A new model to Calibrate a Reference Standard for bovine tuberculin purified protein derivative in the target species

Klaas Frankena, Liesbeth Jacobs, Tonny van Dijk, Margaret Good, Anthony Duignan, Mart C.M. de Jong

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Since 1986, use of a Bovine International Standard (BIS) for bovine tuberculin has been required to ensure national and international uniformity regarding the potency designation of bovine tuberculin Purified Protein Derivative (PPDb) preparations produced by multiple manufacturers. The BIS is the unique golden standard in the guinea pig potency assay, representing 100% potency, where potencies of production batches are calculated as relative potencies in comparison with the potency of the BIS which was set at 32,500 international Unit (IU) per mg. The stock supply and lifetime of the BIS is limited.The aim of this study was to develop a model to determine the potency of a newly produced in-house Reference Standard (RS) for PPDb with great accuracy in the target species (cattle) and to prove its precision and accuracy in the guinea pig potency test. First simulations were done to estimate the required number of cattle needed. Then, 30 naturally bTB infected cattle were subjected to a tuberculin skin test using multiple injections of both the RS and the BIS. Both were applied randomly in the same volume and concentration (1 dose). The potency of the RS against the BIS was directly derived from the least square means (LSMEANS) and was estimated as 1.067 (95% CI: 1.025-1.109), equal to a potency of 34,700 ± 1,400 IU/mg. In six guinea pig potency assays the RS was used to assign potencies to production batches of PPDb. Here, precision and accuracy of the RS was determined according to the parallel-line assay. Relative potencies were estimated by exponentiation of the common slope. The corresponding 95% confidence intervals were obtained according to Fieller's theorem. In sensitized guinea pigs, the relative potency of the RS against the BIS was 1.115 (95% CI: 0.871-1.432), corresponding to an absolute potency of 36,238 IU/mg (95% CI: 28,308-46,540).In conclusion: the method used to determine the potency of the RS against the BIS in naturally bTB infected cattle, resulted in a highly accurate potency estimate of the RS. The RS can be used in the guinea pig test to assign potencies to PPDb production batches with high precision and accuracy.

LanguageEnglish
Article number232
JournalFrontiers in Veterinary Science
Volume5
Issue numberOCT
DOIs
Publication statusPublished - 3 Oct 2018

Fingerprint

tuberculin
reference standards
Tuberculin
chemical derivatives
cattle
proteins
guinea pigs
Guinea Pigs
assays
skin tests
Tuberculin Test
least squares
confidence interval

Keywords

  • Bovine international standard
  • Cattle
  • Guinea pigs
  • Mycobacterium bovis
  • New reference standard
  • Potency estimation
  • Tuberculin

Cite this

@article{46adc79cf4e049a499affd95cb5b702a,
title = "A new model to Calibrate a Reference Standard for bovine tuberculin purified protein derivative in the target species",
abstract = "Since 1986, use of a Bovine International Standard (BIS) for bovine tuberculin has been required to ensure national and international uniformity regarding the potency designation of bovine tuberculin Purified Protein Derivative (PPDb) preparations produced by multiple manufacturers. The BIS is the unique golden standard in the guinea pig potency assay, representing 100{\%} potency, where potencies of production batches are calculated as relative potencies in comparison with the potency of the BIS which was set at 32,500 international Unit (IU) per mg. The stock supply and lifetime of the BIS is limited.The aim of this study was to develop a model to determine the potency of a newly produced in-house Reference Standard (RS) for PPDb with great accuracy in the target species (cattle) and to prove its precision and accuracy in the guinea pig potency test. First simulations were done to estimate the required number of cattle needed. Then, 30 naturally bTB infected cattle were subjected to a tuberculin skin test using multiple injections of both the RS and the BIS. Both were applied randomly in the same volume and concentration (1 dose). The potency of the RS against the BIS was directly derived from the least square means (LSMEANS) and was estimated as 1.067 (95{\%} CI: 1.025-1.109), equal to a potency of 34,700 ± 1,400 IU/mg. In six guinea pig potency assays the RS was used to assign potencies to production batches of PPDb. Here, precision and accuracy of the RS was determined according to the parallel-line assay. Relative potencies were estimated by exponentiation of the common slope. The corresponding 95{\%} confidence intervals were obtained according to Fieller's theorem. In sensitized guinea pigs, the relative potency of the RS against the BIS was 1.115 (95{\%} CI: 0.871-1.432), corresponding to an absolute potency of 36,238 IU/mg (95{\%} CI: 28,308-46,540).In conclusion: the method used to determine the potency of the RS against the BIS in naturally bTB infected cattle, resulted in a highly accurate potency estimate of the RS. The RS can be used in the guinea pig test to assign potencies to PPDb production batches with high precision and accuracy.",
keywords = "Bovine international standard, Cattle, Guinea pigs, Mycobacterium bovis, New reference standard, Potency estimation, Tuberculin",
author = "Klaas Frankena and Liesbeth Jacobs and {van Dijk}, Tonny and Margaret Good and Anthony Duignan and {de Jong}, {Mart C.M.}",
year = "2018",
month = "10",
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doi = "10.3389/fvets.2018.00232",
language = "English",
volume = "5",
journal = "Frontiers in Veterinary Science",
issn = "2297-1769",
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A new model to Calibrate a Reference Standard for bovine tuberculin purified protein derivative in the target species. / Frankena, Klaas; Jacobs, Liesbeth; van Dijk, Tonny; Good, Margaret; Duignan, Anthony; de Jong, Mart C.M.

