Recommendations for the validation of immunoassays used for detection of host antibodies against biotechnology products

Shankar, Gopi; Devanarayan, Viswanath; Amaravadi, Lakshmi; Barrett, Yu Chen; Bowsher, Ronald R.; Finco‐Kent, Deborah; Fiscella, Michele; Gorovits, Boris; Kirschner, Susan; Moxness, Michael; Parish, Thomas H.; Quarmby, Valerie; Smith, Holly W.; Smith, Wendell C.; Zuckerman, L; Koren, Eugen

doi:10.1016/j.jpba.2008.09.020

Cited by 539 publications

(457 citation statements)

References 23 publications

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“…A number of ADA assay formats are available, each with some bias in the type(s) of ADA measured and limitations in sensitivity and susceptibility to interferences. Recommended practices for developing and validating ADA assays for use in clinical development programmes have been developed through multiple collaborative efforts among the pharmaceutical and regulatory agencies and scientific communities under the sponsorship of organizations such as AAPS and EIP 19, 20, 21, 22, 23, 24 and adopted into pharmaceutical regulatory agency guidelines 47, 48, 49, 50.…”

Section: Ada Immune Response Assaysmentioning

confidence: 99%

“…Prior to use, ADA assays should be validated analytically to assure reliable performance over time and establish which changes in ADA measurements are likely to be meaningful 20, 22, 47, 49, 50. Analytical validation typically involves analysis of positive and negative quality control (QC) samples to characterize inter‐ and intra‐assay variability (precision), sensitivity to small changes in conditions (robustness) and interlaboratory variability (ruggedness).…”

Section: Ada Immune Response Assaysmentioning

confidence: 99%

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Standardizing terms, definitions and concepts for describing and interpreting unwanted immunogenicity of biopharmaceuticals: recommendations of the Innovative Medicines Initiative ABIRISK consortium

Rup

Pallardy

Sikkema

et al. 2015

Clinical and Experimental Immunology

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SummaryBiopharmaceuticals (BPs) represent a rapidly growing class of approved and investigational drug therapies that is contributing significantly to advancing treatment in multiple disease areas, including inflammatory and autoimmune diseases, genetic deficiencies and cancer. Unfortunately, unwanted immunogenic responses to BPs, in particular those affecting clinical safety or efficacy, remain among the most common negative effects associated with this important class of drugs. To manage and reduce risk of unwanted immunogenicity, diverse communities of clinicians, pharmaceutical industry and academic scientists are involved in: interpretation and management of clinical and biological outcomes of BP immunogenicity, improvement of methods for describing, predicting and mitigating immunogenicity risk and elucidation of underlying causes. Collaboration and alignment of efforts across these communities is made difficult due to lack of agreement on concepts, practices and standardized terms and definitions related to immunogenicity. The Innovative Medicines Initiative (IMI; www.imi-europe.org), ABIRISK consortium [Anti‐Biopharmaceutical (BP) Immunization Prediction and Clinical Relevance to Reduce the Risk; www.abirisk.eu] was formed by leading clinicians, academic scientists and EFPIA (European Federation of Pharmaceutical Industries and Associations) members to elucidate underlying causes, improve methods for immunogenicity prediction and mitigation and establish common definitions around terms and concepts related to immunogenicity. These efforts are expected to facilitate broader collaborations and lead to new guidelines for managing immunogenicity. To support alignment, an overview of concepts behind the set of key terms and definitions adopted to date by ABIRISK is provided herein along with a link to access and download the ABIRISK terms and definitions and provide comments (http://www.abirisk.eu/index_t_and_d.asp).

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Section: Ada Immune Response Assaysmentioning

confidence: 99%

Section: Ada Immune Response Assaysmentioning

confidence: 99%

Standardizing terms, definitions and concepts for describing and interpreting unwanted immunogenicity of biopharmaceuticals: recommendations of the Innovative Medicines Initiative ABIRISK consortium

Rup

Pallardy

Sikkema

et al. 2015

Clinical and Experimental Immunology

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“…Therefore, we developed a highly sensitive method to detect putative antibodies against FSH, LH and hCG. The methods were validated following the latest guidelines and recommendations 4, 5, 6, 7, 12…”

Section: Discussionmentioning

confidence: 99%

“…The methods to detect antibodies against FSH, LH and hCG were validated following the current guidelines by the FDA4 and EMA 5 and the published recommendations 6, 7, 12. The validation included determination of the cut point, sensitivity, specificity, precision, matrix effects and stability.…”

Section: Methodsmentioning

confidence: 99%

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Assessment of the immunogenicity of gonadotrophins during controlled ovarian stimulation

