Celltex Under Fire by the FDA

A week ago the FDA released its 483 inspection report relating to Celltex Therapeutics Corporation’s practices banking and facilitating the administration of adult stem cells for therapeutic purposes.  News sources (here and here) and the Center for Genetics and Society published portions of its startling findings.  Celltex processes, multiplies, distributes, and facilitates the injections of mesenchymal cells derived from adipose tissue using technology licensed from RNL Bio based out of Seoul, South Korea.  Prominent physician Carl Elliot, MD, PhD and bioethicist Leigh Turner, PhD have both expressed public concern about Celltex’s seemingly flagrant circumvention of FDA regulatory standards, licensing partnership with a controversial corporation, and conflict of interest in the oversight of its operations.

Since its opening in December 2011, Celltex is the largest stem cell bank in the US and facilitates the process and supplies the product for individuals seeking to receive stem cell injections, charging a hefty fee ranging from an estimated $20,000-$30,000 for its services.  It has garnered significant publicity arising in part from Texas Governor Rick Perry’s support, his personal use of stem cell injections for a back injury, and Perry’s push for state legislation to create a state adult stem cell banking initiative and revise Texas Medical Board regulations relating to physicians’ ability to administer non-FDA approved stem cell “treatments” to their patients.

Back in February, Turner compiled a letter of listed concerns relating to Celltex’s practices, requesting that the FDA investigate the company’s practices.  Turner and other media sources have pointed out the following, along with other issues:

Celltex has not offered substantial data or clinical trials to show the stem cells it offers are safe and efficacious.   In January 2012 the FDA issued a Consumer Health Information guide cautioning consumers to make sure that any stem cell treatment they consider has been approved by the FDA or is subject to a current protocol submitted to the FDA to ensure that the stem cells are safe, effective, and have undergone adequate and well controlled clinical trials.  Furthermore, the FDA must oversee the manufacturing process to assure the products’ safety, purity, and potency.

If individuals are receiving experimental injections, Celltex and the physician should thoroughly explain that the procedure is experimental medical research rather proven clinical medicine and the risks associated with the procedure.  Both the FDA and physician commentators have noted that patients seeking to have cells injected face safety risks arising from the procedure, even if they are the patient’s own stem cells and the corporation follows good manufacturing practices.  Jamshid Lofti, MD, a neurologist who has administered injections to more than 20 patients has admitted the need for controlled trials, but has problematically downplayed such risks, asserting that “the worst that can happen is it won’t work.”  Not according to the FDA and numerous other physicians, who list potential risks to include tumors, cancer, and even death.  Such risks are at the forefront of investigation (see here and here) into partner company RNL Bio’s practices in South Korea, where former patients and their families have come forth with allegations of cancer and death linked to receipt of RNL Bio’s stem cells. 

Celltex contends that it merely processes and expands individuals own stem cells, only minimally manipulates the cells, and is currently coordinating prospective clinical studies.  According to Nature, Celltex coordinates with physicians and pays physicians $500 per injection, and each patient receives at least three injections.  Celltex argues that the process of culturing and preparing the stem cells does not constitute the manufacture of a biological drug, so the process stands outside the scope of FDA regulations normally required for biological drugs.  A Colorado court is currently examining this issue arising from the practices of another company Regenerative Sciences, who proffered a similar argument to avoid applicability of FDA requirements. 

However, Rita Chappelle, a spokesperson for the FDA’s Center for Biological Evaluation and Research asserts that any “expanded” cells cannot be considered minimally manipulated.  Importantly, the FDA’s 483 inspection form classifies Celltex as a biological drug manufacturer in the business of manufacturing mesenchymal  stem cells rather than minimally manipulating stem cells.  Independently of how Celltex classifies its processes, the 483 report made news headlines based on the number of alarming deficiencies in the processing and manufacturing procedures.  It found Celltex failed to validate processes to prevent contamination; to distinguish between components being quarantined or approved; to routinely calibrate and check the equipment; to review quality processing systems; and could not guarantee the sterility, uniformity or integrity of the cells.  Celltex’s press release in response is here.

