BILL ANALYSIS                                                                                                                                                                                                    Ó






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          |SENATE RULES COMMITTEE            |                       AB 1668|
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                                   THIRD READING 


          Bill No:  AB 1668
          Author:   Calderon (D), et al.
          Amended:  8/15/2016 Senate
          Vote:     21 

           SENATE HEALTH COMMITTEE:  9-0, 6/22/16
           AYES:  Hernandez, Nguyen, Hall, Mitchell, Monning, Nielsen,  
            Pan, Roth, Wolk

           SENATE BUS., PROF. & ECON. DEV. COMMITTEE:  9-0, 6/27/16
           AYES:  Hill, Bates, Block, Gaines, Galgiani, Hernandez,  
            Jackson, Mendoza, Wieckowski

           SENATE APPROPRIATIONS COMMITTEE:  7-0, 8/11/16
           AYES:  Lara, Bates, Beall, Hill, McGuire, Mendoza, Nielsen

           ASSEMBLY FLOOR:  77-2, 5/31/16 - See last page for vote

           SUBJECT:   Investigational drugs, biological products, and  
                     devices


          SOURCE:    Author


          DIGEST:  This bill permits 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.  


          ANALYSIS:  









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          Existing federal law:


           1) Establishes the federal Food, Drug, and Cosmetic Act, which  
             grants authority to the U.S. Food and Drug Administration  
             (FDA) to oversee the safety of food, drugs, and cosmetics.  
             Prohibits any new drug from being introduced into interstate  
             commerce unless an application has been approved by the FDA. 


           2) Provides, under regulation, for the following:


              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 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. 


          Existing state law establishes the Sherman Food, Drug, and  
          Cosmetic Law (Sherman Law), which regulates the packaging,  
          labeling, and advertising of drugs and devices, administered by  
          the Department of Public Health (DPH).  Prohibits, under the  
          Sherman Law, the sale, delivery, or giving away of a new drug or  







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          device unless it is either:


           1) A new drug or new device for which DPH has approved a new  
             drug or device application, and has not withdrawn,  
             terminated, or suspended that approval; or, 


           2) 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. 


          This bill:


          1)Permits 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.  Prohibits this bill from requiring that a  
            manufacturer make available an investigational drug,  
            biological product, or device to an eligible patient.  


          2)Defines "eligible patient" as a person who:


              a)    Has a serious or immediately life-threatening disease  
                or condition. Defines "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;


              b)    Has considered all other treatment options currently  
                approved by the FDA;


              c)    Has not been accepted to participate in the nearest  
                clinical trial to his or her home for the immediately  
                life-threatening disease or condition within one week of  
                completion of the clinical trial application process, or,  







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                in the treating physician's medical judgment, it is  
                unreasonable for the patient to participate in that  
                clinical trial due to the patient's current condition and  
                stage of disease;  


              d)    Has received a recommendation from his or her primary  
                physician and a consulting physician, as defined, for an  
                investigational drug, biological product, or device. 


              e)    Has given written informed consent for the use of the  
                investigational drug, biological product, or device, or,  
                if he or she lacks the capacity to consent, his or her  
                legally authorized representative has given written  
                informed consent on his or her behalf. Defines "written  
                informed consent" as a written document that has been  
                approved by the primary physician's IRB or an accredited  
                independent IRB, is signed by an eligible patient, or his  
                or her legally authorized representative when the patient  
                lacks the capacity to consent, and attested to by the  
                patient's primary physician and a witness that, as  
                specified.


           3) Permits a manufacturer to provide an investigational drug,  
             biological product, or device 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  
             investigational drug, biological product, or device.


           4) Prohibits this bill from expanding or otherwise affecting  
             coverage provided by health plans or insurers, the Medi-Cal  
             program, or county organized health systems. 


           5) Specifies that this bill does not require a health plan or  
             insurer to provide coverage for the cost of any  
             investigational drug, biological product, or device, or the  
             costs of services related to the use of an investigational  
             drug, biological product, or device under this bill, but  
             permits one to provide such coverage.








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           6) Prohibits an investigational drug, biological product, or  
             device from being offered if a clinical trial for that  
             investigational drug, biological product, or device is closed  
             due to the lack of efficacy or for toxicity. Requires the  
             manufacturer and the patient's primary physician, if notice  
             is given for an investigational drug, biological product, or  
             device 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) Prohibits the heirs and health benefit plan, as specified,  
             of an eligible patient, if he/she dies while being treated by  
             an investigational drug, biological product, or device made  
             available pursuant to this bill, from being liable for any  
             outstanding debt related to the treatment or lack of  
             insurance for the treatment.


           8) Prohibits a state regulatory board 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 investigational drug,  
             biological product, or device if the recommendation or  
             prescription is consistent with protocol approved by the  
             physician's IRB or an accredited independent institutional  
             review board.


