The primary reason the Ministry of Food and Drug Safety decided to cancel Kolon Life Sciences' license for degenerative arthritis gene therapy Invossa was the company’s submission of false data to win approval.
In both the polymerase chain reaction (PCR) test carried out by the Drug Ministry and the PCR test reconducted by Kolon Life Sciences, the kidney-derived cell-specific genes gag and pol were found. However, Kolon Life Sciences stated in its application for license that the two genes did not appear. In a public apology it gave on April 1, Kolon Life Sciences also said, "Gag and pol did not appear in the PCR analysis conducted in 2004, and we identified kidney cells through the short tandem repeat (STR) analysis, which is one of the latest analysis techniques."
Kang Seok-yeon, director of bio-pharmaceuticals at the ministry, explained, "As the PCR test is no new technology, it is impossible that the two genes, which are crucial indicators, did not appear in the verification process in the development stage.”
The ministry also found that distributor Kolon Life Sciences, in addition to developer Kolon TissueGene, also knew as early as in 2017 that the cell line of the second fluid of Invossa was changed. According to the ministry, Kolon TissueGene found out in March 2017 that the second fluid of Invossa contained kidney cells. It notified Kolon Life Sciences of its discovery via e-mail on July 13, 2017, which is one day after the Drug ministry approved Invossa (July 12, 2017). This directly goes against Kolon Life Sciences’ argument that it only knew about the problem in March this year.
The ministry also found problems in the inspection conducted in the United States. In April 2016, Kolon Life Sciences found out that the number and position of the kidney cells inserted in the second fluid of Invossa had been changed, but they failed to disclose the finding. "The number and location of genes in gene therapy products are important information in terms of drug quality and consistency and must be taken into consideration in the approval process," Kang said.
However, the ministry is not free from the criticism that its examination process was insufficient. The ministry is accused of licensing Invossa without proper inspection. Critics say that the ministry ignored problems with safety and efficacy, blinded by its desire to make Invossa the world’s first gene therapy for osteoarthritis.
Civil organizations have filed a complaint against Drug Minister Lee Eui-kyung with the prosecutors’ office for approving a faulty drug.
To prevent similar cases from occurring in the future, the Drug Ministry plans to establish a full-time safety management system by requiring new drugs with a long R&D period to be retested with the latest analysis methods immediately prior to approval. It will also launch a special examination team to carry out, when necessary, tests on latest technologies.
Kang said, "When we approved the world's first gene-based arthritis drug Invossa, the documents that had to be reviewed were about 40,000 pages. We have about 350 medicine screening workforce, which is only 20 percent of the United States.We plan to double the number of screening workforce by 2022 to strengthen the licensing system for advanced drugs and shorten the screening period.”