Cell and Gene Therapy Traceability Solution  (CGTS)

I. Solution Overview

For cell and gene therapy (CGT), paper-based records undoubtedly add to the already complex processes and regulatory challenges of CGT. Hippocrates's Cell and Gene Therapy Traceability Solution(CGTS) is designed to optimize the development and manufacturing of complex cell therapy processes. It monitors the manufacturing processes and supply chains of cell therapy facilities through a unified digital platform, helping enterprises ensure compliance, mitigate risks, and improve efficiency. The CGTS solution consists of three components: Chain of Identity/Chain of Custody (COI/COC), Manufacturing Management, and Quality Suite, as detailed in the figure below:

II. Solution Features

(1) Feature 1: Traceability Information System

Based on international standards and best practices accumulated through years of experience in the Chinese domestic market, Hippocrates has launched a cell therapy traceability system that includes the Chain of Identity (COI) and Chain of Custody (COC). The implementation of COI and COC can effectively help you avoid the risk of misadministration of these specialized pharmaceuticals and prevent mix-ups and errors.

• Chain of Identity (COI): Refers to the permanent and transparent association between a donor’s unique identifier, their tissues or cells (raw materials), and the information of the resulting pharmaceutical products (e.g., manufacturing batch numbers) throughout the entire process from ordering, production, treatment to post-treatment monitoring.
• Chain of Custody (COC): Refers to the data related to who collected, processed, or performed operations on the product, the specific content of the operations, and the location/date/time of the operations, from the start of cell collection to administration.

(2) Feature 2: Digitalized Manufacturing

Electronic Batch Records (EBRs)

EBRs track every manufacturing step and improve production efficiency through automation. In addition, digital EBRs enhance compliance with Good Manufacturing Practice (GMP), improve product safety, and better meet regulatory requirements for cell and gene therapy products.

Manufacturing Management

Our manufacturing management system ensures that personnel perform correct operations and maintain accurate records, while reducing the time spent on record-filling and record management to improve production efficiency. Moreover, through the system’s recording and management of production records, equipment information, and environmental data, automation of the production process is achieved.

Warehouse Management

The barcode and Internet of Things (IoT)-based warehouse management system supports quality status management, batch/lot number management, and inbound/outbound management of pharmaceuticals and raw materials. Combined with electronic supervision code management, it effectively prevents mix-ups and errors in logistics, warehousing, and pharmaceuticals.

Equipment Management

Dynamically connected instruments and equipment enable real-time acquisition of equipment status and sensor readings (e.g., usage status and conditions such as temperature, pressure, and humidity). This avoids quality issues caused by abnormal equipment conditions and allows for preventive maintenance of equipment failures. Meanwhile, this data also provides rich support for process characterization and effective root cause analysis, helping to reduce process development cycle time and costs.

(3) Feature 3: Quality Management

Quality management includes document management, training management, as well as deviation management, Corrective and Preventive Actions (CAPA) management, and release management. Through digital methods, it ensures the correct implementation of Standard Operating Procedures (SOPs) and provides timely training for relevant employees.

The Quality Suite helps enterprises achieve record compliance and data integrity, providing strong support for enterprises undergoing data integrity inspections by regulatory authorities such as the National Medical Products Administration (NMPA), U.S. Food and Drug Administration (FDA), and European Medicines Agency (EMA).

Additionally, we provide virtual data rooms (VDRs) and electronic signatures:

• Virtual Data Rooms (VDRs): Meet users’ needs for online sharing of external documents while complying with regulatory and compliance requirements.
• Electronic Signatures: Facilitate users to sign compliance documents. This application has been widely adopted by well-known pharmaceutical enterprises and national drug research institutions, enabling multi-party signing among global partners and passing overseas audits.

III. Solution Value

The administration method of cell therapy products differs from that of traditional pharmaceuticals. For example, cell therapy requires cell extraction, isolation, modification, cultivation, and subsequent infusion, involving complex processes and higher requirements for quality systems.

Cell therapy products have extremely high environmental requirements. As living cell products, their production is inherently variable—especially for autologous cell therapy products, where each batch is unique to an individual patient. Maintaining records manually or on paper is labor-intensive, error-prone, and incurs high storage costs. For subsequent Quality Assurance (QA) and Quality Control (QC) processes, paper-based records significantly increase the complexity, cost, and scalability challenges of the production process.

