Hi thymus, Thanks for pointing out the stark reality - however,...

Hi thymus,
Thanks for pointing out the stark reality - however, I want to remain just a tad optimistic at least until I've assessed the demands for data coming out of the May meeting. In the medium term I'll be cheering from the sidelines.

I've focussed on the important points you made on classification.
Classification
The FDA classified VitroGro as a combination device/biologic. We might well have been better off with the device/drug combination. But that’s not the case. Anyway, we have a robust trial that demonstrates that satisfies the EMA and the FDA will no doubt require a larger trial 9more expensive) but we can be confident of the results. So let’s set aside device implications.

Our problems
Lie with the biologic component. The EMA very reluctantly allowed a device classification which on the surface was a big win for TIS. However, the EMA have never truly accepted that was correct designation and in light of the FDA’s request for more information to be provided following or accompanying the US trial have found an avenue to get the information they wanted

So what is required by the FDA and now in my view by the EMA?
The following is taken from (bold text mine)
http://www.fda.gov/Drugs/Developmen...TherapeuticBiologicApplications/ucm113522.htm
Regarding the biologic component Biological products, like other drugs, are used for the treatment, prevention or cure of disease in humans. In contrast to chemically synthesized small molecular weight drugs, which have a well-defined structure and can be thoroughly characterized, biological products are generally derived from living material--human, animal, or microorganism-- are complex in structure, and thus are usually not fully characterized.

What are the requirements for licensing a biologic?
Issuance of a biologics license is a determination that the product, the manufacturing process, and the manufacturing facilities meet applicable requirements to ensure the continued safety, purity and potency of the product.
Among other things, safety and purity assessments must consider the storage and testing of cell substrates that are often used to manufacture biologics.  A potency assay is required due to the complexity and heterogeneity of biologics.
Because of the complexity of manufacturing and characterizing a biologic, the PHS Act emphasizes the importance of appropriate manufacturing control for products. The PHS Act provides for a system of controls over all aspects of the manufacturing process. In some cases, manufacturing changes could result in changes to the biological molecule that might not be detected by standard chemical and molecular biology characterization techniques yet could profoundly alter the safety or efficacy profile. Therefore, changes in the manufacturing process, equipment or facilities may require additional clinical studies to demonstrate the product's continued safety, identity, purity and potency.

How is the manufacturing process for a biological product usually different from the process for drugs?
Because, in many cases, there is limited ability to identify the identity of the clinically active component(s) of a complex biological product, such products are often defined by their manufacturing processes. Changes in the manufacturing process, equipment or facilities could result in changes in the biological product itself and sometimes require additional clinical studies to demonstrate the product's safety, identity, purity and potency. Traditional drug products usually consist of pure chemical substances that are easily analysed after manufacture. Since there is a significant difference in how biological products are made, the production is monitored by the agency from the early stages to make sure the final product turns out as expected.

So where to now? Here’s my take…
Short term - Obviously a great deal depends on how demanding the EMA are determined to be in deciding how diligent they want to be in respect of questions/queries on the manufacturing process. We won’t know that until the May meeting. The only positive I can immediately see is that the manufacturer is well established and authorised at both.EMA/FDA quality standards.
Medium/Long-term
I’m not staying around as there appears to be some difficult times ahead in getting approval in the US. ’I additional there is serious competition on the horizon – see other posts.

So I intend to wait until the May meeting before making a decision – after all I’ve lost so much that I might as well hang in.

It's been a huge lesson for me - set a profit target and get out!

Cheers Alan