It would seem
@Pooslice is quick to enlighten us with his concerns but does not read others replies to these concerns. I have cut and pasted these below so that some of you that are more knowledgeable than me (but have him on ignore) may add to my responses.
From the FDA's line of questioning, there is concern around:
An absence of multi-factorial combination analysis of other factors influencing cytokine responses
Inability to describe how and why exactly the mechanism by which immunomodulation actually occurs
Inability to describe exactly how MSB can rigorously ensure treatment consistency/potency.
Inability to describe something simple like how long the treatment actually exists in vivo
I will answer this to the best of my ability based on the responses that were made to you many times, and my understanding of the process.
The FDA asked the ODAC advisory committee to question these aspects about the cells, not because they had concerns, but because they could not fully comprehend the science and wished the committee of experts in their field to look at this with much more experienced eyes.
The first two issues you raise were addressed in the meeting. If you listened to the presentation you would understand this. There was a post meeting comment by one of the committee that the science was complicated but the presenters did an excellent job at explaining it in detail to help with their understanding.
With regard consistency/potency, the FDA was concerned as there is no 'drug' to measure. With something like paracetamol, you measure that there is 500mg per tablet. How do you measure a treatment such as cells? The MSB team also addressed this. They outlined the factors that they would be measuring to ensure consistency of treatments.
With regard how long the cells actually exist in vivo, this was also discussed by the MSB team in the meeting and how they measure this.
The committee were satisfied with all explanations given, except they felt that asking them to expand on possibilities for strengthening consistency/potency issues was beyond their expertise and handballed this back to the FDA.
Your insistence to use thalidamide as an example seems bewildering as years of treatment with MSCs has not produced side effects.
I agree that thalidamide was very well tolerated when introduced and the birth defects not detected at the time. However science has learnt from this experience and has now introduced rigorous checks and balances before declaring a drug safe to use in pregnancy.
You will note that pregnant women are excluded from MSC trials and will continue to be until further evidence with animal models are completed.
Thalidamide also was put through some of these tests, but because the window of damage is so narrow, was missed. This was a damaging lesson learned and the testing now has been strengthened and expanded beyond approval.
It is also worth noting the the TGA in Australia was born out of the thalidamide experience. It was politicians who chose not to withdraw the drug in a timely fashion (even though the side effects had been reported to them by the drug company) because they 'didn't want to frighten the public'. Many children are disabled because of this decision.
When drugs are approved in Australia they are categorized according to the risk of effects on the fetus.
Category A - Drugs that have been taken by a large number of pregnant women and women of childbearing age without any proven increase in the frequency of malformations or other direct or indirect harmful effects of the fetus having been observed.
Up to Category X - Drugs which have a high risk of causing permanent damage to the fetus that they should not be used in pregnancy or when there is a possibility of pregnancy.
As health professionals, we are aware of these categories and explain the risk to our patients who are or may become pregnant.
Medication labeling and product information also highlight these risks.
Before becoming so concerned about possible birth defects of MSCs, perhaps you should think about the fact that NSAIDs such as Brufen or Naprosyn are readily available on supermarket shelves but are Category C. If taken during the latter part of pregnancy, may cause closure of the fetal ductus arteriosus, fetal renal impairment, inhibit platelet aggregation, and delay labour and birth resulting in a still-birth. It would seem society has a high tolerance of these possible side effects.
(20min delay)