BILL ANALYSIS Ó
SENATE COMMITTEE ON
BUSINESS, PROFESSIONS AND ECONOMIC DEVELOPMENT
Senator Jerry Hill, Chair
2015 - 2016 Regular
Bill No: AB 159 Hearing Date: June 29,
2015
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|Author: |Calderon |
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|Version: |June 19, 2015 |
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|Urgency: |No |Fiscal: |Yes |
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|Consultant|Sarah Mason |
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Subject: Investigational drugs, biological products, and
devices.
SUMMARY: Permits a manufacturer of a drug, biological product,
or device that has not yet received federal or state approval to
market to make the product available to eligible patients with
an immediate life threatening condition, as specified.
NOTE: This bill was referred to the Senate Committee on Health
first, and was passed out of that Committee on June 10, 2015 by
a vote of 8-0
Existing federal law:
1)Establishes the United States Food and Drug Administration
(FDA) to protect the public health by assuring the safety,
effectiveness, quality, and security of human and veterinary
drugs, vaccines and other biological products, and medical
devices through the Food, Drug, and Cosmetic Act (FDCA). (21
United States Code (USC) § 301 et seq.)
2)Prohibits any new drug from being introduced into interstate
commerce unless an application has been approved by the FDA.
(21 USC § 505 (a))
3)Under regulation: a) Requires clinical trial sponsors to
submit an Investigational New Drug (IND) application to the
FDA for clinical investigation of a new drug or new indication
AB 159 (Calderon) Page 2
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of an approved drug, with certain exceptions; b) Requires
review and approval from an Institutional Review Board (IRB)
before a clinical study can be initiated under an IND; c)
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, d) 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. (21 Code
of Federal Regulations (CFR) Part 312)
4)Establishes the Office for Human Research Protections (OHRP),
which provides leadership in the protection of the rights,
welfare, and well-being of subjects involved in research
conducted or supported by the U.S. Department of Health and
Human Services (HHS). OHRP helps ensure this by providing
clarification and guidance, developing educational programs
and materials, maintaining regulatory oversight, and providing
advice on ethical and regulatory issues in biomedical and
social-behavioral research. (45 CFR Part 46)
Existing state law:
1)Establishes the Sherman Food, Drug, and Cosmetic Law (Sherman
Law), administered by the State Department of Public Health
(DPH), which regulates the packaging, labeling, and
advertising of drugs and devices. (Health and Safety Code
(HSC) § 109875 et seq.)
2)Establishes parameters for the experimental use of drugs,
requiring review by a committee for the protection of human
subjects, consent by the patient or patient's parent or
guardian, and prohibits a person having an ownership interest
in a skilled nursing facility or intermediate care facility
from prescribing an experimental drug for a patient in the
facility. (HSC §§ 11115 - 111545)
3)Prohibits, in the Sherman Law, the sale, delivery, or giving
away of a new drug or device unless it is either:
a) A new drug or new device for which DPH has approved a
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new drug or device application, and has not withdrawn,
terminated, or suspended that approval; or,
b) A new drug, and a new drug application has been approved
for it by the FDA, pursuant to federal law, or it is a new
device for which a premarket approval application has been
approved, and that approval has not been withdrawn,
terminated, or suspended under the FDA. (HSC § 111550)
1)Prohibits a person from manufacturing any drug or device in
California unless he or she has a valid license from the DPH.
(HSC § 111615)
2)Authorizes the DPH to require any manufacturer, wholesaler, or
importer of any prescription ophthalmic device in California
to obtain a license for each place of manufacture. (HSC §§
111615 and 111620)
3)Establishes the Protection of Human Subjects in Medical
Experimentation Act (PHSME Act) which prescribes various
protections for subjects of medical experimentation relating
to a bill of rights; informed consent procedures and
documentation; and, the provision of specified disclosures,
including the right for a subject to give or withdraw consent
freely and without duress. Imposes penalties for violations of
these protections. (HSC § 24170 et seq.)
