Evidence map›Paper›PMID 36412839›Full record

ReviewAntibodies (Basel, Switzerland)2022

Risk-Based Control Strategies of Recombinant Monoclonal Antibody Charge Variants.

Alain Beck, Christine Nowak, Deborah Meshulam, Kristina Reynolds, David Chen, Dennis B Pacardo, Samantha B Nicholls, Gregory J Carven, Zhenyu Gu, Jing Fang and 4 more

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Antibodies (Basel, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing 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

23 citing papers in PubMed.

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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

14 authors.

Alain BeckCentre d'Immunologie Pierre-Fabre (CIPF), 5 Avenue Napoléon III, 74160 Saint-Julien-en-Genevois, France.ORCID 0000-0002-4725-1777
Christine NowakProtein Characterization, Alexion AstraZeneca Rare Disease, 100 College St, New Haven, CT 06510, USA.
Deborah MeshulamTechnical Operations/CMC, Scholar Rock, 301 Binney Street, 3rd Floor, Cambridge, MA 02142, USA.
Kristina ReynoldsTechnical Operations/CMC, Scholar Rock, 301 Binney Street, 3rd Floor, Cambridge, MA 02142, USA.
David ChenTechnical Operations/CMC, Scholar Rock, 301 Binney Street, 3rd Floor, Cambridge, MA 02142, USA.
Dennis B PacardoTechnical Operations/CMC, Scholar Rock, 301 Binney Street, 3rd Floor, Cambridge, MA 02142, USA.
Samantha B NichollsProtein Sciences, Scholar Rock, 301 Binney Street, 3rd Floor, Cambridge, MA 02142, USA.
Gregory J CarvenResearch, Scholar Rock, 301 Binney Street, 3rd Floor, Cambridge, MA 02142, USA.
Zhenyu GuJasper Therapeutics, Inc., 2200 Bridge Pkwy Suite 102, Redwood City, CA 94065, USA.
Jing FangBiological Drug Discovery, Biogen, 225 Binney St, Cambridge, MA 02142, USA.
Dongdong WangGlobal Biologics, Takeda Pharmaceuticals, 300 Shire Way, Lexington, MA 02421, USA.
Amit KatiyarCMC Technical Operations, Magenta Therapeutics, 100 Technology Square, Cambridge, MA 02139, USA.
Tao XiangDownstream Process and Analytical Development, Boston Institute of Biotechnology, 225 Turnpike Rd, Southborough, MA 01772, USA.
Hongcheng LiuTechnical Operations/CMC, Scholar Rock, 301 Binney Street, 3rd Floor, Cambridge, MA 02142, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Since the first approval of the anti-CD3 recombinant monoclonal antibody (mAb), muromonab-CD3, a mouse antibody for the prevention of transplant rejection, by the US Food and Drug Administration (FDA) in 1986, mAb therapeutics have become increasingly important to medical care. A wealth of information about mAbs regarding their structure, stability, post-translation modifications, and the relationship between modification and function has been reported. Yet, substantial resources are still required throughout development and commercialization to have appropriate control strategies to maintain consistent product quality, safety, and efficacy. A typical feature of mAbs is charge heterogeneity, which stems from a variety of modifications, including modifications that are common to many mAbs or unique to a specific molecule or process. Charge heterogeneity is highly sensitive to process changes and thus a good indicator of a robust process. It is a high-risk quality attribute that could potentially fail the specification and comparability required for batch disposition. Failure to meet product specifications or comparability can substantially affect clinical development timelines. To mitigate these risks, the general rule is to maintain a comparable charge profile when process changes are inevitably introduced during development and even after commercialization. Otherwise, new peaks or varied levels of acidic and basic species must be justified based on scientific knowledge and clinical experience for a specific molecule. Here, we summarize the current understanding of mAb charge variants and outline risk-based control strategies to support process development and ultimately commercialization.

Indexed as

charge variantscomparabilitycritical quality attributesmonoclonal antibodiesspecification

Identifiers

PMID36412839
PMCPMC9703962

What OpenQuestion holds

Textmetadata
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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.