           9) Requires the physician's IRB or an accredited IRB to  
             biannually report to DPH, the Medical Board of California,  
             and the Osteopathic Medical Board of California specified  
             information about requests made under this bill.


           10)Prohibits a state agency from altering any recommendation  
             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 the recommendation from an individual health care provider  
             that a patient have access to an investigational drug,  
             biological product, or device.







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           11)Makes a violation of this bill not subject to the Sherman  
             Law.


           12)Specifies that this bill does not create a private cause of  
             action, and that actions taken pursuant to this bill 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 investigational drug, biological product,  
             or device, 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  
             investigational drug, biological product, or device, 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.


          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 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 the expanded access (also known as compassionate  
          use) program. 

          1)Clinical trials.  According to the Health Affairs 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  







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            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 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. 

          2)Expanded access program.  According to the Health Affairs  
            brief, the expanded access program 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 two of the 2,472 individual,  
            non-emergency protocols, on one of 66 intermediate-size  
            requests, and on none of the 41 widespread expanded-access  
            protocols it received.








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            The Health Affairs brief states that critics of the expanded  
            access program 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  
            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  
            U.S. Supreme Court subsequently declined to review the case. 

          3)FDA action.  According to a June 2, 1016 statement from the  
            Commissioner, the FDA has finalized its efforts to streamline  
            the process used by physicians to request the expanded access  
            program, which was prompted due to reports that navigating  
            that process can be challenging and time consuming. According  
            to the FDA, in order to make things simpler for physicians and  
            reduce the amount of time they spend filling out a request for  
            access to an investigational drug, the FDA released the final  
            Individual Patient Expanded Access Investigational New Drug  
            Application, which is much shorter than the form previously  
            used and should take about 45 minutes for a physician to  
            complete. The FDA also released step-by-step instructions on  
            how to complete it.


          Comments


          Author's statement.  According to the author, AB 1668 seeks to  
          allow terminally ill patients the right to pursue non-FDA  
          approved medications in hopes of saving their lives. Terminally  
          ill patients often do not have the luxury of waiting for the FDA  
          to grant compassionate use or participating in the lengthy  







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          process of clinical trials. AB 1668 gives terminally ill  
          patients a chance to try potentially life-saving treatments  
          after all other options have been exhausted. AB 1668 removes  
          barriers for patients and doctors who believe an investigational  
          drug or device could be their last hope for survival, while also  
          protecting physicians, hospitals, and manufacturers from  
          retribution.


          FISCAL EFFECT:   Appropriation:    No          Fiscal  
          Com.:YesLocal:   No


          According to the Senate Appropriations Committee:


          1)One-time costs of $20,000 and ongoing costs of $10,000 per  
            year to review plan filings by the Department of Insurance  
            (Insurance Fund).


          2)One-time costs of $380,000 in 2015-16 to respond to requests  
            for information about prior independent medical review  
            decisions and ongoing costs of $210,000 per year to respond to  
            consumer complaints and requests for independent medical  
            review for access to investigational drugs by the Department  
            of Managed Health Care (Managed Care Fund).


          3)Uncertain impact on state-funded California Public Employees'  
            Retirement System health care coverage (General Fund and  
            special funds). 


          SUPPORT:   (Verified8/12/16)


          ALS (Amyotrophic Lateral Sclerosis) Association Golden West  
                    Chapter 
          Los Angeles County Board of Supervisors 
          National Association of Social Workers, California Chapter


          OPPOSITION:   (Verified8/12/16)







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          California Nurses Association 
          Medical Oncology Association of Southern California, Inc.

          ASSEMBLY FLOOR:  77-2, 5/31/16
          AYES:  Achadjian, Alejo, Travis Allen, Arambula, Atkins, Baker,  
            Bigelow, Bloom, Bonilla, Bonta, Brough, Brown, Burke,  
            Calderon, Campos, Chang, Chau, Chávez, Chiu, Chu, Cooley,  
            Cooper, Dababneh, Dahle, Daly, Dodd, Eggman, Frazier, Beth  
            Gaines, Gallagher, Cristina Garcia, Eduardo Garcia, Gatto,  
            Gipson, Gomez, Gonzalez, Gray, Grove, Hadley, Harper, Roger  
            Hernández, Holden, Irwin, Jones, Jones-Sawyer, Kim, Lackey,  
            Linder, Lopez, Low, Maienschein, Mathis, Mayes, McCarty,  
            Medina, Melendez, Mullin, Nazarian, Obernolte, O'Donnell,  
            Olsen, Patterson, Ridley-Thomas, Rodriguez, Salas, Santiago,  
            Steinorth, Mark Stone, Thurmond, Ting, Wagner, Waldron, Weber,  
            Wilk, Williams, Wood, Rendon
          NOES:  Levine, Quirk
          NO VOTE RECORDED:  Gordon

          Prepared by:Melanie Moreno / HEALTH / (916) 651-4111
          8/15/16 20:33:20


                                   ****  END  ****