I just came back from 2nd Annual Cell Therapy Bioprocessing conference (Arlington, VA, US). It has been great conference and I was enjoying many talks and networking opportunities. This is unique industry-oriented conference, which precisely focuses on cell therapy products/ clinical trials development and addresses the issues of cell products manufacturing/ bioprocessing. I’m going to write few posts on some interesting topics, which were discussed at conference. Today I’m going to focus on regulatory issues.
Regulatory and legal issues was very highly discussed topic throughout the conference. At the beginning of the first day, Kenneth Kleinhenz (from Cytori Therapeutics) has asked a provocative question: “Do greater regulations lead to higher ethics?”. As he has showed in few examples, the answer is no. How is ethical to shut down a gene therapy trial when 1 out 14 patients got severe adverse event? The level of sensitivity to gene and cell therapy is extremely high, he noted. He said that regulators don’t even consider ethics. One of the reasons, he thinks, the absence of patients from decision making process. He thinks that ethical regulation is a robust debate between all stakeholders, including patients.
The discussion continued in a panel on risk of stem cell tourism. Some people in the audience disagreed with Kleinhenz on the role of patients in regulatory decision making. The patients could not be educated enough, vulnerable or biased due to severity of diseases. The alternative is the patient’s advocacy groups, which are able to collect/ digest valuable information and represent the patients opinion in regulatory process. Panelist Todd McAllsiter (Cytograft) said that we have to rely more on physicians than on patients, but they should be accredited. He thinks that FDA currently is over-regulating some kinds of cell therapies. For example, he said that regulation of cardiac cell therapy trials is unethical in US. He thinks that “proper” clinical trials as we know it today will not guarantee absolute efficacy. We will able to learn it when we will start to treat thousands of patients after approval.
Alexander Denoon gave an overview of cell therapy products regulation in Europe. He noted that, based on current low approval rate (2 products so far) EMA (European Medicines Agency) is very enthusiastic about cell therapy products. He discussed the issue “cell product: graft versus medicine” and pointed out a number of hospital exemptions from Advanced Therapy Medicinal Products (ATMPs), which allow to use cell products as grafts. Yet another interesting thing – in Europe there is an option of so-called conditional market authorization, which granted for 12 months and renewable. The discussions went on compliant versus non-compliant treatments. Lee Buckler (Cell Therapy Group) thinks that FDA continues to lose ground against non-compliant treatments. He also noted that physician’s mentality is very different from cell product developers and regulators. “They don’t even think if they are compliant, they just doing it” – he said.
It was very interesting to hear the other side – regulators. Representatives of FDA gave 2 talks on different issues. Keith Wonnacott (Chief, Cellular Therapies Branch, CBER FDA) gave a lot of tips on how to communicate with FDA. His main message was: “We need to be educated!” He gave an overview of FDA’s capabilities and review process. Cellular Therapies Branch has about 25-30 staff members for review manufacturing protocol, including PI’s with laboratories, scientists and fellows. “We are PhD scientists, but we may not know your product well, we need good communication” – he said. I’ve asked him about the FDA’s position on the most controversial issue – regulation of autologous adipose-derived stem cells for orthopedic applications. He said: “We don’t have uniform answer.” In the following discussion he told me that FDA does not publicly generalize their position on complex issues. Basically, they need to see the case. Evil in the details, guys! Each case (IND submission or consultation) could be interpreted in different way.
Overall, seem like regulators are very very enthusiastic and positive about cell therapy products. They are very open for any questions and early consultations. They want to be educated and learn together with developers. One of my favorite Keith Wonnacott’s tips was: “If reviewer say – you have to change this, this and this, always ask – why? What is the concern, which you’re trying to address by asking me to change this?” Many speakers noted very positive and satisfactory experience with regulators. But, to succeed you have to reach agency as early as possible. It’s much harder to change your product when clinical trial is ongoing. Both sides – cell products developers and regulators agreed that regulation is currently evolving with a field.