T1 Limitations of the quality range approach in analytical similarity assessment: Effect of mean shift and relative variability
A1 Oliva Martín, Alexis Manuel
A1 Llabrés Martínez, Matías Antonio
A2 Ingeniería Química y Tecnología Farmacéutica
A2 Desarrollo Galénico de Medicamentos
K1 Analytical similarity
K1 Biosimilar
K1 Quality range method
K1 Mean shift
K1 Relative variability
AB Recently in 2019, the United States Food and Drug Administration (FDA) circulated a new draft guidance for comparative analytical assessment. They suggest the use of quality range (QR) methods. In this article, selection of the k value, and the effect of mean shifts and relative variability are evaluated. These are expressed as a ratio between the two standard deviations of the tested product and the reference product, σT/σR. In a second step, the two modified versions of the QR method proposed by Son et al. (2020) are also analysed under several scenarios, through simulation studies using real data from a biotechnology company and our own data for bevacizumab. Results indicate that k has a great impact on the probability of passing similarity tests. Pass rates higher than 90 % can be achieved for small relative variabilities (σT/σR ≤ 0.6) and large mean shifts (≈4%) by using k = 3. The situation is totally different for k = 2: the pass rate is higher than 90 % for scenarios with small (<0.5 %) or no differences between the means of the two products, but this percentage decreases by up to 50 % for σT/σR = 1. Effectiveness in detecting the various scenarios was quantified by calculating the probability curves of passing the similarity test, as a function of the two variables for each k value. Alternative methods present the same limitations but with different magnitude in comparison with QR, this being most pronounced in the plausibility-interval QR method.
SN 0731-7085
YR 2021
FD 2021
LK http://riull.ull.es/xmlui/handle/915/39730
UL http://riull.ull.es/xmlui/handle/915/39730
LA Inglés
DS Repositorio institucional de la Universidad de La Laguna
RD 05-ene-2025