4)States that any person who violates any provision of the
Sherman Law, if convicted, is subject to imprisonment for not
more than one year in the county jail or a fine of not more
than $1,000, or both the imprisonment and fine. States that
any person who violates the law by removing, selling, or
disposing of an embargoed food, drug, device, or cosmetic
without the permission of an authorized agent of the
department or court shall, if convicted, be subject to
imprisonment for not more than one year in a county jail or a
fine of not more than $10,000, or both the fine and
imprisonment. States that any person who purchases or sells a
foreign dangerous drug or medical device, an illegitimate
product, or suspect product, that is not approved or otherwise
authorized by the FDA or that is obtained outside of the
licensed supply chain regulated by the FDA, California State
Board of Pharmacy, or DPH, is guilty of a misdemeanor and
subject to imprisonment for not more than one year in a county
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jail, a fine of not more than $10,000 per occurrence, or both
the imprisonment and fine. (HSC §111825)
5)Requires health plans and insurers to provide an external,
independent review process to examine plan's coverage denials
of experimental or investigational therapies for individual
enrollees who have a life-threatening or seriously
debilitating condition and who meet other specified criteria.
(HSC § 1370.4)
6)Requires health plans and insurers to provide coverage for all
routine patient care costs relative to the treatment of an
enrollee or insured diagnosed with cancer and accepted in an
FDA-approved cancer clinical trial, Phase I-IV, if the
enrollee's treating physician, recommends participation in the
clinical trial after determining such participation has a
meaningful potential to benefit the enrollee or insured.
(HSC § 1370.6)
7)Licenses and regulates physicians and surgeons under the
Medical Practice Act (MPA) by the Medical Board of California
(MBC) within the Department of Consumer Affairs (DCA). (BPC §
2000 et seq.)
8)Provides that the MBC shall take action against a physician
who is charged with unprofessional conduct, as specified.
(BPC § 2234)
This bill:
1) Enacts the Right to Try Act (Act).
2) Makes the following definitions:
a) "Consulting physician" as a physician and surgeon
licensed under the MPA or an osteopathic physician and
surgeon licensed under the Osteopathic Act who performs
examines the qualified individual and his or her relevant
medical records, confirms, in writing, the primary
physician's diagnosis and prognosis and verifies, in the
opinion of the consulting physician, that the eligible
patient is competent, acting voluntarily, and has made an
informed decision.
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b) "Eligible patient" as a person who has an immediately
life-threatening disease or condition; has considered all
other treatment options currently approved by the FDA, has
been unable to participate in a clinical trial for the
immediately life-threatening disease or condition within
100 miles of his or her home or has not been accepted to
that clinical trial within one week of completion of the
clinical trial application process, has received a
recommendation from his or her primary physician and a
consulting physician for an investigational drug,
biological product, or device (IDBPD); has given written
informed consent for the use of the IDBPD or his or her
legally authorized representative has given written
informed consent on their behalf, has documentation from
his or her primary physician and a consulting physician
that the patient has met these requirements.
c) "Health benefit plan" as a plan or program that
provides, arranges, pays for, or reimburses the cost of
health benefits, including but not limited to, a health
care service plan contract issued by a health care service
plan, and a policy of health insurance issued by a health
insurer.
d) "Immediately life-threatening disease or condition" as a
stage of disease in which there is a reasonable likelihood
that death will occur within a matter of months.
e) "Investigational drug, biological product, or device" as
a drug, biological product, or device that has successfully
completed phase one of a clinical trial approved by the FDA
but has not been approved for general use by the FDA and
remains under investigation in a clinical trial approved by
the FDA.
f) "Primary physician" as a physician and surgeon licensed
under the MPA or an osteopathic physician and surgeon
licensed under the Osteopathic Act.
g) "State regulatory board" as the MBC or the Osteopathic
Medical Board of California (OMBC).
h) "Written, informed consent" as a written document that
has been approved by the primary physician's institutional
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review board or an accredited independent institutional
review board, is signed by an eligible patient or their
legally authorized representative when the patient lacks
the capacity to consent, and attested to by the patient's
primary physician and a witness, that at a minimum, does
all of the following:
i) Explains that the currently approved products
and treatments for the immediately life-threatening
disease or condition from which the patient suffers.
ii) Attests to the fact that the patient, or when
the patient lacks the capacity to consent his or her
legally authorized representative, concurs with the
patient's primary physician in believing that all
currently approved and conventionally recognized
treatments are unlikely to prolong the patient's life.
iii) Clearly identifies the specific proposed IDBPD
that the patient is seeking to use.
iv) Describes the potentially best and worst
outcomes of using the IDBPD and describes the most
likely outcome, including the possibility that new,
unanticipated, different, or worse symptoms might
result and that death could be hastened by the proposed
treatment. Requires the description to be based on the
primary physician's knowledge of the proposed treatment
in conjunction with an awareness of the patient's
condition.
v) Clearly states that the patient's health benefit
plan, if any, and health care provider are not
obligated to pay for the IDBPD or any care or
treatments consequent to use of the IDBPD.
vi) Clearly states that the patient's eligibility
for hospice care may be withdrawn if the patient begins
curative treatment and that care may be reinstated if
the curative treatment ends and the patient meets
hospice eligibility requirements.
vii) Clearly states that in-home health care may be
denied if treatment begins.
