Date of Hearing: May 8, 2019

ASSEMBLY COMMITTEE ON APPROPRIATIONS

Lorena Gonzalez, Chair

ABPCA Bill Id:AB 617

Author:(Mullin) – As Amended Ver:May 1, 2019

Urgency: No State Mandated Local Program: No Reimbursable: No

SUMMARY:

This bill requires the Medical Board of California (MBC) to convene the Stem Cell Clinic Regulation Advisory Group to review whether consumer protections are adequate and requires the board to adopt emergency regulations, if appropriate, to protect the consumers from stem cell therapies that are not in compliance with federal laws and regulation.

FISCAL EFFECT:

One-time costs to the MBC convene an advisory group of about $100,000 on regulation of stem cell therapy (Medical Board Contingent Fund).

COMMENTS:

1. Purpose. According to the author, California has been a leader in the research and development of stem cell therapies— and this has spurred both effective treatment and unproven or ineffective therapies. The author believes more must be done to ensure the proper regulation of for-profit stem cell clinics.
2. Background. Stem cells are cells from which other cells are made. They divide to form more cells called daughter cells, and these daughter cells either become new stem cells or specialized cells, such as blood cells or brain cells. According to the Mayo Clinic, stem cell therapy, also known as regenerative medicine, promotes the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives.

The U.S. Food and Drug Administration (FDA) is authorized to regulate stem cell products. The FDA has raised alarms about the potential danger of unproven stem cell therapies. They note, for instance, attendees at a 2016 FDA public workshop discussed a patient who became blind due to an injection of stem cells into the eye and another patient received a spinal cord injection that caused the growth of a spinal tumor. Some therapies are FDA-approved or being studied through an FDA-approved clinical investigation plan, but others are unregistered and may offer unproven therapies that are marketed for thousands of dollars.

The FDA has stepped up enforcement, taking action, for instance, to prevent the use of a potentially dangerous and unproven treatment belonging to StemImmune Inc. in San Diego in 2017. FDA inspections confirmed a vaccine that was not commercially available was used to create an unapproved stem cell product, which was in turn administered to cancer patients with potentially compromised immune systems and for whom the vaccine posed a potential for harm. The reach of FDA enforcement appears limited to more egregious cases of consumer harm.

1. Prior Legislation. AB 512 (Roger Hernández) Chapter 428, Statutes of 2017, requires stem cell clinics in California to post a specified notice on site when non-FDA approved stem cell therapies are provided.

Analysis Prepared by: Lisa Murawski / APPR. / (916) 319-2081

Date of Hearing: April 23, 2019

ASSEMBLY COMMITTEE ON HEALTH

Jim Wood, Chair

ABPCA Bill Id:AB 617

Author:(Mullin) – As Amended Ver:April 22, 2019

SUBJECT: Stem Cell Clinic Regulation Advisory Group.

SUMMARY: Requires the Department of Public Health (DPH) to create a Stem Cell Clinic Regulation Advisory Group (SCCRAG) to determine appropriate regulations for stem cell therapies. Specifically, this bill:

1. Defines “HCT/Ps” to mean “human cells, tissues, or cellular or tissue-based products” as specified under federal law.
2. Defines Stem Cell Therapy to mean therapy involving HCT/Ps.
3. Requires the DPH to convene the SCCRAG by February 1, 2020 for the following purposes:
   1. To review current licensing and certification laws and DPH’s procedures to determine whether those laws and procedures provide for adequate consumer protection for the use of stem cell therapies in clinics;
   2. To make recommendations to the Legislature, on or before July 1, 2020, regarding how to improve state oversight of clinics offering or providing stem cell therapies to patients; and,
   3. To adopt, if appropriate, emergency regulations to protect the public against stem cell therapies that are not in compliance with federal laws and regulations, including regulations adopted by the federal Food and Drug Administration (FDA). Requires DPH to consult relevant stakeholders prior to promulgating regulations and provide a 90-day notice to stakeholders prior to adopting regulations.

