A proposed 6-step platform for the cell therapy industry to consider in combating non-compliant cell therapy treatments

Tweet 

Further to my recent post, "Six steps to fighting non-compliant cell therapy treatments. The stuff of grey shades, spades, ivory towers and (ahem) balls.", I have crafted a 6-point platform that I propose to submit (with potential edits based on preliminary feedback) to several of the leading  industry and professional organizations for their consideration including ARM, ISCT, ISSCR, FACT, AABB  ICMS, and perhaps, in due course, to patient groups, physician groups, disease-specific professional organizations (e.g, cardiology, oncology, neurology, cosmetic, etc).

I welcome comments and feedback. 

1. In addition to helping patients distinguish between compliant and non-compliant treatments (and providers) we must do more to help patients distinguish between non-compliant cell therapy treatments (and providers) which are more or less risky. 

2. Whatever we do in response to this issue should be done with an eye to being practical and helpful to patients in the real-life context of their decision about whether or not to buy a non-complaint cell therapy.

3. Our response to this issue should be based on a risk-based approach recognizing that not all non-compliance is created equal.  We should create a framework for risk-based analysis (both for us and our audiences) and focus initiatives around those which present the highest risk.

4. We recognize the problem of non-compliant cell therapies is not just a problem that exists in jurisdictions with little, no, or poor regulation but that is a growing problem even in the most highly regulated jurisdictions meaning the solution cannot be regulated it depends on education and enforcement.

5. We recognize regulatory agencies cannot enforce non-compliance on their own.  We as an industry need to complement their efforts through our own standards and enforcement.

6. Stakeholder groups should support the formation of a multi-organizational  initiative to, based on a risk-based assessment, spotlight the categories or signs of highest-risk offenders for use by patients and/or their physicians in identifying  whether or not treatments (and providers) they may be considering fall into the that category associated with the highest level of risk.

What do you think?

Six steps to fighting non-compliant cell therapy treatments. --- The stuff of grey shades, spades, ivory towers and (ahem) balls.

Tweet 

Today an article entitled "Professors Critique Stem Cell Medical Tourism" appeared in the online version of The Harvard Crimson summarizing a recent panel discussion hosted in least in part by Harvard Law School assistant professor I. Glenn Cohen and University of Alberta law professor Timothy Caulfield.  The article concludes thusly:

The panelists emphasized that more accurate information should be provided to the public regarding stem cell treatments.

Certainly what Cohen and Caulfield concluded is true.  It has now been true for several years.  We keep saying it.  But are we listening to ourselves?  Are we doing anything meaningful to address this?  If so, is it enough?

Sadly (in my opinion, of course) the answer is 'not nearly enough'.*

For several years now, experts and organizations in the cell therapy sector have been saying that more must be done to educate and assist patients who are seeking stem cell or other cell-based treatments which do not comply with existing regulation and/or widely accepted medical or clinical research practices (hereafter called "non-compliant cell therapies").  

In my opinion, attempts to address this need by the sector's professional organizations, while important, have been unnecessarily feeble, not gone nearly far enough, and legitimately appear by many to be high-minded and pedantic. 

Almost all efforts to-date to address this issue by ISSCR, CIRM, ISCT and others including authors such as Caufield - as laudable and needed as they are - have been focused on helping distinguish between compliant and non-compliant treatments (and providers).  This is certainly much needed.  But what is left, I submit, is an even greater unmet need.

What almost all efforts to-date have failed to recognize or address is that where real help is needed is in helping patients distinguish between the many shades of grey among non-compliant treatments (and providers).

Emerging organizations like ICMS (now in partnership with AABB) have recognized and attempted to address this unmet need through a commitment to create some level of certification, accreditation or standardization of clinics participating in this business of selling non-compliant cell therapies.

While their intentions appear on-target as one meaningful way to address this unmet need and certainly their willingness to tackle this issue in a bold way is to be lauded, the ICMS is inexperienced and underfunded.  I remain hopeful that now through their new partnership with AABB they will be able to provide something that really addresses this unmet need but the jury remains out on whether they will succeed.

Anyone who has followed this blog and/or my threads on LinkedIn know I have been thinking about and discussing this issue for some time. In a desire to move to very concrete suggestions, I want to recommend the following 6 steps to my industry colleagues and professional organizations:

1.  50 shades of grey. Let's admit that this issue is not black-and-white but, as is almost always, involves a broad spectrum of grey in the middle.  

In addition to helping patients distinguish between compliant and non-compliant treatments (and providers) there are a lot of ways to help patients distinguish between non-compliant cell therapy  treatments (and providers) which are more or less risky.  

Let me use examples.  

On the one end of the non-compliant spectrum I would put forward a clinical like Okyanos Heart Institute which (as I understand it) intends to provide cell therapy treatments in the Bahamas to US patients using the Cytori system for cardiac conditions as soon as such treatments are perfectly legal and available to European patients but years before such treatments will be available in the US.  

Non-compliant?  Yes.  But certainly no evidence I'm aware of to support a belief that seeking treatment from them would be any more risky than travelling to Europe to receive the same treatment in a manner perfectly compliant with European regulations.

On the other end of the spectrum are the kinds of clinics highlighted recently by 60 minutes or which are the subject of ongoing lawsuits.

In between - in my opinion - are clinics like Stem Cell Institute and StemCellMD.

2.  Step out of the ivory tower.  Let's recognize that in certain circumstances patients are going to go pay for non-compliant cell therapies and we must do more to help these patients than simply shake our finger and tell them they mustn't.

For some, helping patients distinguish between the better and worst non-compliant clinics might involve a fair amount of nose-pinching but this is the equivalent of the methadone clinic for heroine addicts.  By supporting the better of two evils we are not endorsing it as 'good', we are simply recognizing it is better.

This is a recognition that we cannot just abandon people because they made (or are going to make) decisions with which we ultimately disapprove.   It is a recognition that sometimes the most righteous thing to do is not only to help people do what we would ideally want them to do but to help them do the best they can in their circumstances and on their terms - even terms with which we may ultimately disagree.

3.  A risk-based strategy.  Let's recognize that even the FDA triages their response to non-compliance and we would do well to do the same.  As a regulated industry we are perfectly comfortable with risk-based assessments and it should be applied here.  

Rather than treating all non-compliance as equally evil, let's apply some risk-based analysis to the situation and develop a strategy to root out the worst (highest-risk) offenders.  

