China CDE Launches Consultations on 3 Draft Guidelines: Oligonucleotide Drugs, Advanced Therapies, and Post-Approval Changes to Biologics

On 8 and 11 September 2025, China’s Center for Drug Evaluation (CDE) launched three public consultations on draft guidelines that could reshape regulatory pathways for oligonucleotide drugs, advanced therapies, and biologics.

The consultations close on 8 October 2025 for oligonucleotide drugs and advanced therapies, and on 11 October 2025 for biologics. These drafts reflect China’s push to modernize its regulatory framework and align with global standards.

To explore a summary of each draft, click to scroll directly to:

The drafts strengthen scientific oversight and aim to give developers clearer, more predictable pathways for bringing innovative medicines to patients in China.

Draft Guidelines for Chemically Synthesised Oligonucleotide Drugs

Oligonucleotide-based medicines such as ASOs, siRNAs, and aptamers represent a fast-evolving frontier of advanced therapies. To support their evaluation, the CDE released the draft “Technical Guidelines for Pharmaceutical Research on Chemically Synthesised Oligonucleotide Drugs (Innovative Drugs)” on 8 September 2025.

The draft sets out detailed requirements for:

Active pharmaceutical ingredients
Finished products
Stability studies
Comparability assessments
Quality research, process control, material management, structural characterisation, and biological activity studies

As more companies explore these modalities, clear regulatory guidance is essential to reduce development risk and accelerate approvals.

Impurity Categories

Given the structural complexity of oligonucleotides, the draft places strong emphasis on impurity control, defining four categories, each with distinct safety evaluation thresholds:

Category I: structurally identical to major metabolites (e.g. truncated terminal nucleotides), no evaluation required even if above limits
Category II: natural nucleic acid structures (e.g. phosphodiester replacing phosphorothioate), no evaluation required even if above limits
Category III: sequence variants (e.g. n-1/n+1 internal deletions or base substitutions), attribution study required, safety evaluation if above 1.5%
Category IV: non-natural structural elements (e.g. base-free impurities), process optimisation or safety evaluation required if above 1.5%

The guidelines also encourage applicants to adopt risk management and lifecycle approaches to both pharmaceutical research and quality control, including special considerations for delivery systems such as lipid nanoparticles.

Regulatory Significance

This is China’s first detailed technical framework for chemically synthesised oligonucleotide drugs. It provides a systematic pathway for R&D and regulatory submissions.

Next Steps for Oligonucleotide Developers

Oligonucleotide developers are encouraged to:

Benchmark current R&D and quality systems against the draft standards
Review impurity profiling and control strategies to ensure alignment with the four defined categories
Strengthen lifecycle management processes, particularly for complex formulations using delivery systems
Engage with the CDE during the consultation period to help shape a practical and innovation-friendly framework

Creating Channels for Advanced Therapy Product Communications

For cutting-edge modalities like cell and gene therapies, regulatory dialogue is critical to development timelines. On 8 September 2025 the CDE also released the draft “Working Procedures for Type I Meetings on Advanced Therapy Product Communications.” This draft offers a clearer pathway for multinational developers navigating China’s regulatory landscape for ATMPs.

Definition and Purpose

Type I meetings are defined as priority communication channels for addressing major safety concerns, critical technical issues, or regulatory pathway questions, particularly during key stages such as pivotal trials or pre-market applications.

Application Requirements

To request a Type I meeting, applicants must prepare and submit a complete package including the following elements:

Agenda items
Background information
A list of questions
Preliminary study data

The CDE, in turn, commits to timely feedback and structured management of the meetings, with clear and scientifically justified conclusions to guide subsequent R&D.

Regulatory Significance

Inspired by international practice such as the FDA’s Type A meetings, the CDE’s draft procedures are tailored to China’s regulatory and R&D environment, offering more structured feedback mechanisms. They aim to reduce uncertainty, accelerate development timelines, and improve registration efficiency, offering multinational companies a clear and structured communication pathway for cell and gene therapy development in China.

