The International Standard for Netilmicin.

An International Standard for Netilmicin has been established on the basis of a collaborative assay. There were five participating laboratories in five countries. The activity of the contents of each ampoule of the International Standard for Netilmicin is defined as 4810 IU of netilmicin.

The International Standard for Endotoxin: evaluation in an international collaborative study.

An ampouled preparation of bacterial endotoxin, coded 84/650, was evaluated in 35 laboratories in 12 countries for its suitability to serve as the International Standard for Endotoxin. The ampouled preparation was calibrated in terms of the USA National Standard, EC5, in Limulus Amoebocyte Lysate gelation, turbidimetric and chromogenic tests and in rabbit pyrogen tests. On the basis of the results reported here, with the agreement of the participants in the study, and with the authorization of the Expert Committee on Biological Standardization of the World Health Organization, the preparation coded 84/650 was established in 1986 as the International Standard for Endotoxin for Limulus Gelation Tests with an assigned unitage of 14,000 IU of endotoxin per ampoule.

The International Standard for sisomicin.

An International Standard for Sisomicin has been established on the basis of a collaborative assay. There were seven participating laboratories in seven countries. The activity of the contents of each ampoule of the International Standard of Sisomicin is defined as 35,200 International Units of Sisomicin.

British standard for human serum vitamin B12.

Seven laboratories took part in a collaborative study of an ampouled preparation of normal serum labelled 81/563. Each laboratory calibrated the preparation in terms of pure cyanocobalamin by use of Euglena assay. The inclusion of pernicious anaemia serum in the study and additional tests for safety and stability indicated that 81/563 would be a suitable standard for diagnostic testing. In 1985 the National Biological Standards Board established the preparation as the British Standard for Human Serum Vitamin B12 and, with the agreement of participants in the study, assigned it a potency of 320 picograms per ampoule.

The International Standard for Kanamycin.

The International Reference Preparation of Kanamycin has been replaced by the International Standard for Kanamycin. The potency of the standard is based upon a collaborative study in ten laboratories in ten countries. Each ampoule of the International Standard of Kanamycin is defined as containing the activity of 10345 International Units of Kanamycin.

The International Standard for Amikacin.

An International Standard for Amikacin has been established on the basis of a collaborative assay. Seven laboratories, in seven countries, took part. Each ampoule of the International Standard of Amikacin is defined as containing the activity of 50 600 International Units of Amikacin.

International collaborative study for the establishment of the second International Reference Preparation of plasmin.

An international collaborative study involving seven laboratories was undertaken to assess the suitability of a freeze-dried preparation of human plasmin to replace the current International Reference Preparation (IRP) for plasmin. Chromogenic and fibrinolytic assays were used by all participating laboratories to assess the potencies of the Proposed International Reference Preparation (PIRP) and two other freeze-dried plasmins, one of human and one of porcine origin. The data suggest that the PIRP is a more suitable standard for plasmin than the IRP in that the former binds to fibrin whereas only 50% of the latter binds. The PIRP compared well to other plasmin preparations and the potency assays were independent of the assay procedure and substrate used. Degradation studies indicated that the PIRP was far more stable than the glycerol solution of the IRP, surviving for 12 months at 37 degrees C with no significant loss in either amidolytic or fibrinolytic activity. The International Committee for Thrombosis and Haemostasis (Bergamo, 1982) has recommended the use of this material as a standard and it has been established by the Expert Committee on Biological Standardization of the World Health Organization as the second International Reference Preparation for Plasmin with a defined potency of 10 International Units of Plasmin per ampoule.

Stability of the 4th International Standard for Insulin.

The stability of the (W.H.O.) 4th International Standard for Insulin, has been assessed by accelerated thermal degradation studies. This is a crystalline preparation of insulin, freed from proteolytic enzymes, sealed in ampoules containing air and with a moisture content of 5--6%. Of the original biological activity 95.8 (92.8--98.9;P = 0.95)% was retained after storage for 12 years in the dark at 20 degrees C and 65.7 (63.4--68.1;P = 0.95)% after 14 years at 37 degrees C. Degradation rate constants were calculated from these data for the Standard at 20 degrees C and 37 degrees C, assuming first order kinetics. The degradation constant at 37 degrees C did not differ significantly from those found in earlier degradation studies at 37 degrees C over shorter periods, thereby supporting the assumption that the degradation of crystalline insulin, at least at 37 degrees C, is a first order reaction. Extrapolation of these data suggest that the Standard stored at -20 degrees C for 20 years would have retained at least 99.93% (P = 0.95) of its original activity and so for practical purposes can be considered to be stable.

The second international reference preparation of procaine benzylpenicillin in oil with aluminium monostearate.

The second International Reference Preparation of Procaine Benzylpenicillin in Oil with Aluminium Monostearate was established in replacement of the first international reference preparation. The blood-level duration test (WHO Requirements for Biological Substances, No. 9), used to evaluate batches of manufactured material in relation to this reference preparation, was revised to relate to the new reference preparation. Thus a batch now passes the test if the lower confidence limit of the ratio is greater than 0.45, instead of 0.50-the value that related to the first international reference preparation. This change will ensure that material passing the test in the future will be of the same quality as in the past.

The international standard for rolitetracycline.

An International Standard for Rolitetracycline has been established and the international unit of this antibiotic defined as the activity contained in 0.001004 mg of the international standard. The definition of the international unit was based on the results of a collaborative assay in which 8 laboratories in 6 different countries participated; a total of 133 assays were performed. The assay was in terms of the Working Standard of the USA Food and Drug Administration; mean potencies for individual laboratories varied within a range of only 2% of the mean for all assays although 7 different test organisms were used in both diffusion and turbidimetric assays. Individual assays, however, provided potencies that varied within a range of 40%.

The second international standard for chlortetracycline.

As supplies of the International Standard for Chlortetracycline were practically exhausted, it was replaced. The potency of the second international standard was defined on the basis of an international collaborative assay comprising 157 individual assays performed in 9 laboratories in 6 countries. The mean potencies obtained in the participating laboratories, although they varied by only 7%, were heterogeneous. However, the mean potency for all the laboratories combined did not differ significantly from that of the first international standard. The International Unit for chlortetracycline was therefore defined as the activity contained in 0.001 mg of the second international standard, corresponding to a potency of 1 000 IU/mg.

The second international reference preparation of erythropoietin, human, urinary, for bioassay.

A collaborative study of the second international Reference Preparation of Erythropoietin, Human, Urinary, for Bioassay was carried out in 10 laboratories. Combined potency estimates obtained by comparison with the International Reference Preparation, indicate that ampoules of the second Preparation contain 10.0 IU (weighted mean potency) or, taking the unweighted mean potency, 9.8 IU, with fiducial limits (P=0.95) of 8.4-11.5 IU. The second Preparation could be used as a standard in estimating the potency of a preparation of sheep plasma erythropoietin (68/307) although, as with the International Reference Preparation, there was a tendency for the sheep plasma preparation to produce log-dose-log-response regression lines that were steeper than those produced by the second Preparation.In accelerated degradation studies of the second Preparation stored as the dry product in ampoules for up to 1 year, there was no consistent trend to indicate instability of the preparation.Following its establishment in 1971, the Second International Reference Preparation was allocated a potency of 10 IU/ampoule.