BILL ANALYSIS                                                                                                                                                                                                    Ó



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          Date of Hearing:  March 29, 2016


                   ASSEMBLY COMMITTEE ON BUSINESS AND PROFESSIONS


                                  Rudy Salas, Chair


          AB 1668  
          (Calderon) - As Amended March 7, 2016


          NOTE: This bill is double referred, having been previously heard  
          by the Assembly Committee on Health on March 15, 2016 and  
          approved on an 18-0 vote.


          SUBJECT:  Investigational drugs, biological products, and  
          devices.


          SUMMARY:  Permits a manufacturer of an investigational drug,  
          biological product or medical device to make the product  
          available to eligible patients, with a serious or immediately  
          life-threatening disease or condition, and authorizes a health  
          benefit plan to provide coverage;  prohibits the Medical Board  
          of California and the Osteopathic Medical Board of California  
          from taking any disciplinary action against a licensee based  
          solely on the physician's recommendation, prescription of a  
          biological product or device or treatment of a patient with such  
          products or devices;  prohibits a state agency from altering any  
          recommendation made to the federal Centers for Medicare and  
          Medicaid Services regarding a provider's certification to  
          participate in the programs based solely on the recommendation  
          that a patient have access to a drug, product or device;  and  
          prohibits an official, employee or agent of the state from  
          blocking an eligible patient's access to the drug, product or  
          device.








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          EXISTING LAW:


          The Business and Professions Code


          1)Establishes the Medical Board of California (MBC), within the  
            Department of Consumer Affairs (DCA), which provides for the  
            licensure and regulation of physicians and surgeons, and  
            requires the MBC to take action against a licensee who is  
            charged with unprofessional conduct.  (Business and  
            Professions Code (BPC) § 2000 et seq.)
          2)Provides for the licensure and regulation of osteopathic  
            physicians and surgeons by the MBC within the DCA and requires  
            the Osteopathic Medical Board (OMB) to enforce the Medical  
            Practice Act.  (BPC § 2000 et seq.) 


          The Health and Safety Code


          1)Establishes the Sherman Food, Drug, and Cosmetic Law, which  
            regulates the packaging, labeling, and advertising of drugs  
            and devices, administered by the Department of Public Health  
            (DPH).  Health and Safety Code (HSC) § 109875 et seq.

          2)Prohibits the sale, delivery or giving away of a new drug or  
            device unless it is either:  (HSC § 111550)

             a)   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, 



             b)   A new drug, and a new drug application has been approved  
               for it by the U.S. Food and Drug Administration (FDA),  








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               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.



          3)Establishes the Protection of Human Subjects in Medical  
            Experimentation 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)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)

          5)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)


          Federal Law


          1)Establishes the federal Food, Drug, and Cosmetic Act, which  
            grants authority to the FDA to oversee the safety of food,  
            drugs, and cosmetics.  (Title 21 United States Code (USC) §  








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            321 et seq.)

          2)Prohibits any new drug from being introduced into interstate  
            commerce unless an application has been approved by the FDA.   
            (21 USC § 355)



          3)Under federal regulation: (Title 45 Code of Federal  
            Regulations (CFR) § 46.101 et seq.)





             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.








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          4)Establishes the Office for Human Research Protections (OHRP),  
            which provides leadership in the protection of the rights,  
            welfare and wellbeing of subjects involved in research  
            conducted or supported by the U.S. Department of Health and  
            Human Services (HHS).  (45 CFR § §46.103)
          THIS BILL:


          1)Permits a manufacturer of an investigational drug, biological  
            product, or device may make available the manufacturer's  
            investigational drug, biological product, or device to an  
            eligible patient. 



          2)Specifies that a manufacturer may do both of the following:



             a)   Provide an investigational drug, biological product, or  
               device to an eligible patient without receiving  
               compensation.



             b)   Require an eligible patient to pay the costs of, or  
               associated with, the manufacture of the investigational  
               drug, biological product, or device.



          3)Defines "consulting physician" as a physician and surgeon  
            licensed under the Medical Practice Act or an osteopathic  
            physician and surgeon licensed under the Osteopathic Act who  
            performs the following: 









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             a)   Examines the qualified individual and his or her  
               relevant medical records.



             b)   Confirms, in writing, the primary physician's diagnosis  
               and prognosis.



             c)   Verifies, in the opinion of the consulting physician,  
               that the eligible patient is competent, acting voluntarily,  
               and has made an informed decision.



          4)Defines "eligible patient" as a person who meets all of the  
            following conditions:



             a)   Has an immediately life-threatening disease or  
               condition.



             b)   Has considered all other treatment options currently  
               approved by the United States Food and Drug Administration.



