NMPA Issues Guidance on Subject Selection for Anti-Tumor Drug BE and PK Studies

In March 2026, China’s Center for Drug Evaluation (CDE), issued “Notice No. 22 of 2026” announcing the release of the guidance titled “Considerations for Population Selection of Subjects for Anti-tumor Drug Bioequivalence and Pharmacokinetic Comparison Studies,” which took effect immediately upon publication.

NMPA Clarifies Subject Selection Principles for Anti-Tumor Drug Studies

The newly issued guidance provides a structured framework for selecting appropriate study populations in bioequivalence (BE) and pharmacokinetic (PK) comparison studies for anti-tumor drugs. These studies are critical for both generic drug development and biosimilar evaluation, where PK endpoints are used to demonstrate equivalence or similarity to reference products. The guidance may also be referenced for other clinical pharmacology studies involving anti-tumor drugs.

The CDE emphasizes that anti-tumor drugs present unique safety considerations compared to non-oncology products. As a result, subject selection must balance scientific validity, safety, and ethical requirements. Sponsors must determine whether healthy volunteers or patients are more appropriate based on risk exposure and the ability to detect meaningful PK differences.

Risk-Based Approach Drives Population Selection

The guidance emphasizes a risk–based approach integrating safety, ethics and scientific considerations to subject selection, requiring a comprehensive assessment of drug-specific factors, available data, and study design.

Mechanism of Action Influences Risk Profile

Different classes of anti-tumor drugs carry varying safety risks, which directly impact subject eligibility:

• Cytotoxic chemotherapy agents are generally recommended for study in patient populations due to their non-selective toxicity and potential harm to healthy subjects.
• Small molecule targeted therapies and certain monoclonal antibodies may be studied in healthy volunteers when supported by sufficient nonclinical and clinical data demonstrating acceptable safety.
• Immune checkpoint inhibitors and radiopharmaceuticals are typically recommended for patient-based studies due to the risk of significant or unpredictable adverse effects.

The guidance highlights that even targeted therapies may pose risks depending on their biological targets, such as immune system modulation or effects on normal tissue.

Existing Clinical and Nonclinical Data Must Be Considered

Subject selection should be based on available evidence, including:

• Clinical data on pharmacokinetics, safety, and exposure–response data
• Differences in pharmacokinetics or target expression between healthy subjects and patients
• Immunogenicity risks (for biologics)
• Nonclinical toxicity data (general, reproductive, genetic, immunotoxicity)

If data are limited or inconclusive, a conservative approach — typically patient studies — or regulatory consultation is recommended.

Dosing Regimens Affect Safety Thresholds

Dose and exposure are central to the decision. F Higher exposure levels or prolonged pharmacodynamic effects can increase risk in healthy subjects.

In such situations, studies should generally be conducted in patients to ensure appropriate risk control and ethical acceptability.

Distinct Requirements for Healthy Volunteers and Patients

The guidance distinguishes between requirements for healthy volunteer and patient studies, emphasizing that study design should be adapted to the selected population.

Considerations for Healthy Volunteer Studies

When healthy subjects are used:

• Dose selection must be justified and within an acceptable safety range.
• Lower-than-clinical doses may be used if the results remain interpretable

Key considerations include:

• Pharmacokinetic linearity when extrapolating from lower doses
• Differences in clearance and distribution between populations
• Reproductive safety measures, including contraception requirements
• Exclusion of individuals at risk from developmental or hormonal effects

In addition, subject characteristics such as age and sex may need to be restricted depending on the drug’s mechanism and safety profile.

Considerations for Patient-Based Studies

For higher-risk drugs, studies should be conducted in patients with the target indication. Key considerations include:

• Enrolling representative and clinically stable patients
• Aligning dosing regimens with standard clinical use
• Managing or accounting for concomitant medications
• Selecting appropriate study designs (e.g., crossover or parallel)
• Addressing variability through appropriate design and randomization Expanded Oversight on Ethics and Risk Management

The guidance also reinforces broader clinical trial conduct:

• Sponsors: responsible for risk management planning and appropriate site selection
• Investigators: responsible for safety monitoring and implementing of risk control
• Ethics committees: responsible for reviewing scientific validity and ethical acceptabilityAs emphasized in the guidance, no clinical trial may proceed without ethics approval and regulatory authorization.

Implications for International Drug Developers

For international drug developers, subject selection in anti-tumor BE and PK studies will be based on scientific efficiency, but also on whether safety, representativeness, and ethical acceptability are adequately justified in the China regulatory context.

Companies developing generics or biosimilars for the Chinese market should review their study strategies accordingly and consider early-stage regulatory engagement, particularly for complex modalities such as antibody-drug conjugates or cell therapies.

For companies navigating these requirements, Cisema provides regulatory intelligence and end-to-end support to help align development programs with China’s regulatory requirements – contact us today.

Further Information

Explore Cisema’s pharmaceutical development and regulatory services:

• Pharmaceutical Development & Strategy Consulting
• Pharmaceutical Regulatory Affairs Consulting

References

Consideration for the Selection of Subjects for the Bioequivalence and Pharmacokinetic Comparison of Anti-tumor Drugs (No. 22 of 2026)