4.  This is not just about tourism anymore - the problem has come home to roost. Let's recognize that this is no longer just a problem of patients leaving a regulated jurisdiction seeking a non-compliant treatment in a jurisdiction with no or more permissive regulation.  

Non-compliant treatments are growing rapidly even in the most highly regulated jurisdictions.  No where is this more true than in the United States.

5. Take responsibility.  Let's recognize that we cannot expect our regulatory enforcement agencies to do it all.  They are under-staffed and under-funded.  They - and the people we all serve - need our active participation in dealing with offenders and those risking patient safety.  

From a self-interested perspective, we owe it to our industry to help crack down on those who put the credibility and legitimacy of cell therapies at highest risk.

6.  Let's grow a pair and call a spade a spade.  If a non-compliant clinic is providing treatments that we believe represent a high-risk to patient safety and the industry's credibility, let's have the b*lls to call them on it.  They can't sue everyone.  

ISSCR backed down on their stem cell tourism initiative after being threatened by lawsuits. Who has stepped up in their absence?  Individual bloggers and authors like Paul Knoeplfer, Alexey Bresenev, Leigh Turner, and myself all who have been threatened with litigation several times for having the audacity to call certain non-compliant clinics out for what we deem - in our own risk-based analysis - to be the worst offenders.  

By way of example, several of my colleagues have recently committed to doing all they can do to call out David Steenblock and his non-compliant cell therapy treatments, many of which are provided at his clinic in California for a plethora of conditions.  In their opinion, many of his treatments represent some of worst examples of non-compliance in the United States right now.  There are many faces or fronts to his practice including www.davidsteenblock.com, www.stemcellmd.org, www.strokedoctor.com, www.davidsteenblock.net, etc.

If, as an industry, we act with more cohesion (collaboratively applying a risk-based assessment of non-compliant clinics) and speak with a more cohesive voice in terms of calling out those clinics and treatments which we conclude pose the greatest risk based on an objective set of criterion, this will present a multi-pronged, formidable and existential threat to clinics that they can't ignore or threaten away.

___

I will be taking these 6 recommendations to any organization who will listen.  I hope you will consider doing the same.

In the meantime - as always - I welcome your comments.

___

* This is my opinion not necessarily the opinion of any clients I represent or organizations I serve. Judge me - not them - accordingly.

The cost of clinical trial data bias/loss, FDA's new job and the need for bold leadership.

Tweet 

The scandal of clinical trial data loss is eroding the fundamentals of evidence-based research and clinical medicine.

Before you right this post off as the stuff of conspiracy theories, fear-mongering, and 'alternative world views' consider that this view is shared by the likes of the FDA, the International Committee of Medical Journal Editors, the Cochrane Collaboration, and researchers at institutions like Johns Hopkins School of Medicine.

Here's the underlying premise as succinctly described by author Ben Goldacre:

"Drugs are tested by the people who manufacture them, in poorly designed trials, on hopelessly small numbers of weird, unrepresentative patients, and analysed using techniques that are flawed by design, in such a way that they exaggerate the benefits of treatments. Unsurprisingly, these trials tend to produce results that favour the manufacturer.

When trials throw up results that companies don't like, they are perfectly entitled to hide them from doctors and patients, so we only ever see a distorted picture of any drug's true effects. Regulators see most of the trial data, but only from early on in a drug's life, and even then they don't give this data to doctors or patients, or even to other parts of government. This distorted evidence is then communicated and applied in a distorted fashion."

Authors M. Todwin and J. Abramson summarize it thusly:

"Trials with positive results generally are published more frequently than studies that conclude that a new drug poses greater risks or is no more effective than standard therapy or a placebo. Furthermore, some articles may distort trial findings by omitting important data or by modifying prespecified outcome measures. Lack of access to detailed information about clinical trials can undermine the integrity of medical knowledge."

Here is a great list of very recent resources that may convince you of the merits of this concern:

• What doctors don't know about the drugs they prescribe (2012: TED video)
• The drugs don't work: a modern medical scandal (2012: The Guardian)
• Clinical Trial Data as a Public Good (2012: JAMA [subscription req'd])
• Registering Clinical Trial Results. The Next Step (2010: JAMA [subscription req'd])
• The Imperative to Share Clinical Study Reports: Recommendations from the Tamiflu Experience (2012: Plos Medicine)

Yesterday, the US Secretary of Health and Human Services announced (in an FR notice) that the FDA was now charged with ensuring all organizations comply with the heretofore enacted but relatively unenforced  requirement to submit all relevant clinical trial data to www.clinicaltrials.gov. 

For further commentary on this move see the following reports from:

• Nature News Blog
• Fierce Biotech
• PharmaLot

What is abundantly clear to me is that the FDA is left almost powerless - and if not powerless than certainly without sufficient resources - to successfully enforce its new power.  This requires collective industry leadership.  Bold, industry-initiated standards, infrastructure and old-fashioned peer pressure.

Here's what I wish.  

I wish that as a cell therapy industry we - through organizations like ISSCR, ARM, ISCT, etc and leading publishers of some of our leading journals like Regenerative Medicine, Cytotherapy, Cell Stem Cell, Stem Cells, etc - would take a leadership position on an issue like this.

I believe that as a relatively small and nascent sector of the biopharma industry we are more likely capable of collaborating on something important like this than larger, more established [entrenched] and diverse sectors.  Of course it requires the political will and cajones.

The payoff from our sector in taking a leadership role on this issue could potentially be enormous in terms of providing our sector with truly transparent and useful data.  Perhaps even more important would be the public profile such leadership would provide the sector.  Such a move requires bold leadership, pain, and cost but this is the kind of stuff that moves the needle and goes down as critical pivot points in history. 

Just my thought for the day...

--Lee

ISCT 2009 Corporate Tutorials and Symposia

Here is a listing of the corporate tutorial and symposia sessions being held at the International Society for Cellular Therapy conference Sunday-Wednesday in San Diego. For more information see www.celltherapy.org.

