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Tuesday, September 16, 2008

Regenerative Medicine Industry in Need of a Voice?

Chris Mason (University of London) and I would like to get you talking.

Chris and his co-author Peter Dunhill have recently published an Editorial in the journal Regenerative Medicine entitled "The need for a regen industry voice".

They make a number of cogent arguments why the regen industry needs more to support its maturation than is currently provided by the existing organizations which represent pieces but not the whole of the regen industry. This is not to be critical of their support and, indeed, much acknowledgment must be given to their commitments to the industry. It is simply to suggest that it is not enough going forward and to pose the query - what does the regen industry need and how can we best put that in place?

They start by delineating some of the activities they believe could be addressed by an industry association (or cabal of industry associations) working on behalf of what they have have termed the “regen” sector. This is drawn largely from what has been done in the larger biotech sector.
Box 1 – Potential roles of an industry association addressing the regen sector

Business issues
1. Supporting pioneer companies who lack the critical mass to address the many issues that affect them.
2. Organising promotion of both technology push and market pull.
3. Helping to ensure sensibly drafted regulation and planning towards unified international agreement on regulations.
4. Working to achieve a balance on patents and disclosure of intellectual property which encourages risk taking entrepreneurs but does not block broad progress.
5. Addressing issues of reimbursement and health insurance and the necessity of cost assessment based on the short and longer term.
6. Cooperating to formulate national and international standards for terminology and technology.

Broader issues
7. Achieving a sensible expectation from regenerative medicine by being both proactive and also reactive to events and by avoiding hype.
8. Acting to address unethical and unregulated medical tourism and dubious practices.
9. Helping to build bridges between academics, clinicians and companies, and providing professional education.
10. Providing soundly based comment on difficult issues such as the use of embryo derived cells.
11. Facilitating dialogue between those developing human cell-based therapies and others addressing options such as gene based treatment and those using molecular agents.
Some of the issues facing existing associations in addressing the regen sector are summarized in Box 2.
Box 2 - Issues for existing biotech industrial associations contemplating embracing regen

1. Will biotech industry association members accept some diversion of resources to regen needs?
2. Is it possible for existing association to represent regen companies in the differing environments of the USA, EU and other key regions such as Asia?
3. Will there be conflicts of interest with biotech in encouraging investment from pharma and venture funds?
4. Could a biotech/pharma image on issues such as generics/biosimilars affect regen negatively?
5. Does regenerative medicine represent an opportunity to seek a better public-private partnership in medicine which would help all of the pharmaceutical sector?
They conclude as follows:
At present it would seem there is a real prospect that the existing biotech industrial association could provide at least some of what is needed. However, to achieve the roles summarised in Box 1 will take a core of interested, knowledgeable people who come together regularly with some secretariat help.

It will not be enough to just add occasional sessions to association internal discussions or public events though the latter does help to raise profile. As indicated earlier there are aspects where professional associations of scientists and clinicians can help as in educating their members on the new opportunities which regenerative medicine represents. They may also be important in arguing for sensible regulations and in helping to maintaining high professional standards. However, the interests of new companies need organisations with commercial and reimbursement issues deeply embedded in their instincts.

Though we seek solely to promote discussion, perhaps one possible attractive solution will be for regen companies to work hard to create proactive and effective groups within existing biotech associations. These could have the advantage of access to central resources but would allow a focus on those distinctive issues related to regen companies. Possibly too, where there are high local concentrations of regen companies it will be possible for them to have both some self-organised functions and an affiliation with national biotech organisations. From the comments we have received from those who have no particular vested interest, this approach seems to have support.

It has been suggested to us that without the equivalent of an Amgen or a Genentech no amount of work on associations or groups will really move the field forward. Though such a development plainly would help, the nurturing of regen to become the third arm of pharmaceuticals alongside small molecule drugs and biopharmaceuticals will be a patient process.

