Strategies for NMPA Registration of Intraocular Lenses: Non-Clinical, Clinical Studies and Practical Insights Based on Three Recently Approved Innovative Devices (II)

3. Clinical Evaluation Strategies

Clinical studies are the decisive point for the registration of innovative Class III devices. The NMPA reports provide clear examples of two major pathways:

1. superiority trials for products that claim added functional benefit
2. non-inferiority trials for products focused on material updates or incremental improvements

3.1 Superiority Trial for Functional Claims

The Aibo Nuode EDOF IOL used a superiority trial design to demonstrate improved intermediate vision and broadened depth of focus.

3.1.1 Study Design

• prospective, randomized, multicenter
• double-masked
• superiority and non-inferiority hybrid design
• the company’s monofocal aspheric IOL served as the control

3.1.2 Primary Endpoints

The study used three co-primary endpoints:

1. BCDVA (best corrected distance visual acuity): non-inferiority
2. DCIVA (distance-corrected intermediate visual acuity): superiority
3. depth-of-focus range: superiority

This combination ensured that the new functionality did not compromise basic distance vision while requiring statistically demonstrated benefits in intermediate vision.

3.1.3 Secondary Endpoints

Secondary endpoints included:

• uncorrected intermediate vision
• contrast sensitivity
• defocus curve profiles
• spectacle independence rate
• patient-reported visual quality

The accumulated evidence clearly supported the lens’s functional claims.

3.2 Non-Inferiority Trials for Material-Innovation or Basic-Function Products

The products from Xi’an Yandele and Tianjin Shiji Kangtai followed non-inferiority strategies.

3.2.1 Rationale

Non-inferiority is appropriate when:

• the product’s primary claims do not involve new functional advantages;
• the main innovation lies in material, biocompatibility, or mechanical design;
• the manufacturer aims to demonstrate equivalence in clinical safety and effectiveness relative to standard-of-care monofocal IOLs.

3.2.2 Study Components

Typical primary endpoints include:

• uncorrected distance visual acuity
• best corrected distance visual acuity
• refractive stability
• incidence and severity of adverse events

Secondary endpoints often include optical quality, contrast sensitivity, posterior capsular opacification rate, and patient-reported outcomes.

Both products successfully established non-inferiority, providing the required assurance of clinical safety and effectiveness.

4. Practical Recommendations for Companies Planning NMPA Registration

Based on the analysis of the three approved innovative IOL products, companies should consider the following points when planning a registration project.

4.1 Clarify Product Type and Regulatory Positioning at an Early Stage

Is the product:

• a functional innovation (e.g., EDOF, multifocal, aberration-modulating), or
• a material/process innovation (e.g., new polymer, new haptic design)?

This decision influences:

• optical testing plan
• sample size and clinical endpoint selection
• level of biological evaluation
• comparator selection
• regulatory risks and timelines

4.2 Build a Non-Clinical Package that Directly Supports the Claimed Features

For functional innovation:

• include defocus curve analysis
• show intermediate vision enhancement at the optical level
• provide misalignment stability evidence

For material innovation:

• add chemical characterization
• conduct long-term degradation studies
• supplement chronic toxicity if indicated

4.3 Design Clinical Studies Directly Tied to Product Functions

Claims must match endpoints.
Endpoints must match statistical design.
Statistical design must match comparator selection.

Misalignment of these three layers is a common cause of failed submissions.

4.4 Preloaded Delivery Systems Need Dedicated Evaluation

If using a preloaded injector:

• verify loading accuracy
• evaluate injection force profiles
• assess lens recovery after injection
• ensure no structural damage to haptics or optic

4.5 Consider Life-Cycle Management and Post-Market Planning

Given the increasing scrutiny of ophthalmic implants, companies should prepare long-term post-market plans including:

• surveillance of adverse events
• annual updates of manufacturing consistency
• material stability monitoring
• real-world evidence programs

The three NMPA evaluation reports released in September and October 2025 represent important reference cases for the registration of innovative IOL products in China. Together, they demonstrate the regulator’s structured approach to evaluating high-risk ophthalmic implants and highlight the key differences in how functional and material innovations are assessed.

Extended depth-of-focus IOLs require strong, targeted evidence demonstrating genuine enhancement in intermediate vision without compromising baseline distance acuity. Material-innovation lenses require thorough characterization and long-term safety assurance, as well as clinical non-inferiority to existing products.

As cataract surgery demand continues to grow and patient expectations rise, the Chinese market will likely see further expansion in advanced IOL categories. Understanding the regulatory logic and evidence expectations shown in these three reports will help manufacturers plan development pathways, reduce regulatory risk, and bring innovative solutions to market more efficiently.