A Collaborative Study to Establish the 6th International Standard for Factor VIII Concentrate

2001 ◽  
Vol 85 (06) ◽  
pp. 1071-1078 ◽  
Author(s):  
A. B. Heath ◽  
T. W. Barrowcliffe ◽  
S. Raut
Keyword(s):  
Factor Viii ◽  
Collaborative Study ◽  
World Health Organisation ◽  
World Health ◽  
Assay Method ◽  
Expert Committee ◽  
International Standard ◽  
One Stage ◽  
The One ◽  
Good Agreement

SummaryA study was carried out to replace the 5th WHO International Standard (IS) for factor VIII concentrate, because of depletion of stocks. Two candidate concentrates (X and Y) were assayed as potential replacements against the 5th IS for FVIII concentrate, in a collaborative study involving 33 laboratories. Collaborators were asked to use the ISTH/SSC recommendations, including pre-dilution of concentrates in FVIII deficient plasma in their assays. Several laboratories performed more than one assay method and altogether there were 21 sets of assays with the one-stage method, 6 with the two-stage method and 26 with the chromogenic method. There was good agreement between laboratories using each method for the comparison of concentrates X and Y against the 5th IS, but the overall potencies by one-stage and chromogenic methods each differed by approximately 5% from the overall mean, with the chromogenic potency approximately 10% higher than the one-stage. Inter-laboratory agreement was slightly better for concentrate Y than X, and stability studies indicated that Y was more stable than X. After considering all the information, together with comments from participants and from the FVIII/FIX Subcommittee of the ISTH/SSC, candidate Y (NIBSC code [97/616]), was proposed and accepted in October, 1998, by the Expert Committee on Biological Standardisation of the World Health Organisation to be the 6th International Standard for Factor VIII Concentrate with an assigned potency of 8.5 IU/ampoule.

Standardization of Factor VIII – IV. Establishment of the 3rd International Standard for Factor VIII: C Concentrate

1983 ◽  
Vol 50 (03) ◽  
pp. 697-702 ◽  
Author(s):  
T W Barrowcliffe ◽  
A D Curtis ◽  
D P Thomas
Keyword(s):  
Factor Viii ◽  
High Purity ◽  
Collaborative Study ◽  
World Health ◽  
Current Standard ◽  
Two Stage ◽  
International Standard ◽  
One Stage ◽  
The One ◽  
Health Organization

SummaryAn international collaborative study was carried out to establish a replacement for the current (2nd) international standard for Factor VIII: C, concentrate. Twenty-six laboratories took part, of which 17 performed one-stage assays, three performed two-stage assays and six used both methods. The proposed new standard, an intermediate purity concentrate, was assayed against the current standard, against a high-purity concentrate and against an International Reference Plasma, coded 80/511, previously calibrated against fresh normal plasma.Assays of the proposed new standard against the current standard gave a mean potency of 3.89 iu/ampoule, with good agreement between laboratories and between one-stage and two- stage assays. There was also no difference between assay methods in the comparison of high-purity and intermediate purity concentrates. In the comparison of the proposed standard with the plasma reference preparation, the overall mean potency was 4.03 iu/ampoule, but there were substantial differences between laboratories, and the two-stage method gave significantly higher results than the one stage method. Of the technical variables in the one-stage method, only the activation time with one reagent appeared to have any influence on the results of this comparison of concentrate against plasma.Accelerated degradation studies showed that the proposed standard is very stable. With the agreement of the participants, the material, in ampoules coded 80/556, has been established by the World Health Organization as the 3rd International Standard for Factor VIII :C, Concentrate, with an assigned potency of 3.9 iu/ampoule.