	ISCT 2009 Corporate Tutorial and Symposium Listing

			Sunday May 3, 2009 Time: 3:00pm – 5:00pm / Grand Ballroom B Miltenyi Biotec
			Emerging treatments enabled by cellular therapy ……………………………………………………………………………………………………………… Chairperson: Shelly Heimfeld, PhD, Fred Hutchinson Cancer Research Center, Seattle, WA, USA Topics and Speakers: Notch-mediated expansion of human cord blood stem/progenitor cells: cell processing and translation to the bedside ……………………………………………………………………………………………………………… Shelly Heimfeld, PhD / Colleen Delaney, MD, MSc, Fred Hutchinson Cancer Research Center, Seattle, WA, USA NK cell therapy in the pediatric leukemia ……………………………………………………………………………………………………………… Wing H. Leung, MD, PhD, St. Jude Children's Research Hospital Memphis, Memphis, TN, USA Antiviral T cell immunotherapy—present and future perspectives ……………………………………………………………………………………………………………… Mark W. Lowdell, PhD, FRCPath, MICR, Royal Free & University College London, London, UK The role of cell processing in the emerging regenerative medicine applications ……………………………………………………………………………………………………………… Denis-Claude Roy, MD, FRCP(C), Hopital Maisonneuve-Rosemont, University of Montreal, Canada

Monday May 4, 2009 Time: 7:30am – 8:30am / Nautilus 4 WuXi AppTec

Topics and Speakers: Validation of a rapid PCR method for the detection of mycoplasma contaminants according to European Pharmacopoiea 5.8, 2.6.7, 2007. Use in release testing of cell therapy products. ……………………………………………………………………………………………………………… Garry B. Takle, Ph.D. Vice President, Operations. WuXi AppTec Philadelphia. Recent publication of a revised section for mycoplasma testing in the European Pharmacopoeia (5.8, section 2.6.7) has led to interest in validating a nucleic acid amplification technique for use in detection of mycoplasma contaminants in cellular therapies. The replacement or supplementation of the existing culture based methods with a PCR-based method has several advantages for the biopharmaceutical industry, mainly with respect to turnaround time for results, and cost. Replacement or substitution of existing methods by a PCR method requires the demonstration of equivalent assay LOD and specificity. The experimental requirements for this comparability validation have been spelled out in detail in the EP section referenced above. In this presentation, we describe the validation and comparability analysis of a PCR method exactly according to the EP guidance. Completion of this validation activity has resulted in the availability of an assay that meets or exceeds EP compliance requirements for a mycoplasma detection method. Comprehensive testing panels for cellular therapeutics. ……………………………………………………………………………………………………………… Chris Larson, MS., Lab Manager, Cell Biology and Flow Cytometry. WuXi AppTec, Philadelphia. In this presentation WuXi AppTec will describe the current regulatory landscape for appropriate testing programs for cellular therapies, focusing on safety and identity assays. A multiuse contract manufacturing facility for the production and release of cellular therapies. ……………………………………………………………………………………………………………… John Bermel, Sr Manager, Cell banking/Cell therapy. WuXi AppTec, Philadelphia. WuXi AppTec will present a summary of the design and operation of the contract GMP cell therapy and cell banking facility located within the Philadelphia site. Design, start up and validation activities will be discussed with reference to specific projects and case studies.

Monday May 4, 2009 Time: 12:15pm - 1:30pm/ Nautilus 2 CellGenix Technologie Transfer GmbH and American Fluoroseal Corporation

Topics and Speakers Application of DC Maturation and T Cell Expansion in a Clinical Setting ……………………………………………………………………………………………………………… Dr. Gunnar Kvalheim, Radium Hospital - Oslo, Norway Purpose: Description of methods and materials for DC maturation and autologous T cell expansion in cancer therapy and a report of clinical outcomes. Expansion of Young Tumor Infiltrating Lymphocytes (Y-TIL) as a Therapeutic Agent in Cancer Treatment ……………………………………………………………………………………………………………… Dr Nina Garlie, Aurora-St. Lukes Medical Center - Milwaukee, WI. Purpose: Description of materials and methods used for a therapeutic Y-TIL expansion protocol Description of Materials and Methods for Cord Blood Expansion with Clinical Outcomes ……………………………………………………………………………………………………………… Dr. Colleen Delaney, Fred Hutchinson Cancer Center - Seattle, WA Purpose: The application of double cord transplants with one expanded cord using cytokines and notch ligand, and one cord left unmanipulated in cancer therapy.

Tuesday May 5, 2009 Time: 7:30am – 8:30am / Nautilus 5 Invitrogen

Come join the leading innovators in cell therapy for a breakfast session on safer cell therapies. One of the key concerns of regulatory agencies around the world is ensuring that candidate cell therapies for clinical trials and ultimate approval have adequate safety profiles. During this session, four leading industry experts will share the technologies and strategies they have identified and employed at different stages of cell therapy development to ensure phase-appropriate safety profiles and streamlined regulatory review of their clinical products. Chair Eric Roos, Business Development Leader, Stem Cell Therapy, Life Technologies Corporation Panelists Leslie Wolfe, PhD, VP, Technology Development, Cellular Therapies, Genzyme Biosurgery Patricia Whelton, Senior Director, Regulatory and Process Development, Osiris Therapeutics, Inc. John T. Kemshead, PhD, Director, Clinical Affairs, Baxter Cellular Therapies For more information on the session: www.invitrogen.com/isctmeeting Register for the breakfast session: www.invitrogen.com/isct-register

Tuesday May 5, 2009 Time: 12:30pm – 1:30pm / Nautilus 1 Pall Medical

Culture and expansion of cord blood MNCs enriched by the Pall Purecell Select System, a new alternative to density gradient Description Enriched MNCs are used for variety of research and clinical applications. The new Pall Purecell™ Select System is a rapid, easy to use, single use disposable for the isolation of Mononuclear cells (MNC) from whole blood and other samples. Purecell Select System was evaluated for enrichment of MNCs from cord blood samples in two different research studies with direct comparison to cells isolated by density gradient method. In one study, enriched cells were subsequently used for CD34+ cell selection followed by hematopoietic progenitor cell expansion. In the second study, MNC enriched cells were used for production of Endothelial Colony Forming Cells (ECFCs®). Results of these studies will be presented and participants will walk away from the tutorial with an awareness of how the Purecell Select System can be suitable for certain research applications and it’s potential future use in clinical cell manufacturing processes. Speaker Christine Smith-Steinhart, PhD EndGenitor Technologies, Inc.

