Search
Close this search box.
    • Small Molecules
    • Biologics
    • Other Drug Modalities
    • SynVent Integrated Drug Discovery
      • SynVent Integrated Drug Discovery

        SynVent is Syngene’s platform for fully integrated therapeutic discovery and development across large and small molecules. 

    • Industries
    • Emerging Biopharma
      • Emerging Biopharma

        Emerging biopharma work at the forefront of science, often venturing into disease areas where little or no real-world data exists to work with or regulatory frameworks to work within.

    • Dedicated Centers
      • Dedicated Centers

        Our Dedicated Centers offer dedicated multi-disciplinary scientific teams, support personnel, and a tailormade ring-fenced and fire-walled infrastructure as per client specifications to support their  R&D  goals

    • Center for Advanced Protein Studies (CAPS)
      • Center for Advanced Protein Studies (CAPS)

        Centre for Advanced Protein Studies [CAPS] is a state-of-the-art advanced national facility located in the Syngene campus, Bangalore.

  • Careers
Search
Close this search box.

Enhancing nanofiltration efficiency in mAb production process

High Throughput Screening (HTS) solutions enable identification of chemical and biological compounds for various applications. Both enzyme/protein and cell-based assays are employed in combination with fluorescence, absorbance, luminescence, and scintillation detection methods. The complexity and need for significant upfront expenditures often drive discovery stage organizations to outsource HTS activities.

Expanding beyond target identification

 HTS was initially used for lead identification and candidate optimization, and these two applications continue to remain prominent. It dramatically accelerates these activities, reducing the cost and time required for drug discovery and early-phase development. In addition, cost-effective, rapid screening of vast compound libraries, which can consist of many different types of small to large molecules, can find compounds that function via previously unknown mechanisms of action.

Today, high-throughput mass spectrometry solutions, DNA-encoded library technology (DEL), and advanced off-the-shelf, scalable software and automation tools are enabling the application of HTS to activities beyond target identification to include HT-ADME screening, tox studies, and the identification of optimum excipients and formulations.1 Use of artificial intelligence and machine learning, meanwhile, are facilitating in silico screening and the development of novel models.

Increased reliance on third-party HTS services

 HTS benefits cannot be attained without significant upfront investment in specialized equipment and expertise required to perform these experiments and analyze the data they generate. Reliance on contract research organizations (CROs) has, not surprisingly, increased as a result.

Many CROs have responded by adding HTS capabilities to their portfolios. They typically perform screens, assay development, miniaturization, automation, and validation and provide data storage and analysis, among other services.

It is estimated that the value of the global HTS market will reach nearly $37 billion by 2030, expanding at a compound annual growth rate of 7.82%.2 The services segment is expected to grow fastest, as is the drug discovery segment (based on application) and the CRO segment (based on end-user).

Selecting the ‘right’ HTS outsourcing partner

With more CROs establishing flexible HTS capabilities, even small, emerging biopharma companies now have access to this effective means for accelerating drug discovery. When outsourcing HTS projects, drug developers must select CROs with trained and experienced staff, state-of-the-art equipment and software, numerous and varied compound libraries, and insight into when medium to ultra-high-throughput solutions are appropriate.

However, technical capabilities should not be the only consideration. To achieve maximal outcomes in HTS projects, the HTS service provider should act as a true partner, serving as an extension of their clients. A commitment to open communication and transparency and the provision of results on time, in full, and at the highest level of quality are equally important attributes.

By choosing the right CRO to support drug discovery and development efforts leveraging HTS techniques, drug developers can increase their chances of identifying truly novel candidates, accelerate projects, lower development costs, and reduce time-to-market.

Syngene’s capability in HTS

Syngene allows for collaboration with third parties to access compound libraries for HTS. Our two strategic partners include Pivot Park Screening Center (The Netherlands) and Axcelead (Japan). We offer in-house HTS virtual screening and fragment-based screening services. We also have in-house capability for delivering high-purity and high-quality protein, reagent, and cell-line generation for HTS.

We assure quick turnaround time for assay development in multiple formats (biochemical, biophysical, and cell-based), including in HTS formats. Further, we have multiple liquid handlers and plate readers of different technologies to cater to different client requirements.