A Collaborative Study to Establish an International Standard for Alpha-Thrombin

1992 ◽  
Vol 67 (04) ◽  
pp. 424-427 ◽  
Author(s):  
P J Gaffney ◽  
A B Heath ◽  
J W Fenton II
Keyword(s):  
Elevated Temperatures ◽  
Collaborative Study ◽  
World Health Organisation ◽  
Significant Loss ◽  
Thrombin Inhibitors ◽  
World Health ◽  
Expert Committee ◽  
International Standard ◽  
Assay Procedure ◽  
And Control

SummarySince 1975 an International Standard for Thrombin of low purity has been used. While this standard was stable and of value for calibrating thrombins of unknown potency the need for a pure a-thrombin standard arose both for accurate calibration and for precise measurement of thrombin inhibitors, notably hirudin. An international collaborative study was undertaken to establish the potency and stability of an ampouled pure a-thrombin preparation. A potency of 97.5 international units (95% confidence limits 86.5-98.5) was established for the new a-thrombin standard (89/ 588) using a clotting-assay procedure. Stability data at various elevated temperatures indicated that the standard could be transported and stored with no significant loss of potency.Ampoules of lyophilised a-thrombin (coded 89/588) have been recommended as an International Standard for a-thrombin with an assigned potency of 100 international units per ampoule by the International Society for Thrombosis and Haemostasis (Thrombin and its Inhibitors Sub-Committee) in Barcelona, Spain in July 1990 while the Expert Committee on Biological Standardisation and Control of the World Health Organisation will consider its status at its next meeting in Geneva in 1991.

An International Collaborative Assay of Factor VIII Clotting Activity

1978 ◽  
Vol 40 (02) ◽  
pp. 260-271 ◽  
Author(s):  
T W Barrowcliffe ◽  
T B L Kirkwood
Keyword(s):  
Factor Viii ◽  
World Health ◽  
Expert Committee ◽  
Two Stage ◽  
International Standard ◽  
One Stage ◽  
Normal Plasma ◽  
Freeze Dried ◽  
The Mean ◽  
International Collaborative

SummaryAn International Collaborative Study was organised to replace the first International Standard for factor VIII. A freeze-dried concentrate, 73/552, and a freeze-dried plasma, 75/510, were assayed against the International Standard, and also compared to fresh normal plasma and local standards.In assays of the concentrate 73/552 against the first I.S. the mean potency was 1.14 i.u./ ampoule and there was no significant difference between one-stage and two-stage methods. When assayed against average fresh normal plasma, the potency was 1.05 “normal plasma units” per ampoule. It was agreed by the participants that the potency of 73/552 be regarded as the mean of these two figures, i.e. 1.10 i. u./ampoule.In assays of the freeze-dried plasma, 75/510, against the first I.S. the mean potency was 0. 68 i. u./ampoule, but the one-stage assays gave significantly higher potencies (mean 0.74 1. u./ampoule) than the two-stage assays (mean 0.59 i. u./ampoule). The same trend was also seen in the fresh normal plasmas, and in the local plasma standards. This finding has important implications for the standardisation of factor VIII.Stability studies on the concentrate 73/552 gave a predicted loss of 0.02% per year at – 20° C. All participants agreed that the material was suitable to serve as an International Standard, and at the 26th meeting of the Expert Committee on Biological Standardisation of the World Health Organization, the material in ampoules coded 73/552 was established as the 2nd International Standard for factor VIII, with a potency of 1.10 i. u./ampoule.

A Collaborative Study to Establish the 5th International Standard for Unfractionated Heparin

2000 ◽  
Vol 84 (12) ◽  
pp. 1017-1022 ◽  
Author(s):  
A. Walker ◽  
Barbara Mulloy ◽  
Trevor Barrowcliffe ◽  
Elaine Gray
Keyword(s):  
Molecular Weight ◽  
Unfractionated Heparin ◽  
Specific Activity ◽  
Collaborative Study ◽  
World Health Organisation ◽  
The Other ◽  
World Health ◽  
Expert Committee ◽  
International Standard ◽  
The World

SummaryTwenty-four laboratories participated in a collaborative study to calibrate a replacement for the 4th International Standard for Unfractionated Heparin (82/502). Both candidate materials A and B, gave excellent intra- and inter-laboratory variations (majority of mean %gcv <10%) when assayed against the 4th International Standard. No major differences of potency estimates were found between methods, although the USP method generally gave lower potencies than the other methods and candidate B gave a greater variation between methods than A. Overall, this study showed that the differences between the candidates are marginal. Based on its narrower molecular weight profile, higher specific activity and slightly lower inter-method variation, candidate A, 97/578, was proposed and accepted in October, 1998, by the Expert Committee on Biological Standardisation of the World Health Organisation to be the 5th International Standard for Unfractionated Heparin with an assigned potency of 2031 IU/ampoule.

