Over a four-year period, FDA issued five warning letters to a physician and associated entities and organizations—one from CDER for marketing unapproved new drugs, and four related to clinical studies under the Bioresearch Monitoring (BIMO) Program.

This is the first time a single individual or entity has received four BIMO warning letters, all for different roles regarding the same investigational product—one as a sponsor, one as a clinical investigator, one as an institutional review board (IRB), and one as a GLP facility.

[Related: For more GCP insights from Jerry Chapman, view the recording of his recent webinar, “FDA GCP Inspection Trends Identified Using AI.”]

At the Food and Drug Law Institute (FDLI) Enforcement Conference in December 2021, CDER Office of Compliance Director Donald Ashley discussed the series of warning letters and what led to them.

Regarding the four BIMO letters, he commented that they “cover all the bases of what not to do in clinical research.”

The Story of Dr. Benedict Liao

Ashley relayed a story that began in 2011. Dr. Benedict Liao operated the Oeyama-Moto Cancer Research Foundation in California and submitted an Investigational New Drug Application to the FDA, in which he stated that he planned to engage in clinical trials of a product called Allesgen. He told the FDA and stated in his promotional materials that Allesgen was intended to treat and cure many different types of late-stage cancer.

He submitted a second application in 2012 under the alias “Masao Wada, M.D.” FDA received those applications, and both times informed Liao that the IND applications for Allesgen would be placed on clinical hold due to deficiencies of the submissions. Clinical trials that are issued a clinical hold must suspend all operations, including administration of the investigational drug.

However, the clinical hold did not deter Liao, who continued to administer Allesgen and sell it to customers in the United States and overseas until January 2018.

Ashley commented, “it is a very interesting story that helps to demonstrate the real public health impact of the work we do in CDER Compliance, specifically, how actions related to the marketing of unapproved new drugs and actions related to clinical research enforcement can work together to protect the public health, and in this case, lead to very significant criminal liability.”

[Related: “General Responsibilities of Investigators Conducting Study” and “Investigator Recordkeeping and Record Retention > Case Histories” were the Top 2 most common FDA 483 GCP observations for clinical investigators last year. What were the other common observations? Contact us today to learn how Redica can help you with inspection preparation regarding FDA GCP inspections.]

Federal Law Violated

“But the reason we are here today discussing it is that rather than simply stop those clinical studies after FDA put them on hold, Dr. Liao continued his activities, including marketing his product as a supplement, and charging patients around $2,000 a bottle for what he described as a life-saving treatment,” Ashley explained. “It is a messy story, preying on the desperation of people looking for any ray of hope.”

As a sponsor, the CDER director maintained that the “big ticket violation” was that Liao continued to enroll subjects in the clinical trial.

The other violation in the sponsor letter highlights a general lack of understanding of clinical research. It charges that Dr. Liao failed to properly monitor the clinical investigators involved in the research, though he claimed that his IRB was monitoring the study.

“Here is a helpful hint,” Ashley said: “IRB and sponsor obligations are different. An IRB cannot fulfill a sponsor’s obligation regardless of who owns them. I do not have time to discuss the other three BIMO warning letters in detail, but they are worth reading online.”

He characterized the incident as “an egregious example of systemwide failures in the conduct of clinical research. This was so significant that we referred it to the manager of the Office of Criminal Investigations, and that is where the story takes another turn.”

In November 2021, Liao was tried and found guilty of over two dozen felony charges. At the trial, the jury found that he schemed to defraud buyers of Allesgen by failing to inform them it was not an approved cancer treatment.

It was pointed out in the trial that FDA had placed the research on clinical hold, that Liao was not allowed to charge anything for the product, and that it could have had side effects that were unpredictable and could be quite serious.

Dr. Art Simone from CDER Compliance testified as an expert witness at the trial. Several of the patients also testified about their experiences sending tens of thousands of dollars to Dr. Liao, and that they would not have purchased the product had they been told it was unapproved.