Next Steps for Advanced Therapy Developers

To make the most of the new communication channels and reduce regulatory uncertainty, advanced therapy developers are recommended to:

Plan Type I meetings into development planning at key milestones
Prepare comprehensive data packages to support discussion and decision-making
Use early dialogue with the CDE to clarify expectations and minimise risk
Use this mechanism strategically to accelerate clinical milestones and reduce regulatory delays

Draft Guidelines for Post-Approval Change Management of Biologics

Innovation continues after approval. To guide this process, the CDE issued the draft “Technical Guidelines for Drafting and Evaluating Post-Approval Pharmaceutical Change Management Plans for Therapeutic Biologics” on 11 September 2025. As companies expand manufacturing or adopt new technologies, clear change management guidance is essential to maintain compliance.

Classification Framework

The draft introduces a framework for categorising post-market changes as major, moderate, or minor, with each level linked to specific submission pathways that define what companies must file with the CDE, for example a supplementary application, a filing, or an annual report.

Notably, major changes — such as new manufacturing sites or critical process adjustments — require extensive comparability and stability data, and in some cases clinical data.

ClassificationExamples of ChangesSubmission PathwayMajor (重大变更)Change in drug substance expression vector;Change in drug product manufacturing siteSupplemental applicationModerate (中等变更)Preparation of new master seed lot for drug substance;
Change in excipient supplier for drug product;
Adjustment of non-critical parameters in drug substance purification processFilingMinor (微小变更)Change in cryoprotectant for drug substance seed (virus) / cell bank;
Change in drug product packaging size;
Tightening of drug substance process control parametersMostly via annual report;
Some via filing

Technical Requirements

Applicants must use a risk-based, lifecycle approach to evaluate the impact of changes on product quality, supported by comprehensive data and validation materials. Change management plans should include:

The scientific and regulatory justification for the change
Study content and results
Quality control strategies
Stability assessment plans

Because biologics are complex and sensitive, the guidelines stress careful evaluation of potential impacts on physicochemical properties, biological activity, impurity profiles, and immunogenicity. For example, changes to cell culture or purification steps require multi-level comparability studies.

Submission dossiers must follow CTD format, with change-related data clearly identified to facilitate regulatory review.

Regulatory Significance

The framework is consistent with international practices, such as ICH Q12, while reflecting the needs of China’s biopharmaceutical industry. It provides a practical pathway for companies to optimise manufacturing processes and expand production capacity without compromising product quality.

Next Steps for Biopharmaceutical Manufacturers

To manage change efficiently and stay compliant with evolving expectations, manufacturers are advised to:

Align internal change management systems with the draft’s classification of major, moderate, and minor changes.
Develop the capability to conduct comparability studies and generate supporting data.
Engage with the CDE before implementing major changes to clarify requirements early.
Ensure dossiers are CTD-compliant and clearly highlight change-specific data to streamline CDE review.

The Bottom Line

The three draft documents together signal a decisive shift toward lifecycle-based oversight in China, enhancing clarity and predictability for innovative drug development.

Key highlights include:

Oligonucleotide draft guidelines: Establish China’s first detailed framework for R&D and registration of chemically synthesised oligonucleotide drugs
Type I meeting procedures: Create structured communication mechanism to reduce regulatory uncertainty and accelerate development timelines for advanced therapies
Post-approval biologics guidelines: Provide a clear pathway for managing post-approval changes without compromising product quality or compliance

For the industry, this means stronger regulatory alignment, improved engagement with authorities, and more efficient lifecycle management.

Cisema encourages stakeholders to participate in the consultation process and align their development and regulatory strategies with these evolving standards. With more than 20 years of experience and a proven record of supporting life sciences companies in China, Cisema is well-positioned to guide you through these changes.

Get in touch with Cisema today to discuss what these draft guidelines mean for your products.