Morte¹,

Celma²,

Geyter

et al. 2017

American J Rep Immunol

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ProblemGonadotrophin hormones are used for the controlled ovarian stimulation (COS) as part of the in vitro fertilization techniques. Therapeutic proteins have the potential to induce an unwanted immune response.Method of studyThe presence of anti‐FSH, anti‐LH and anti‐hCG antibodies were determined in patients from two different clinical trials after the repeated administration of hMG or FSH.ResultsIn the first study, 27 subjects were screening for the presence of anti‐FSH antibodies. From the 27 patients, only one patient showed the presence of low levels of antibodies. In a second study, 25 patients were screened for the presence of anti‐FSH, anti‐LH and anti‐hCG antibodies. At the end of the study, no patients showed the presence of antibodies.ConclusionThe results of this study suggest that repeated treatment cycles with FSH or hMG in patients undergoing COS for in vitro fertilization can be safely and effectively applied without concerns for immunogenicity.

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Aflibercept Biosimilar MYL-1701P vs Reference Aflibercept in Diabetic Macular Edema

Bressler,

Barve,

Ganapathi

et al. 2024

JAMA Ophthalmol

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ImportanceBiosimilars may be lower-cost alternatives to originator biologic products, potentially offering expanded access or reduced economic burden, but have not been evaluated with aflibercept in diabetic macular edema (DME).ObjectiveTo compare efficacy and safety of MYL-1701P, an aflibercept biosimilar, with reference aflibercept (Eylea [Regeneron]) in DME.Design, Setting, and ParticipantsThis was a double-masked, randomized clinical trial that included participants at 77 centers across the US, Europe, Japan, and India. Included in the analysis were individuals 18 years and older with type 1 or type 2 diabetes with central DME and best-corrected visual acuity (BCVA) letter score of 73 to 38 in the study eye using an Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Study data were analyzed from October to December 2021.InterventionsFormulations of MYL-1701P (0.5-mg vial) or reference aflibercept every 4 weeks for 5 consecutive intravitreal injections, followed by every 8 weeks through week 52.Main Outcomes and MeasuresThe primary outcome was the adjusted difference in least squares mean (SE) change from baseline BCVA letter score at week 8 with an equivalence margin of −3 to +3 letters. Secondary outcomes included change in central subfield thickness (CST), BCVA, number of injections over 52 weeks, incidence of adverse events (AEs), and antidrug antibodies (ADAs).ResultsA total of 355 participants (mean [SD] age, 62.2 [9.2] years; 216 male [60.8%]) were randomized to MYL-1701P (179 participants [50.4%]) and aflibercept (176 participants [49.6%]). At week 8, mean (SE) change in BCVA was 6.60 (0.55) letters vs 6.56 (0.55) letters in the MYL-1701P vs aflibercept groups. The adjusted mean difference of 0.04 letters (90% CI, −1.16 to 1.24 letters) met the primary outcome. At week 8, mean (SE) change in CST was −112 (7) μm vs −124 (7) μm in the MYL-1701P vs aflibercept groups (adjusted mean difference, 12 μm; 90% CI, −3 to 26 μm). The incidence of treatment-emergent AEs in the MYL-1701P and aflibercept arms were ocular (30.9% [55 of 178] vs 29.5% [52 of 176]), serious ocular (0.6% [1 of 178] vs 1.1% [2 of 176]), nonocular (65.2% [116 of 178] vs 65.3% [115 of 176]), and serious nonocular (16.9% [30 of 178] vs 11.9% [21 of 176]). The mean (SD) total number of injections was 8.4 (2.1) vs 8.7 (1.8) in the MYL-1701P vs aflibercept groups. The incidence of treatment-induced or treatment-boosted ADAs was 2.8% (5 of 177) vs 5.7% (10 of 176) in the MYL-1701P vs aflibercept arms.Conclusions and RelevanceMYL-1701P demonstrated clinical equivalence in regard to efficacy, with comparable safety and immunogenicity, to reference aflibercept. These findings support use of MLY-1701P as an alternative to reference aflibercept.Trial RegistrationClinicalTrials.gov Identifier: NCT03610646

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Recommendations for the validation of immunoassays used for detection of host antibodies against biotechnology products

Cited by 539 publications

References 23 publications

Standardizing terms, definitions and concepts for describing and interpreting unwanted immunogenicity of biopharmaceuticals: recommendations of the Innovative Medicines Initiative ABIRISK consortium

Standardizing terms, definitions and concepts for describing and interpreting unwanted immunogenicity of biopharmaceuticals: recommendations of the Innovative Medicines Initiative ABIRISK consortium

Assessment of the immunogenicity of gonadotrophins during controlled ovarian stimulation

Aflibercept Biosimilar MYL-1701P vs Reference Aflibercept in Diabetic Macular Edema

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