Had there been any uncertainty about the scope of FDA regulation, the Consumer Health Information guide back in January clarified that the manufacture of stem cells must undergo FDA review.  Yet Celltex continued its operations charging clients tens of thousands of dollars for unproven and unregulated “treatments,” evaded FDA’s clarification, and exposed consumers to additional risks based on its manufacturing deficiencies detailed in the 483 inspection.  More problematically, associated figures such as Gov. Perry and physicians who administer the injections provide the imprimatur of  Celltex’s practices- creatively flouting regulatory requirements, downplaying risks of the procedure, and reaping hefty profits.  Even in the name of therapeutic progress and statewide economic growth, it is time for the FDA to set an example that such disregard for its jurisdiction and review process will not be tolerated. 

--Katherine Drabiak-Syed

Second Lawsuit Against Texas Department of State Health Services Over Alleged Misuse of Newborn Blood Spots

Last week parents in Texas filed a lawsuit against Texas Department of State Health Services (TDSHS) relating to the storage and distribution of their child’s newborn blood spots (NBS). Emerging approximately a year after a settlement over the NBS last December, this news headline looked like déjà vu. The new lawsuit focuses on the gaps of last December’s settlement agreement of the prior case against TDSHS and facts discovered after the settlement.

This separate class action lawsuit led by parent Jeffrey Higgins takes issue with how and for what purposes TDSHS shared the NBS. During the Beleno suit last year, the Beleno plaintiffs repeatedly asked TDSHS with whom they were sharing the NBS and for what purposes. During each of those discussions in the spring of 2009 and before a House Public Health Committee Hearing, TDSHS maintained it shared the NBS for the purpose of public health research but disclosed minimal additional information.

However, a large number of NBS were not used for public health research and this information did not become public until after the settlement. TDSHS numerous NBS to for-profit entities such as Perkin Elmer and bioMerieux in exchange for laboratory supplies. TDSHS only fully shared the extent of how many samples it shared, with what entities it shared the samples, and for what reasons on its website as part of the settlement agreement.

Perhaps most shocking, however, was that TDSHS sent 800 NBS to the Armed Forces Institute of Pathology (AFIP) to build a mitochondrial DNA (mtDNA) registry. AFIP designed this registry as a forensics tool to identify missing persons, solve old crimes, and eventually, share the samples internationally for law enforcement and anti-terrorism efforts. An investigative report that discovered this project surfaced in the media months after the settlement agreement in the Beleno case. [Read our commentary on the mtDNA registry here.]

The Higgins lawsuit focuses on TDSHS’s lack of transparency during the Beleno settlement discussions and alleges that TDSHS intentionally withheld pertinent information that would have substantially altered that case’s discussions and outcome. Similar to the Beleno complaint, Higgins argues that selling or trading the NBS to outside corporations and giving the NBS to the AFIP to build the mtDNA registry rises to Constitutional violations.

1. First, he maintains that taking his child’s NBS and sharing it with outside entities without consent constitutes a violation of his child’s right against seizure of deeply private genetic information.
2. Second, he asserts that sharing his child’s NBS without consent constitutes a violation of privacy.

The Higgins complaint emphasizes TDSHS’s alleged failure to disclose significant facts and communicates the plaintiffs’ concerns about misuse of the hundreds of thousands of NBS that were sent to outside entities. Importantly, the settlement agreement last December 2009 only provided that TDSHS was required to destroy the NBS in its possession. This meant the settlement had no legal effect on what other entities did with the NBS they received from TDSHS.

Accordingly, the complaint asks the court for injunctive relief to stop TDSHS from sharing the NBS with outside entities without consent in the future and for the court to order outside entities that previously received the NBS to destroy the blood samples and any associated data they may have. The first request is significant because it directly challenges the current law in Texas that requires parents to opt-out if they do not want TDSHS to use and share their child’s NBS for research and instead argues that TDSHS must actually obtain consent.

