China IIT - what do we learn from the recent patient death

These are the copies of my LINKEDIN posts in the aftermath of multiple trial patient death from China IIT reported in 2026. Part I is a summary of the public reporting and my analysis is included in Part II-V:

China IIT - PART II

Since my last post, very sadly, a third patient death from China IIT has been reported. RIBOX with their LNP-delivered circular RNA therapy had a death in their IIT, even though US FDA has just recently cleared their IND application (which RIBOX apparently used IIT data to support). (Link in the comment below).In Part I of my posting, I asked the critical question - Is Order 818 from the Chinese State Council sufficient to alleviate the increasing concern from the western biotech community regarding safety and transparency of China IIT? My answer is - "ONLY PARTIALLY" or, "NOT ENOUGH".The reason for my answer is that Order 818 only addressed the clinical research practices involved, but the one huge risk in IIT pathway by design is not addressed; that is, CMC and Quality in producing the IIT trial materials used.As the IIT is regulated by the National Health Commission (NHC, 卫生部), which handles public health policy, medical care delivery, and hospital administration. It does not have jurisdiction or expertise in drug manufacturing. The National Medical Products Administration (NMPA 药监局), which acts as China's FDA has the jurisdiction and expertise to regulate, approve and monitor pharmaceuticals, medical devices, and cosmetics. NMPAs official responsibilities include Product approval: reviews and approves clinical trials, new drugs, medical devices, and cosmetics. Quality and safety: enforces Good Manufacturing Practices (GMP) and Good Clinical Practices (GCP). Standard-setting: develops the Chinese Pharmacopoeia and product safety standards. Post-market oversight: monitors adverse drug reactions and investigates product quality issues. These responsibilities are not covered in the 818 Order.As such, the standard and level of rigor to ensure quality in the manufacturing of the materials used in IIT do not have set criteria. To put it bluntly, there is no requirement for GMP; instead, it is up to the investigators, biotech companies, and their chosen partners to produce materials used both for pre-clinical studies, as well as for IIT. As a veteran in the biotech industry, I understand the concept of phase-appropriate GMP, and why and how it should be applied in product development, especially for novel therapeutics. The most important principles for clinical trial material manufacturing in early phase, is to ensure safety of the product. This goes into all systems needed to ensure the environment, the materials, the operators, the process controls, the quality control methods etc., are adequately assured to not introduce unknown contaminants, impurities to your therapeutics. Quality Control testing for safety related quality attributes is trustworthy to be used to guide the dosing levels, as well as ensuring safety from unintended toxicity and immunogenicity. Without exercising basic GMP in mfg, it's impossible to determine where the deadly side effects actually came from.

China IIT - Part III

Continuing from Part II, the deaths, reported, and other SAEs, presumably not yet reported put a damp on Western biotech’s enthusiasm to pursue a faster development strategy for innovative therapeutics by leveraging China’s now proven strength in early-stage drug development, including first-in-human clinical trials via IIT.  Although the 818 Order by the Chinese government does bring in some sign of enhanced regulation, the concrete directives therein almost entirely focus on the entry and monitoring of the clinical trial activities. As such, emphasis on “QUALITY” is also referring to quality assurance areas related to clinical research. The specific languages are summarized below:

“Quality in Clinical Translational Application

1.     Approval and Standards

o   Translational application to clinical practice requires review and approval, including technical and ethical evaluation (Articles 29-31).

o   Medical institutions must comply with operating specifications and ensure the quality and safety of care (Article 34).

2.     Continuous Monitoring

o   Institutions must report on clinical application status and handle adverse events according to regulations (Article 35).

o   Re-evaluation is mandated if new risks or adverse reactions emerge (Article 37).

Legal Liability for Quality Failures

·       Strict penalties are imposed for violations related to quality, such as conducting research without proper review, falsifying records, or failing to implement risk controls (Articles 43-53).”

Here, in my opinion, as a biotech cGMP quality expert who have focused on manufacturing and quality in the past 20 years, A MAJOR RISK IN IIT MANAGEMENT THAT HAS BEEN OVERLOOKED by most – how do we know that the major safety events in these trials are not due to lack of Quality Control to reliably detect product quality risks when the manufacturing of these CGT products are not yet under cGMP systems.

