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Quality Specifications (quality + specifications)
Selected AbstractsQuality specifications for peptide drugs: a regulatory-pharmaceutical approachJOURNAL OF PEPTIDE SCIENCE, Issue 11 2009Valentijn Vergote Abstract Peptide drugs, as all types of pharmaceuticals, require adequate specifications (i.e. quality attributes, procedures and acceptance criteria) as part of their quality assurance to ensure the safety and efficacy of drug substances (i.e. active pharmaceutical ingredients) and drug products (i.e. finished pharmaceutical dosage forms). Compendial monographs are updated regularly to keep up with the most recent advances in peptide synthesis (e.g. reduced by-products) and analytical technology. Nevertheless, currently applied pharmacopoeial peptide specifications are barely harmonized yet (e.g. large differences between the European Pharmacopoeia and the United States Pharmacopeia), increasing the manufacturers' burden of performing analytical procedures in different ways, using different acceptance criteria. Additionally, the peptide monographs are not always consistent within a single pharmacopoeia. In this review, we highlight the main differences and similarities in compendial peptide specifications (including identification, purity and assay). Based on comparison, and together with additional information from peptide drug substance manufacturers and public evaluation reports on registration files of non-pharmacopoeial peptide drugs, a consistent monograph structure is proposed. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd. [source] Influence of temperature and time before centrifugation of specimens for routine coagulation testingINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 4 2009G. L. SALVAGNO Summary The accurate standardization of the preanalytical phase is of pivotal importance for achieving reliable results of coagulation tests. Because information on the suitable storage conditions for coagulation testing is controversial, we aimed at investigating the sample stability with regard to the temperature and time before centrifugation. The activated partial thromboplastin time (aPTT), prothrombin time (PT), fibrinogen and D-dimer were assayed in specimens collected from 26 consecutive patients on antivitamin K therapy on the ACL TOP analyzer. Three primary 3.6-ml siliconized evacuated tubes containing 0.109 mol/l buffered trisodium citrate were sequentially collected from each patient. These three tubes were mixed, pooled and divided into seven identical aliquots. The first aliquot was immediately centrifuged according to the standard protocol [1500 g for 15 min at room temperature (RT)] and analyzed. The other aliquots were left for 3, 6 and 24 h, respectively, at RT or 4 °C, and then centrifuged and analyzed. Test results were compared with those obtained on the reference specimen. Statistically significant prolongations were observed for aPTT in all the samples. Such differences exceeded the analytical quality specifications for desirable bias in the samples stored for 24 h. A significant reduction, yet comprised within the desirable bias, was observed for PT and fibrinogen in uncentrifuged specimens stored at RT for 3 and 6 h. No significant biases could be recorded in D-dimer. In conclusion, a 6-h storage of uncentrifuged specimens at either RT or 4 °C may still be suitable to achieve results of routine coagulation testing comprised within the analytical quality specifications for desirable bias. [source] Venous stasis and routine hematologic testingINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 5 2006G. LIPPI Summary Prolonged venous stasis, as generated by a long tourniquet placement, produces spurious variations in several measurable analytes. To verify to what extent venous stasis influences routine hematologic testing, we assessed routine hematologic parameters, including hemoglobin, hematocrit, red blood cell count (RBC), main cell hemoglobin (MHC), main cell volume (MCV), platelet count (PLT), main platelet volume (MPV), white blood cell count (WBC) and WBC differential on the Advia 120 automated hematology analyzer in 30 healthy volunteers, either without venous stasis (no stasis) or after application of a 60 mmHg standardized external pressure by a sphygmomanometer, for 1 (1-min stasis) and 3 min (3-min stasis). Although the overall correlation between measures was globally acceptable, the mean values for paired samples were significantly different in all parameters tested, except MCV, MHC, PLT, MPV, eosinophils, basophils and large unstained cells after 1-min stasis and all parameters except MCV, MHC, MPV and basophils after 3-min venous stasis. As expected RBC, hemoglobin and hematocrit displayed a significant trend towards increase, whereas WBC and the WBC subpopulations were decreased. Difference between measurements by Bland and Altman plots exceeded the current analytical quality specifications for desirable bias for WBC, RBC, hemoglobin, hematocrit, lymphocytes and monocytes in samples collected after either 1- and 3-min stasis. These results provide clear evidence that venous stasis during venipuncture might produce spurious and clinically meaningful biases in the measurement of several hematologic parameters, prompting further considerations on the usefulness of adopting appropriate preventive measures for minimizing such influences. [source] The chemical and pharmaceutical equivalence of sulphadoxine/pyrimethamine tablets sold on the Tanzanian marketJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 6 2005Y. Hebron BPharm MSc Summary This study investigated chemical and pharmaceutical equivalence of 11 brands of pyrimethamine,sulphadoxine combination tablets sold on the Tanzanian market. Physical and chemical tests were performed for all the 11 brands. These tests included hardness test, friability, disintegration, dissolution, weight uniformity and assay for the active components. All the brands passed all the quality specifications of the United States Pharmacopoeia (USP) and British Pharmacopoeia (BP) in terms of hardness, friability, disintegration, assay and dissolution test, except for three brands that failed the hardness, disintegration or friability tests. One brand failed both the hardness and disintegration test; one failed the hardness test, whereas another one failed the friability test. The percentage content of pyrimethamine in the brands was in the range of 91·04,100·20% whereas that of sulphadoxine ranged from 91·53% to 99·88%. There were no major differences between the different brands of tablets containing pyrimethamine and sulphadoxine and the innovator product (Fansidar®), and all brands were physically and chemically equivalent. The results indicate that the post-market surveillance and registration process in Tanzania is having an impact on product quality as there was no brand which could be considered of very poor quality. Impurity profiling of all the locally produced brands indicated that they all contained the same sulphadoxine impurity, which was absent in the innovator product, suggesting a common source of generic raw material. [source] A Grade Transition Strategy for the Prevention of Melting and Agglomeration of Particles in an Ethylene Polymerization ReactorCHEMICAL ENGINEERING & TECHNOLOGY (CET), Issue 7 2005M. R. Rahimpour Abstract To satisfy the diverse product quality specifications required by the broad range of polyethylene applications, polymerization plants are forced to operate under frequent grade transition policies. During the grade transition, the reactor temperature must be kept within the narrow range between the gas dew point and the polymer melting point, otherwise the particles melt or agglomerate inside the reactor. In the present study, a dynamic well-mixed reactor model is used to develop a grade transition strategy to prevent melting and agglomeration of particles in an ethylene polymerization reactor. The model predicts the conditions under which the temperature of the reactor is outside the allowable range in continuous grade transition. Manipulation of feed flow and cooling water flow rates has shown that the reactor temperature cannot be maintained within the allowable range. Hence, a semi-continuous grade transition strategy is used for this case so that the temperature is maintained within the allowable range. In addition, several continuous and semi-continuous grade transition strategies for the production of linear low-density polyethylene (LLDPE), medium density polyethylene (MDPE), and high-density polyethylene (HDPE) are compared. [source] | |||||||||||||