Carrie Williams, spokesperson for TDSHS, maintains that these issues have already been resolved and stated that the Texas Civil Rights Project representing the plaintiffs merely wants “to double dip back into this issue with baseless assertions.”

Despite Williams’ response, mounting evidence does show a startling lack of transparency on the part of TDSHS. Furthermore, if the case goes before the same judge that heard the Beleno case, the result may have a substantial impact. As with other highly unexpected court rulings recently relating to gene patents and embryonic stem cell funding, this case could potentially constitute a monumental turn for whether it is acceptable to collect blood to use and share for research by the opt-out method. In the last Beleno case, Judge Biery in the Western District of Texas denied TDSHS’s motion to dismiss, meaning the court planned to hear the merits of the those Constitutional issues. However, before the parties argued the merits they arrived at a settlement agreement, taking the question out of the courtroom.

The case is still in its infancy, and TDSHS has yet to file a response to Higgins’ complaint. As the case progresses and if Judge Biery eventually hears the merits, we may see another highly surprising court ruling impacting future collection of blood for research purposes.

--Katherine Drabiak-Syed

Timeline of Events

• March 2001- December 2010: TDSHS sends NBS to outside entities for various other projects.

• May 2003: TDSHS sends 200 NBS to the Armed Forces Institute of Pathology to build their mtDNA registry.

• December 2006- December 2007: TDSHS sends a total of 3600 NBS to bioMerieux in exchange for laboratory supplies.

• May 2007: TDSHS sends 600 NBS to the Armed Forces Institute of Pathology to build their mtDNA registry.

• March 2009: Parents led by Andrea Beleno (Beleno plaintiffs) file a complaint against TDSHS.

• March 2009: Beleno plaintiffs question where TDSHS has sent the NBS and for what purposes. TDSHS maintains they use and share the NBS for public health research.

• December 2009: Beleno plaintiffs and TDSHS settle the lawsuit out of court.

• March 2010: An investigative report reveals TDSHS sent a total of 800 NBS to the AFIP’s mtDNA registry. TDSHS spokesperson, Carrie Williams, still asserts that this project falls within the category of “public health research.”

• December 2010: Parents led by Jeffrey Higgins file a complaint against TDSHS.

Read past PredictER News coverage relating to newborn blood spots here:

Oklahoma Legislature Requires Express Consent to Retain Newborn Blood Spots

Transparency of Texas' NBS Transfer and Reassessing Evasive Statutory Interpretation

Newborn Blood Spot Banking in Canada

Minnesota Judge's Dismissal of Newborn Blood Spot Case Misses the Mark

Newborn Blood Spot Litigation Continues in Minnesota and Texas

Critiquing HHS's Summary Recommendations on Newborn Blood Spots: Opt-Out is Not Optimal

Newborn Screening: an Update on Minnesota

Minnesota and Genetic Privacy: Why the Rule of Law is Good for Research

See also:

Jere Odell. Newborn Blood Spots, Biobanks, and the Law: Research Ethics in the News. Indiana Bioethics. February 2010.

Katherine Drabiak-Syed. Newborn blood spot banking: approaches to consent. PredictER Law and Policy Update.Indiana University Center for Bioethics. March 12, 2010.

Oklahoma Legislature Requires Express Consent to Retain Newborn Blood Spots

During the past several months, states continue splitting on the issue of how to approach their state health department’s retention and research use of newborn blood spots (NBS).

On September 13, The Edmond Sun ran an article on Oklahoma’s enrolled Senate Bill 1250, a new law that prevents the state health department from storing and using NBS. The text of the law reads:

“A laboratory, medical facility, hospital, or birthing place is prohibited from the unathorized storage, transferring, use, or databasing of DNA from any newborn child without express parental consent.