             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 identified in  
               paragraph (1) within one week of completion of the clinical  
               trial application process, or, in the treating physician's  
               medical judgment, it is unreasonable for the patient to  








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               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 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.



             f)   Has documentation from his or her primary physician and  
               a consulting physician attesting that the patient has met  
               the requirements of this subdivision.



          5)Defines "health benefit plan" as a plan or program that  
            provides, arranges, pays for, or reimburses the cost of health  
            benefits. "Health benefit plan" includes, but is not limited  
            to, a health care service plan contract issued by a health  
            care service plan, as defined in HSC § 1345, and a policy of  
            health insurance, as defined in § 106 of the Insurance Code,  
            issued by a health insurer.



          6)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.









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          7)Defines "investigational drug, biological product, or device"  
            means 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.



          8)Defines "primary physician" as a physician and surgeon  
            licensed under the Medical Practice Act or an osteopathic  
            physician and surgeon licensed under the Osteopathic Act.



          9)Defines "state regulatory board" as the Medical Board of  
            California or the Osteopathic Medical Board of California.



          10)Defines "written, informed consent" means a written document  
            that has been approved by the primary physician's  
            institutional review board or an accredited independent  
            institutional review board, 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, at a minimum,  
            does all of the following:



             a)   Explains the currently approved products and treatments  
               for the immediately life-threatening disease or condition  
               from which the patient suffers.











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             b)   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.



             c)   Clearly identifies the specific proposed investigational  
               drug, biological product, or device that the patient is  
               seeking to use.



             d)   Describes the potentially best and worst outcomes of  
               using the investigational drug, biological product, or  
               device and describes the most likely outcome. This  
               description shall include the possibility that new,  
               unanticipated, different, or worse symptoms might result  
               and that death could be hastened by the proposed treatment.  
               The description shall be based on the primary physician's  
               knowledge of the proposed treatment in conjunction with an  
               awareness of the patient's condition.



             e)   Clearly states that the patient's health benefit plan,  
               if any, and health care provider are not obligated to pay  
               for the investigational drug, biological product, or device  
               or any care or treatments consequent to use of the  
               investigational drug, biological product, or device.



             f)   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  








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               eligibility requirements.



             g)   Clearly states that in-home health care may be denied if  
               treatment begins.



             h)   States that the patient understands that he or she is  
               liable for all expenses consequent to the use of the  
               investigational drug, biological product, or device, 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.



          11)Requires that written, informed consent shall be consistent  
            with the informed consent requirements of the Protection of  
            Human Subjects in Medical Experimentation Act (HSC § 24170 et  
            seq.).



          12)Specifies that a health benefit plan is not required 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. 



          13)Indicates if the clinical trial for an investigational drug,  
            biological product, or device is closed due to the lack of  
            efficacy or for toxicity, the investigational drug, biological  
            product, or device shall not be offered. If notice of closure  
            of a clinical trial is given for an investigational drug,  








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            biological product, or device taken by a patient outside of a  
            clinical trial, the manufacturer and the patient's primary  
            physician shall notify the patient of the information from the  
            safety committee of the clinical trial.



          14)Indicates if an eligible patient dies while being treated by  
            an investigational drug, biological product, or device made  
            available pursuant to this article, the patient's heirs are  
            not liable for any outstanding debt related to the treatment  
            or lack of insurance for the treatment.



          15)Prevents 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 institutional review board or an accredited  
            independent institutional review board.



          16)Requires the physician's institutional review board or an  
            accredited institutional review board to biannually report the  
            following information to the State Department of Public  
            Health, the Medical Board of California, and the Osteopathic  
            Medical Board of California:



             a)   The number of requests made for an investigational drug,  
               biological product, or device.










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             b)   The status of the requests made.



             c)   The duration of the treatment.



             d)   The costs of the treatment paid by eligible patients.



             e)   The success or failure of the investigational drug,  
               biological product, or device in treating the immediately  
               life-threatening disease or condition from which the  
               patient suffers.



             f)   Any adverse event for each investigational drug,  
               biological product, or device.



          17)States that a state agency shall not alter 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.



          18)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, as specified. 








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          FISCAL EFFECT:  Unknown.  This bill is keyed fiscal by the  
          Legislative Counsel.





