Micro Developability | Protein Sciences

Integrated Discovery Service

Industry-leading expertise, state-of-the-art facilities, and multiple antibody generation technology platforms for the discovery of novel monoclonal, bispecific and multispecific antibodies, immunocytokines and other biologics.

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Protein Sciences

Specializing in monoclonal, bispecific, and multi-specific antibodies, fusion-proteins, cytokines, enzymes, and other biologics, we offer our customers high productivity and high quality antibody and protein production services for all of your research needs.

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Cell Line Engineering

Provided as either a standalone service offering or as part of our integrated CMC development platforms, WuXi Biologics provides extensive expertise and industry-leading timelines for cell line engineering and strain development across a wide range of biotherapeutics.

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Analytical Sciences

Our extensive analytical testing services offer top-tier expertise in method development for in-process, release, and stability assays, and support of cell line, process, and formulation development activities, product characterization, developability assessments and other key IND- and BLA-enabling studies.

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Process Development & Scale Up

Multiple upstream and downstream PD labs facilitate the establishment and scale-up of fed-batch, intensified fed-batch, and continuous manufacturing approaches for diverse biotherapeutic modalities in both early and late-stage development.

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Formulation & Drug Product Development

We provide advanced drug product development services spanning biologics, vaccines, and small molecules, with expertise in formulating clinical and commercial products in liquid, frozen, and lyophilized forms, compatible with various container closure systems such as vials, prefilled syringes, and other combination product types.

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Cell Banking & Characterization

Offering in-house, one-stop cell banking and cell line characterization services, compliant with global GMP regulations and ICH guidelines, we operate over 20 cGMP cell banking suites ensuring capacity availability and timely execution of this critical CMC development activity.

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Viral Clearance

Our extensive experience and expertise, along with EMA, ISO (CNAS), and CMA-certified laboratories, and exceptional track record for IND- and BLA-enabling viral clearance study acceptance by global regulatory agencies, form the cornerstones for this pivotal aspect of any CMC development program.

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Clinical DP GMP Manufacturing

Multiple, highly flexible clinical-scale drug product (DP) manufacturing facilities for the formulation, fill, labelling and packaging of biologics and parenterals under Current Good Manufacturing Practice (cGMP) conditions as defined by global regulatory agencies.

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Commercial DS GMP Manufacturing

We provide a global dual source manufacturing network that employs multiple large-scale drug substance (DS) GMP manufacturing facilities for the production of biologics utilizing our world-class operations and regulatory agency-approved quality systems.

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Commercial DP GMP Manufacturing

Multiple large-scale drug product (DP) manufacturing facilities located across the globe for the high-quality formulation, fill, labelling and packaging of biologics, parenterals and placebo into a wide array of container closure systems.

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Biosafety Testing

High quality, in-house and EMA, ISO (CNAS) and CMA certified biosafety testing facilities for adventitious agent screening of raw materials, cell lines and unprocessed bulk along with our extensive viral clearance capabilities is available to provide our clients with a single-source biosafety testing service offering.

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Global Quality Control (QC)

Regulatory compliant, in-house, QC labs support all clinical and commercial GMP sites pre- and post-production, ensuring top-quality testing for products and oversight of other critical functions (e.g., environmental monitoring, cleaning validations, instrument life-cycle and sample/retain management and audits).

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Global Compliance

Oversees global quality system and audit, IT quality, internal compliance, and risk analytics functions. This team embeds quality and compliance across the entire organization to ensure the products we manufacture are of the highest efficacy and safety standards and in line with your expectations.

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Quality Control

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Regulatory Affairs

Our experienced regulatory affairs team supports our client’s CMC dossier, drug filing and registration needs. Since 2015 this team has supported 550+ INDs, CTAs, BLAs, MAAs, NDAs and EUAs, and written 200+ Module 3 CMC packages on behalf of our global clients.

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Target to Lead

Providing expertise, highly efficient tailored solutions, state-of-the-art technologies and world-class facilities for the engineering, generation, and optimization of antibodies and other biologics from target identification to final lead selection.