It being immediately necessary for the preservation of the public peace, health and safety, an emergency is hereby declared to exist…”

Sen. Nichols explained he sponsored the bill as a deliberate pre-emptive measure in response to ethical and privacy concerns related to unauthorized “databasing” and use of NBS in other states. According to Sharon Vaz, the Oklahoma State Department of Health genetics coordinator, Oklahoma only retains the samples for 42 days and does not have plans for long term NBS retention or to use the NBS for research purposes.

Oklahoma’s law demonstrates that different jurisdictions are arriving at starkly divergent interpretations of seemingly simple definitions such as what is or is not encompassed in the meaning of DNA. SB 1250 refers to storing or using DNA, and Sen. Nichols unequivocally explains that he intends this to encompass the retention of NBS- a blood sample. This interpretation is significant because it means the law will use the term DNA to include biological materials from which DNA can be derived.

Unlike Sen. Nichols’ inclusive approach, in late August the Court of Appeals in Minnesota affirmed that NBS do not fall within the definition of “genetic information.” We previously wrote on the Bearder case here. Minnesota has determined that biological samples (such as NBS) that contain DNA and genetic information are not genetic information.

This distinction of separating the source of raw materials (the blood) used for research from the substance of the raw materials (the DNA) is also playing out in the stem cell legal battles- although here, the debate centers around using embryos to create embryonic stem cells v. research using embryonic stem cells. In both arenas, interpreting uncertainty or disagreement of how to apply a law to favor rsearch connects to the decision to splice parts of the process to circumvent barriers to using raw materials.

SB 1250 attempts to rectify several terms that have been disputed when determining the rules for retaining and using biological materials from newborns. Although Sen. Nichols references the law with regard to NBS, the language broadly refers to “DNA from any newborn child,” which would include NBS as well as other biological samples such as umbilical cord blood that contains DNA. This would mean that if an Oklahoma hospital or a partnering research entity wanted to retain and use other biological samples containing DNA from the newborn, the hospital would need to seek parental consent. Furthermore, this law clarifies that the hospital and state health department are not exempt from compliance with the law under a research exception.

Interestingly, the text refers to the law as necessary to preserve the “public peace, health and safety” in Oklahoma. The law is set to be codified in the Oklahoma statute in the same location as crimes consisting of public disturbances, safety hazards, and physical violations against one’s person- examples of tangible harm to indivduals and society at large. This classification itself nods a recognition to the Beleno case in Texas, where plaintiffs’ emphatically argued unauthorized retention of NBS constituted a serious privacy violation and an unlawful seizure of one’s deeply private medical and genetic information.

Whether other state legislatures and health departments agree with Oklahoma’s requirement for express parental consent or the current state of “emergency,” this law reminds us that each jurisdiction should adopt a prospective law or departmental policy to address these questions in a deliberate manner.

--Katherine Drabiak-Syed

Transparency of Texas’ NBS Transfer and Reassessing Evasive Statutory Interpretation

A recent investigative report from the Texas Tribune revealed new information relating to the sharing of newborn blood spots (NBS) in Texas.

In November 2009, Texas Tribune reporters contacted the Texas Department of State Health Services (TDSHS) with a record request to review agency information and activities related to the NBS as permitted under the state’s Sunshine laws. TDSHS refused, maintaining that the NBS records were confidential. After parties filed the settlement with the court, Texas Tribune inquired again to obtain the records and found that TDSHS transferred hundreds of de-identified NBS to the Armed Forces Institute of Pathology to build a mitochondrial DNA (mtDNA) registry.

The Armed Forces Institute of Pathology designed the mtDNA registry as a forensics tool to identify missing persons, solve old crimes, and eventually, share the samples internationally for law enforcement and anti-terrorism efforts. Throughout the plaintiffs’ allegations and questions, TDSHS asserted it was storing and using the NBS for medical research, never mentioning any forensic use even through plaintiffs’ attorney James Harrington specifically inquired how TDSHS used the samples. TDSHS’ provision of information relating to the mtDNA registry would have been both directly pertinent and material to answering plaintiffs’ questions about the NBS disposition and how plaintiffs chose to proceed with the lawsuit.