          COMMENTS:


          


          Purpose.  This bill is sponsored by the author.  According to  
          the author, "Terminally ill patients often do not have the  
          luxury of waiting for the FDA to grant compassionate use of  
          participating in the lengthy process of clinical trials.  [This  
          bill] gives terminally ill patients a chance to try potentially  
          life-saving treatments after all other options have been  
          exhausted.  It removes barriers for patients who need to  
          immediately obtain investigational treatments, while also  
          protecting physicians, hospitals, and manufacturers from  
          retribution."


          Background.  The FDA has jurisdiction over all drugs that are  
          sold across state lines.  State law provides DPH with the  
          authority to approve for market a drug or device that is sold in  
          California.  If a product has received the FDA approval, then  
          the DPH automatically recognizes the product's approval.  In  
          rare instances when a drug or device will be sold only in the  
          state of California, and will not be distributed through  
          interstate commerce, then California would be the approving  
          body.  According to the DPH, this has resulted in a few  
          instances where California has approved a new drug or device  
          application. 


          Independent from drug or device applications, manufacturers of  








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          drugs and devices must be licensed to manufacture in the state  
          of California.  The FDA does not approve manufacturers, but they  
          do conduct inspections to ensure manufacturers are in compliance  
          with good manufacturing practices.  Under California Law, drug  
          manufacturers must be licensed with the DPH even if not  
          registered with FDA.   


          Clinical Trials.  A clinical trial is a study that is carefully  
          designed to test the benefits and risks of a specific medical  
          treatment or intervention, such as a new drug.  The FDA requires  
          a multi-phase clinical trials process to be completed before  
          deciding if an investigational medicine is safe and effective  
          for a broader patient population.   





          According to the author's office, the FDA has been having great  
          difficulty in getting patients to participate in clinical trials  
          of investigational drugs, because patients do not want to take  
          the chance that they will be in the control group and not  
          receive the experimental drug.  


          Expanded Access.  If a patient is unable to enroll in a clinical  
          trial, the FDA expanded access exemption, also commonly referred  
          to as "compassionate use," provides a pathway for patients to  
          gain access to investigational drugs or devices for serious  
          diseases or conditions.  A licensed physician is able to apply  
          for expanded access under a single patient IND Application on  
          behalf of the patient.  The supervising physician must be  
          willing to commit to oversee the treatment, work with the  
          manufacturing company and the FDA, obtain the drugs, monitor the  
          patient during the course of treatment, and file necessary  
          paperwork.  The FDA states that they receive approximately 1,000  
          expanded use applications per year, and has approved more than  
          99% of those applications.  In the last four years, the FDA has  








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          denied only 33 of nearly 6,000 expanded access requests.  


          The FDA allows physicians to request expanded access for  
          patients in an emergency situation over the phone or by "other  
          rapid means of communication."  The FDA states that  
          authorization of the emergency use may be given by an FDA  
          official over the telephone, provided the physician explains how  
          the expanded access use will meet federal requirements for  
          expanded access use and agrees to submit an expanded access  
          submission within 15 working days of FDA's initial authorization  
          of the expanded access use. 


          Critics of the FDA process have raised concerns that the  
          expanded access application is too cumbersome for physicians and  
          patients to complete.  On February 4, 2015, the FDA announced  
          that it would be streamlining the expanded use application  
          process, and stated that the proposed application will allow  
          physicians to apply for experimental drugs in just 45 minutes.   
          This process includes a 60-day public comment period.  The FDA  
          reviews the comments and makes revisions based on the comments.  
          The FDA then seeks approval from the Office of Management and  
          Budget, which includes an additional 30-day public comment  
          period, which commenced on March 10, 2016. 


          Institutional Review Board (IRB).  Any FDA expanded access  
          requests for any investigational drug must be reviewed by an IRB  
                                                     in order to understand the risks of an experimental treatment  
          and ensure that the patient understands them as well.  


          A physician submits the proposed experimental protocol, to an  
          IRB, which reviews them to make sure patients are fully aware of  
          potential risks and are willing to accept the level of potential  
          risk associated with the drug.  IRBs are usually associated with  
          a hospital or research institution, but there are independent  
          IRBs available for physicians not associated with such an  








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          institution.  Physicians are governed primarily by the IRB  
          committee policies set up by their specific institution.  The  
          FDA maintains the right to overrule the physician and the IRB.


          Physician Liability and Enforcement Action Against a Physician.   
          Physicians may be concerned about facing a liability risk for  
          investigational drugs, biological products or devices that they  
          recommend to patients or help them gain access to.  The  
          Compassionate Access Act of 2010 (H.R. 4732) sought to address  
          this issue by providing immunity to the manufacturer,  
          distributor, administrator, sponsor or physician from suit or  
          liability.  