Collaborative Study of a Proposed International Standard for Plasma Fibrinogen Measurement

1992 ◽  
Vol 68 (04) ◽  
pp. 428-432 ◽  
Author(s):  
Patrick J Gaffney ◽  
M Y Wong
Keyword(s):  
Collaborative Study ◽  
World Health Organisation ◽  
Plasma Fibrinogen ◽  
World Health ◽  
Expert Committee ◽  
International Standard ◽  
Assay Procedure ◽  
Artery Disease ◽  
And Control ◽  
The Relationship

SummaryThere is increased interest in the relationship between plasma fibrinogen levels and the incidence of coronary artery disease. The National Institute for Biological Standards and Control (UK) has completed a study to establish an International Standard for plasma fibrinogen. This study was conducted using a recommended assay procedure to measure the clottable material present in the proposed lyophilised Standard (coded 89/644). Twenty-two laboratories from nine countries took part in the study and analysis of the data allowed the calibration of 89/644 at 2.4 mg/ml clottable protein. Agreement with this figure was established in two laboratories using three or more different assays for plasma fibrinogen. Degradation studies of the proposed plasma fibrinogen Standard suggested that no loss of clottable protein was observed when the lyophilised material was stored at 20° C for 1 year.The Fibrinogen Sub-Committee of the ISTH (Amsterdam, The Netherlands, June 1991) supported the establishment of 89/644 as an International Standard. This collaborative study will be presented to the Expert Committee on Biological Standardisation of the World Health Organisation at their 1992 session. In the meantime 89/644 will be distributed as the proposed International Standard for plasma fibrinogen measurement containing 2.4 mg/ ml clottable protein.

A Collaborative Study to Establish the 2nd International Standard for Fibrinogen, Plasma

2000 ◽  
Vol 84 (08) ◽  
pp. 258-262 ◽  
Author(s):  
C. M. Whitton ◽  
D. Sands ◽  
P. J. Gaffney ◽  
A. R. Hubbard
Keyword(s):  
Geometric Mean ◽  
Collaborative Study ◽  
World Health Organisation ◽  
World Health ◽  
Expert Committee ◽  
Washington Dc ◽  
International Standard ◽  
Freeze Dried ◽  
Assay Methods ◽  
Almost All

SummaryAn International Collaborative Study involving 12 laboratories in 7 different countries was undertaken in order to replace the 1st International Standard (IS) for Fibrinogen, Plasma (89/644). The candidate replacement standard was the ampouled and freeze-dried residue of solvent/detergent treated plasma and was calibrated as coded duplicates (A and B) versus the 1st IS Fibrinogen, Plasma by automated Clauss assay and by a recommended clot collection (gravimetric) assay. This latter method had been used to calibrate the 1st IS Fibrinogen, Plasma.Comparing the ratios of the potency estimates of sample A to sample B (the coded duplicates), all of the laboratories obtained a ratio within 5% of the expected value of 1.0 by automated Clauss assay, which suggests that the laboratories were able to perform this assay well. Scrutiny of the data obtained from the gravimetric assays revealed that in almost all cases the results were invalid. The results of these assays are included in this report but clearly should be treated with caution and indeed produced significantly lower mean estimates of potency than the other assay methods. The overall geometric mean of all estimates of potency of the proposed 2nd IS Fibrinogen, Plasma (98/612) is 2.19 mg/ampoule by the automated Clauss assay. These data have been presented to the Fibrinogen Sub-Committee of the Standardisation and Scientific Committee (SSC) of the International Society on Thrombosis and Haemostasis (ISTH) (Washington, DC, August 1999), which recommended the establishment of 98/612 as the 2nd IS Fibrinogen, Plasma. This report has been presented to the Expert Committee on Biological Standardisation of the World Health Organisation (ECBS-WHO) at their 1999 session and 98/612 was established as the 2nd IS Fibrinogen, Plasma with a potency of 2.2 mg/ ampoule.

