Victims of Drug-Induced Creutzfeldt-Jakob Disease

1. what is Creutzfeldt-Jakob disease?

Creutzfeldt-Jakob disease is caused by the proliferation of a protein called “abnormal prion. There is an incubation period of several years to several decades between infection and onset of the disease, but once onset occurs, the disease causes movement disorders and dementia, leading to death within months to years. The drug-induced Jakob’s disease is caused by the transplantation of human dried dura mater contaminated with abnormal prion protein into the brain. Dried human dura mater is a biologically derived product made from dura mater harvested from the brain of a dead person and used to replenish the dura mater removed during neurosurgery or other operations.

Japan began importing Riodura in 1973, and it was used in neurosurgical procedures for brain tumors, trigeminal neuralgia, and subarachnoid hemorrhage. Even after 1997, when its use was banned, there have been some cases of disease due to the use of stock, as a result of inadequate recalls. As of 2014, there have been 143 cases of Creutzfeldt-Jakob disease using dried dura mater, according to the Ministry of Health, Labor, and Welfare. Because Creutzfeldt-Jakob disease is a rare disease, inaccessible to medical care, and fatal, families faced great shock and difficulty.

2. sloppiness in the manufacturing and approval stages

In Japan, in addition to “Riodura”, a product called “Tutoplast” from another company was imported for use in human dried dura mater for neurosurgery. However, only “Raiodura” has so far been seen to be associated with the development of Creutzfeldt-Jakob disease. This is believed to be due to problems in the selection of donors from which dried human dura mater was harvested and in the manufacturing methods of B. Braun, the company that produced “Riodura.

B. Braun, the manufacturer of the “LioDura” human dried dura mater, did not select donors for use in human dried dura mater, nor did they properly record the donors, for example, not even checking the names of diseases of deceased persons. Furthermore, during production, the collected dura materiel was stored together in large plastic bags, and when washed, multiple pieces were processed at the same time (pooled washing), resulting in the spread of abnormal prion contamination even to healthy dura materiel. Sterilization methods were also said to have been inadequate. When Japan began importing Riodura in 1973, the existence of “abnormal prions” was not known, but it was pointed out from the approval stage that there were problems with sterilization against microorganisms at that time.

In addition, problems have been pointed out regarding the importation of the LioDura. First of all, human dried dura mater is a biologically-derived product, and using human dried dura mater in surgery means using human tissue as a living transplant, but in reality, the importation was easily approved as a medical tool just like tweezers or gauze. It is also pointed out that no clinical trials of “Riodura” were conducted in Japan, and that there was collusion between the former Ministry of Health and Welfare and the company with regard to the approval of import applications. Due to these safety issues, an order banning the use of “Riodura” was issued in the U.S. in 1987, and warnings were issued worldwide.

In Japan, on the other hand, the use of “Riodura” continued despite many experts’ suggestions, and its use was only discontinued in 1997. 1996’s mad cow disease outbreak triggered an urgent nationwide investigation of Creutzfeldt-Jakob disease, and 43 of the 826 cases of Jacob’s disease were found to have been transplanted with B. It was discovered that 43 of the 826 cases of Jacob’s disease had been transplanted with human dried dura mater from the B. Braun company. In response, the former Ministry of Health and Welfare issued a notice banning the use of dried human dura mater in 1997.

3. the struggle of the bereaved families and lessons for the pharmaceutical administration

In 2002, a settlement was reached and all the victims were granted relief. Initially, the government claimed that it was not responsible for the damage caused by Riodura before 1987, when a worldwide warning was issued after an order banning its use was issued in the United States, because it was not aware of the dangers of Riodura until then. However, it was deemed that the 1973 import license itself was problematic in the first place, and all victims after 1973 were subject to the settlement.

The damage caused by drug-induced Jacob’s disease was also utilized in pharmaceutical administration: the Pharmaceutical Affairs Law, which was revised in 2003, strengthened safety controls for biological products, including donor screening and record keeping, as well as record keeping at the stage of use. In addition, more than half of the world’s dried human dura materia are exported to Japan, and most of the damage caused by drug-induced Jacob’s disease has been reported in Japan. Similar cases have been noted in the importation of unheated coagulation factor products for drug-induced AIDS, and verification of why so many biologically-derived products are used for surgery in Japan is also awaited.

References

1. Foundation for Regulatory Science of Pharmaceuticals and Medical Devices, 2012, “Lessons Learned from Drug Injury: Voices from Victims Hoping for the Prevention of Recurrence,” Yakuji Nippo Co.
2. Japan Association for Public Publications, 2011, “Knowledge of Drug Hazards You Should Know–To Prevent Health Damage Caused by Drugs,” Jiho.