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Bispecific & Multispecific Antibodies - WuXiBody™

The WuXiBody™ platform for the generation of bispecific (bsAb) and multispecific (msAb) antibodies speeds up drug development by 6-18 months, cuts production costs, and enables flexible assembly of mAb sequence pairs into various formats with different valency.

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Advanced Hybridoma Platform - WuXiHybrid™

Using advanced technologies to generate diverse monoclonal antibodies (mAb) for various targets. Our experienced scientists overcome technical challenges to deliver high-quality mAbs to our clients worldwide.

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Naive Phage Display Library - WuXiLiAb™

Offering high-quality phage display library construction and customized library selection and screening services via our WuXiLiAb® human naïve / synthetic phage display libraries, VHH naïve / humanized VHH synthetic libraries and antibody immune libraries.

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VHH-based Multispecific Antibody Platform - SDARBody™

Novel technology platform to enable the development of multispecific proteins. Highly flexible platform capable of generating multispecific antibody and protein therapeutics with high affinity, low immunogenicity risk and excellent developability characteristics.

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ScFv-based BsAb & MsAb Antibody Platform - SKYBody™

An innovative scFv (single-chain fragment variables)-based platform for the generation of bispecific or multispecific antibodies from nearly any sequence pair. The platform significantly improves scFv stability providing bsAbs and msAbs with strong developability characteristics.

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Ultra-Intensified Fed-batch platform - WuXiUI™

Ultra-intensified fed-batch bioprocessing platform utilizes an intermittent perfusion approach to achieve 3-6-fold higher productivity and 60 – 80% reduction in manufacturing cost of goods compared to traditional fed-batch processes.

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Rapid Research Material Generation - WuXian™

Custom protein generation services, producing high-quality, research-grade proteins/antibodies by using our industry-leading team of cell culture, purification and analytical experts and high-throughput, cost-effective production technologies.

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Continuous Bioprocessing - WuXiUP™

This ultra-high productivity continuous bioprocessing platform, achieves 5-15X greater productivity, delivering high-yield, quality drug products with flexibility and cost-effectiveness through intensified perfusion culture, continuous harvest and optional downstream continuous product capture step.

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High Concentration & HTP DP Platform - WuXiHigh™

Advanced high throughput formulation platform for development of high concentration biologics drug products using distinctive viscosity reducers and synergistic excipient combinations to enhance formulation stability and reduce viscosity.

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Scale-Out Biomanufacturing

Helping to pioneer this biomanufacturing strategy for higher volume production, we can help you reduce risk and increase manufacturing flexibility across the entire product lifecycle by using multiple, same-scale bioreactors to meet clinical and market demand.

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Robotic Aseptic Filling

Reducing manufacturing risk through the use of this fully programmable, robotic, gloveless, isolator-based technology for advanced aseptic drug product fill processing. These systems provide extensive flexibility to support complex fills across a wide range of biologics and container closure systems.

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Frequently Asked Questions for our Micro Developability Services

Q: Have you observed any degradation of the His tag in vivo? Could this impact the detection of molecules in PK assays?

During stage 2 development, when evaluating 50 to 100 molecules, degradation trends are generally consistent across candidates, making comparative assessments more relevant than individual evaluations. In a VHH-based example, instability was primarily attributed to the inherent poor stability of the VHH itself rather than degradation of the His tag. For cases involving only one or two His-tagged molecules, a thorough understanding of the molecule is essential to assess potential impacts on PK analysis. If His tag degradation is a concern, targeted proteomics offers an alternative approach, enabling peptide digestion and direct targeting without relying on His tag-based immunoprecipitation.

Q: Are most of your developability case studies related to IgG1? Do study outcomes apply to other subclasses (e.g., IgG2, IgG3, IgG4)?

Yes, most of our data focus on IgG1, as it serves as a well-established benchmark for later-stage development and manufacturing. IgG2 is less commonly used due to the risk of disulfide bond scrambling, which can be identified through in silico analysis. IgG3 is also less prevalent. Our assays have been applied to bispecific antibodies, Fc fusion proteins and other modalities, demonstrating similar trends across these formats.