Developing supportive infrastructure and an articulate vision will help to clear obstacles that presently hold back the full flowering of early companies. It is in this sense that the issue is urgent. Whatever its form, regen needs a voice and we believe it needs it now.
I helped ISCT create its Cell Therapy Commercialization Committee to assist in addressing some of the needs Chris and Peter outline. But there are several obvious restrictions on that group's abilities, not the least of which are (a) it only pertains to the cell therapy sector of the regen industry, and (b) I try to chair the group in a volunteer capacity while keeping a day job or two and as the past few months have demonstrated that does not allow much time. I'm the first to acknowledge its limitations.

We'd like to hear from you on any of this but specifically we need input on two simple-to-state but not-easy-to-answer questions:
What kind of infrastructure and/or actions do you believe the industry needs (from existing or new orgs) to assist in its maturation?

What form (org, group, etc) would best beget and support that infrastructure and/or action?
Post your thoughts and comments

It's your industry. Make it what you want. Let's give it what it needs.

Let's talk.


Thursday, September 11, 2008

Cell therapy is not the practice of medicine

I have several doctor friends who in the early days of cell therapy years ago argued that autologous cell therapies should be considered the practice of medicine - like stem cell transplants - and not require regulatory approval like drugs or devices. Indeed some of the motivation for the creation of industry self-accreditation bodies like FACT was to attempt to convince regulatory agencies that cell therapy products were best regulated by medical industry bodies. The FDA and other regulatory agencies were engaged in this discussion - they heard, they listened...and in large part they disagreed. My doctor friends came to grips with that reality and worked with the FDA to help create a regulatory framework that they now work within.

Even under the strictest regulatory frameworks there are some types of products which do not require formal approval. This blog will not be an overview of the regulatory distinctions between - for instance - s.351 and s.361 products (per FDA) but suffice it to say the differences between the products which do and do not require formal approval are, by now, fairly well defined in both US and Europe (albeit the latter only more recently). Furthermore, the regulatory agencies are eager to engage in dialogue with anyone who has questions about the proper regulatory pathway for their product.

And yet...there are those even now in the US and Europe who attempt to skirt the regulatory framework by conducting unauthorized and/or non-compliant clinical research and/or offering for sale commercial products without regulatory approval despite them falling clearly under the rubric of the regulatory requirements that such products be approved for such purposes.

It's one thing to be offering clinical products in unregulated markets that would would be or are regulated in other markets. I've previously opined here about the medical tourism industry and the issues it raises. But trying to conduct clinical research or sell clinical therapies that are not approved, in markets where there are clear rules governing the authorization to do so? Really?

Regrettably, yes. Two recent examples are described below. I'm not here to cast aspersions, don't want to spark any skirmishes, and certainly have no basis for suggesting impropriety on the part of those involved in these examples. I refer to these examples because they are recent, part of the public record, and, in my opinion, exemplify actions which should justifiably be called out and discouraged (if not penalized).

1. The first example comes out of Europe as described in recent reports in Science, MedPage Today, etc where the Lancet recently retracts a published article stating "... the editors rejected Dr. Strasser's assertion that products of tissue engineering are not medical products and therefore not subject to the Good Clinical Practice requirements."

Following is the report from MedPage Today (5 Sept 2008) :

Lancet Retratct Article on Incontinence Cell Therapy - Free Legal Forms

2. The second example comes from the US. Below is a copy of a recent letter sent to Regenerative Sciences, Inc (doing business as Regenexx) by the FDA .

FDA Warning Letter to Regenexx (Regenerative Sciences Inc - RSI) - Free Legal Forms

There are only three possible explanations I can come up with for why anyone would act as these two teams of people have done in clear contravention of the guidelines regulating their actions: (a) they simply don't understand, (b) they are looking to wage a fight or make a point, and/or (c) they believe their license to practice medicine supersedes regulatory authority (an argument long-ago tried, tested, and proven a loser). None of those reasons are justifiable in the circumstances.

In some instances, those who push the envelope help to shift the paradigm and improve the system they buck against. Even civil disobedience can - at least in retrospect - be occasionally justified if not even heralded as the impetus for positive change. This is not that.

