CGT In the pharmaceutical manufacturing chain, there is a category of “invisible players” that has long been underestimated. Though they do not become part of the final drug product, they are involved throughout the entire process—from cell recovery to the formulation of the finished product—pervading every stage: these are excipients. Culture media provide nutrients to cells, while serum and… Platelet lysate They supply growth factors and provide buffer solutions to maintain a stable microenvironment; much like water, electricity, and gas, they underpin the entire production system. Yet, due to the long-standing absence of a unified national standard, they have become one of the most uncontrollable risk factors in the industry.

As China’s CGT industry accelerates, the number of clinical trials and the product pipeline are expanding rapidly, while the lack of standardized regulations is increasingly exposing critical issues: substantial batch-to-batch variability and pronounced quality fluctuations, which may even harbor significant biosafety risks such as viral contamination. Meanwhile, domestic CGT‑related ancillary materials have long relied on imports, leaving the supply chain vulnerable to bottlenecks at any time and introducing unpredictable uncertainties into R&D and manufacturing.

Recently, the State Administration for Market Regulation (National Standardization Management Committee) has officially approved and released Biotechnology: Auxiliary Materials Used in the Production of Cell Therapy and Gene Therapy Products The national standard (GB/T 47528-2026) will come into effect on November 1, 2026. As the first nationwide unified standard in China’s CGT field specifically addressing production‑supporting materials, its promulgation fills a regulatory gap in the industry and lays a solid foundation for the sector’s standardized development. This standard adopts ISO 20399:2022 as an equivalent international standard and, taking into account domestic industry realities, establishes comprehensive provisions covering the definition and classification of auxiliary materials, biosafety requirements, risk assessment, supplier management, traceability systems, and documentation standards.

Benchmarking against international standards: By adopting ISO 20399:2022 as equivalent, we ensure that the technical content aligns with global consensus, helping domestic enterprises’ products and services gain international recognition and reducing compliance barriers for raw material imports and exports as well as for overseas market access.

Emphasizing risk management: The standard does not aim to exhaustively enumerate specific indicators; instead, it establishes a risk‑based assessment and management system that requires both suppliers and users to implement end-to-end control over the sourcing, manufacturing, characteristics, and any changes associated with auxiliary materials, thereby ensuring the safety and consistent quality of the final product.

Supporting industrial upgrading: Standards will exert a systemic impact across the upstream raw-material supply chain, the midstream drug‑development phase, and the downstream clinical application stage. Upstream suppliers will be required to enhance their quality‑management practices in accordance with unified standards; midstream R&D firms, operating under more controllable material‑quality conditions, will be able to allocate greater resources to core technologies and to improving clinical efficacy; and downstream healthcare institutions can expect cell‑therapy products that are more consistent in quality and more reliable in safety, thereby advancing the standardization and large‑scale deployment of clinical applications.

The standard is clearly structured, offering comprehensive guidance from macro-level strategies to specific operational steps. Its core content can be summarized as follows:

Strategy and Responsibilities (Chapter 5): Clarifies the core principles of ancillary material management and delineates the respective responsibilities of suppliers and users, introducing key concepts such as “Animal-Derived Component-Free (ADCF)” to lay the groundwork for subsequent risk assessments.

Risk Assessment (Chapter 6): Emphasizes conducting a dedicated risk assessment for ancillary materials containing bio‑derived components, particularly those of human or animal origin. Risk probability and severity are determined through supplier audits, document reviews, and other methods—this approach also serves as the logical foundation for virus inactivation requirements.

Quality and Safety (Chapters 7 and 8): These chapters provide detailed specifications for the quality attributes of ancillary materials, including composition, purity, and stability, and, from the manufacturer’s perspective, set forth control requirements for the quality management system, manufacturing processes, and biosafety—particularly with respect to risks associated with animal- and human-derived components.

Performance and Change Management (Chapters 9 and 11): Require performance testing to ensure batch-to-batch consistency, and mandate stringent management measures for supplier‑initiated changes that could affect product quality—such as alterations in raw material sources or manufacturing processes—to enable users to promptly assess potential impacts.

The following section provides an in-depth analysis of the underlying rationale and specific requirements in the standard pertaining to “viral inactivation.”

(1) Source of Risk: Why Should Viruses Be a Concern for Auxiliary Materials?

Cell and gene therapy products are “living” drugs, and the final product typically cannot be subjected to… Terminal sterilization Therefore, any human‑ or animal‑derived ancillary materials used in the manufacturing process—such as serum, albumin, transferrin, and pancreatic enzymes—may serve as vectors for viral transmission. Historical incidents involving contamination of blood products with HIV, HCV, and other pathogens have provided stark lessons. Chapter 8 of the standard, “Manufacture of Ancillary Materials and Biosafety,” specifically addresses these risks by establishing source‑control requirements.

(II) Implementation Path: How to Achieve Virus Security?

