BoRuiCe Bio and Alioth Co-host Antibody Drug Enterprise Tour – Yantai Station: Advancing Biopharmaceutical Quality and Safety

Yu Lingju | Senior Technical Manager, ALIOTH

Key Takeaways:Sources of HCP and HCD and their potential hazards to the quality of biological products, including immunogenic responses, exacerbated side effects, and product stability issues; regulations impose strict limits on such impurities. During depth filtration, how to effectively reduce HCP and HCD levels by adjusting operating parameters (such as appropriate loading capacity, flow rate, filtration pressure, and buffer conditions), optimizing cell viability, and employing filters with superior performance, such as the various models provided by ALIOTH.

Pre-removal of DNA can significantly reduce the difficulty of HCP clearance. Teacher Yu demonstrated the superiority of domestically produced filters in reducing turbidity, increasing binding capacity, and maintaining protein recovery rates through specific case studies, while also helping enterprises reduce costs and successfully achieve the localization of commercial products. The optimization direction for HCP and HCD removal strategies via depth filtration includes selecting appropriate filters and optimizing process parameters to achieve efficient impurity removal.

▲Yu Lingju | ALIOTH Senior Technical Manager

Hu Xiao | Director of Operations, BRC BIOTECHNOLOGY

▲Hu Xiao | BRC BIOTECHNOLOGY, Operations Director

Liu Qiulin | ALIOTH

Regulatory Advisor and Head of Filter Product Development

Key Takeaways:Latest Regulatory Developments in Sterile Filtration, the Significance of Updates to the EU GMP Annexes, and a Forward-Looking Perspective on China’s 2018 Guidelines. Regarding PUPSIT (Pre-Use Post-Sterilization Integrity Test), although requirements vary across countries, the European Union stands out for its stringency. Despite operational challenges in certain scenarios, regulations generally mandate PUPSIT, while permitting exceptions under specific circumstances. In practice, most companies, particularly Chinese firms, tend to comply with this requirement to avoid the complexities associated with regulatory scrutiny.

Regarding Redundant Filtration and Its Integrity Testing: While regulations do not mandate redundant filtration, most companies opt to implement it in practice as a precautionary measure to mitigate economic risks.

Regarding Sterilizing-Grade Filtration ValidationWhen process conditions remain unchanged, frequent re-validation of sterilizing-grade filtration is not required. However, any changes—such as those involving manufacturing facilities, batch sizes, suppliers, or sterilization conditions—necessitate a re-evaluation. For instance, when facility expansion leads to a change in filter size, validation must be considered even if the scale-up is proportional. Particular attention should be paid to the increased level of extractables resulting from the larger filter surface area, and an assessment must be conducted to determine whether these levels remain within patient safety thresholds.

Regarding the requirements for filters in Contamination Control Strategies (CCS), it is emphasized that the criticality of filters must be assessed from the initial design phase, taking into account scale-up selection, supplier management, sterilization validation, as well as Standard Operating Procedures (SOPs) and deviation records during use. Online integrity testing has emerged as a new trend, offering greater compliance compared to traditional offline testing.

▲Liu Qiulin | Regulatory Consultant and Head of Filter Product Development at ALIOTH

Wang Xin | BRC BIOTECHNOLOGY Chief Strategy Officer CSO

Key Takeaways:Different biomaterials and biological products are classified into various biosafety levels based on their hazard potential. Practical cases demonstrate that even in highly clean production environments, operators can be the primary source of contamination, underscoring the complexity and necessity of biosafety control.

In terms of regulatory compliance, the system systematically reviews domestic and international biopharmaceutical regulatory frameworks, with a particular focus on the guidelines from China, the United States, and Europe, such as the U.S. FDA’s Guidance documents and the European EMA’s guidance materials, while analyzing the subtle differences among these national or regional guidelines.

Three Steps of Risk Management: Risk Identification, Risk Control, and Risk Review. Taking the use of bovine serum as an example, this article discusses how to identify and control the risk of bovine-origin viruses through rational experimental design. It emphasizes the importance of phase-appropriate GMP and CMC throughout the entire lifecycle of drug development—from preclinical stages and clinical trials to commercialization—and details the specific implementation of these concepts at different stages. For instance, the non-clinical stage focuses on raw material safety verification; after IND approval, attention shifts to process stability and consistency of product quality; and near or post-launch, the focus is on ensuring process determinism and product quality reliability.

▲Wang Xin | BRC BIOTECHNOLOGY Chief Strategy Officer (CSO)

Zhao Shikun | BRC BIOTECHNOLOGY Senior Technical Compliance Manager

Key Takeaways:Detailed Procedures for the Characterization of Rodent Cell Lines, Compliant with Global Regulatory Standards Including Specific Requirements from the WHO, ICH, China, the EU, and the US.

Sterility testing of cells, including screening for bacteria, fungi, mycoplasma, and mycobacteria. Bacterial and fungal detection employs both the direct inoculation method and the membrane filtration method; mycoplasma is detected using a combination of culture methods and indicator cell assays; and mycobacteria are identified through culture methods. To meet the demand for rapid testing, BRC BIOTECHNOLOGY has developed a rapid biological assay based on respiratory signal analysis. Taking into account regulatory differences across countries, such as the specific requirements of the Chinese Pharmacopoeia, the assay integrates various standards to ensure compliance.

In viral factor testing, the detection process for retroviruses is outlined, including transmission electron microscopy (TEM) observation of viral particles, reverse transcriptase activity assays, and indicator cell methods, as well as specific handling for endogenous retroviruses. For pathogen testing in specific species, animal antibody generation experiments are employed, or a shift is made toward faster next-generation sequencing (NGS) technologies to reduce animal testing, in alignment with EU initiatives.

Genetic Stability Study ReportBLAPrerequisites for Filing: Assess monoclonality and the presence of genomic structural variations by comparing the genomes of cell bank samples and post-production samples to ensure the stability of antibody expression.

▲Zhao Shikun | BRC BIOTECHNOLOGY Senior Technical Compliance Manager

After the event, to gauge its effectiveness and capture attendee feedback, we conducted random on-site interviews with two participants to gain an in-depth understanding of the event from their perspectives: