Ahead of this year's Extractables & Leachables Asia, we spoke with Chunxin Lin, Vice President at Milestone to get a sneak peek of what we can expect from his presentation on 'Regulatory requirements and study strategies for E&L studies in dual China-US submissions' Here's what he had to say…




Q1. Why is this message particularly critical for industry professionals to hear right now?

The harmonization of E&L requirements between China and the U.S. remains a significant challenge due to divergent regulatory philosophies and technical expectations. For instance, the U.S. FDA mandates full-scan migration studies for stability testing to capture all potential leachables, while China’s NMPA often prioritizes targeted analysis of known additives (e.g., plasticizers, antioxidants). This discrepancy creates compliance complexities for dual submissions. With the impending release of ICH Q3E (2026), which aims to standardize E&L assessment frameworks globally, companies must prepare for evolving guidelines that may bridge—but not fully eliminate—these regional differences. For example, ICH Q3E emphasizes analytical evaluation thresholds (AET) derived from patient safety limits (e.g., PDEs), aligning more closely with FDA’s risk-based approach, whereas China’s current practices still lean toward prescriptive additive lists. Industry professionals must navigate these nuances to avoid costly delays, particularly as China’s NMPA increasingly adopts ICH principles but retains localized requirements (e.g., stricter documentation for biologics packaging).
 
Q2. How do evolving guidelines like USP <1663> and ICH Q3E reshape Asia's E&L regulatory landscape?

The adoption of USP <1663> and ICH Q3E in Asia signals a shift toward risk-based, lifecycle-oriented E&L management. USP <1663> formalizes extractables studies for packaging systems, requiring extreme-condition extraction and comprehensive profiling of potential migrants, which contrasts with China’s historical focus on stability-dependent leachables testing. Meanwhile, ICH Q3E introduces safety thresholds (e.g., SCT, AET) and encourages prior knowledge to reduce redundant testing—a paradigm that may conflict with Asia’s traditional preference for empirical data . For example, Japan’s PMDA and China’s NMPA are likely to integrate Q3E’s toxicological risk assessment frameworks but may impose additional requirements, such as elemental impurity testing per ICH Q3D for injectables. Companies should anticipate asynchronous implementation across Asia: South Korea and Singapore may adopt Q3E swiftly, while China could phase in changes to align with domestic priorities
 
Q3. How can resource-limited companies prioritize E&L testing without compromising compliance?

A risk-tiered approach is essential. First, prioritize high-risk products: parenterals, biologics, and inhaled medications require full E&L studies, whereas oral solids may leverage simplified assessments. Second, utilize supplier data: packaging material manufacturers in China are increasingly required to provide extractables profiles, reducing duplication. Third, adopt screening tools: for example, GC-MS headspace analysis can identify volatile leachables quickly, while threshold-based triaging (e.g., AET = 1.5 µg/day) helps focus resources on clinically relevant compounds. Fourth, leverage regulatory flexibilities: China’s NMPA permits stability-condition bracketing for leachables testing, allowing companies to test only worst-case scenarios . Finally, partner with specialized CROs: outsourcing complex analyses (e.g., unknown identification via HRAM-MS) ensures compliance while minimizing capital expenditure .
 
Q4. How do sustainable/biodegradable materials complicate E&L profiling?

Sustainable materials (e.g., PLA, bio-based polymers) introduce novel extractables from degradation byproducts (e.g., lactic acid oligomers) and unintentional additives (e.g., catalysts from production) . Unlike conventional plastics, these materials may lack historical extractables data, necessitating aggressive extraction studies under varied pH and temperature conditions to simulate real-world degradation . For example, biodegradable coatings in prefilled syringes could release aldehydes or ketones during storage, requiring sensitive LC-MS/MS methods for detection. Additionally, recycled materials pose risks of cross-contamination (e.g., residual APIs from prior use), demanding stringent supplier audits and traceability protocols . Regulatory agencies are still catching up: the FDA has issued draft guidance on biocompatibility for eco-friendly packaging, while China’s NMPA emphasizes accelerated aging tests to assess long-term stability .
 
Q5. Proposed Industry-Wide Initiative: Harmonized E&L Risk Assessment Framework

A unified risk assessment framework bridging U.S. and Chinese regulatory expectations would significantly reduce compliance burdens. This initiative could involve:
Shared Toxicological Databases : Develop a centralized repository for leachables’ safety data, co-funded by industry and regulators, to eliminate redundant assessments.
Harmonized Analytical Standards : Align U.S. full-scan requirements with China’s targeted approach by defining thresholds for unidentified peaks (e.g., 0.1 µg/day) acceptable to both jurisdictions.
Cross-Training Programs : Establish joint workshops between FDA, CDE, and industry experts to standardize interpretations of terms like “analytical evaluation threshold” (AET) or “reportable threshold.”
Predictive Modeling Tools : Promote machine learning algorithms trained on historical E&L data to predict high-risk materials, reducing empirical testing needs.
Such collaboration, modeled after the ICH’s success in impurity control, would streamline submissions, reduce costs, and enhance patient safety. By fostering transparency and mutual recognition of studies, this framework could set a precedent for global regulatory convergence beyond E&L testing