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viii) States that the patient understands that he or
she is liable for all expenses consequent to the use of
the IDBPD, and that this liability extends to the
patient's estate, except as otherwise provided in the
patient's health benefit plan or a contract between the
patient and the manufacturer of the drug, biological
product, or device.
1) Clarifies that written consent must be consistent with the
informed consent requirements of the PHSME Act.
2) Authorizes a manufacturer of an IDBPD to make the IDBPD
available to an eligible patient pursuant to the Act, but
clarifies that a manufacturers is not required to make the
IDBPD available to an eligible patient.
3) Authorizes a manufacturer to provide an IDBPD to an eligible
patient without receiving compensation and to require an
eligible patient to pay the costs of or associated with the
manufacture of the IDBPD.
4) Prohibits the Act from expanding or otherwise affecting
coverage provided by health plans or insurers, the Medi-Cal
program, or county organized health systems.
5) Specifies that the Act does not require a health plan or
insurer to provide coverage for the cost of any IDBPD, or the
costs of services related to the use of an IDBPD, under the
Act, but authorizes a health plan or insurer to provide such
coverage.
6) Prohibits an IDBPD from being offered if a clinical trial for
that IDBPD is closed due to the lack of efficacy or for
toxicity. Requires the manufacturer and the patient's primary
physician, if notice is given of closure of a clinical trial
for an IDBPD taken by a patient outside of a clinical trial,
to notify the patient of the information from the safety
committee of the clinical trial.
7) Clarifies that the heirs of an eligible patient, if he or she
dies while being treated by an IDBPD made available pursuant
to the Act, are not liable for any outstanding debt related
to the treatment or lack of insurance for the treatment.
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8) Prohibits a state regulatory board, notwithstanding any other
law, from revoking, failing to renew, or taking any other
disciplinary action against a physician's license based
solely on the physician's recommendation to an eligible
patient regarding, or prescription for, or treatment with, an
IDBPD if the recommendation or prescription is consistent
with protocol approved by the physician's institutional
review board or an accredited independent institutional
review board.
9) Requires the physician's institutional review board or an
accredited institutional review board to biannually report
information to DPH, MBC and OMBC regarding the number of
requests made for an IDBPD; the status of the requests made;
the duration of the treatment; the costs of the treatment
paid by eligible patients; the success or failure of the
IDBPD in treating the immediately life-threatening disease or
condition from which the patient suffers and; any adverse
event for each IDBPD.
10)Prohibits a state agency from altering recommendations made
to the federal Centers for Medicare and Medicaid Services
regarding a health care provider's certification to
participate in the Medicare or Medicaid program based solely
on a recommendation that a patient have access to an IDBPD.
11)Provides that a violation of the Act shall not be subject to
penalties for other violations of provisions of the Sherman
Act.
12)Specifies that the Act does not create a private cause of
action, and that actions taken pursuant to the Act do not
serve as a basis for a civil, criminal, or disciplinary claim
or cause of action, including, but not limited to, product
liability, medical negligence, or wrongful death, against a
manufacturer of an IDBPD, or against any other person or
entity involved in the care of an eligible patient for harm
done to the eligible patient or his or her heirs resulting
from the IDBPD, or the use or nonuse thereof, if the
manufacturer or other person or entity has complied with the
terms of this article in relation to the eligible patient,
unless there was a failure to exercise reasonable care.
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FISCAL EFFECT: This bill is keyed "fiscal" by Legislative
Counsel. According to the Assembly Committee on Appropriations
analysis dated May 13, 2015, this bill will result in minor and
absorbable costs to DPH, MBC, and OMBC to receive and review
biannually reports from institutional review boards on the
requests for treatment with an investigational product.