This is playing with people's lives in clear contravention of the rules. That's not to say the FDA always has it right or that there are not issues to discuss or changes to make. The fact that neither of these treatments appear to pose any real risk to patient safety is certainly part of the argument for relaxed regulatory controls - I understand. But does that justify flagrant contravention of the guidelines as they exist using patients as pawns in the argument?

There are other ways to make this case. Go to a jurisdiction where the treatment is permitted, employ patient groups to lobby or litigate, engage industry and FDA in discussions to affect change in the regulatory regime.

Dear Doctor. The fact these therapies may be relatively harmless is no excuse for acting outside the regulatory framework and guidelines created to protect those people you're treating - agree with it or not, like it or not. Thanks.


Monday, September 1, 2008

10 take-aways from CHI's CELLutions Summit

I attended CHI's Third Annual CELLutions summit in Boston August 11-13, 2008. Here's my 10 take-away items (in no particular order) bridged from my notes* :

1. David J. Mooney (Harvard School of Engineering & Applied Sciences) and team are bringing together disciplines in a way that may revolutionize cell therapy but are not yet hitting the headlines.

In mouse models they are currently loading biodegradable devices ex vivo with human PBMCs or cordblood-derived MNCs on a matrix to affect muscular regeneration or angiogenesis. The cells multiply inside the device and are then activated (via loaded agents) to migrate at a controlled rate undifferentiated into the region, then differentiate, and affect a therapeutic target.

The next generation device is intended to be implanted and then recruit cells in vivo rather than rely on cells being loaded ex vivo thus avoiding all the regulatory, technical, and scientific challenges of ex vivo cell manipulation. Early research has used the devise to generate immune responses by loading the device with antigen and APC activators for targeting cancer. This was definitely the technology-to-watch presentation of the conference.

2. One of the strengths of the conference has always been that it throws people in a room together that might not otherwise interact - from tissue engineering, cells-as-tools, cell therapy, etc. In keeping with point #1, interdisciplinary research is where some of most exciting research is happening today building on solid progress in each of the disciplines.

3. Unfettered optimism has been beaten out of all but the most inexperienced. There is much caution about ensuring there is no overreaching and little hype in presentations and projections. While this occasionally comes across almost like pessimism, keep in mind these are still people betting their careers on the sector - they're not THAT negative.

4. While there is no doubt that costs are higher for autologous therapies making investors less excited about them as a model than allogeneic therapies, price is the other 1/2 of the equation defining profit margin. Furthermore the cost differential may not be a as great as most believe depending on the therapy and particularly when compared to a point-of-care (PoC) model.

It is certainly too early to predict the end of the future of autologous cell therapies. For those using this as an excuse for their fear of a new business model -- we understand...

5. We still have yet to have a sustained and focused discussion on the business of cell therapies. As is so often the case, the commercial aspects of the sector was relegated to the last session of the conference when many had already left. This is regrettably typical. We need a conference primarily focused on the business side of the sector - business models, reimbursement, IP, leadership, financing, etc.

6. The war over MSCs (whatever that acronym has come to mean) is warming up but has real potential to get real hot. The true battle may emerge only once there is money to chase. Here's hoping constructive negotiations win the day and litigation does not crush the benefits of all the progress in the field. If there is no IP crusher, will MSCs quickly become a commodity? With so many MSCs out there from all sorts of sources working relatively similarly, will the real winners simply be determined by the marketplace?

7. 3D models and the companies that have them are about to make a significant impact in drug testing.

8. The work on iPS cells and hESCs are both incredible science a long way from the clinic and companies trying to race to the clinic with these cells would do well to study the lessons to be learned from the first generation of cell therapy and tissue engineering companies that commercialized products much earlier than could be done successfully/profitably.

9. Women in science are shattering the glass ceiling. I chaired what was a great panel discussion to end the conference and all 3 panelists were very experienced (but very young looking!) biotechnology executives in the cell therapy sectors.

10. Fenway Park is a rare time capsule of Americana that should be treated as a national treasure!

Just my thoughts...