Tuesday May 5, 2009 Time: 12:30pm – 1:30pm / Nautilus 2 Biosafe SA

From Stem Cell Banking to Bedside Biosafe is honoured to have 2 renowned experts presenting some of the leading advances in the field of cellular therapy. Topics and Speakers Dr. Joanne Kurtzberg, Chief of Pediatrics and Blood & Marrow Transplantation at Duke University, NC, USA will provide an overview of the Carolinas Cord Blood Bank, one of the world’s largest and most respected public cord blood banks, before presenting recent developments in the use of cord blood to treat non-haematopoietic diseases. Dr. Riccardo Saccardi from the Haematology Department, Careggi University Hospital, Florence, Italy, will present the different work performed by his laboratory in the study and therapeutic use of cellular products. Careggi is Europe’s leading transplant centre for autoimmune diseases and Dr. Saccardi will go on to discuss the use of stem cells in the treatment of such diseases.

Tuesday May 5, 2009
Time: 12:30pm – 1:30pm / Nautilus 3


BioLife Solutions Inc.

Biopreservation Yield in Cell Therapy: Process Optimization From Source Material to Finished Product Description Participants in the Biopreservation Yield in Cell Therapy: Process Optimization workshop will experience presentation and discussion of a new class of preservation media products which result in the optimization of supply chain logistics and biopreservation processes in hypothermic storage and cryopreservation of various biologic source materials and manufactured cell therapy products. In addition, this workshop will provide a new and detailed understanding of preservation induced cellular injuries and the resultant impact on functional yield of source material and clinical therapeutic yield of manipulated cell therapy products. Critical analysis of traditional post-preservation assay type and timing and how the status quo impacts therapeutic effectiveness of cell therapy products will be introduced through the review of scientific data and selected case studies. This data will support cumulative yield improvements of source material and manufactured cell therapy products using BioLife Solutions’ HypoThermosol® and CryoStor™ products. Speaker Ian B. Nicoud, Ph.D., Director of Technology & Business Development Bio Dr. Nicoud served as an intellectual property and technology consultant for BioLife and joined the Company in September 2007. He has a strong background in transplantation medicine and preservation biology and holds a Ph.D. in Cancer Biology from Vanderbilt University and a B.S. in Biology from Saint Norbert College. He is a co-author of several of the Company’s recent patent applications and manages BioLife’s intellectual property portfolio and technology licensing activities.

Wednesday May 6, 2009 Time: 12:00pm – 1:00pm / Grand Ballroom B STEMCELL Technologies Inc.

Topics and Speakers Expansion of Mesenchymal Progenitor Cells (MPCs) in a Novel Serum- and Animal Component-Free Culture Medium ………………………………………………………………………………………………………………. Ravenska Wagey, PhD Senior Scientist, STEMCELL Technologies Inc. To address the need for serum-free MPC culture, STEMCELL Technologies has developed a novel serum- and animal component-free culture medium which promotes superior clonogenic growth and long-term expansion whilst maintaining multi-lineage differentiation potential of human bone marrow-derived MPCs. Dr. Ravenska Wagey will present performance characteristics of the medium as well as optimal procedures for the isolation, characterization and expansion of MPCs. A Rapid Hematopoietic Colony Assay for Measuring the Potency of Umbilical Cord Blood Grafts ………………………………………………………………………………………………………………. Michelle Bowie, PhD Global Product Manager, STEMCELL Technologies Inc. To meet the need for rapid and easy-to-use potency assays, STEMCELL Technologies has developed a new hematopoietic colony assay that can be completed in 7 days, is easier to score than standard CFU-assays and provides accurate measurement of hematopoietic progenitor cell frequencies in cord blood units that correlate well with results of standard CFU-assay formats. Dr. Michelle Bowie will present an overview of the hematopoietic CFU assay as well as the performance characteristics of STEMCELL’s 7-day CFU-assay.

Will the real regenmed association please stand up?

Further to my post on this topic back in September last year and ongoing discussions I have been having, I have decided to create a quick 4-question poll to get your opinion.

I am not representing anyone or any organization with this survey. I'm out on a limb on my own. I'm curious to see your response to this quick 4-question survey.

Click here to see the survey.

CIRM & friends join efforts for one-day focus on translating stem cells into products

This is my public service announcement for the week. ISCT continues to stack on the value to it's annual meeting this year in San Diego with the recent announcement that ISCT, CIRM, and ISSCR are collaborating to bring a unique cell therapy translational development workshop to California.

Translation of Stem Cell Therapies:
Best Practices and Regulatory Considerations

Sheraton San Diego Hotel and Marina

Saturday, May 2, 2009

DRAFT PROGRAM

7:00am – 7:50am Registration

7:50am – 8:00am Welcome + Introduction

8:00am – 10:00am Introduction to Translation of Stem Cell Therapies
Session chair: EJ Read MD

CIRM’s Initiatives for Translation of Stem Cell Therapies
Marie Csete, MD PhD (CIRM)

FDA’s Approach to Stem Cell Therapies
Kimberly Benton PhD (FDA/CBER/OCTGT)

IND Planning & Preparation for Stem Cell Therapies
EJ Read, MD (BSRI/UCSF-CTSI)

CMC Preparation & Pitfalls for Stem Cell Therapies
Darin Weber, PhD (Biologics Consulting Group)

Q&A/Panel Discussion


10:00am – 10:20am Break


10:20am – 11:50pm Late-Stage Translation: Cell Banking and GMP Manufacturing Models
Session chair: Shelly Heimfeld PhD

Cell Banking: FDA Perspective
Brenton McCright PhD (FDA/CBER/OCTGT)

Banking/Manufacturing Approach for Banked, Off-the-Shelf hESC-Derived Allogeneic Product (Oligodendrocytes, for spinal cord injury)
Anthony Davies, PhD (Geron)

Manufacturing Approach for a Banked, Off-the-Shelf Allogenic Fetal-Derived Product (CNS Stem Cells, for neurology applications)
Stewart Craig, PhD (StemCells Inc)

Manufacturing Approach for a Patient-Specific Allogeneic Expanded Cord Blood Progenitor Cell Product
Shelly Heimfeld, PhD (Fred Hutchinson Cancer Research Center)

Q&A / Panel Discussion


11:50pm – 12:50pm Lunch


12:50pm – 2:20pm Mid-Stage Translation: Assay Development and Preclinical Safety Testing
Session chair: Darin Weber PhD
FDA panelists: Theresa Chen PhD, Thomas Finn PhD

Assay Development for Stem Cell Products
Melissa Carpenter, PhD (Carpenter Group)

Preclinical Safety Program for Myeloid Progenitor Cell Product for Neutropenia and Radiation Injury
Holger Karsunky, PhD (Cellerant)

