FDA issues Complete Response Letter to Fibrocell Science BLA

In follow up to an earlier post on Fibrocell Science, Inc., according to the company on 21-December the FDA issued a ‘complete response’ letter that identifies the need to provide histopathology biopsy data on patients treated with the autologous fibroblast product as well as to resolve some manufacturing issues (CMC). The details of the letter provided by the company are not exactly abundant, but my guess is that the request for histopathology data from patient biopsies may relate to some of the potential safety concerns discussed at the FDA Advisory Committee meeting in October.  This is quite interesting since there is a general perception that autologous cellular therapies are inherently safer than an equivalent allogeneic therapy.   It appears at the end of the day it is always going to come down to what does the safety data indicate, regardless of whether or not it is autologous or allogeneic.  To be fair, this is the consistent message that FDA has given all along, though it has at times fallen on deaf ears.  If you are working with autologous therapies, now would be a good time to challenge any assumptions concerning the obvious safety of your product and make sure there is data that verifies your assumption that can be presented to regulators.

What the CMC issues are is not clear, but perhaps issues arose during the FDA preapproval inspection or the company was hoping to implement some changes in the manufacturing process for commercial ‘scale out’ of the autologous manufacturing process and the FDA did not agree their was sufficient data to support the manufacturing change. In my experience, the FDA is appropriately conservative when it comes to allowing CMC changes to be made. It is also my experience that company’s tend to be overly optimistic in the ability to easily implement process changes without first carefully developing a plan and the supporting comparability data that is typically required.   It also a good practice to engage the FDA early in any discussions concerning changes in CMC.

Responding to the FDA’s complete response letter is going to take some time (how long is unknown), but presuming there are no safety signals in the biopsy data and a workable solution can be developed for the CMC issues, it seems that Fibrocell Science is still on a path to an approvable BLA.

My 2008 Presentations & Articles Relevant to Regenerative Medicine

2008 was an extremely busy year for me, as I am sure it was for you as well. The net result is that I have been slow to post updates and thoughts regarding translation of regenerative medicine products to the clinic. In the ‘better late than never” category, I thought I would share some of the presentations and relevant articles I have written over the past year.

Links are provided for most of the presentations and articles I have generated over the past year.

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How Does the FDA View the World of Regenerative Medicine?

A major focus of the Regenerative Medicine Guru Blog is the development of new medical interventions based on regenerative medicine.

Therefore, it is important to understand how the ‘gatekeepers’ view this field. In the U.S., the Food and Drug Administration (FDA) is the key gatekeeper. You may be surprised to learn that there is not a specific regulatory pathway spelled out for regenerative medicine products.

Instead, the FDA’s approach is to examine each specific regenerative medicine product and determine the regulatory pathway based on the most important component(s) of the regenerative medicine product. To accomplish this, the FDA essentially conducts a thought experiment in which the regenerative medicine product is ‘de-constructed’ in order to identify the key components and ask the question, which component(s) are most important in providing benefit to the patient.

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