Hippocrates’s digital Cell and Gene Therapy Traceability Solution helps enterprises better meet GMP regulatory requirements, optimize production processes, and comprehensively improve production management capabilities. The specific benefits are as follows:

• End-to-End Sample Traceability: The digital solution provides digital traceability services for the entire cold chain transportation of samples, from collection at hospitals, preparation at production bases, to infusion back at hospitals. This helps cell therapy enterprises establish a standardized product management system and ensure the quality and safety of cell therapy products.
• Digital Management of Production Processes: The digital solution manages the entire production process of cell therapy products, realizing digital and compliant control over all links, including donor material receipt, production and testing, and release. This reduces the time and effort required for material transfer and batch release, and significantly lowers the risk of human error.
• Quality Control and Compliance: The digital system supports the analysis of production process data, contributing to the continuous optimization of production processes and the improvement of production management capabilities. Meanwhile, full-process data traceability is maintained throughout production, ensuring data integrity and reliability, and meeting regulatory requirements in major regulated markets.
• Data Management and Analysis: The digital solution provides centralized data management, including sample location tracking, sample temperature tracking, data storage and audit trails, and data analysis and management. This optimizes R&D processes and improves the efficiency of production batch management.
• Scientific Data Platform: Through data analysis functions, centralized data storage and analysis are realized, simplifying workflows, providing a single source of truth, and supporting platform expansion for the integration of advanced equipment.
• Risk Control and Regulatory Burden Reduction: The digital process traceability system enables real-time, online monitoring throughout the entire lifecycle, reducing regulatory burdens, lowering the risk of contamination of operation records during preparation, and ensuring the accuracy, authenticity, real-time nature, and immutability of operation records.
• Enhanced Decision Support: Business intelligence functions provide in-depth insights, helping management make more informed decisions, optimize resource allocation, and drive process improvements.
• Promotion of Innovation and R&D: Through detailed data analysis and report generation, the digital solution supports R&D teams in better understanding process performance and accelerating the development and market launch of new therapies.
• Supply Chain Optimization: The digital solution helps optimize supply chain management, enabling tracking of cell preparation, transportation, and distribution, and improving supply chain transparency and efficiency.
• Patient Safety and Efficacy Tracking: Through a real-time intelligent platform, the digital solution supports the optimization of clinical treatment plans and the evaluation of efficacy tracking, ensuring patient safety and treatment outcomes.
  
• In summary, the digital cell therapy solution not only improves the operational efficiency and product quality of cell therapy companies but also enhances control over complex production processes, meets regulatory requirements, and helps more high-quality cell therapy products accelerate their market launch.

IV. Application Scenarios

(1) Application Scenarios

Hippocrates’s cell therapy solution offers functional modules suitable for different stages of enterprise development. Enterprises can select a solution that aligns with their development stage through modular configuration to initiate digitalization early, ensure pharmaceutical compliance with regulatory requirements, and accelerate product market launch.

V. Technical Information

(1) Overall Architecture

Hippocrates’s CGTS is built on the Aotai Platform. Aotai is a digital platform jointly developed by Xingdi’s industry experts and IT specialists, with "Quality and Compliance Expert" as its management philosophy and market positioning. It helps enterprises improve quality and compliance standards, meet industry regulations, enhance management capabilities, and accelerate the market launch of more safe, effective, and high-quality products.

(2) Application Architecture

Applications on the Aotai Platform can be customized to meet an enterprise’s quality system requirements. The built-in configuration tools already include multiple functions of quality solutions, eliminating the need for customization or programming to implement certain special processes. Trained personnel can quickly customize forms, decision trees, and dashboards to meet specific business needs.

(3) Business Architecture

Hippocrates’s cell therapy solution realizes business planning and digital functions through four phases, greatly helping enterprises free themselves from cumbersome manufacturing and supply chain processes, allowing them to focus solely on improving the efficacy and safety of cell and gene therapy drugs.

(4) Technical Architecture

Quality and compliance processes are built on commonly used master data, which only needs to be set up once and can be used across different modules of the entire system. New processes automatically reference these data dictionaries, ensuring that enterprises continue to use a "common language" as their quality system evolves.

Features of the technical architecture include:

• The organizational hierarchy configuration is fully consistent with the company’s structure.
• It supports data aggregation or further viewing of detailed data at any level.
• It allows restricting access to different organizational nodes in complex hierarchies.

(5) Data Architecture

The superior design of the Aotai Platform ensures that users can quickly access large volumes of records and data, thereby improving work efficiency.

• "Intelligent loading" of forms minimizes loading time.
• Frequently used data is cached to maximize network bandwidth utilization.
• Data is stored in an efficient manner, and the distributed architecture is optimized for server expansion.
  
• Access efficiency is greatly improved through standard APIs, including:
  

• Automated email notifications, SMS notifications, and dashboard alerts are integrated into workflows, significantly reducing the risk of missing tasks or approvals.
• The background task submission and management mode allows users to perform other tasks simultaneously.
• A standard middleware layer is provided to support integration with any third-party system, facilitating data exchange between the Aotai Platform and other application systems.