Preclinical Safety Program for hESC-Derived Products for Neurology Applications
Hans Keirstead, PhD (California Stem Cell and UC-Irvine)

Q&A / Panel Discussion


2:20pm – 3:20pm Mid-Stage Translation: Process Development and Product Characterization
Session Chair: Shelly Heimfeld PhD

FDA Perspective on Development & Characterization Issues
Thomas Finn, PhD (FDA/CBER/OCTGT)

Universal Donor Adult Stem Cell Product (for cardiovascular and other applications): Development and Characterization
Robert Deans, PhD (Athersys)

Gene-Modified Adult Stem Cell Product (for neurology applications): Development and Characterization
Casey Case, PhD (SanBio)

Q&A / Panel Discussion


3:20pm – 3:40pm Break


3:40pm – 4:20pm Early-Stage Translation: Challenges for Developing Combination Products
Session chair: Darin Weber PhD

Case study: Development of a Complex Combination Product (Device + Cells + Genetic manipulation)
B. Lynn Allen-Hoffman. PhD (Stratatech)

Q&A

4:20pm – 5:30pm Early-Stage Translation: Induced Pluripotent Stem Cells
Session chair: Marie Csete MD PhD

IPS cells in Amyotrophic Lateral Sclerosis
Evangelos Kiskinis, PhD (Harvard Stem Cell Institute)

IPS cells in Spinal Muscular Atrophy
Clive Svendsen, PhD (U of Wisconsin)

5:30pm – 5:40pm Wrap Up

5:45pm – 7:15pm Reception

Cell Therapy Industry HiLites 2009-03-27

Here's a big thank you shout out to the growing cadre of great readers, subscribers, and participants in the network of cell therapy colleagues I'm proud to be part of whether it is here on this blog or on our LinkedIn Cell Therapy Industry Group. We're proving cell therapy means business! Keep up the outstanding repartee.

In keeping with the biblical proposition that "nothing new is under the sun", a new physician group as been formed to "oppose FDA's position on adult stem cells". The newly formed "American Stem Cell Therapy Association (ASCTA)" this week posted its manifesto online and issued a press release saying the "organization was formed in response to the Food and Drug Administration's (FDA) recent position that the adult stem cells found in everyone's body are drugs, a position the ASCTA opposes." I'm not sure which move the FDA made recently that would make these docs think this is the FDA's recent position. As I wrote on this blog back in September last year, doctors have been trying to tell the FDA that cell therapy is the "practice of medicine" for years and it hasn't worked. Of course, it will come as no surprise to you that central to this new movement of doctors lobbying for the right to treat patients with their own stem cells however they see fit, is Dr. Chris Centeno of Regenexx and other doctors like Dr. Zannos Grekos who are involved with stem cell treatment clinics marketing to US patients for clinics performing their magic outside the USA.

In a classic case of overstating the point, ASCTA member Dr. Frank Falco states, "The FDA's position against someone using their own stem cells is taking it too far." Of course, saying that is the FDA's position, is taking his point too far but subtleties like that don't get people engaged in a revolution!

Enough of that. On to the news & analysis. It wasn't a great week for cell therapy with Osiris stopping its phase III trial for Chron's and all but that had more to do with the difficulties of designing good clinical trials than it did cell therapy.

FINANCIAL

Intercytex Group Plc (AIM: ICX) announced it is in talks which may lead to an offer for the company. In February, the company said it was reviewing options, including a possible sale or merger, after it stopped work on Cyzact, one of its main products, to preserve cash. The company's product Vavelta has reportedly now treated 120 people in a commercial setting and its ICX-SKN skin graft replacement for burns and acute wounds is fully funded by the US Armed Forces Institute of Regenerative Medicine. Inercytex reported revenues of £17,000 for the year.

*

Taiwan is angling to be one of the major biotech hubs of Asia by making biotechnology the country's third major industry in the next 10 years. To that end, it has proposed a $1.76 billion dollar VC fund. The Taiwan government's National Development Fund will have a 40 percent stake in the venture, and the private sector will see to the other 60 percent. The economic development plan also calls for the establishment of a biotech incubation center that will introduce new medicines to existing biotech parks. Taiwan has a strong interest in cell therapies and the country's regulatory authority(the BFDA) is investing heavily in establishing a well-defined regulatory framework for cell, gene,and tissue based products. Unlike Singapore's investment in stem cell research, Taiwan appears to be positioning itself to support later-stage commercial entities already working on translation of research into clinical products.

CLINICAL

And here's the big news of the week. Osiris Therapeutics, Inc. (NASDAQ: OSIR) announced it was stopping its phase III clinical trial of Prochymal for the treatment of acute Crohn’s disease (CD).

The good news? It was not for safety concerns. The decision was made after the trial's final scheduled interim analysis showed that one of the two Prochymal dose arms (they don't know which because that has not yet been unblinded) in one of the two trials in the program had crossed a futility boundary (would not achieve statistical significance) according to the study's DSMB.

Osiris’ phase III CD program consisted of 2 trials, and induction trial (S-603) and a maintenance trial (S-610). The Study-603 “Induction” trial was randomized into three arms, one-high dose Prochymal (400M cells for the 1st two infusions and 200M cells for the next two) , one low-dose Prochymal (200M cells in the 1st two infusions and 100M cells in the next two) and placebo. After 28 days of dosing, patients were evaluated by a subjective evaluation for a reduction in the Crohn’s disease activity index (CDAI). Patients with a 100-point drop in CDAI score according to the self-evaluation were then eligible for re-randomization into the longer-term Study-610 “Maintenance” trial. It is this design that management now believes presented an inducement for patients to "over-report" improvements so as to be eligible to participate in the longer, subsequent trial. This is evidenced, they believe, by the fact that 56% of the participants in the in the S-603 program enrolled in the S-610 program when they would have expected the number to be more around 30 - 40%.

The other pieces of good news to salvage out of the day are (a) Genzyme supports the decision, and (b) the trial had already enrolled 210 of its expected 270 patients. Osiris is going to complete the study as if it were a 210-patient study in hopes that there is significant data from the trial that can not only be used in redesigning subsequent trials but also to bolster Prochymal’s overall safety database. Regarding Genzyme's position, this is certainly reason for them to be disappointed but this saves them milestone payouts in the short-term and they are not on the hook for the additional costs that will be incurred because of the decision so as long as they still believe in the fundamentals of the product, they have no reason to pull out of the relationship now.