          If AB 1668 is enacted, the MBC and the OMB would be prohibited  
          from taking action against physician's license for prescribing  
          or treating a patient with an investigational drug, biological  
          product or device. 


          Other States.  Since 2014, several states have passed similar  
          legislation including: 1) Alabama, 2) Arkansas, 3) Colorado, 4)  
          Florida, 5) Indiana, 6) Louisiana, 7) Michigan, 8) Minnesota, 9)  
          Mississippi, 10) Missouri, 11) Montana, 12) Nevada, 13) North  
          Dakota, 14) Oklahoma, 15) South Dakota, 16) Tennessee, 17)  
          Texas, 18) Utah, 19) Virginia, and 20) Wyoming.  Additionally,  
          Arizona passed a "Right to Try" ballot measure.


          Current Related Legislation.  SB 128 (Wolk) of the current  
          Legislative Session, permitted a competent, qualified individual  
          who is a terminally ill adult to receive a prescription for aid  
          in dying medication if certain conditions were met.  STATUS:   
          This bill is pending in the Assembly Health Committee. 


          Prior Related Legislation.  AB 159 (Calderon) of 2016 was  
          identical to this bill.  NOTE: This bill was vetoed by Governor  








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          Brown. In his veto message he stated: patients with life  
          threatening conditions should be able to try experimental drugs,  
          and the FDA's compassionate use program allows this to happen.   
          The proposed changes to this program will streamline access to  
          these drugs.  Before authorizing an alternative state pathway,  
          we should give this federal expedited process a chance to work.


          SB 715 (Anderson) of 2015, is largely similar to this bill.   
          NOTE: SB 715 died in the Senate Health Committee.


          SB 149 (Stone) of 2015, was largely similar to this bill, with  
          differences primarily in definitions and liability exemptions.   
          NOTE: SB 149 was held on the Senate Appropriations suspense  
          file. 

          ARGUMENTS IN SUPPORT: 


          The  Amyotrophic Lateral Sclerosis (ALS) Association Golden West  
          Chapter  supports the bill and writes in their letter, "The ALS  
          Association has a long history of supporting and advocating for  
          expanded access to experimental treatments for people living  
          with ALS.  We are also champions of the research process, as  
          robust enrollment and participation in clinical trials is  
          essential to ultimately finding treatments and a cure for ALS." 


          The  County of Los Angeles Board of Supervisors  also supports the  
          bill and writes, "Patients with a life-threatening disease or  
          condition, 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."


          The  EveryLife Foundation for Rare Diseases  strongly supports,  








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          "rational early access to safe and effective treatments for  
          patients battling life-threatening illnesses.  Patients with  
          rare diseases and terminally ill patients have an urgent need  
          and deserve an opportunity for treatment, especially when the  
          risk of the disease far outweighs the risks of potential  
          treatments."


          ARGUMENTS IN OPPOSITION:


          The  California Nurses Association/ National Nurses United   
          opposes the bill and writes, "This bill does not address the  
          real barriers to 'compassionate use' revealed in a recent  
          article in the esteemed New England Journal of Medicine.   
          Nothing in this legislation or any other legislation 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.  This legislation? is unlikely to withstand a  
          constitutional challenge based on conflict with the FDA's  
          enabling legislation and existing expanded-access regulation  
          under the Supreme Court's long-standing preemption doctrine."


          The  Medical Oncology Association of Southern California, Inc.   
          writes in their opposition letter, "Concerns with AB 1668  
          include the difficulty of identifying an 'immediately  
          life-threatening condition,' the lack of a sufficient informed  
          consent process to protect patients seeking investigational  
          drugs, and the lack of appropriate physician supervision of the  
          use of these drugs?While we appreciate the interest in  
          supporting patients, there are substantive dangers in a 'right  
          to try' outside the context of a clinical trial, including the  
          damage to adults clinical trial enrollment, which hold the  
          promise of the future of medicine.  Despite very low adult  
          clinical trial enrollments, this nation's clinical trial system  
          has resulted in the relatively rapid evolution of cancer care.   
          Any threat to adult clinical trial enrollment would result in  
          solving the development of cancer care in the future."








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          REGISTERED SUPPORT:  


          Amyotrophic Lateral Sclerosis (ALS) Association Golden West  
          Chapter


          County of Los Angeles Board of Supervisors


          EveryLife Foundation for Rare Diseases




          REGISTERED OPPOSITION:  
          California Nurses Association/National Nurses United


          Medical Oncology Association of Southern California, Inc.







          Analysis Prepared by:Le Ondra Clark Harvey, Ph.D. / B. & P. /  
          (916) 319-3301
















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