Q: Have you used any methods besides Mass Spec to analyze serum stability results?

Yes, we have compared the data with ELISA. However, ELISA has certain limitations, particularly in reproducibility. In contrast, Mass Spec offers higher sensitivity, enabling detection at concentrations as low as 0.5 mg/mL.

Q: Can in vitro serum incubation predict in vivo stability?

In vitro serum incubation can indicate potential stability risks but does not fully correlate with in vivo stability. In vivo degradation involves both direct degradation and protein recycling pathways, which cannot be entirely replicated in vitro. Using both assays allows for a comparative assessment, but due to the high cost, in vivo studies are typically reserved for later development stages.

Q: Do you verify binding and PTMs during the developability stress test?

Yes, verifying binding and PTMs during stress testing is beneficial, like under thermal stress, freeze-thaw, and low pH conditions. However, early-stage assessments are often limited by material availability and the large number of candidates (e.g., 50–100 molecules). At later stages, PTM testing under stress conditions is recommended to ensure stability and mitigate risks before entering CMC development. Proper timing of these evaluations is crucial for optimizing resource use and ensuring robust candidate selection.

Q: Do study results using transiently produced mAbs closely align with those from stable cell lines?

For most early-stage assessments, such as AC-SINS, heat hydrophobicity, and charge distribution, the choice of cell line has minimal impact, making transiently produced mAbs suitable for evaluation. However, PTMs are highly dependent on the cell line and culture conditions, so final assessments should be performed using stable cell lines. Additionally, WuXi Biologics utilizes the same parental cell line for both transient and stable pool production, ensuring greater consistency in key attributes, particularly glycosylation, and enhancing the reliability of early-stage assessments.

Q: Why is high pH hold testing less critical than low pH hold?

High pH hold testing is typically recommended in later development stages but is less prioritized early on due to limited material availability and its lower relevance compared to low pH hold or freeze-thaw studies.

Q: How do you determine whether a peak decrease is due to actual degradation or stress during immunoprecipitation?

To differentiate real degradation from immunoprecipitation-induced stress, we assess protein recovery before and after immunoprecipitation, ensuring over 95% recovery. Additionally, we incorporate an internal control, such as Herceptin, in our experiments. If Herceptin shows no decrease, we can confidently conclude that the immunoprecipitation process is functioning as expected and not contributing to protein degradation.

Q: How much antibody is needed for each protein characterization assay?

A: We only require a small amount of antibody for each assay. Approximately 1 mg of antibody is sufficient for most assays except for forced degradation and stability studies. Specific requirements needed for each assay are detailed in the above table.

Q: What does a change in iCIEF percentage indicate for the 40°C sample?

A: The change in iCIEF percentage shows alterations in the distribution of main, acidic, and basic protein species. High-temperature stress causes these changes mainly due to post-translational modifications (PTMs) and chemical alterations, like deamidation and oxidation, which can alter the charge properties of these protein species.

Q: Can you briefly introduce your in silico analysis service?

A: Our in silico analysis includes three main categories: sequence liability, aggregation propensity, and immunogenicity prediction. Sequence liability uses an open-source algorithm to predict PTMs that might affect antigen-binding in the complementarity-determining regions (CDRs). Aggregation propensity is assessed based on the solvent-accessible surface area of hydrophobic residues and the presence of free cysteine, categorizing potential aggregations as high, medium, or low. It’s important to note that the formation of protein aggregates is affected by several factors, including the solvent micro-environment, concentration, storage time, and storage conditions. So, our predictions only reflect the potential impacts of hydrophobicity and unwanted disulfide bonds. Lastly, our immunogenicity prediction demonstrates approximately a 0.6 correlation between the generation of anti-drug antibodies (ADA) and our predictions, which are based on publicly available data.

Q: What in silico tools do you use for aggregation profiling? Is this open source or proprietary?