The General Principles for Biological Products, Part III, in the 2020 edition of the Chinese Pharmacopoeia, explicitly outlines a comprehensive strategy of “source control + process control + product testing + process validation,” which is highly aligned with the risk‑assessment approach advocated by national standards. With respect to excipients used in human‑derived blood products, key measures include:

Source‑level control: Suppliers are required to provide certificates of pathogen screening for raw materials (e.g., HIV, HBV, HCV), constituting the first line of defense.

Virus Removal/Inactivation Process Validation: When source control cannot completely eliminate risks—such as the presence of a detection window period or unknown viruses—specific physical or chemical treatment steps must be employed, such as nanofiltration, solvent/detergent treatment, Pasteurization etc.) to remove or inactivate viruses. National standards require validation of the efficacy of such process steps, specifically through scale-down studies that employ surrogate viruses to demonstrate that the process achieves the intended virus‑removal performance.

(3) Core Challenge: Balancing “Inactivation” and “Function”

Viral inactivation processes, such as heat treatment, may compromise the active ingredients in culture supplements, including growth factors. Consequently, a key challenge is to ensure that, while achieving effective viral inactivation, the core functions of these supplements continue to meet the requirements of cell culture. This necessitates a risk‑based approach to select mild processes—such as nanofiltration—that exert minimal impact on bioactivity, coupled with rigorous testing of critical quality attributes.

In light of the requirements for “virus inactivation” stipulated in the national standard and the practical context of using human blood products as excipients, the underlying rationale is as follows: Viral inactivation is not optional; it is a fundamental requirement for ensuring product safety.

(1) Risk Qualification of Auxiliary Materials under the Standard

In CGT manufacturing, human-derived biological products—such as serum, albumin, and transferrin—are typically classified as high-risk ancillary materials. National standards require companies to implement controls based on risk levels, with the core principles including:

Source control: Suppliers are required to provide pathogen screening certificates; however, this measure cannot completely eliminate the risk of the window period or unknown pathogens.

Process validation: It is emphasized that the efficacy of virus inactivation and removal steps must be validated, and such validation must be conducted under conditions that simulate actual production. 
 

(II) The Critical Importance of Viral Inactivation

With regard to the requirement that “virus removal or inactivation should be performed,” its importance is primarily reflected in the following aspects:

Blocking the “vertical transmission” pathway of pathogens: Human blood‑derived products can serve as potential viral vectors (e.g., HIV, HBV, HCV, B19). Because cell therapy products are “living” therapeutics, any viruses introduced via ancillary materials will replicate as the cells expand, and the final product cannot undergo terminal sterilization; therefore, inactivation represents the sole barrier to prevent such contamination.

Addressing the risk of “cryptic” viruses: Even when donors pass screening, blood‑derived products may still contain virus particles or mycoplasma that have not been fully inactivated. Employing specific physical (such as nanofiltration) or chemical (such as solvent/detergent treatment) inactivation processes can effectively mitigate both known and potential unknown risks—capabilities that source‑level screening cannot replace.

Balancing “efficacy” and “functionality”: Standards employ the term “should” in their wording, which also implicitly acknowledges the technical challenges involved. Inactivation processes—such as irradiation or heat treatment—may compromise the activity of growth factors in serum. Consequently, rigorous process validation is essential: it must strike a balance between achieving “effective inactivation” and “preserving critical functions,” while demonstrating that the process does not introduce new toxic impurities.

Recently, Hycells is set to launch a GMP‑grade platelet lysate, with clearly traceable and compliant raw material sources, strengthening material safety management at the source. This product supports on‑site customer audits and fully meets the requirements for drug development and regulatory submissions, helping CGT projects advance efficiently and in compliance. In addition, we offer irradiated GMP‑grade platelet lysate; the irradiation process minimizes the risk of viral transmission, providing a robust safety safeguard for critical upstream materials in CGT applications. Stay tuned!

GB/T 47528-2026 is a principled, framework‑based guidance document that adopts ISO international standards in an equivalent manner. Compliance with this standard facilitates international mutual recognition and creates favorable conditions for product exports. Although GB/T is a voluntary standard, as the only national standard in China currently covering CGT ancillary materials and aligned with the ISO system, it often enjoys de facto authoritative status in drug registration and review processes.

This standard, by incorporating internationally recognized risk management principles, elevates the management of auxiliary materials to a strategic level and requires enterprises to establish systems that begin from… Supplier Audit A comprehensive system spanning from risk assessment to performance verification. With regard to virus inactivation, the core requirement is that, based on a risk assessment, high-risk excipients—including human‑derived blood products—must undergo validated virus removal or inactivation procedures, and the entire risk‑control process must be documented. The selection of specific manufacturing processes and the validation of associated methods must be conducted in accordance with the Chinese Pharmacopoeia and relevant technical guidelines. Overall, this requirement elevates risk control for ancillary materials from “relying on supplier declarations” to a level of “science-based control grounded in process validation,” thereby ensuring that the viral safety of the final product is aligned with the quality‑control system and providing clear guidance for the high‑quality development of China’s CGT industry.