COMMENTS:
1. Purpose. The Author is the Sponsor of this bill. According
to the Author, while the FDA administers a compassionate use
program which makes investigational drugs and devices
available to terminally ill patients, it often takes months
for patients to become approved for participation in the
program. The Author states that this bill removes barriers
for patients and doctors who believe an investigational drug
or device could be their last hope for survival.
2. Background. According to an April 9, 2015 Health Policy
Brief on the issue of right-to-try laws in Health Affairs,
under current federal regulations, patients with serious or
life-threatening illness have two primary options to access
experimental therapies that may treat their condition but
that have not yet been approved by the FDA: participate as a
human subject in a clinical trial or, for patients who cannot
be enrolled in that trial (because of their medical status or
geographic location, for example), apply to the FDA for
access to the experimental drug under the Expanded Access
Program (also known as compassionate use) (EAP).
According to the brief, clinical testing of an experimental
drug is typically a three-phase process. Phase I trials are
small (20 to 80 patients) and are used primarily to evaluate
safety and dosing ranges, usually in healthy volunteers.
Phase II trials are larger (typically 100 to 300 patients)
and are designed to show early evidence of efficacy in the
patients that the drug is intended to treat. Phase III
trials may include hundreds or thousands of patients and are
used to demonstrate that the drug is effective compared to a
control (such as a placebo or a comparator drug). Typically,
a manufacturer submits an application to the FDA for
marketing approval once a drug has successfully completed
Phase III trials. Any drug company wishing to conduct a
clinical trial must first submit an IND application to the
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FDA, which allows the company to manufacture the drug and
ship it across state lines for use in the trial. The drug
may be only administered to patients who are formally
enrolled in that clinical trial. The study population for
that trial may be limited based on any number of factors,
including specific diagnosis, age, stage of illness, or
comorbidities.
The EAP is an attempt at flexibility in the regulatory
process and to allow patients with no other treatment options
a chance to try therapies they may not otherwise have access
to. The program allows patients who meet certain eligibility
requirements to receive an experimental therapy outside of
the formal clinical research process. An application for
expanded access can be submitted by either the drug
manufacturer or a licensed physician. There are three
categories of expanded access: treatment, single patient, and
intermediate, which are further split into two subcategories.
One is "expanded access INDs," through which the
manufacturer submits a separate IND for a patient or group of
patients, and the other is "expanded access protocols,"
whereby the manufacturer amends the protocol under an
existing IND to include the patient (or patients) seeking
access. Under treatment INDs, a relatively large group of
patients (hundreds or thousands) are permitted to access an
experimental drug, provided that the sponsor is actively
pursuing FDA approval and is in later stages of testing (or
has already submitted trial results to the FDA for review).
According to an article published in the January 15, 2015 New
England Journal of Medicine, the FDA has permitted almost all
expanded access requests regardless of category. The FDA
estimated that by 2006, approximately 100,000 patients had
obtained expanded access to experimental drugs. Between 2010
and 2013, the FDA imposed clinical holds on only 2 of the
2,472 individual, non-emergency protocols, on 1 of 66
intermediate-size requests, and on none of the 41 widespread
expanded-access protocols it received.
The Health Affairs brief states that critics of the EAP have
argued that the application process is unnecessarily
burdensome and lengthy (it is estimated that the IND
application requires about 100 hours to complete), which
discourages doctors and manufacturers from applying. An IRB
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review adds an additional layer of paperwork and potential
delay. These requirements were put in place in response to
highly publicized incidents of harm caused by unsafe drugs.
In the past decade, there have been several attempts made at
the federal and judicial levels to further relax restrictions
on the administration of experimental therapies to terminally
ill patients. One, led by the Abigail Alliance for Better
Access to Developmental Drugs, submitted a Citizen Petition
to the FDA in 2003 requesting that it make experimental
therapies available to terminally ill patients, provided that
the drug had passed Phase I testing. Following several years
of litigation, the DC Court of Appeals ruled against the
Abigail Alliance, stating that terminally ill patients have
no constitutional right to access experimental therapies.
The US Supreme Court subsequently declined to review the
case. Several bills have been introduced in Congress that
aim to relax FDA restrictions on access to experimental
therapies. The most recent of these (HR 4475, the
Compassionate Freedom of Choice Act of 2014) failed to make
it out of committee.
