NGS in GMP Manufacturing: Reducing Risk, Increasing Return
November 6, 2025
Christoph Bredack
The formal inclusion of next-generation sequencing (NGS) in the ICH Q5A(R2) guideline published for the first time in November 20231, marked a major milestone for the biopharmaceutical industry. For the first time, an international regulatory framework officially recognized NGS as a method for detecting adventitious viruses in the manufacturing of biotechnological products derived from human or animal cell lines. This update reflects a broader shift in how regulators view molecular methods and their role in ensuring product safety.
This evolution builds on earlier regulatory efforts. In 2010, FDA guidance on the characterization of cell substrates introduced flexibility for using alternative virus detection methods with broad capabilities and a “fit-for-purpose” approach, laying the groundwork for technologies like NGS2.
Further momentum came from WHO guidance, which explicitly supported high-throughput sequencing (HTS) as an alternative to in vivo and in vitro virus testing, provided it meets validation and sensitivity requirements3.
Building on this foundation, both the EMA and FDA have now adopted the Q5A(R2), emphasizing that NGS must be implemented with the same rigor expected of any GMP-compliant method. This includes full validation if it is intended to replace a “traditional” assay, such as in vivo methods, as well as ensuring reproducibility and adherence to GxP standards. To support industry adoption, regulators have released training materials that clarify key aspects of the guideline, including a non-exhaustive list of examples illustrating how to apply the guideline and highlight the flexibility it provides regarding viral safety assessments for other potential modalities.
The significance of NGS is further reinforced by the European Pharmacopoeia. While chapters 2.6.16 and 5.2.3 recognize molecular and nucleic acid-based methods in vaccine and cell substrate testing4,5, the recent general chapter 2.6.41 is the first to offer detailed guidance on NGS-based assays for detecting adventitious viruses, from wet lab implementation and bioinformatics to validation6. Together, these guidelines reflect a growing regulatory consensus: NGS is becoming an essential component of modern, risk-based strategies in biologics manufacturing.
NGS: What It Takes to Meet GMP Standards
Integrating NGS into GMP environments demands technical expertise, operational maturity, reliable software solutions, and infrastructure. These components are essential for managing complex workflows and large data volumes, which require coordination across multiple functions. Every step, from sample preparation to sequencing, bioinformatics, and data management, must be validated and fully traceable. Data must be handled to ensure security, auditability, and regulatory compliance.
While introducing NGS for virus safety presents challenges, the benefits and return on investment (ROI) are significant. In-house NGS offers real-time insights into potential contamination and guides follow-up strategies. It supports rapid decision-making and enhances control over critical quality attributes, not just virus safety, but also aspects like construct identity and the integrity of vectors such as AAV.
Successful implementation of NGS under GMP relies on effective collaboration among teams that often operate with different technical languages and priorities. Wet lab scientists, bioinformaticians, quality assurance, manufacturing, and IT personnel need to work together so that NGS data is both scientifically accurate and operationally actionable, while remaining compliant.
Many organizations recognize that, although the scientific foundation for NGS is well-established, supporting systems and processes are not yet fully in place. Bridging this gap is essential to making NGS a reliable and scalable element of manufacturing.
Building Infrastructure for Compliance and Scale
Genedata Selector® exemplifies how companies are enabling in-house NGS for manufacturing and Chemistry, Manufacturing, and Controls (CMC). Purpose-built for GMP environments, it supports validated QC assays for virus safety and product characterization, ensuring full traceability and data integrity.
By centralizing NGS workflows on a single platform, organizations can significantly reduce assay time, lower sample costs, and streamline regulatory reporting. A unified, compliant platform also simplifies assay validation across modalities, enabling faster deployment of new tests and more consistent quality oversight throughout development and manufacturing.
Why In-House Means Smarter Spend
Outsourcing NGS can be a practical choice for organizations with limited upfront capital, as it avoids the investment in expensive sequencing equipment and infrastructure. However, as sample volume and throughput grow, the cumulative costs of outsourcing rise sharply, making it less financially sustainable for larger-scale operations.
In contrast, bringing NGS in-house requires an initial investment but significantly lowers the cost per sample over time. This shift improves long-term cost effectiveness and delivers a higher ROI for high-volume projects. Ultimately, NGS in-house offers better scalability and becomes the more economical and strategic choice as demand scales.
NGS: A Versatile and Compliant Solution for Diverse Drug Modalities
Throughout the R&D and manufacturing lifecycle, NGS plays a critical role in supporting a wide range of innovative drug modalities, including antibodies, proteins and peptides, cell and gene therapies, nucleic acids, and oncolytic viruses. Although these modalities differ biologically, they follow similar development steps where NGS can be effectively applied, from vector design to drug stability studies. In the early development phases, workflows often run in parallel to accelerate progress. To keep pace, NGS assays must be scalable and aligned with regulatory requirements.
Genedata Selector enables biopharmaceutical teams to manage and optimize NGS workflows in regulated environments as of all stages of development, supporting companies in their compliance journey, from development of assays and standards to preparing for IND submission.
A Strategic Shift for CMC and Manufacturing
NGS is increasingly adopted as a core capability in CMC and manufacturing, offering a robust, scalable approach to quality control. Its ability to generate high-resolution data, support assay standardization, and accelerate decision-making is driving industry interest.
Many biopharmaceutical companies are integrating NGS into CMC QC, motivated by its strong ROI, reliable performance, and potential to shorten product release timelines. In addition, in-house implementation offers greater control over data and workflows, which is crucial to meet evolving regulatory expectations, but also for achieving the scalability and flexibility needed to support dynamic business needs.
As NGS becomes more embedded in GMP operations, organizations investing in the right infrastructure and expertise will be well-positioned to improve quality, reduce risks, and foster innovation across the product lifecycle.
Despite the progress, open questions remain and need to be addressed. For example, how can the application of NGS be extended to also replace assays like in vitro and other targeted virus safety read-outs? How is the ultra-sensitivity of NGS affected in various matrices? What needs to be validated, or when is an assay qualification sufficient? Partnership with Genedata Selector helps you to solve this.
References
- ICH. International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use ICH: Q5A Guideline on Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin: Training Materials Module 0-3 0-3; 2025.
- FDA; CBER. Guidance for Industry- Characterization and Qualification of Cell Substrates and Other Biological Materials Used in the Production of Viral Vaccines for Infectious Disease Indications; 2010. www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.
- World Health Organization. WHO Expert Committee on Biological Standardization; 2013. www.who.int/bookorders.
- European Pharmacopoeia. 2.6.16: Tests for Extraneous Agents in Viral Vaccines for Human Use.
- European Pharmacopoeia. 5.2.3: Cell Substrates for the Production of Vaccines for Human Use.
- European Pharmacopoeia. 2.6.41. High-Throughput Sequencing for the Detection of Viral Extraneous Agents-Draft.