Evidence map›Paper›PMID 39707070›Full record

ArticleThe AAPS journal2024

Cell-Based Assays to Detect Innate Immune Response Modulating Impurities: Application to Biosimilar Insulin.

Cheng Her, Seth Thacker, Joseph Balsamo, Logan Kelley Baker, Derek Dc Ireland, Eric Pang, Daniela Verthelyi

Abstract read
PubMed Publisher
In one paragraph

Article in The AAPS journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Cheng HerLaboratory of Immunology, Office of Pharmaceutical Quality Research Division-IV, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, 20993, USA.
Seth ThackerLaboratory of Immunology, Office of Pharmaceutical Quality Research Division-IV, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, 20993, USA. Seth.Thacker@fda.hhs.gov.ORCID 0000-0001-9944-8937
Joseph BalsamoLaboratory of Immunology, Office of Pharmaceutical Quality Research Division-IV, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, 20993, USA.
Logan Kelley BakerLaboratory of Immunology, Office of Pharmaceutical Quality Research Division-IV, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, 20993, USA.
Derek Dc IrelandLaboratory of Immunology, Office of Pharmaceutical Quality Research Division-IV, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, 20993, USA.
Eric PangDivision of Therapeutic Performance, Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, 20993, USA.
Daniela VerthelyiLaboratory of Immunology, Office of Pharmaceutical Quality Research Division-IV, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, 20993, USA. Daniela.Verthelyi@fda.hhs.gov.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Characterizing and mitigating factors that impact product immunogenicity can aid in risk assessment and/or managing risk following manufacturing changes. For follow-on products that have the same indication, patient population, and active product ingredient, the residual immunogenicity risk resides predominantly on differences in product and process related impurities. Characterizing differences in innate immune modulating impurities (IIRMI), which could act as adjuvants by activating local antigen presenting cells (APCs), can inform the immunogenicity risk assessment potentially reducing the need for clinical trials. To date, assays to detect trace levels of IIRMI are being used to support regulatory decisions by FDA for selected synthetic peptide drug products that refer to reference listed drugs of rDNA origin but not recombinant protein or peptide products where more complex mixtures of trace impurities including host cell proteins are expected. Here we describe an exercise to explore whether or not there are differences in the innate immune response elicited by an insulin glargine (produced in E. coli) and its interchangeable biosimilar insulin (produced in P. pastoris) that could indicate differences in IIRMI. Our results suggest the two products elicit comparable innate immune responses as determined by the expression of 90 immune-related genes, including IL-1α, IL-1β, IL-6, CCL3, CCL2, and CXCL8. The data suggest that these assays can provide useful information when assessing recombinant proteins for the presence of IIRMI.

Indexed as

Biosimilar PharmaceuticalsImmunity, InnateDrug ContaminationHumansInsulin GlargineBiosimilar PharmaceuticalsInsulin Glargineimmunogenicityimmunology risk assessmentinnate immune response

Identifiers

PMID39707070

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.