EXISTING LAW:

1. Establishes, in the California Constitution, through the passage of Proposition 71 in 2004, the California Stem Cell Research and Cures Act (the Act) and the California Institute for Regenerative Medicine (CIRM), to provide $3 billion in bond funding over a period of 10 years to fund stem cell research. Requires the Independent Citizens Oversight Committee of CIRM to establish certain standards for the use of the funds provided by the Act, including a prohibition against compensation to donors or participants of the research, beyond reimbursement of expenses.
2. Requires stem cell clinics in California to post a specified notice on site when non-FDA approved stem cell therapies are provided.
3. Exempts any clinic from the notice requirements in 2) above when stem cell therapies offered are approved an Investigational New Drug (IND) from the FDA.
4. Requires the Medical Board of California to publish complaints, disciplinary actions, and administrative actions regarding licensees providing stem cell therapies.
5. Establishes, under federal law, the Food, Drug, and Cosmetic Act, which grants authority to the FDA to oversee the safety of food, drugs, and cosmetics.
6. Requires, under federal regulation:
7. Clinical trial sponsors to submit an IND application to the FDA for clinical investigation of a new drug or new indication of an approved drug, with certain exceptions;
8. Review and approval from an Institutional Review Board (IRB) before a clinical study can be initiated under an IND;
9. Defines an IRB as an appropriately constituted group that has been designated to review and monitor biomedical research involving human subjects, to ensure that a clinical trial is ethical and that the rights of study participants are protected; and,
10. Authorizes an IRB to approve, require modifications in, or disapprove research, or to suspend or terminate approval of research that is not being conducted in accordance with the IRB's requirements or that has been associated with unexpected serious harm to subjects.

FISCAL EFFECT: This bill has not yet been analyzed by a fiscal committee.

COMMENTS:

1. PURPOSE OF THIS BILL. According to the author, California has been a leader in the research and development of stem cell therapies. As a result of California’s leadership, doctors have used stem cells to treat patients with cancer and disorders of the blood and immune system and other conditions. The author states that the motivation behind this bill is the growing number of for-profit stem cell clinics that have bypassed the FDA’s approval process and are offering unproven treatments to patients which sometimes cause harm and/or patients’ spending money they cannot recover. In other words, this is an issue of consumer safety and consumer protection. The author states that as the Chair of the Select Committee on Biotechnology, they have heard from patients who have experienced both sides of the treatment continuum. The author concludes that it is clear that more must be done to ensure the proper regulation of for-profit stem cell clinics.
2. BACKGROUND. Stem cells are the precursor cells that develop into blood, brain, bones, and organs. Stem cells have the ability to divide and develop into many different cell types in the body during early life and growth. Stem cells may also help repair the body by dividing to replenish cells that are damaged by disease, injury, or normal wear. When a stem cell divides, each new cell has the potential either to remain a stem cell or to become another type of cell with a more specialized function, such as a nerve cell, a skin cell, or a red blood cell. Three types of stem cells have been identified: a) adult stem cells; b) human embryonic stem cells; and, c) induced pluripotent stem cells. Their promise in medical treatments is that they have the potential to repair, restore, replace, and regenerate cells that could then be used to treat many medical conditions and diseases.
   • 1. FDA guidance and approval. Stem cells, like other medical products intended to treat, cure, or prevent disease generally require FDA approval before they can be marketed. Current federal law requires sponsors of a new drug to submit to the FDA an IND application and to then conduct a series of clinical trials to determine the safety, efficacy, and pharmacological effects (including toxicity, side effects, incompatibilities, and interactions) of the drug. These include Phase I, II, and III clinical trials under FDA regulations. Results are submitted to the FDA to obtain final approval. Unfortunately, a growing number of for-profit stem cell clinics have bypassed the FDA review process and are selling unproven treatments to patients, with sometimes harmful results.

In response to the rise in stem cell use, the FDA published draft guidance on the minimal manipulation of human cells and tissues, including stem cells. The FDA draft guidance states that FDA approval is necessary when cells are utilized and altered beyond their original function in the body, as they can be classified as a biological drug. The FDA guidance also provides advice for consumers to ask their physician if the necessary FDA approval has been obtained or if you will be part of an FDA-regulated clinical study. The FDA recommendations also apply to treatments that use a consumer’s own cells, such as adipose, or fat cells.