Randy Mills spent some time in a webcast on Friday explaining the details of what transpired, the decision, what they theorize went wrong or was wrong with the trial, and where they anticipate going from here. He made it very clear a number of times that there is no reason to believe this will have any impact on the Prochymal trial for GvHD. One of the other things he explained was that Osiris never believed this current phase III program for Crohn's was going to be sufficient to support a BLA. They had always anticipated another phase III trial. What Randy didn't say was whether this decision would mean another one or two trials would be required.

Analyst Jason Napodano is on record stating he believes "it could be a year or so before Osiris can re-initiate the Crohn’s program, which will most likely include two separate phase III trials, one induction and one maintenance, but once initiated the program should enroll quickly given management’s experience from just halted program and the inclusion of several additional new centers that did not participate the first time." Despite the setback he believe the news presents a buying opportunity for Osiris shares which were down as much as 22% in Friday's trading.

He believes "Osiris remains financially sound and should exit 2009 with over $100 million on the books" and expects "Prochymal will be on the market in the U.S. by the end of next year for GvHD". They have a target of $25 per share.

In Friday's investor teleconference, Randy stated he expects the company will be reporting top-line data on the Prochymal trial for steroid-refractory GvHD in 3Q 2009 given that enrollment in that trial is already complete and, based on enrollment rates for the acute GvHD trial, he expects to be reporting data from that trial in the same Quarter.

*

Neurotech Pharmaceuticals, Inc. announced that the Company's lead product candidate, NT-501, substantially slowed the loss of vision in a Phase 2 clinical trial in subjects with dry age-related macular degeneration involving geographic atrophy. NT-501 is an intraocular implant that consists of human cells that have been genetically modified to secrete ciliary neurotrophic factor (CNTF) which is delivered directly to the back of the eye in a controlled, continuous basis by means of the Company's proprietary Encapsulated Cell Technology platform, thereby bypassing the blood-retinal barrier. The Phase 2 study is a multi-centered, randomized, double-masked, sham-controlled study of 51 subjects with GA. Patients received either a high or low dose NT-501 implant or a sham treatment in one eye only. The high dose of NT-501 stabilized best corrected visual acuity at 12-months, with 96.3% (p=0.078) of treated-patients losing fewer than three lines of vision, or 15 letters, versus 75% of the patients in the sham-treatment group.

What I find interesting about the study is that five devices from this trial have now been explanted 12 months following implantation and all have been found to have uniformly healthy, viable cells that continue to produce therapeutic levels of CNTF. This is reportedly consistent with data from multiple trials of NT-501 in which, to date, 23 devices have been explanted between 12 and 18 months following implantation and all devices have contained healthy, viable CNTF-producing cells.

The clear implication is that the implanted devices would continue to excrete therapeutic levels of CNTF longer than the 1-year threshold for the study. This is proof-of-principle for Neurotech's Encapsulated Cell Technology platform which may well have sundry other applications.

*

Will Dendreon's unblinding and announcement of interim analysis data for Provenge back in October be its final bad decision? Four top statisticians say Dendreon may have compromised the integrity of the trial by putting out the release. They say it was unorthodox for Dendreon to even know such a detailed result, much less to publicize it. The danger: The company, patients or doctors might have changed what they were doing once they knew how the study was going. If the final outcome is only marginally statistically significant, it might be tossed, putting Dendreon and its drug back at square one. The statisticians are left scratching their heads at the data release. "I have no idea what their rationale would have been," says Susan Ellenberg, a statistician at the University of Pennsylvania. "I can't rule out the possibility that they did have a reason I'd be comfortable with, but I can't think what it might be."

*

Finally there is some news about a US company treating patients in a clinic outside the US in a way that many would say has hallmarks of scientific credibility. Two years ago DaVinci Biosciences, headquartered in Costa Mesa, California, treated 52 acute and chronic spinal cord injury patients in Ecuador with injections of their own bone marrow-derived stem cells. They conducted follow-up studies and have now published the results for the first 8 patients in issue 17(12) of Cell Transplantation. The follow-up report claims that MRIs have revealed "noticeable morphological changes within the spinal cord after administration of autologous bone marrow derived stem cells." There was no tumor formation, increased pain or deterioration of function following administration of the stem cell treatment. The researchers conclude that the therapy proved safe and effective in improving their quality of life. Although there are plenty of stem cells clinics claiming anecdotal evidence (not published in peer-reviewed journals) of the therapeutic effect of such treatments and there have been numerous studies in animals demonstrating the benefits of stem cell treatment for the treatment of spinal cord injury, this may be the first published study of its kind.

COMMERCIAL

In what is now becoming a trend between large pharma and research institutes, the Salk Institute announced a strategic alliance agreement with Sanofi-Aventis establishing the Sanofi-Aventis Regenerative Medicine Program (SARP). Financial terms of the three- to five-year agreement were not revealed.

Saying that the program was without "restrictive preconditions", the announcement was vague on details about the anticipated nature of the collaboration other than it would sponsor "institute-wide discovery grants in promising research areas that address the organizations’ mutual interests" It was also unclear what types of results or products Sanofi expected to get from the program other than "research retreats and "extended working lab visits". The San Diego Business Journal reports that Sanofi-Aventis will have the option to license any discoveries that result from the collaboration. It's not clear to me how this fits with the deal Salk made last year when it partnered with another French pharmaceutical company, Ipsen, in a deal worth $10 million over five years. It's also not clear to me if this is an investment in cell as therapies or more about cells as tools. We can not necessarily infer the former simply from the "Regenerative Medicine" name put to the program.

*

Stratatech Corp. announced that it has launched the StrataTest® human skin model. Composed of both an epidermis and a dermis, the StrataTest® human skin model is said to display the physical, chemical and histological characteristics of native human skin. The tissue is supplied in a 24-well format for consumer product testing, drug discovery and toxicity screening.The StrataTest® human skin model, which is intended for research use only, is manufactured using Stratatech’s proprietary NIKS® human keratinocytes. Stratetech believes the product offers a "superior, cost-effective, in vitro testing skin model that it believe enables better prediction of in vivo biological response for consumer product, drug discovery and other toxicity testing applications.”