In addition to the information on the mtDNA registry, the records request also uncovered email communications from the time when TDSHS began storing NBS at Texas A & M University. When the storage began, Texas A & M asked to issue a press release, but a TDSHS official stated that releasing this information made him “nervous” and would “only generate negative publicity.”

Although the decision revealed in the emails prevented public knowledge of storage for research use, it demonstrates a problematic mentality that transparency poses an unnecessary burden. Remaining in the dark about research using NBS is one issue, but failing to disclose (even when asked on several occasions) that the NBS are included in a registry for forensic and future law enforcement purposes creates a multitude of distinct issues. Both explicit knowledge and consent should be required to include one’s DNA in such a database.

Following terms of the settlement agreement, TDSHS’s website lists projects for which TDSHS uses the NBS. The mtDNA registry is now included on this list of projects, and TDSHS spokesperson Carrie Williams maintains that it falls within the category of “public health research.”

Sweeping forensic and law enforcement uses into the definition of public health research warrants close analysis. First, a plain reading of each definition would clearly show that the purpose of research into the causes of autism is not remotely connected to using DNA to identity a suspected criminal. Applying such a definition extends the limits of creative statutory interpretation too far. Second, states’ legislatures have attempted to impose limits on the use of NBS and other biological samples by creating exemptions or abbreviated pathways when the samples are used for public health research. Including forensic and law enforcement purposes ignores this precision and opens the possibility that samples would be shared for even more uses that would not disclosed to the public because the state health department could use this precedent to assume this use also would constitute “public health research.”

The potential for negative publicity alone should not serve as a barrier to transparency, but rather encourage public education for why TDSHS thought giving NBS to the mtDNA registry (with proper consent) would be beneficial. Dodging specific inquiries related to the uses of NBS, failing to disclose that they were given to this registry, and subsequently classifying the registry as a public health project have created even more of a publicity nightmare than TDSHS could have imagined. Other state health departments may be wise to assess whether their own policies encourage transparency, public engagement, and a sincere interpretation of what projects constitute public health research.


--Katherine Drabiak-Syed

Newborn Blood Spot Litigation Continues in Minnesota and Texas

The litigation occurring in Minnesota and Texas regarding the unauthorized retention and research use of newborn blood spots (NBS) continues, and has developed into respective battles seeking judicial recognition for a property and privacy interest in one’s genetic material from which governmental entities such as state health departments are not exempt.

In September 2009, the Minnesota district court heard the defendants’ motion to dismiss and motion for summary judgment in Bearder et al. v. Minnesota et al. (MDH). MDH argued that there are no genuine issues of material fact so the court could simply rule as a matter of law in its favor to exempt the application of the Minnesota Genetic Privacy statute to the state health department's activities as well as preclude any of the plaintiffs’ privacy claims. Following this interpretation, two active bills in the Minnesota House (HF 1341) and Senate (SF 1478) seek to alter Minnesota state law by creating a compliance exemption for the state health department.

According to Bearder et al.'s attorney Randall Knutson, the parties are waiting for the court’s ruling, which is scheduled for return before December 18, 2009. Plaintiffs contend that NBS are genetic information, individuals have a property and privacy interest in their DNA, both tort and Constitutional law protect these interests, and they seek to compel MDH’s compliance with the Minnesota Genetic Privacy Act.

Bearder et al.’s memorandum of law submitted to the court prior to the hearing developed concerns related to MDH’s continued noncompliance with the Minnesota Genetic Privacy Act. Mark McCann, Manager of Public Health Laboratory in the Newborn Screening Program testified before the Minnesota Senate that “the number of parents who have given consent to store…the residual dried blood spots with the Minnesota Department of Health is zero” and despite the Minnesota Genetic Privacy Law requiring that the MDH obtain parental consent for retention and research use, according to McCann, actually obtaining consent is not a current practice.