In response to criticisms, the FDA recently sought to provide
a streamlined alternative for submitting an Investigational
New Drug Application (IND) for use in cases of individual
patient expanded access and announced it would simplify and
accelerate the application process for unapproved
investigational drugs that have passed Phase I safety trials.
It is estimated that the new application form will take 45
minutes to complete, asks attending physicians to fill in
eight pieces of patient information, and requires only one
attachment. The FDA issued draft guidance and included a
copy of the new form, asking for comment until April 13, 2015
which is available at
https://www.federalregister.gov/articles/2015/02/10/2015-02561
/individual-patient-expanded-access-applications-form-fda-3926
-draft-guidance-for-industry)
3. Efforts in Other States. Right to try laws are already in
place in Arizona, Arkansas, Colorado, Indiana, Louisiana,
Michigan, Mississippi, Missouri, Montana, North Dakota,
Oklahoma, South Dakota, Utah, Virginia, and Wyoming.
Lawmakers in Tennessee have sent a similar bill to their
governor for approval. Twenty additional states are
considering the law this year. Laws in many states generally
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allow terminally ill patients to have access to experimental
drugs while others also allow health insurers to choose to
provide coverage for the cost of these treatments and remove
liability for physicians for recommending treatments.
4. Related Legislation This Year. SB 149 (Stone) is
substantively similar to this bill and also enacts the Right
to Try Act, permitting a manufacturer of an investigational
drug, biological product, or device to make available an
investigational drug, biological product, or device to an
eligible patient, as defined. ( Status: The bill is pending
in the Assembly Committee on Health.)
SB 715 (Anderson) is similar to this bill and SB 149 above
and permits a manufacturer of a drug, biological product, or
device that has not yet received federal or state approval to
market to make the product available to eligible patients
with terminal illnesses, as specified. ( Status: The measure
is currently pending in the Senate Committee on Health.)
SB 128 (Wolk) permits a qualified adult with capacity to make
medical decisions, who has been diagnosed with a terminal
disease to receive a prescription for an aid in dying drug if
certain conditions are met. ( Status : This bill is pending
in the Assembly Committee on Health.)
5. Arguments in Support. The Amyotrophic Lateral Sclerosis (ALS)
Association Golden West Chapter writes in support of this
bill, noting that there is no known prevention, cause or cure
for ALS and that there is only one FDA-approved drug
available to manage ALS symptoms which is known to extend
life by a few months.
According to the Los Angeles County Board of Supervisors ,
seriously ill patients who have exhausted their options to
find a cure and who have identified physicians and a
pharmaceutical company willing to assist them, deserve the
right to experimental treatments that could improve their
health conditions or prolong their lives.
6.Concerns. The Pharmaceutical Research and Manufacturers of
America (PhRMA) writes with concerns about this bill, stating
that it could have serious unintended consequences that must
be taken into consideration. According to PhRMA, the bill may
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be premature, the FDA already operates the EAP through which
patients are able to access investigational drugs in the early
stages of clinical development, the FDA has announced plans to
streamline the program and it may be prudent for the
Legislature to hold off on passing this bill in order to allow
the federal process to continue.
7.Arguments in Opposition. The Association of Northern
California Oncologists is opposed to this bill for several
reasons, including the difficulty of identifying terminally
ill patients, the danger a right to try outside the context of
a clinical trial would present to clinical trial enrollment
and the lack of appropriate physician supervision of the use
of these drugs. According to the group, any threat to adult
clinical trial enrollment would result in slowing the
development of cancer care in the future.
According to the California Nurses Association and National
Nurses United , this bill promises vulnerable patients and
their families that there will be a state program for
obtaining drugs that is similar to the FDA EAP only shorter,
the bill does not address the real barriers to compassionate
use and nothing in this bill impacts the availability of drugs
to terminally ill patients unless the manufacturers of the
drugs allow it to be used in advance of FDA approval. The
organizations state that the only right that is being promoted
in this legislation is the right of wealthy individuals who
can afford to fund the process and associated costs to access
those drugs that pharmaceutical companies in their infinite
greed and focused self-interest are willing to make available.
SUPPORT AND OPPOSITION:
Support:
Amyotrophic Lateral Sclerosis (ALS) Association Golden West
Chapter
Los Angeles County Board of Supervisors
Concerns:
Pharmaceutical Research and Manufacturers of America (PhRMA)
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Opposition:
Association of Northern California Oncologists
California Nurses Association and National Nurses United
-- END --