Drug-Induced Creutzfeldt–Jakob Disease (CJD)

1. What is Creutzfeldt–Jakob disease?

Creutzfeldt–Jakob disease (CJD) is a fatal neurodegenerative disorder caused by the proliferation of abnormal prion proteins. Its incubation period can span several years to decades, but once symptoms appear—such as motor impairment and dementia—death typically follows within months to a few years. No effective treatment exists to date. Drug-induced CJD in Japan was caused by the transplantation of prion-contaminated human-derived dried dura mater (Lyodura) during neurosurgery. Dried dura mater is a biological product made by processing the meninges of deceased donors and was used to replace excised dura during brain surgery. Japan began importing Lyodura in 1973, and it was used in surgeries for brain tumors, trigeminal neuralgia, and subarachnoid hemorrhage. Even after its use was banned in 1997, incomplete recalls allowed remaining stock to be used, leading to further infections. As of 2014, Japan’s Ministry of Health, Labour and Welfare (MHLW) had identified 143 cases of CJD linked to Lyodura. Because CJD is rare and invariably fatal, families faced severe psychological and social hardship as they watched loved ones deteriorate rapidly.

2. Negligence in manufacturing and approval

In Japan, two brands of human-derived dried dura mater were imported: Lyodura (by B. Braun) and Tutoplast (by another company). To date, CJD cases have been linked only to Lyodura because of major flaws in donor screening and production processes at B. Braun. The manufacturer failed to screen donor medical histories and did not record causes of death. Donor records were incomplete or nonexistent. During production, multiple dura mater pieces were pooled together in large plastic bags and washed simultaneously—a practice known as pool washing—which spread contamination from one infected sample to many others. Sterilization methods were also inadequate. Although prions were not yet scientifically recognized in 1973, the Japanese approval process had already noted concerns about insufficient sterilization for microorganisms in general. Regulatory oversight was also lax. Human dura mater is a biological product, and its implantation constitutes a human tissue graft. Nevertheless, it was imported under the same category as surgical tools such as forceps and gauze, requiring only simple medical-device approval. No domestic clinical trials were conducted before approval, and evidence later surfaced of collusion between the MHW and importers during the approval process. Because of these safety issues, the U.S. Food and Drug Administration banned Lyodura in 1987 and issued a global warning. However, in Japan, despite repeated expert warnings, its use continued until 1997. The outbreak of bovine spongiform encephalopathy (BSE, “mad cow disease”) in 1996 prompted a national emergency survey, which found that 43 of 826 CJD cases had received Lyodura transplants. This led the MHW to order a formal nationwide suspension that same year.

3. Victims’ lawsuits and lessons for regulation

In 1996 (Ōtsu District Court) and 1997 (Tokyo District Court), victims and their families filed lawsuits against the government, the importing company, and B. Braun. In 2002, the courts recommended settlement, and all victims were granted relief. Initially, the government argued that it had been unaware of Lyodura’s dangers until the 1987 U.S. ban and, therefore, bore no responsibility for earlier cases. However, the courts ruled that the 1973 import approval itself had been flawed and that all victims since 1973 were entitled to compensation. This established a precedent for government accountability in cases of drug-induced harm involving biologics. The case also led to significant reforms of Japan’s pharmaceutical regulation. The 2003 amendment of the Pharmaceutical Affairs Law introduced strict safety controls for biological products, including donor screening, record preservation, and traceability of use. Japan had been the largest global importer of human dura mater—accounting for more than half of Lyodura exports—and most known Lyodura-related CJD cases occurred domestically. Similar issues later arose with imported non-heat-treated blood products in drug-induced HIV/AIDS, highlighting systemic overreliance on foreign biologics in Japanese surgery and medicine.

References

1. The Pharmaceutical and Medical Device Regulatory Science Society of Japan (2012), 『知っておきたい薬害の教訓――再発防止を願う被害者からの声』YAKUJI NIPPO, (ISBN 4840812136).
2. The Pharmaceutical and Medical Device Regulatory Science Society of Japan Pharmacopoeia Association (2011), 『知っておきたい薬害の知識』Jiho, (ISBN 4840741743).