China IIT - PART IV

China State Council 818 Order focuses on tighter regulations on the IIT trials but there is no mention of the word "GMP" in it as it pertains directly to all clinical aspects of a FIH trial, including evaluation of the preclinical data packages. The huge risks mentioned in my last post, therefore, are not addressed. However, the consideration of trial material product quality, and how they could directly cause some of the SAEs, is definitely on the minds of the government, and on industry leaders who likely know more of the details on those trials including history of the manufacturing and quality control. In a subsequent communication (September 17, 2026) from the Chinese Health Ministry, as part of a Q&A for the 818 Order, this is highlighted:

"(1) On strengthening the quality foundation and comprehensively improving independent, standardized testing capacity for stem cells. Your suggestions — pressing enterprises to fulfill their principal responsibility and incorporating independent testing capacity as a core admission criterion for the industry — are of significant value for safeguarding product quality and clinical safety at the source. The Regulation currently already specifies clinical research institutions as the responsible party accountable for the entire process of cell preparation manufacturing and quality control. Our Commission will earnestly take your suggestions on board, and will strengthen requirements for the independence and standardization of quality testing methods across all stages of cell preparation handling — including collection, isolation, culture, preparation, and transport. We will make the development of enterprises' or institutions' independent testing capacity a key factor in evaluating their technical strength and level of quality assurance."

Additionally, based on my communication with leading medical doctors and leading PIs for these IIT trials, these are additional questions that are being asked as part of the recent Health Ministry inspections at their medical centers for re-assessing their renewed qualifications.

So now comes the question - given that the principles and procedures for these new requirements are basic requirement under cGMP, medical institutions usually do not have the appropriate quality management systems to handle these requirements. How would they build that muscle, when there is very limited experience, and especially for CGT and other novel therapeutics? As I mentioned in my last post, a flexible quality management for early stage products should be enhanced by additional and more robust testing. When there is a general lack of standards in ways of Quality Control testing for CGT in the world, how would China meet this challenge given very few China-based companies in biologics and CGT areas have proven themselves to be reliable in QC, if for nothing else, the safety testing of these innovative products?

China IIT - PART V

The "BLACK BOX" that the Western biotech in general is not paying enough attention to, is the reliability of quality control for these IIT trial materials, which is critically important when the manufacturing is not done under cGMP conditions.

The analytical methods for CGT, in general, are not as established as those for traditional biologics such as monoclonal antibodies. The acceptable standards for biosafety testing, in China are still very different from that of the West. For AAV production, the MCB release testing panel includes roughly 47 different tests. Besides the ones where Chinese Pharmacopeia method is different from USP or EP (about 1/3), there are compendia tests (2/3) that do not have standard methods, nor the method fit-for-purpose is being questioned by Chinese regulators, even in a regular IND submission. The focus is highly on product testing, not critical starting materials such as cell banks, and plasmid DNAs. This brings high safety risks to the CGT products.

Based on my knowledge, not only these IIT trial materials were produced by Chinese CDMOs who have not been audited by the US FDA or EMA (not Wuxi Bio, which has been audited), hence their QC systems lack compliance to the high standards established for the leading Western CDMOs. Additionally, even established CDMOs in the West would commonly use one of the few global leaders in contract testing services for their biosafety testing, as the complexity and the criticality for product safety are not risks innovative drug developers can take. The similar rigor and standards in biosafety testing, and other process/product related QC tests are currently not being applied in China.

No information has been publicly disclosed regarding the testing of these trial materials so I am giving a few examples to illustrate my point further: 1)Adventitious virus testings were sub-standard, the packaging cells could carry the contamination to the final product; 2) same if the mycoplasma test (different compendia) was inadequate; 3) AAV Capsid full/empty ratio was not accurately measured and well controlled, the active viral dose vs. empty used is not well controlled; 4) if HCP, HCD tests were inaccurate, the contamination in final product was underestimated. All of these could cause SAEs in patients.

Therefore, I highly recommend that CGT developers pay attention to this huge risk as you embark on your IIT journey.