Currently, there is only one FDA-approved stem cell therapy which utilizes a blood transplant (such as from bone marrow or umbilical cord) to replace a patient’s blood or immune system. For more than 50 years, doctors have been using bone marrow transplants to transfer blood stem cells to patients, and more advanced techniques for collecting blood stem cells are now being used to treat leukemia, lymphoma and several inherited blood disorders. Umbilical cord blood, like bone marrow, is often collected as a source of blood stem cells and in certain cases is being used as an alternative to bone marrow transplantation.

• • 1. Stem cell clinics. According to a 2018 report in the Journal of American Medical Association entitled, “Unproven But Profitable: The Boom of U.S. Stem Cell Clinics” there were over 500 documented for-profit stem cell clinics as of 2016 and this industry has been growing at a rate of 90-100 more stem cell clinics per year. One in five of every stem cell clinic is located in California.

For-profit stem cell clinics that have bypassed the FDA review process and are selling unproven treatments to patients, with potentially harmful results. Currently, in regards to for-profit stem cell clinics, there is no public registry of these clinics, nor any specific licensing authority at the state or federal level, and the FDA has only been able to respond to cases where clinics have caused repeated consumer harm.

• • 1. Stem cell treatment and complications. In the past year, there have been numerous news articles depicting a number of stem cell therapies that have caused harm to the consumer. According to the Centers for Disease Control and Prevention in the past year, at least 17 individuals across five states were hospitalized after being injected with therapeutic products made from umbilical cord blood. These particular illnesses have been identified as bacterial infections that have caused swollen spinal disc, infected bones and joints, and abscesses on their backs. Of the 17 infections, 15 have been linked to a single California based company that sells vials of a solution containing umbilical cord blood that they market to ‘stimulate regenerative healing.’ The FDA has given out warnings to the company and the stem cell clinics involves in these bacterial infections.

Another potential harm that could arise with unproven stem cell therapeutics are with those that utilize a patient’s own adult stem cells. According to data provided in the 2015 Journal of Cell Stem Cell study, treatments provided by stem cell clinics often utilize stem cells from the adipose (fat) tissue or bone marrow. By using the patient’s own stem cells, the treatment may avoid donor-to-host immune rejection problems as sometimes seen with donated cells. The retrieval of stem cells from the patient is achieved through procedures like liposuction or bone marrow aspirate, after which the cells are isolated using enzymes, and re-injected into the patient at the site of the disease or injury. The FDA warns that some complications can occur when stem cells are implanted into new sites in the body that differ from the origin of the stem cells. For example, using bone marrow stem cells to treat a neurological disease like Alzheimer’s places the cells into a foreign environment, where they have a decreased chance of alleviating symptoms and more likely to result in adverse side effects. A 2017 publication in the New England Journal of Medicine entitled “Vision Loss after Intravitreal Injection of Autologous “Stem Cells” for AMD” reported that three women suffered severe, permanent eye damage after adipose stem cells were injected into their eyes to treat macular degeneration.

The aforementioned examples are just some of the most publicized and dire reports of adverse outcomes related to unproven stem cell therapies. These therapies are marketed anywhere from $2,000 to $20,000 for consumers. In additional to harmful side effects, according to a Washington Post article in 2018, a Cornell University regenerative medicine researcher tested nine products and found that they did not contain stem cells at all, thus there is also a question of oversight to ensure that products are not misleading, which is already prohibited by federal law.

1. SUPPORT. According to the California Institute for Regenerative Medicine (CIRM), clinics are charging patients thousands of dollars for stem cell injections purported to treat ALS, Parkinson’s disease, stroke and other diseases. These clinics are preying on vulnerable patients while putting patient’s physical and economic health at risk. CIRM concludes that the media is replete with stories about the harm done to patients when injected with cell-based products that are not appropriate for their diseases and/or do not meet rigorous safety standards.
2. PREVIOUS LEGISLATION. AB 512 (Roger Hernández) Chapter 428, Statutes of 2017, requires stem cell clinics in California to post a specified notice on site when non-FDA approved stem cell therapies are provided.

REGISTERED SUPPORT / OPPOSITION:

Support

California Institute for Regenerative Medicine

Opposition

None on file.

Analysis Prepared by: Marissa Kraynak / HEALTH / (916) 319-2097