A: We use a proprietary algorithm for aggregation profiling. It analyzes the solvent-accessible surface region of hydrophobic residues and the presence of free cysteine from structural information.

Q: Do you conduct high pH hold for forced degradation studies?

A: Yes, we can perform high pH hold conditions upon request for forced degradation studies.

Q: How do you determine if observed degradation in serum stability assays is due to incubation in serum or stress from capture/elute post-incubation?

A: We use Herceptin as a control in serum stability assays. By comparing the percent intensity of each sample at 48 hours and 96 hours to Herceptin’s percent intensity, we determine if the degradation is systematic or specific to the sample.

Q: What is the throughput of your Micro Developability platform?

A: Our Micro Developability platform typically handles about 100 molecules but can easily accommodate several hundred if necessary.

Q: What is the typical turnaround time for your full Micro Developability package?

A: We can complete most of our pharmacokinetic-predicting assays within two weeks. The duration for forced degradation studies varies based on the conditions requested, and it typically takes an additional 1-2 weeks to generate the final report after experiments conclude.

Q: What instruments do you use for TM measurements?

A: For TM measurements, we have two main options: Differential Scanning Fluorimetry (DSF) and Differential Scanning Calorimetry (DSC). DSF is a more cost-effective choice while DSC is more expensive. The selection depends on your specific needs.

Q: For AC-SINS assays, do you only test antibodies with human Fc domain?

A: Most of the samples tested are human antibodies, and we have a default stock of AuNP for human antibody measurements. We can also adapt to customized species, such as mouse or canine. Please inform us in advance so that we can prepare the corresponding reagents to produce customized AuNP.

Q: Why are AC-SINS results related to pharmacokinetics (PK) predictions?

A: Molecules prone to self-association or aggregation suggests fast clearance in vivo and can be predicted through AC-SINS.

Q: Why are Baculovirus (BV), DNA, and Insulin chosen? How is the ELISA score evaluated?

A: DNA and Insulin: These were adapted from assays identifying autoreactive antibodies in lupus patients and are highly sensitive in detecting charge-based, low-affinity, or above-background off-target binding (DOI: 10.1080/19420862.2017.1417718 and 10.1080/19420862.2015.1016696).

BV Virions: These stable particles mimic infected cell surfaces, presenting a complex mixture of phospholipids, carbohydrates, glycoproteins, extracellular matrix and nucleic acids, as well as the viral capsid. This allows for the detection of various interactions, such as electrostatic and hydrophobic interactions.

The ELISA score of each sample is the percentage referenced to our positive control mAb, which has fast clearance in actual PK studies. Thresholds for low, medium and high risk are set based on publications from pharmaceutical companies, such as Pfizer and Genentech as well as our own experience.

Q: Why is mouse serum selected for serum stability studies?

A: Mouse serum is used because it aligns with animal study results. The components in the mouse matrix are different from human antibody Fc-domains, which is beneficial for target antibody enrichment in the mouse serum. However, IgG depleted human serum will be up and running very soon!

More FAQs

Service Item	Description	Request A Quote
In Silico Analysis	Liability Immunogenicity Aggregation	Request A Quote
Mass Spec	Intact: Clipping Peptide Mapping: PTM Disulfide/Glycan CE-MS: Charge
Biophysical	DSF/DSC (T_m, T_agg) Solubility/Viscosity for High Concentration DLS
Affinity	SPR/BLI/ELISA
Off-Target/PK Predicting	Human FcRn (SPR/BLI) AC-SINS/HIC (self-interaction/hydrophobicity) BVP/DNA/Insulin ELISA (poly-reactivity) Serum Susceptibility (cleavage)
Early Stability Assessment	Forced Degradation Study (thermal stress, low pH stress, freeze/thaw) SEC iCIEF CE-SDS (NR/R) Peptide Mapping SPR

Our Micro Developability Service

AC-SINS (Affinity-Capture Self-Interacting Nanoparticle Spectroscopy)

AC-SINS HIC Correlation

Baculovirus/DNA/Insulin ELISA

Frequently Asked Questions for our Micro Developability Services

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