Variability of in vivo potency tests of Diphtheria, Tetanus and acellular Pertussis (DTaP) vaccines
| Autor: | Arnoud M. Akkermans, Irene A. Retmana, Coenraad F.M. Hendriksen, Coen A.L. Stalpers, Marcel H.N. Hoefnagel, Jeroen L. A. Pennings, Rob J. Vandebriel |
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| Rok vydání: | 2021 |
| Předmět: |
Drug
Assay variability Whooping Cough media_common.quotation_subject 030231 tropical medicine In vivo potency test Pharmacology Biology Diphtheria-Tetanus-acellular Pertussis Vaccines 3Rs 03 medical and health sciences 0302 clinical medicine Pertussis Antigen In vivo medicine Animals Potency 030212 general & internal medicine Diphtheria-Tetanus-Pertussis Vaccine media_common Tetanus General Veterinary General Immunology and Microbiology Diphtheria Public Health Environmental and Occupational Health In vitro toxicology medicine.disease 3. Good health Infectious Diseases Molecular Medicine Critical quality attributes |
| Zdroj: | Vaccine |
| ISSN: | 0264-410X |
| DOI: | 10.1016/j.vaccine.2021.03.078 |
| Popis: | For batch release of legacy vaccines such as DTaP, in vivo potency release assays are required. We quantified the variability of in vivo potency release assays for four DTaP (Diphtheria, Tetanus, acellular Pertussis) products of different manufacturers. With their large CV (Coefficients of Variance) ranging from 16% to 132%, these in vivo assays are of limited value to ensure their potency is consistent and similar to the clinical batches used for the marketing authorisation. Our data show that, although individual potency test results show high variability, the DTaP batches are manufactured with great consistency, because repeated potency testing yields similar averages for the different batches. The economic impact of variability of in vivo tests is significant since it may result in the need for greater amount of antigen than may be required or for repeating a test. For monitoring the consistency of potency, in vitro assays are superior to in vivo assays. Animal-free potency determination is common practice for newly developed vaccines under modern GMP quality systems. However, replacement of in vivo potency tests for legacy vaccines like DTaP is challenging and would require a 'reverse characterisation' strategy in which the antigens are further characterised at the level of drug substance and drug product to identify critical quality attributes (CQA) that can be tested with in vitro assays. Based on these an updated set of release tests without animal tests can be proposed. Our data can serve as benchmark for the innovative methods. |
| Databáze: | OpenAIRE |
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