Reproductive/Developmental Toxicity Assessment of Biopharmaceuticals in Nonhuman Primates

Weinbauer, Gerhard F.; Frings, Werner; Fuchs, Antje; Niehaus, Michael; Osterburg, Ingrid

doi:10.1002/9780470292549.ch18

Cited by 23 publications

(37 citation statements)

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“…New world primates, such as marmosets, can also be used for DART studies; however, there is less historical data available, the reproductive physiology is less similar to that of humans, and the extent of placental transfer of antibodies may be less than in old world primates (Coe et al, 1994;Zuhlke et al, 2002;Weinbauer et al, 2008).…”

Section: Use Of Non-traditional Animal Speciesmentioning

confidence: 99%

“…For NHP fertility studies, one of the challenges is the inherently low-fertility rate (40 to 70%), high pre-implantation loss (approximately 25%), and high spontaneous abortion rate (10 to 30%) (Hendrie et al, 1996;Weinbauer et al, 2008;Meyer et al, 2006). Evaluation of the number of successful pregnancies is a quantitative endpoint that is highly dependent upon statistical power.…”

Section: Fertility Studies In Nhpsmentioning

confidence: 99%

“…Using the number of successful NHP pregnancies as a measure of fertility would require approximately ninety NHPs per group to attain an 80% power to detect a 20% change in fertility, which is obviously not practical or ethical. Reproductive potential can, however, be assessed in non-terminal NHP studies by evaluation of menstrual cycles, hormone analysis, semen parameters, and testicular size (Vogel and Bee, 1999;Weinbauer 2002;Weinbauer et al, 2008;Meyer et al, 2006). For terminal studies in NHPs, spermatogenesis can be evaluated morphologically (Dreef et al, 2007).…”

Section: Fertility Studies In Nhpsmentioning

confidence: 99%

“…Common study designs have included initiation of dosing anywhere from GD20 to 120 and discontinuation of dosing at term or at one-month postpartum during the lactation period (Weinbauer et al, 2008;Martin et al, 2007;Martin, 2008). The selected study design will depend on the pharmacology and the intended clinical use relative to pregnancy.…”

Section: Pre/postnatal Development Studies In Nhpsmentioning

confidence: 99%

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Considerations in assessing the developmental and reproductive toxicity potential of biopharmaceuticals

Martin¹,

Breslin

Rocca

et al. 2009

Birth Defects Research Pt B

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This report discusses the principles of developmental and reproductive toxicity (DART) testing for biopharmaceuticals. Biopharmaceuticals are large‐molecular‐weight proteins or peptides produced by modern biotechnology techniques incorporating genetic engineering and hybridoma technologies. The principles of DART testing for biopharmaceuticals are similar to those for small‐molecule pharmaceuticals and in general follow the regulatory guidance outlined in International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) document S5(R2). However, because many biopharmaceuticals are species‐specific, alternate approaches may be needed to evaluate DART potential as outlined in ICH S6. For molecules that show species‐specific cross‐reactivity restricted to non‐human primates (NHP), some aspects of DART may require NHP testing. For biopharmaceuticals that are uniquely specific and only active on intended human targets or human and chimpanzee targets, surrogate molecules that cross‐react with the more traditional rodent species may need to be developed and used for DART testing. Alternatively, genetically modified transgenic animals may also need to be considered. Surrogate molecules and transgenic animals may also be considered for DART testing even if the biopharmaceutical is active in NHPs in order to reduce the use of NHPs. Because of the unique properties of biopharmaceuticals, a case‐by‐case approach is needed for DART and general toxicity evaluation, which requires consideration of specific product attributes including biochemical and biophysical characteristics, pharmacological activity, and intended clinical indication. Birth Defects Res (Part B), 33:176–203, 2009. © 2009 Wiley‐Liss, Inc.

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Section: Use Of Non-traditional Animal Speciesmentioning

confidence: 99%

Section: Fertility Studies In Nhpsmentioning

confidence: 99%

Section: Fertility Studies In Nhpsmentioning

confidence: 99%

Section: Pre/postnatal Development Studies In Nhpsmentioning

confidence: 99%

See 2 more Smart Citations

Considerations in assessing the developmental and reproductive toxicity potential of biopharmaceuticals

Martin¹,

Breslin

Rocca

et al. 2009

Birth Defects Research Pt B

View full text Add to dashboard Cite

show abstract

“…For Fc-bb dosing is best extended to GD90 or GD100 (end of second trimester) or even later (late third trimester) to ensure fetal exposure (Fujimoto et al, 1983;Coe et al, 1993;Leach et al, 1996). Extending dosing allows increased fetal exposure due to the increased expression of the F c Rn receptor during this time (Henck et al, 1996;Weinbauer et al, 2008). As with the standard EFD study, immunopathology of lymphoid tissues is the DIT end-point evaluated at the termination of the study.…”

Section: Nhpmentioning

confidence: 99%