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In the era of precision medicine, gene and cell therapies are advancing at an unprecedented pace. Viral vectors serve as core delivery tools for gene therapy, widely used in the preparation of therapeutic products, including T cells, stem cells, and other cellular therapies. However, during vector production and application processes, replication-competent viruses (RCVs) may emerge, including RCL, RCR, RCA, rcAAV, and others. Once these contaminate the final product, they pose serious safety risks, including gene insertional mutagenesis, potential tumorigenicity, and re-infection.
To mitigate RCV risks, regulatory agencies have designated RCV testing as a quality control priority, mandating comprehensive testing requirements throughout the product lifecycle. Establishing systematic, efficient, and compliant RCV testing systems has become essential for the healthy development of gene and cell therapy industries.
Creative Biogene leverages P2/P3-level biosafety laboratory platforms and years of project experience to establish standardized testing systems covering four major types of replication-competent viruses. Our services comply with global regulatory requirements from NMPA, FDA, EMA, and other agencies, covering the entire process from R&D to commercialization, helping clients achieve safe product approval.
Regulatory agencies have consistent requirements for RCV control stages and testing protocols. RCV testing is conducted at various stages of product manufacturing and in subsequent monitoring of patients receiving viral vector-based gene therapy products to rule out RCV presence.
Part 01
Research & Development Stage
Establish safety screening to identify potential recombination risks in vector systems, reducing downstream development risks
Part 03
Clinical Application/Registration Stage
Provide internationally standardized, compliant testing reports and method validation packages to accelerate product approval
Part 02
GMP Production Stage
Complete UPB/EOPC/final product batch testing, supporting release testing, and quality documentation
Part 04
Clinical Sample Follow-up
Monitor potential RCV activation or amplification risks in patients, enhancing safety assurance
Our testing systems are designed and implemented in strict accordance with the following international guidance principles:
| Regulatory Agency | Regulation Name | Publication Date | Scope/Description |
| FDA | Guidance for Industry: Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs) | January 2020 | Provides CMC-related submission content guidance |
| FDA | Guidance for Industry: Testing of Retroviral Vector-Based Human Gene Therapy Products for Replication Competent Retrovirus During Product Manufacture and Patient Follow-up | January 2020 | Specifically for RCR testing and follow-up requirements |
| EMA | Guideline on quality, non-clinical and clinical aspects of medicinal products containing genetically modified cells | November 2020 | Applicable to therapeutic products containing genetically modified cells (e.g., CAR-T) |
| EMA | Guideline on the quality, non-clinical and clinical aspects of gene therapy medicinal products | November 2020 | For all gene therapy medicinal products' quality and clinical design |
One-Stop Service
From process development to GMP production, from product release to clinical follow-up, covering all critical milestones
Global Regulatory Compliance
Testing protocols strictly follow international regulatory standards including NMPA, FDA, and EMA guidelines
Dual Platform Support
Equipped with both P2 and P3 laboratories to meet different viral system testing requirements
Complete Method Validation
Provides comprehensive validation reports directly supporting regulatory submissions
Extensive Experience
Successfully served 100+ gene therapy projects covering popular areas including CAR-T, AAV, iPSC, and others
Whether you're in early-stage development or preparing for IND submission, RCV testing is a crucial component you cannot overlook. Creative Biogene is committed to providing solid safety assurance for every innovative therapy. Please contact our project specialists anytime to obtain personalized testing solutions and quotes.
Q1: Is testing required for every batch?
A1: Depends on the development stage. UPB, EOPC, and final products are recommended for batch-by-batch testing; MCB/WCB typically require one-time testing only.
Q2: Is P3 laboratory mandatory for RCL testing?
A2: P3 laboratory is required only when using HIV as positive control. We offer both P2/P3 dual-channel solutions for selection.
Q3: How to choose testing methods?
A3: We recommend sensitive cell assays for confirmation, RT-qPCR for rapid screening, with combination use balancing efficiency and accuracy.
Q4: Can you provide validation reports for regulatory submission?
A4: Yes, we provide complete validation packages according to pharmacopoeia and ICH standards, directly supporting NMPA/FDA/EMA and other submission requirements.
Q5: Can RCL release testing be exempted?
A5: Under specific conditions (safe vector design, 30 batches of negative historical data, no additional risks), exemption may be applied for, but periodic review is still required.
Q6: Can digital PCR replace infection assays?
A6: Not completely yet. Digital PCR is suitable for process monitoring; release testing still requires cell infection assay confirmation.
Q7: How to determine testing sample size?
A7: Based on statistical principles, commonly using the formula: Sample size = 1/Detection limit × ln(1-Confidence level)/ln(1-Contamination rate) We can provide scientific recommendations.
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