Saturday, January 08, 2005

Introduction

In the most recent development in this matter, on January 6th the FDA denied an application for 'emergency IND' authorization to resume cord blood transfusions to an ALS patient who had previously benefited from cord blood transfusions with no ill effects.

This denial ignored a request by four U.S. Congressmen and one U.S. Senator for the FDA to give its prompt, humane approval.

The following presents the history of this matter.

After learning of positive effects gained through transfusions of whole, untreated human umbilical cord blood in mice with an animal model of ALS, several dozen American patients and their families wished to try this approach towards slowing this fatal, disabling disease that has no cure, no effective treatment, and for over 95% of patients no known cause.

The following slides present email correspondence between Mrs. Marisabel Alcalde, daughter of an ALS patient, and Ms. Lorrie Harrison McNeil, Director of Consumer Affairs for FDA’s Center for Biological Evaluation. The purpose of this contact was to determine the FDA’s position regarding the use of human umbilical cord blood to treat Mrs. Alcande’s father.

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Friday, January 07, 2005

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FDA/Patient Correspondence: Notes & Comments

Note 1: the FDA considers cord blood cells to be the same as hematopoietic stem cells.

Note 2: Cord blood cells are not subject to FDA pre-market review or approval.

Note 3: Cord Blood is not approved for any specific use.

Note 4: FDA “IND” authorization is not required for cord blood, or cord blood stem cells provided the cells are only minimally manipulated prior to use.

Comment 1: If cord blood is not subject to FDA pre-market approval or review, then the FDA has no business concerning itself in this matter, or inhibiting qualified medical practitioners from using cord blood in treating patients.

Comment 2: Cord blood can not be approved for any specific use, since it’s not subject to pre-market review or approval. For the same reason, nor can it be barred from specific uses.

Comment 3:An IND is required when using cord blood stem cells that have been more than minimally manipulated prior to use. However, this does not apply to the present case, as the patients were receiving transfusions of whole, untreated cord blood.


The following slides present an inquiry by U.S. Senator Joseph Lieberman (D-CT) into FDA actions that blocked ALS patient access to cord blood transfusions.

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Notes on Senator Lieberman's Inquiry

1) According to correspondence in Senator Lieberman’s possession, the FDA had indicated to families and physicians of ALS patients that no regulations barred ALS patients from receiving transfusions of whole, untreated umbilical cord blood.

2) Despite these assurances, in 2003 the FDA contacted two American physicians treating ALS patients in this manner, instructing them that the FDA required that they apply for- and be granted IND approval to continue the treatments.

3) This ended all development of this therapy. The prohibitive labor and costs of filing for an IND and conducting a controlled clinical trial under IND guidelines were well beyond the means of these private practitioners.

4) Patients who had received initial therapeutic benefits from transfusions of whole, untreated cord blood were barred from further treatment.


The following slides present the FDA's response to Sen. Lieberman's inquiry.

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FDA Response: Notes, Comments, & Questions

Note 1: The FDA states that “cord blood stem cells” are biological products subject to the Federal Food, Drug, and Cosmetics Act and the Public Health Services Act.

Comment: These treatments involved no stem cell extraction or manipulation. They involved transfusions of whole, untreated cord blood.

Comment: Cord blood contains stem cells, as does human blood from any source. However, unrelated transfusions of ‘human blood’ are not regulated or restricted by FDA stem cell policies. Nor is cosmetic surgery involving liposuction, although human fat also contains stem cells. Nor are liver transplants, despite liver’s well-known hepatic stem cell content.


Note 2: The FDA claims to have maintained a consistent policy in regulating the use of “cord blood stem cells” since 1993, citing an Oct. 14th, 1993 Federal Register including “cells obtained from cord blood.”

Comment:The question here is not whether the FDA’s stem cell policy has remained constant, but whether its policy (and legal authority) concerning whole, untreated cord blood have changed. The FDA initially states (to Mrs. Alcalde) that whole, untreated cord blood from is not subject to FDA pre-market review or approval. It now claims that whole, untreated cord blood is subject to FDA ‘stem cell’ regulations, and requires an IND for non-hematopietic use.


Note 3: The FDA claims it does not have a separate policy for cord blood use regarding ALS applications.