*

Stepping into a space owned primarily by MaxCyte and Lonza's Amaxa BioSystems, Invitrogen, a division of Life Technologies (NASDAQ:LIFE) announced the launch of it's "Neon Transfection Device", a bench-top device for the delivery of DNA, RNA, and proteins into a wide range of mammalian cell types, especially difficult to transfect cells, such as many types of primary and stem cells. The Neon Transfection Device is reportedly well suited for gene and siRNA delivery into stem cells, features a unique transfection chamber that minimizes cell death, has minimal reagent requirement, and works with many different cell types.

*

Progenitor Cell Therapy, LLC (PCT) announced that Lisa Doria-Cavuoto will be joining the company as Vice President of Commercial Cell Therapies, effective April 1, 2009. In this role, she will be responsible for managing the day-to-day business operations of PCT's commercial stem cell processing, storage, and clinical distribution service.

*

Former GE Healthcare & Thermogenesis executive, Dan Segal, is heading up a newly minted private cord blood bank in Orange County, California called PacificCord.

RESOURCES, EVENTS, & MISCELLANEA

ISCT has released a call for Late Breaking Abstracts in the following categories:

• Mesenchymal and Tissue Stem Cells
• Hematopoietic Stem Cells
• Gene Therapy
• Immunotherapy and Dendritic Cells
• Cell and Tissue Evaluation
• Lab Practices
• Legal and Regulatory Affairs
• Translational Process Development
  

Deadline for Submissions: April 3, 2009. Notification of Abstract Status: April 10, 2009

Click here to submit.

Sign-off...

I spoke this week to an American-trained plastic surgeon now practicing in Asia. In 2006 he paid (presumably handsomely) to attend a symposium hosted by 3 European "professors" on commercial "cell therapy" techniques that are being sold today in select jurisdictions and which could bring longevity and youthfulness to clients everywhere and, I assume, fame and fortune to the doctors brave enough to sell them. One was "live stem cell therapy" using rabbit fetal cells and the other was "fresh/frozen cell therapy" using cells from sheep embryos (or placenta?). He was so impressed he bought into the program, tried it on himself, his family, and then, convinced it was safe, started to sell it to clients. The good doctor I spoke with was using the sheep product, as many others are doing, and administering them not topically but intra-muscularly for "skin rejuvenation".

Long story short, he is now being prosecuted by his Medical Council for providing non-evidenced based medicines. Here's the rub. This all sound quite ghastly to many of us but there is at least one clinic in Switzerland that has been injecting sheep cells into people for over 50 years without any apparent safety issues and to the endless, anecdotal accolades of clients who claim enhanced youthful visages, energy, sex drive, longevity, etc. What's more, there is an internet site where you can buy sheep placenta capsules and even human placenta injectibles. I won't link to any of these sites because I don't want to give them the web traffic but a quick Google search will lead you to multiple clinics and distributors.

I don't envy the position of regulators. As much as a clear and enforceable regulatory framework is critical to the industry, so is a strong and properly financed regulatory authority. Equally important is that we as an industry be vigilant in protecting the quality of our science, our medicines, and our patient's health. We are not grappling with easy issues here. Perhaps the injection of sheep or rabbit fetal cells are the cure-all they are reported to be but what it they're not and we're injecting them into human for non-life-threatening conditions?

...

That's the kind of week its been. Feel better about yourself and tell a friend about the Cell Therapy Blog today! :-)

Cell Therapy Industry HiLites 2009-03-25

I am more intrigued every day by the potential for identifying opportunities in the convergence of cell therapies, diagnostics, personalized medicines, theragnostics, regenerative medicine, and more traditional biotechnologies and pharmaceuticals.

I wonder to what extent we will look back on these primitive days of ex vivo cell therapy and chuckle at its ephemeral but educational existence much like betavision or pervasive therapeutic bloodletting. I suspect many of these therapies will have a role in future medicine but I'm starting to believe more and more that the future of cell therapy will be more about in vivo manipulations than ex vivo manufacturing.

In an attempt to catch up from my brief hiatus and to have more frequent and less tome-like posts, I bring you this mid-week edition of Cell Therapy Industry HiLites.

___________________________________________________________________

Contact Lee [at] celltherapygroup [dot] com

____________________________________________________________________

FINANCIAL

Given the continued extraordinary market conditions, NASDAQ has further suspended enforcement of the rules requiring a minimum $1.00 per share. closing bid price and a minimum market value of publicly held shares until Monday, July 20, 2009. Good new for many including Aastrom Biosciences, Inc. (Nasdaq:ASTM) which now has until September 18, 2009 to regain compliance with the $1.00 minimum closing bid price rule in order to remain listed on the Nasdaq Capital Market.

As promised, International Stem Cell Corporation (OTCBB:ISCO) has received the third $1 million tranche of an anticipated private equity financing of up to $5 million the remainder of which is says will be funded over the next several months.

Now that Cell Genesys, Inc. (NASDAQ:CEGE) has no products to develop things are looking up for it! The company reported financial results for the fourth quarter and full year ended December 31, 2008. The company reported a net loss of $13.3 million ($0.15 per fully diluted share), for the fourth quarter of 2008, compared to a net loss of $33.4 million ($0.43 per fully diluted share) for the corresponding period in 2007. The net loss for the year ended December 31, 2008 was $47.0 million ($0.56 per fully diluted share), compared to a net loss of $99.3 million ($1.39 per fully diluted share) for the year ended December 31, 2007. As of December 31, 2008, the Company had $86.1 million in cash, cash equivalents and short-term investments. The Company currently expects to have approximately $73 million and $69 million in cash, cash equivalents and short-term investments at March 31, 2009 and June 30, 2009, respectively. The Company continues to explore strategic alternatives, including merger with or acquisition by another company, further restructuring, allocation of its resources toward other biopharmaceutical product areas, and sale of the Company’s assets and liquidation of the Company.

CLINICAL

As a result of ongoing and active discussions in our LinkedIn Cell Therapy Industry Group, it has come to my attention thatprivately-held Harvest Technologies Corp - a company known for its bone marrow and platelet concentrate devices - has entered into the therapeutics business. It recently obtained an Investigational Device Exemption (IDE) from the FDA to conduct a randomized, controlled, double-blind, multicenter clinical trial using the Company’s BMAC System to prepare a composition of bone marrow stemcells to treat patients with Critical Limb Ischemia (CLI). This “feasibility trial” will enroll a total of 48 subjects. Subjects who enroll in this study will have to have exhausted all surgical and procedural options and are at extreme risk for major amputation. The BMAC System is a point-of-care device for concentrating a patient’s own (autologous) bone marrow stem cells in approximately 15 minutes at the bedside. The clinical study design provides for injecting these cells into the affected limb to reduce the potential for limb amputation. It also will offer data with respect to the safety of this procedure.