scholarly journals The fourth International Standard for Human Urinary FSH and LH: specificities of LH seminal vesicle weight gain assays in the collaborative study differ between laboratories

2001 ◽  
Vol 171 (1) ◽  
pp. 119-129 ◽  
Author(s):  
PL Storring ◽  
RE Gaines Das
Keyword(s):  
Weight Gain ◽  
Seminal Vesicle ◽  
Geometric Mean ◽  
Collaborative Study ◽  
World Health ◽  
Assay Method ◽  
Expert Committee ◽  
International Standard ◽  
Seminal Vesicle Weight ◽  
Urinary Fsh

The fourth International Standard for Human Urinary FSH and LH (IS; in ampoules coded 98/704) was compared with the third International Standard for Urinary FSH and LH (IS 71/264) by 10 laboratories in nine countries, using FSH and LH in vivo bioassays. Estimates of the FSH content of the IS by augmented ovarian weight gain assays were homogeneous within each laboratory and over all laboratories. The combined weighted geometric mean estimate of FSH content of the IS (with 95% fiducial limits) in terms of IS 71/264 was 71.9 (69.0-74.9) IU/ampoule. Although estimates by seminal vesicle weight gain (SVW) assays of the relative LH activities of the IS and IS 71/264 were homogeneous within laboratories, estimates were heterogeneous between laboratories. This indicated differences between the spectrum of LH isoforms in the IS and IS 71/264, which were obtained from different manufacturers, and differences between the specificities of SVW assays performed in different laboratories. The differences between the specificities of SVW assays appeared to be related to interactions among mean laboratory seminal vesicle weights, age and genetic strain of rat. The finding of inter-laboratory differences in the specificities of SVW assays is of some significance, as this assay method has been generally adopted by Pharmacopoeias for the control of the LH content of therapeutic products. The combined unweighted geometric mean estimate of LH content of the IS (with 95% fiducial limits) in terms of IS 71/264 by SVW and ovarian ascorbate depletion assays was 70.2 (61.7-80.0) IU/ampoule. Estimates of the FSH and LH content of ampoules of the IS kept at increased temperatures suggested that the IS would be adequately stable under normal storage conditions. On the basis of these results, the World Health Organization Expert Committee on Biological Standardization established the preparation in ampoules coded 98/704 as the fourth International Standard for Human Urinary FSH and LH, and assigned to the contents of each ampoule an activity of 72 International Units of urinary FSH and an activity of 70 International Units of urinary LH.

Standardization of Factor VIII – III. Establishment of a Stable Reference Plasma for Factor VIII-Related Activities

1983 ◽  
Vol 50 (03) ◽  
pp. 690-696 ◽  
Author(s):  
T W Barrowcliffe ◽  
M S Tydeman ◽  
T B L Kirkwood ◽  
D P Thomas
Keyword(s):  
Factor Viii ◽  
Collaborative Study ◽  
Expert Committee ◽  
Normal Plasma ◽  
Freeze Dried ◽  
Biological Standardization ◽  
Reference Preparation ◽  
The One ◽  
Good Agreement

