PMID- 31997031
OWN - NLM
STAT- MEDLINE
DCOM- 20210126
LR  - 20210126
IS  - 1550-7416 (Electronic)
IS  - 1550-7416 (Linking)
VI  - 22
IP  - 2
DP  - 2020 Jan 29
TI  - Development and Utility of an ELISA Method for Sensitive and Specific Detection 
      of IgE Antidrug Antibodies.
PG  - 36
LID - 10.1208/s12248-020-0413-z [doi]
AB  - Biologics can potentially induce unwanted immune responses, leading to formation 
      of antidrug antibodies (ADA) of various affinity, isotypes, and subclasses. Among 
      them, antigen and drug-specific immunoglobulin E (IgE) antibodies have been 
      reported to have potential correlation with hypersensitivity and anaphylaxis in 
      particular. Recent regulatory guidance on immunogenicity testing has recommended 
      the measurement of antigen-specific IgE antibodies for biologics with a reported 
      high risk of anaphylaxis using assays with sensitivities in the high pg/mL to low 
      ng/mL range. Nevertheless, IgE ADA remains challenging to detect due to their 
      being the least abundant isotype in blood serum samples and the potential for 
      interference in the bioanalytical methods due to high levels of endogenous 
      immunoglobulin G (IgG) and immunoglobulin M (IgM) ADA, not to mention the 
      nonspecific total serum IgE antibodies. Another challenge in developing IgE ADA 
      assays is the need to create a surrogate drug-specific IgE antibody positive 
      control to monitor the performance of the assay for the intended use. In this 
      case study, utilizing a human IgE antidrug antibody positive control and a human 
      IgE receptor as capture, an enzyme-linked immunosorbent assay (ELISA) method was 
      developed for the measurement of IgE ADA, meeting the regulatory expectations, 
      with excellent assay sensitivity, selectivity, specificity, and tolerance towards 
      potential interference in serum samples. This assay format could be readily 
      adapted and implemented to assess drug-specific IgE antibodies in the event of 
      drug-related anaphylaxis in clinical and in nonclinical development programs.
FAU - Zhong, Zhandong Don
AU  - Zhong ZD
AD  - Specialty Bioanalytics, Teva Pharmaceuticals Inc., West Chester, Pennsylvania, 
      19380, USA. don.zhong@tevapharm.com.
FAU - Jiang, Lynn L
AU  - Jiang LL
AD  - Specialty Bioanalytics, Teva Pharmaceuticals Inc., West Chester, Pennsylvania, 
      19380, USA.
FAU - Khandelwal, Puneet
AU  - Khandelwal P
AD  - Specialty Bioanalytics, Teva Pharmaceuticals Inc., West Chester, Pennsylvania, 
      19380, USA.
FAU - Clarke, Adam W
AU  - Clarke AW
AD  - R&D, Biologics, Lead Antibody Discovery, Teva Pharmaceuticals, Sydney, NSW, 
      Australia.
FAU - Bakhtiar, Ray
AU  - Bakhtiar R
AD  - Specialty Bioanalytics, Teva Pharmaceuticals Inc., West Chester, Pennsylvania, 
      19380, USA.
FAU - Zou, Linglong
AU  - Zou L
AD  - Biologics Assays & Technology, Teva Pharmaceuticals Inc., West Chester, 
      Pennsylvania, 19380, USA.
LA  - eng
PT  - Journal Article
PT  - Validation Study
DEP - 20200129
PL  - United States
TA  - AAPS J
JT  - The AAPS journal
JID - 101223209
RN  - 0 (Biological Products)
RN  - 37341-29-0 (Immunoglobulin E)
SB  - IM
EIN - AAPS J. 2020 Mar 16;22(3):57. PMID: 32185532
MH  - Biological Products/adverse effects/*immunology
MH  - Drug Hypersensitivity/blood/*diagnosis/immunology
MH  - *Enzyme-Linked Immunosorbent Assay/standards
MH  - Humans
MH  - Immunoglobulin E/*blood
MH  - Predictive Value of Tests
MH  - Reproducibility of Results
OTO - NOTNLM
OT  - ELISA
OT  - IgE
OT  - antidrug antibody
OT  - hypersensitivity
OT  - immunogenicity
EDAT- 2020/01/31 06:00
MHDA- 2021/01/27 06:00
CRDT- 2020/01/31 06:00
PHST- 2019/06/17 00:00 [received]
PHST- 2019/12/27 00:00 [accepted]
PHST- 2020/01/31 06:00 [entrez]
PHST- 2020/01/31 06:00 [pubmed]
PHST- 2021/01/27 06:00 [medline]
AID - 10.1208/s12248-020-0413-z [pii]
AID - 10.1208/s12248-020-0413-z [doi]
PST - epublish
SO  - AAPS J. 2020 Jan 29;22(2):36. doi: 10.1208/s12248-020-0413-z.