In: Frontiers in Veterinary Science, Vol. 5, No. OCT, 232, 03.10.2018.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - A new model to Calibrate a Reference Standard for bovine tuberculin purified protein derivative in the target species

AU - Frankena, Klaas

AU - Jacobs, Liesbeth

AU - van Dijk, Tonny

AU - Good, Margaret

AU - Duignan, Anthony

AU - de Jong, Mart C.M.

PY - 2018/10/3

Y1 - 2018/10/3

N2 - Since 1986, use of a Bovine International Standard (BIS) for bovine tuberculin has been required to ensure national and international uniformity regarding the potency designation of bovine tuberculin Purified Protein Derivative (PPDb) preparations produced by multiple manufacturers. The BIS is the unique golden standard in the guinea pig potency assay, representing 100% potency, where potencies of production batches are calculated as relative potencies in comparison with the potency of the BIS which was set at 32,500 international Unit (IU) per mg. The stock supply and lifetime of the BIS is limited.The aim of this study was to develop a model to determine the potency of a newly produced in-house Reference Standard (RS) for PPDb with great accuracy in the target species (cattle) and to prove its precision and accuracy in the guinea pig potency test. First simulations were done to estimate the required number of cattle needed. Then, 30 naturally bTB infected cattle were subjected to a tuberculin skin test using multiple injections of both the RS and the BIS. Both were applied randomly in the same volume and concentration (1 dose). The potency of the RS against the BIS was directly derived from the least square means (LSMEANS) and was estimated as 1.067 (95% CI: 1.025-1.109), equal to a potency of 34,700 ± 1,400 IU/mg. In six guinea pig potency assays the RS was used to assign potencies to production batches of PPDb. Here, precision and accuracy of the RS was determined according to the parallel-line assay. Relative potencies were estimated by exponentiation of the common slope. The corresponding 95% confidence intervals were obtained according to Fieller's theorem. In sensitized guinea pigs, the relative potency of the RS against the BIS was 1.115 (95% CI: 0.871-1.432), corresponding to an absolute potency of 36,238 IU/mg (95% CI: 28,308-46,540).In conclusion: the method used to determine the potency of the RS against the BIS in naturally bTB infected cattle, resulted in a highly accurate potency estimate of the RS. The RS can be used in the guinea pig test to assign potencies to PPDb production batches with high precision and accuracy.

AB - Since 1986, use of a Bovine International Standard (BIS) for bovine tuberculin has been required to ensure national and international uniformity regarding the potency designation of bovine tuberculin Purified Protein Derivative (PPDb) preparations produced by multiple manufacturers. The BIS is the unique golden standard in the guinea pig potency assay, representing 100% potency, where potencies of production batches are calculated as relative potencies in comparison with the potency of the BIS which was set at 32,500 international Unit (IU) per mg. The stock supply and lifetime of the BIS is limited.The aim of this study was to develop a model to determine the potency of a newly produced in-house Reference Standard (RS) for PPDb with great accuracy in the target species (cattle) and to prove its precision and accuracy in the guinea pig potency test. First simulations were done to estimate the required number of cattle needed. Then, 30 naturally bTB infected cattle were subjected to a tuberculin skin test using multiple injections of both the RS and the BIS. Both were applied randomly in the same volume and concentration (1 dose). The potency of the RS against the BIS was directly derived from the least square means (LSMEANS) and was estimated as 1.067 (95% CI: 1.025-1.109), equal to a potency of 34,700 ± 1,400 IU/mg. In six guinea pig potency assays the RS was used to assign potencies to production batches of PPDb. Here, precision and accuracy of the RS was determined according to the parallel-line assay. Relative potencies were estimated by exponentiation of the common slope. The corresponding 95% confidence intervals were obtained according to Fieller's theorem. In sensitized guinea pigs, the relative potency of the RS against the BIS was 1.115 (95% CI: 0.871-1.432), corresponding to an absolute potency of 36,238 IU/mg (95% CI: 28,308-46,540).In conclusion: the method used to determine the potency of the RS against the BIS in naturally bTB infected cattle, resulted in a highly accurate potency estimate of the RS. The RS can be used in the guinea pig test to assign potencies to PPDb production batches with high precision and accuracy.

KW - Bovine international standard

KW - Cattle

KW - Guinea pigs

KW - Mycobacterium bovis

KW - New reference standard

KW - Potency estimation

KW - Tuberculin

U2 - 10.3389/fvets.2018.00232

DO - 10.3389/fvets.2018.00232

M3 - Article

VL - 5

JO - Frontiers in Veterinary Science

T2 - Frontiers in Veterinary Science

JF - Frontiers in Veterinary Science

SN - 2297-1769

IS - OCT

M1 - 232

ER -