SummaryAn international collaborative study has been carried out to establish a reference plasma for Factor VIII-related activities. The freeze-dried reference plasma, coded 80/511, was assayed against fresh normal plasma, local standards and another freeze- dried plasma. There was good agreement between laboratories for the comparison of the two freeze-dried plasmas, but wide variation in the comparison of plasma 80/511 with fresh normal plasma and local standards, indicating the differences in Factor VIII content of local pooled plasmas. There were no significant differences between the one-stage and two-stage assays of VIII :C, or between electroimmunoassay (EIA) and immuno- radiometric (IRMA) assays of VIII R:Ag. However, in VIII R: RCoF (ristocetin co-factor) assays, the aggregometry methods gave lower values than the macroscopic and counting methods for the comparison of freeze-dried against fresh normal plasmas. From the combined results of assays against each laboratory’s fresh normal plasma, potencies were assigned to plasma 80/511.Results from accelerated degradation studies indicated that losses of each VIII-related activity in plasma 80/511, when stored at -20° C, should be less than 0.01% per year, indicating its suitability to serve as a long-term reference preparation. Plasma 80/511 has been established by the WHO Expert Committee on Biological Standardization as the 1st International Reference Preparation for Factor VIII-Related Activities in Plasma.

A Collaborative Study to Establish the 2nd International Standard for Antithrombin Concentrate

1999 ◽  
Vol 82 (07) ◽  
pp. 46-50 ◽  
Author(s):  
A. Dawn Walker ◽  
Alan B. Heath ◽  
Elaine Gray
Keyword(s):  
Excellent Agreement ◽  
Collaborative Study ◽  
World Health Organisation ◽  
World Health ◽  
Expert Committee ◽  
International Standard ◽  
The World

SummaryEighteen laboratories participated in a collaborative study to calibrate a replacement for the 1st International Standard for Antithrombin, Concentrate (88/548). Excellent agreement between laboratories, as indicated by mean % gcv of 3.3 and 5.9 for functional and antigenic assays, was observed when the candidate concentrate (96/520) was assayed against the 1st International Standard for Antithrombin, Concentrate (88/548). The functional potency was found to be 7.9% (p <0.05) lower than the antigenic potency. Based on the results and with the agreement of the participants of this study and the authorisation of the Expert Committee on Biological Standardisation of the World Health Organisation, the antithrombin concentrate, coded 96/520, has been established as the 2nd International Standard for Antithrombin, Concentrate, with labelled potencies for both functional (4.7 IU/ampoule) and antigenic (5.1 IU/ampoule) activities.

A Collaborative Study to Establish the 2nd International Standard for Tissue Plasminogen Activator (t-PA)

1987 ◽  
Vol 58 (04) ◽  
pp. 1085-1087 ◽  
Author(s):  
P J Gaffney ◽  
A D Curtis
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Collaborative Study ◽  
Chinese Hamster ◽  
World Health ◽  
Clot Lysis ◽  
Expert Committee ◽  
Single Chain ◽  
International Standard ◽  
Tissue Plasminogen

SummaryAn international collaborative study involving ten laboratories located in eight different countries was undertaken in order to replace the current International Standard (I.S.) for tissue plasminogen activator (t-PA). Two lyophilised candidate preparations of high purity were assessed in comparison with the current I.S. for t-PA using only a clot lysis assay. One preparation (coded 861670) was purified from a cultured melanoma cell supernatant and was about 98% single chain t-PA while the other preparation (coded 861624) was derived from Chinese hamster ovary (CHO) cells following DNA recombinant procedures and was 75% single chain t-PA.Both candidate preparations of t-PA compared in quite a satisfactory manner with the current I.S. from the viewpoint of the biometrics of parallel line bioassays and both preparations were quite stable for long periods at low temperatures and stable from up to 1 month at temperatures of 20° and 38° C. Both fultil the criteria to serve as a satisfactory Znd International Standard for t-PA. The Fibrinolysis Subcommittee of the International Committee for Thrombosis and Haemostasis recommended the melanoma source t-PA (861670) as the next I.S. in order to maintain continuity with the 1st I.S. which was also a melanomatype preparation. The data from the ten laboratories indicated that each ampoule of the new proposed standard contains 850 international units of t-PA activity by the clot lysis assay. It is planned to present the results of this study to the Expert Committee on Biological Standardization of the World Health Organization at its next meeting and to request that the preparation of t-PA, coded 861670, be established as the 2ndlnternational Standard for t-PA.

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