Welcome to our Asia Regulatory Roundup, our weekly overview of the top regulatory news in Asia.
Korean Gene Therapy Probe Triggers Accusations of Data Fabrication, Lawsuit
The publication of an interim analysis of the cells used in the Invossa gene therapy has intensified the pressure on its producer, Kolon Life Science. Following the release of the regulatory report, Kolon had to defend itself against accusations of data fabrication, and a law firm began recruiting participants for a class action lawsuit.
Kolon stopped making and selling its gene therapy treatment for degenerative arthritis at the start of the month at the request of the Korean Ministry of Food and Drug Safety (MFDS). MFDS made the request in response to evidence that the cell lines in the approval materials and real-world products were different.
Now, MFDS has published the interim results of its review of the discrepancy. The analysis of the approval materials showed cells with DNA fingerprints, plus protein and gene expression profiles indicative of cartilage-derived cells, were present. The surface proteins suggested the cells were derived from cartilage, too, and lab animals injected with the cells experienced cartilage regeneration. However, analysis of current lots of Invossa shows GP2-293 kidney cells are present.
Kolon claims the kidney cells accidentally entered the formulation during the production process and that it has unknowingly been using GP2-293 cells since it first began developing Invossa. Those claims have led to questions about why, if kidney cells have always been used in the production of Invossa, the data submitted at the time of the gene therapy’s approval suggest cartilage-derived cells were involved.
“It is impossible that 293 cells expressed the characteristics of cartilage cells in various tests. Comprehending this with scientific logic is difficult. I think Kolon might have changed the story,” a ministry official told Korea Biomedical Review (KBR)
At this stage, the accusation that Kolon may have changed its story is unproven. If it is proven, it could mean that Kolon won approval using cartilage-derived cells but later started using kidney cells, or that it fabricated data to make it look like it was using cartilage-derived cells to win approval. KBR
reports that MFDS thinks it is more likely that Kolon fabricated data but the company has disputed that accusation.
“It is nonsense to claim that we fabricated data,” a spokesperson for the company told KBR
MFDS published the interim analysis that underpins the accusation on the same day as a law firm put out an advertisement to recruit people for a class action lawsuit against Kolon. The law firm is using a Korean website designed to help orchestrate class action lawsuits to find people who received Invossa. The law firm claims the use of kidney cells violated the Pharmaceutical Affairs Act and exposed patients to the risk of developing malignancies. Kolon says it mitigated the cells’ potential tumorigenicity.
Efforts to put together a lawsuit against Kolon are advancing in parallel to the ongoing MFDS probe. The regulator has asked Kolon to submit more data as it seeks to ascertain how kidney cells came to be used in the production of Invossa.
, Lawsuit Advert
(both Korean), Korea Biomedical Review
China Starts Clampdown on Unregistered Devices, Threatens Severe Punishments
China has begun an eight-month drive to stop the use and sale of unregistered medical devices. The first stage of the crackdown will require organizations to audit themselves and report their findings to regional regulatory offices.
The first stage of the National Medical Products Administration (NMPA) campaign, dubbed Clearnet, will run from late April to June. Over that period, NMPA expects organizations involved in the sale of medical devices to inspect their operations. The self-inspections should look at information including sales records, the establishment and implementation of management systems and the conditions in which devices are stored and shipped.
NMPA is asking the organizations to share the results of the self-inspections with its regional offices. These regulatory offices will oversee the second stage of Clearnet from July to October. Over those months, the regional offices will review and act on the the self-inspection reports by performing their own inspections and taking other actions. NMPA will evaluate the impact of Clearnet in the third and final stage of the campaign during the last few months of 2019.
Through the campaign, NMPA hopes to identify organizations that have failed to obtain the required authorizations or comply with rules on their technical capabilities and personnel. NMPA thinks that focus will lead to regulatory and legal actions against websites and individuals that are involved in the sale of devices but lack the authorizations and infrastructure required of such operations.
The effects of the campaign are expected to last beyond its conclusion in December. NMPA wants its regional offices to strengthen legal training for medical device sales networks and increase corporate awareness of the law and how to comply with it.
China Adopts Policies to Strengthen Oversight of Fentanyl Painkillers
China is set to enact policies to strengthen oversight of the trade and use of the highly potent synthetic opioid fentanyl. The policies, which go live on 1 May, are designed to stop the diversion of the drugs out of the legal supply chain and ensure enterprises investigate and resolve potential problems.
Following a meeting to discuss the management of fentanyl, China is set to encourage construction of a drug traceability system for the painkiller and task regulators with performing special inspections of companies involved in the supply of the products. The goal is to ensure the risks fentanyl poses are understood and to stop deliberate and inadvertent misuse of the painkiller.
NMPA shared details of the meeting and actions it triggered but the initiative involves multiple parts of the Chinese government, from a body formed of the top leaders of the Communist Party of China down.
NMPA Establishes Guidelines on Animal Testing of Medical Devices
NMPA has established guidelines covering the use of animal testing in the development of medical devices in China. The guidelines address when companies need to test devices in animals by looking at the value of preclinical data for multiple different classes of product.
A product-by-product analysis of the need for animal testing makes up the bulk of the guideline. In this section, NMPA sets out how the impact of materials used in drug-eluting stents on the release and absorption of therapeutic molecules means it sees value in testing such products on animals, even though the wider class of devices has a long history of use in humans.
NMPA performs similar analyses of the role of animal testing in the development of hip implants, electrocardiograms, external defibrillators, implantable cardiac pacemakers and other categories of widely used medical devices.
In assessing when to perform animal testing, NMPA wants companies to consider the 3R principles covering the replacement, reduction and refinement of the use of animals in product development.
Australia's Therapeutic Goods Administration
(TGA) has updated its safety alert about infections associated with heater-cooler devices. Nine Australians have suffered Mycobacterium chimaera
infections following heart surgery involving the devices. TGA Notice
has suspended Point Of Care Diagnostics Australia
’s LeadCare II Blood Lead Analyzer. The device is set be off the market for six months, but TGA also said there may be grounds for canceling the registration of the product. TGA Notice