The memorandum also describes the intersection of problematic shortcomings related to parental requests for destruction, “de-identification,” and research sharing with outside entities such as MDH’s $6 million contract with the Mayo Clinic. According to plaintiffs’ affidavits, some parents were not even told that the specimens would be retained and used for genetic research purposes (undermining the ability to request their destruction) or their requests for destruction were not honored. MDH refers to its system of storing and sharing the NBS as “de-identified” but it provides linked and coded NBS to the Mayo Clinic, retains the key to re-link the specimens (meaning they are not in fact “de-identified,”) and admits there is no standardized procedure for this process.

In Texas, the companion case Beleno et al. v. Texas Department of State Health Services et al. (TDSHS) asserts that individuals have a fundamental privacy interest in their DNA, which exists even absent any statutory provision specifically recognizing genetic privacy. On September 22, 2009, the Texas district court judge denied TDSHS’s motion to dismiss, meaning the court would schedule a hearing for the merits of the case unless the parties arrived at an alternate settlement. The Texas Civil Rights Project which represents plaintiffs indicated that the parties are in settlement negotiations, but as of November 20, 2009, parties have yet to sign an agreement.

Even if parties reach a settlement, Beleno et al.’s arguments used in this case merit pause and further examination. In plaintiffs’ response to defendants’ motion to dismiss, Beleno et al. argue that the defendants committed unlawful and unreasonable seizure, because although parents may have consented to providing the NBS for screening tests, they did not consent to the retention and research use of NBS. Even if the NBS were de-identified, plaintiffs argue that TDSHS unlawfully seized the specimens if they did not obtain actual parental consent, highlighting that issues of consent and privacy are both distinct yet inextricably linked both in practice and legal analysis. Importantly, Beleno et al. also argue that passive storage even absent any additional research or sharing of NBS constitutes a per se violation of Constitutional and tort privacy principles given the fact that they contain deeply private medical and genetic information.

Independent of how these courts proceed, these two cases continue to ask:

• Do, or should, we have a property or privacy interest arising from tort or Constitutional principles in our genetic material (here, in the form of NBS) that requires consent to transfer this interest?
• Can we minimize the potential for future litigation simply by obtaining parental consent for retention and research use?
• Would creating codified exemptions for state health departments deter or encourage privacy advocates from litigation?
  

-Katherine Drabiak-Syed

Texas: Your Boss, Your Medical Records and the Information Economy

According to the CDC's Public Health Law News (19 March 2008) and the Houston Chronicle, Texas is now the first state in the nation to require (as of Jan. 1, 2008) that insurance providers hand over employees' health records to their employers. Currently, employees have no way of knowing of (or resisting) their bosses' efforts to acquire their medical records.

This new Texas law, HB 2015 [PDF], passed the legislature despite the opposition of the insurance industry. Thus, at least this time, the insurance industry was arguing in favor of protecting patient privacy rights. As L. M. Sixel writes in the Houston Chronicle: "Medical privacy has been protected for years by the most unlikely guardians: insurance companies." But, before we imagine the insurance industry as a giant defending the front lines in the battle to secure the privacy of medical records, we should think about what was really at stake in this legislative tussle: information in the information economy.

Employers argued that they needed access to their employees' medical records to better assess and more wisely purchase health plans for their workforce. Insurers, on the other hand, would want to restrict access to information they already possess; information, which allows them (and not their customers) to make better bets on their investments. Of course, many worry that employers will misuse medical information about their employees, but I doubt that the insurance industry cares much about discriminatory employment practices. Would, for example, the insurer suffer if employees with increased health risks were some how trimmed from an employer's payroll?

Readers of this blog will want to know what this means for the exchange of genetic and other predictive medical information between insurers and employers. According to the Houston Chronicle, there's nothing to fear in Texas, because "employers still cannot obtain health information protected by other state or federal laws, such as HIV status, genetic test results or mental illness". I'm not a legal scholar, so this was news to me. Do we already have federal protections against the discriminatory use of genetic information in the work place? If so, how will the much discussed GINA add to these protections? - J.O.