Being a global CRO/CDMO with 30 years of experience, we have expertise working with traditional drug targets (kinases, GPCRs), non-traditional (epigenetic modifiers, transcription, translational and post-translational targets), and novel modalities such as targeted-protein regulation with hetero-bifunctional molecules. Our skilled personnel and subject matter experts have deep knowledge of assay development and target biology. Hence, our scientists can undertake HTS data analytics to monitor assay performance, quality control, and ensure the appropriate selection of hits based on analysis.

References

  1. 20/15 Visioneers, “Trends in High Throughput Screening,” Bog, November 8, 2021, https://www.20visioneers15.com/post/throughput-screening
  2. Zion Market Research, “Global High-Throughput Screening Market Size is Projected to Grow to Be Worth USD 36.84 Billion by 2030, Expanding at a CAGR of 7.82%,” Press Release, January 23, 2023. https://www.globenewswire.com/en/news-release/2023/01/23/2593099/0/en/Global-High-Throughput-Screening-Market-Size-is-Projected-to-Grow-to-Be-Worth-USD-36-84-Billion-by-2030-Expanding-at-a-CAGR-of-7-82.html

The context

Nanofiltration is a highly effective viral clearance method in mAb manufacturing, primarily based on size exclusion. An essential part of validating the efficacy of the nanofiltration step are virus spiking studies to ensure the nanofiltration process can reliably remove viruses and meet regulatory requirements for product safety.

The requirement

A major pharmaceutical company was facing challenges in the nanofiltration step of their mAb production process. During virus spiking at 1% – 0.5% of the load volume, they encountered reduced filtration efficiency and flux decay. These issues affected the overall performance of the nanofiltration step, including increasing operational costs due to the need for frequent filter changes.

The pharma company decided to partner with Syngene to address these problems. Their goal was to improve the efficiency of the nanofiltration process in order to achieve viral clearance and reduce operational costs

Challenges posed by the nanofiltration process

  • Low protein concentration: Low protein concentration passing through the membrane resulting in reduced filtration efficiency.
  • Filter flux decay: High flux decay during protein processing affecting filter performance.
  • Low virus clearance efficiency: Need to ensure effective virus clearance while maintaining high throughput.
  • Compatibility issues: Adapting the spike percentage so that it was compatible with the filter, protein matrix, and virus concentration.

The solution

Our team approached the problem by focusing on optimizing the nanofiltration process. The solution involved a multi-step methodology.

  1. Optimization of viral load: Our Viral Testing team adjusted the viral load used in the spiking studies to a level that ensured high throughput while maintaining effective virus clearance. This was crucial for overcoming the limitations of low protein concentrations and improving filter performance.
  2. Adjustment of spike percentage: By decreasing the spike percentage in the suspension, we enhanced compatibility with the filter and protein matrix. This adjustment was critical for minimizing flux decay and maintaining effective virus clearance.
  3. Enhanced filter compatibility: We carefully matched the filter, protein matrix, and virus concentration to improve overall filtration efficiency. This included selecting filters with optimal characteristics for handling the adjusted spike percentage.
  4. Implementation and monitoring: We implemented the process in a controlled manner with continuous monitoring to ensure the flux decay remained low and the virus aggregates also remained controlled. Real-time data was used to make necessary adjustments and optimize performance.

Impact and results

After implementing our solution, the client successfully achieved the desired target throughput with flux decay levels at under 40%. The virus aggregates were effectively controlled, resulting in a more efficient and cost-effective nanofiltration process. The optimized process enabled the client to operate at higher flow rates, while maintaining effective virus clearance throughout the process. The new process also required fewer filter changes, significantly reducing overall costs.

Impact and results

The client is considering further collaboration with Syngene to explore additional optimizations and innovations in their manufacturing processes. Our expertise continues to be a key driver in advancing the client’s production capabilities and ensuring continued success in drug manufacturing.

Our ongoing capability and capacity expansion in biologics have established Syngene as one of the largest CRDMOs in India. As a trusted biologics partner, we have delivered 100 commercial batches in the last two years. Our track record of over 250 GMP batches, 150+ projects, and support for over 25 INDs across biologics modalities is a testament to our expertise

To know more about our Viral Testing and Clearance services, contact our experts

Your browser does not support this function.

To download, Please share your details

To view or email, Please share your details view

To download, Please share your details