What's even more interesting is that reportedly the company has submitted an investigation device exemption for a double-blind placebo cardiac safety study—to inject BMAC cells into the myocardium during bypass surgery in patients with severely compromised heart function.

This presents an interesting regulatory pathway for a couple of business models both in providing point-of-care devices and providing therapeutic service employing such devices. More on that in an upcoming blog (and in our LinkedIn discussions).

The Indian Council of Medical Research and the Drug Controller General of India is said to have now approved protocols Bangalore-based firm Stempeutics Research for multi-center phase I/II double blind randomized clinical trials of bone marrow derived ex vivo cultured adult mesenchymal stem cells for Elevated Acute Myocardial Infarction and Critical Limb Ischemia. The cells are to be administered by injection.

COMMERCIAL

MultiCell Technologies, Inc. (OTC Bulletin Board: MCET - News) announced it has entered into a cooperative research and development agreement with Maxim Biotech, Inc. to develop products for the study of liver stem cells and liver cancer. The cooperative research and development agreement with Maxim Biotech, Inc. will initially focus on the development of a family of life science research reagent tool kits which can be used to isolate liver stem cells, and help to elucidate liver stem cell gene function and their encoded proteins. MultiCell plans to further leverage this research effort involving liver stem cells to identify therapeutic targets, and diagnostic and prognostic markers of liver cancer. MultiCell will also seek to develop and patent therapeutic product opportunities specifically targeting the treatment of primary liver cancer and intrahepatic bile duct cancer.

Kosdaq-listed RNL Bio (famous for dog cloning) faces a KFDA ban on its cosmetic containing human-derived stem cells.

J&J's Therakos, Inc. announced the U.S. Food and Drug Administration (FDA) approval of the THERAKOS™ CELLEX™ Photopheresis System for the palliative (reducing the severity of symptoms) treatment of the skin manifestations (appearance) of cutaneous T-cell lymphoma (CTCL) that are unresponsive to other forms of treatment. The THERAKOS™ CELLEX™ Photopheresis System is a system that uses extracorporeal (outside the body) photopheresis (ECP) cell therapy to relieve the symptoms of CTCL. The system also has been cleared recently in Canada and Europe. The new THERAKOS™ CELLEX™ Photopheresis System is said to feature several improvements over but retain the primary benefits of the predecessor THERAKOS™ UVAR™ XTS™ Photopheresis System. The improvementa are said to open up this treatment option to patients for whom it was previously unfeasible including lower weight patients.

Stem Cell Therapy International, Inc. (OTCBB: SCII) decided it was worthwhile to announce that they are in "strategic meetings" with unnamed "global stem cell representatives" and they are "not wasting any time...with the merger of Stem Cell Therapy International, Inc. and Histostem, Ltd. of South Korea" to create the newly name company, AmStem International. Now that's great news.

StemCelDigest.net outlined the single-digit degrees of similarity between companies (STEM, ISCO, ACT) pursuing stem cell solutions for diseases of the retina. Other companies in this space include the Pfizer-backed EyeCyte and UK's ReNeuron.

RESOURCES & EVENTS

Watch for an announcement from ISCT announcing a call for late-breaking abstracts.

Jon Rowley (Lonza) reports that there is more stem cell content - from science to manufacturing - at BIO2009 this year. Dare we think it's not a bubble this time?

Sign-off

A proposal to change the name of the American Society of Gene Therapy (ASGT) to the American Society of Gene and Cell Therapy (ASGCT) has been nanimously approved by the Board of Directors and the proposal is now being forwarded to the general membership of the Society for a final vote in April of 2009. In an editorial in December issue of Molecular Therapy, Membership Committee Chair and Past ASGT President, Savio LC Woo, stated that the Membership Committee has recommended that the following concrete steps,among others, be implemented to maximize its positive impact.

• First, the term “cell therapy” must be included in the Society’s mission statement.
• Second, the Society’s leadership should contact the leadership of the International Society for Cellular Therapy (ISCT) to assure them that our name change represents an opportunity for both societies to collaborate and advance our common interests and to initiate a dialogue with them onthe needs and interests of cell therapists so as to better recruit these researchers into our society.
• Third, the Society leadership should reach out to leading investigators and the research communities in adult and ES cell biology as well as iPS cell biology.
• Fourth, the Program Committee should ensure that cell therapy is richly represented in the symposium programs of the Society’s annual meetings.
• Fifth, the Nominating Committee will need to make a concerted effort to identify and nominate prominent cell therapists into the Society’s leadership positions.
• Finally, the editorial team of Molecular Therapy—the Society’s official journal—is encouraged to increase even further the important efforts they have made over the past few years to recruit Editorial Board members with expertise in cell therapy and stem cell engineering, in additionto continuing their successful solicitation of outstanding articles in these areas.
  

Professional organizations, it seems to me, are facing the collective pressures of increasing financial constraints, the rise of online access to publications minimizing the need for member-rate subscriptions, and the networking power of online social networks, all combining to make their value proposition much less obvious to many - particularly the younger set.

I understand ASGT's desire to ensure its mandate stays relevant and inclusive of all aspects of therapies employing genes. I also believe the increasing overlap between organizations representing "cell therapy" is not in the best interests of the sector. While ISCT remains the only organization with cell therapy of all types at the core of its mission, AABB has encroached into the cell therapy space from the blood banking side, ISSCR from the basic stem cell research end of the spectrum, ASBMT from the clinical stem cell transplant side, TERMIS from the tissue enginering, and now ASGT (following the precedent set by ESGT-ESGCT) from the gene therapy end.

As C. Mason & P. Dunhill wrote last year in Regenerative Medicine, what the industry needs is a strong voice generated by a powerful industry association. As long as we continue to create more silos of representation, we will continue to stray farther away from what's needed. While I have strong ties to ISCT and continue to serve that organization in several capacities, I am increasingly frustrated by the dilution of this nascent industry's time, money, and efforts spread over too many organizations and conferences without creating the voice for industry that is needed.

I'm not sure where this frustration will take me but my increasing conviction is that the companies in the cell therapy sector are ill-represented in any organization and spattering attempts at representation throughout all of them (including BIO which has to-date all but ignored the sector) is increasingly insufficient.

Am I off base here? Is this a real need or am I making something out of nothing? What do you think?