Note 4: Therapeutic use of “cord blood stem cells” that are unrelated to the donor (allogeneic), more than minimally manipulated, or used other than their normal functions represent a “biological product” and thus require clinical testing under IND guidelines and FDA pre-market approval.

Note 5: FDA does not require IND submission when allogeneic cord blood is used for hematopoietic reconsititution.

Note 6: Because the use of allogeneic cord blood in treating ALS does not represent hematopoietic reconstitution, its use for ALS requires an IND approval.

Comment: How can the FDA claim it has “no separate policy” regarding cord blood use for ALS, when immediately following this claim it admits to having a totally different policy regulating its use for hematopoietic reconsititution?

Comment: FDA claims that its “flexibility” concerning cord blood’s use for hematopoietic reconsititution does not “change the fact that cord blood is not licensed for any application.” FDA’s position in both matters stems not from its compassionate “flexibility,” but rather from the fact that whole, untreated cord blood is not subject to pre-market review or approval.


Note 7: The FDA denies that the original request in this matter addressed cord blood use for ALS, but rather concerned its use for hematopoietic reconstitution.

Comment: All correspondence between the FDA and the patient’s mother was under the subject, “Administration of Human Cord Blood into ALS Patients.” This includes three letters written by Ms. Lorrie Harrison-McNeal, Director of Consumer Affairs for FDA’s Center for Biological Evaluation and Research. (One is presented here; two others are available through Congressman Smith’s office.)


Note 8: The FDA claims its “laws and regulations are flexible enough to allow patients with few alternatives to have access to promising, but unapproved treatments while preserving the system of well-controlled clinical trials.”

Comment: Clearly this is not the case. In fact, the FDA’s actions in this matter may have hastened the tragic decline of several ALS patients who had no alternatives at all. Without further explanation these actions can only be considered an irresponsible, arbitrary, capricious breach of Public trust.


QUESTIONS

1) If whole, untreated cord blood is not subject to pre-market review or approval, why is the FDA impeding qualified physicians from treating patients in this matter?

2) If the FDA now claims that treatments using transfusions of whole, untreated cord blood are ‘stem cell’ treatments, what process was used to arrive at this position, when was it determined, and by whom?

3) If the FDA’s Lorrie Harrison McNeil believed her correspondence with Mrs. Alcalde concerned hematopoietic reconstitution, why did she repeatedly email Mrs. Alcalde under the subject “Administration of human cord blood in ALS patients?”

4) How can the FDA claim (to Senator Lieberman) that it has “no separate policy” regarding cord blood use for ALS, when immediately following this claim it admits to having a totally different policy regulating its use for hematopoietic reconstitution?

5) How can the FDA claim to have been “consistent in its stem cells policy since 1993,” when (according to Director Harrison-McNeil) prior to 2003 this policy did not regulate the use of whole, untreated cord blood, but now it does?

6) Has the FDA ever placed an IND requirement on a biological product that it had already approved, or that was already widely in use without specific approval? If so, what was the product and what was the reason?

7) Has the FDA ever placed an IND requirement on a pharmaceutic product that it had already approved, or that was already widely in use without specific approval? If so, what was the product and what was the reason?

8) Prior to its present ruling regarding the use of cord blood for ALS, has the FDA previously required an IND for the use of whole, untreated blood transfusions of any type for any reason?

9) If the FDA does have pre-market and IND authority over the use of whole, untreated cord blood, but it “chooses” to permit cord blood’s unregulated use for hematopoietic conditions, why does it choose to block patients from benefiting from possible uses of cord blood for non-hematopoietic conditions?

10) Does the FDA have any evidence that cord blood transfusions to an individual without immunosuppression is any more dangerous that blood transfusions?

11) If a physician had scientific evidence that blood transfusions in an ALS patient slowed the disease process would the FDA require the physician to obtain an IND before he could administer the blood?

12) How can the FDA claim that its “laws and regulations are flexible enough to allow patients with few alternatives to have access to promising, but unapproved treatments while preserving the system of well-controlled clinical trials” when the FDA’s actions in this matter clearly disprove this claim?
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The Petition
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Cord Blood Research
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Letters of Anger and Hope
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FDA says "No!" to Congressional request