (CD) spectroscopy. Only the more extensively mutated double and triple substitutions showed measurable reductions in alpha-helical structure by CD. We conclude that in this system, GCSF does not readily adopt a reduced-activity altered conformational state which can be detected by low resolution techniques such as CD. In contrast, reductions in biological activity do reflect reductions in conformational stability, possibly caused by time-dependent degradation of the protein in the cell-proliferation bioassay. Although not a formal model of biosimilarity, we suggest that our results could inform the regulatory process in determining appropriate experimental approaches to meeting regulatory requirements for higher order structural analysis of therapeutic proteins.","PeriodicalId":39192,"journal":{"name":"Pharmeuropa bio & scientific notes","volume":"2012 ","pages":"103-17"},"PeriodicalIF":0.0,"publicationDate":"2012-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31169403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Calibration of the human immunoglobulin BRPs for ACA and molecular size (batch 1) and for Fc function and molecular size (batches 1 & 2). 校正人免疫球蛋白BRPs的ACA和分子大小(第1批)以及Fc功能和分子大小(第1批和第2批)。

Pharmeuropa bio & scientific notes Pub Date : 2012-04-01

E Sandberg, A Costanzo, A Daas, K-H Buchheit

{"title":"Calibration of the human immunoglobulin BRPs for ACA and molecular size (batch 1) and for Fc function and molecular size (batches 1 & 2).","authors":"E Sandberg, A Costanzo, A Daas, K-H Buchheit","doi":"","DOIUrl":"","url":null,"abstract":"The current European Pharmacopoeia (Ph. Eur.) Biological Reference Preparation batch 3 (BRP3) for Human Immunoglobulin was established in 2005. Stocks of this BRP are dwindling and a replacement batch is needed to serve as working standard in the tests for distribution of molecular size by HPLC, anticomplementary activity (ACA) and Fc function, in accordance with the requirements of the Ph. Eur. monographs Human normal immunoglobulin (0338) and Human normal immunoglobulin for intravenous administration (0918). The European Directorate for the Quality of Medicines & HealthCare (EDQM) carried out a project (BSP099) to establish replacement batches for this BRP. The project was run in 2 phases, a prequalification phase (Phase 1) and an international collaborative study (Phase 2) involving 19 laboratories. Three batches of candidate materials of various sizes, Samples A, B and C, were procured from 2 different manufacturers on the European market. Based on the results of the study, Sample A was shown to be suitable as a reference standard for the ACA test and for molecular size determination by HPLC, whereas Samples B and C were demonstrated to be suitable for the Fc function test and for the molecular size determination by HPLC. All 3 BRPs are to be used in conjunction with the monographs Human normal immunoglobulin (0338) and Human normal immunoglobulin for intravenous administration (0918). The BRPs were adopted by the Ph. Eur. Commission at its 141st session in November 2011 as official Ph. Eur. Human Immunoglobulin BRPs for ACA and molecular size Batch 1 (Sample A) and Fc function and molecular size Batch 1 and Batch 2 (Samples B and C respectively).","PeriodicalId":39192,"journal":{"name":"Pharmeuropa bio & scientific notes","volume":"2012 ","pages":"1-15"},"PeriodicalIF":0.0,"publicationDate":"2012-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31170023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Study of the risk of heavy metal transfer to homoeopathic mother tinctures. 重金属转移到顺势母亲酊剂的风险研究。

Pharmeuropa bio & scientific notes Pub Date : 2012-04-01

J Busch, W Werner, A Huwer

{"title":"Study of the risk of heavy metal transfer to homoeopathic mother tinctures.","authors":"J Busch, W Werner, A Huwer","doi":"","DOIUrl":"","url":null,"abstract":"To assess the risk of heavy metal contamination of homoeopathic mother tinctures, 9 plant species and 1 fungus used in the manufacture of homoeopathic medicaments were investigated. Mother tinctures were prepared according to the manufacturing procedures described in the European Pharmacopoeia. The original herbal drug and the material processed during production were analysed for their cadmium (Cd), lead (Pb) and mercury (Hg) content. The plant components were harvested from 2 sites contaminated by different heavy metal exposure pathways and compared with reference material from Deutsche Homöopathie-Union (DHU). It was confirmed that in all cases a significant depletion of all heavy metals studied occurred during manufacture of the mother tincture, regardless of the starting material used. In all cases, most of the heavy metal content was retained in the press cake; low levels only were detected in the mother tincture. None of the mother tinctures of plant origin exceeded the required limits, not even those of plant starting materials originating from highly contaminated sites. Substantial heavy metal concentrations could only be detected in the mother tincture of the fungus Amanita muscaria, calculated from the dry weight of the starting material. According to the results obtained, a risk-based approach to heavy metal assessment is suggested where permanent control is focused on the heavy metals accumulating in organisms such as fungi.","PeriodicalId":39192,"journal":{"name":"Pharmeuropa bio & scientific notes","volume":"2012 ","pages":"55-71"},"PeriodicalIF":0.0,"publicationDate":"2012-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31170026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0