BILL ANALYSIS                                                                                                                                                                                                    �



                                                                            



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          |SENATE RULES COMMITTEE            |                        SB 598|
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                                    THIRD READING


          Bill No:  SB 598
          Author:   Hill (D)
          Amended:  4/16/13
          Vote:     21


           SENATE BUSINESS, PROF. & ECON. DEV. COMM.  :  10-0, 4/8/13
          AYES:  Price, Emmerson, Block, Corbett, Galgiani, Hernandez,  
            Hill, Padilla, Wyland, Yee

           SENATE HEALTH COMMITTEE  :  6-1, 5/1/13
          AYES:  Hernandez, Anderson, Beall, De Le�n, Pavley, Wolk
          NOES:  Nielsen
          NO VOTE RECORDED:  DeSaulnier, Monning

           SENATE APPROPRIATIONS COMMITTEE  :  Senate Rule 28.8  
           

           SUBJECT  :    Biosimilars

           SOURCE  :     Author


           DIGEST  :    This bill authorizes pharmacists to substitute a  
          "biosimilar" for a biologic under specified circumstances, and  
          defines "biological product," "biosimilar," and  
          "interchangeable" according to their definitions within the  
          Federal Public Health Services Act (PHSA).

           ANALYSIS  :    Existing federal law creates an abbreviated pathway  
          for biological products that are similar to or interchangeable  
          with licensed biological products, known as the Biologics Price  
          Competition and Innovation Act of 2009 (BPCIA); requires that,  
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          for a biological product to be considered biosimilar to a  
          reference product, data must be derived from analytical, animal  
          and clinical studies as specified; clarifies that a product is  
          biosimilar to a reference product under the BPCIA if the  
          proposed biosimilar product is highly similar to the reference  
          product notwithstanding minor differences in clinically inactive  
          components and that no clinically meaningful differences exist  
          between the proposed biosimilar product and the reference  
          product in terms of safety, purity and potency; and clarifies  
          that state law governs how and when pharmacists may make  
          prescription drug substitutions.

          Existing state law:

          1.Defines biologics as human whole blood; human whole blood  
            derivatives specified by regulations; serum, vaccine, live  
            vaccine, killed vaccine, tissue vaccine, autogenous vaccine,  
            live virus, killed virus, live bacterial culture, killed  
            bacterial culture, bacterin, hormone, tissue extract, gland  
            extract, gland preparation, insulin, and similar products made  
            from human or animal tissues or micro-organisms.

          2.Under the Pharmacy Law, provides for the licensure and  
            regulation of pharmacies, pharmacists and wholesalers of  
            dangerous drugs or devices by the Board of Pharmacy within the  
            Department of Consumer Affairs.

          3.Specifies certain requirements regarding the dispensing and  
            furnishing of dangerous drugs and devices, and prohibits a  
            person from furnishing any dangerous drug or device except  
            upon the prescription of a physician, dentist, podiatrist,  
            optometrist, veterinarian or naturopathic doctor.

          4.Authorizes pharmacists filling prescription orders for drug  
            products prescribed by their trade or brand names to  
            substitute generic drugs for orders if the generic contains  
            the same active chemical ingredients of equivalent strength  
            and duration of therapy, subject to a patient notification and  
            bottle labeling requirement, unless the prescriber specifies  
            that a pharmacist may not substitute another drug product by  
            either indicating on the form submitted for the filling of the  
            prescription drug orders "Do not substitute" or words of  
            similar meaning or selecting a box on the form marked "Do not  
            substitute."

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          5.Authorizes pharmacists filling prescription orders for drug  
            products prescribed by their trade or brand names to  
            substitute a drug product with a different form of medication  
            with the same active chemical ingredients of equivalent  
            strength and duration of therapy as the prescribed drug  
            product when the change will improve the ability of the  
            patient to comply with the prescribed drug therapy, subject to  
            a patient notification and bottle labeling requirement, unless  
            the prescriber specifies that a pharmacist may not substitute  
            another drug product by either indicating on the form  
            submitted for the filling of the prescription drug orders "Do  
            not substitute" or words of similar meaning or selecting a box  
            on the form marked "Do not substitute."

          This bill:

          1.Updates permitted functions for pharmacists to allow a  
            pharmacist to substitute a biosimilar for a prescribed  
            biological product if (a) the product is approved by the Food  
            and Drug Administration (FDA) under the BPCIA; (b) the  
            prescriber has not indicated "Do not substitute;" (c) for  
            prescriptions filled prior to January 1, 2017, the pharmacy  
            notifies the prescriber of the substitution or enters  
            information about the substitution in a patient record system  
            shared by the prescriber within five days of the selection;  
            and (d) for prescriptions filled prior to January 1, 2017, the  
            pharmacy keeps a record of the biosimilar substitution for at  
            least three years.

          2.Clarifies that "Do not substitute" means a biosimilar may not  
            be substituted for a biologic product and that physicians are  
            not liable for biosimilar substitution by a pharmacist.

          3.Requires a patient to be notified when a biosimilar is  
            substituted for a biologic.

          4.Requires the Board to maintain a list of interchangeable  
            biosimilars, if available, on its Internet Web site.

          5.Defines the following terms:

             A.    "Biological product," "biosimilar," and  
               "interchangeable" according to their definitions within the  

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               PHSA.

             B.   "Prescription," for purposes of a biological product,  
               according to the definition under the federal Food, Drug,  
               and Cosmetic Act (FDCA).

             C.   "351(k) pathway," refers to the licensure of a  
               biological product as a biosimilar or an interchangeable  
               biosimilar under the federal BPCIA.

          1.Clarifies that a pharmacist may still give immunizations  
            pursuant to a protocol with a prescriber. 

          2.Adds all of the above provisions to the Pharmacy Law section  
            specifying actions for substitution of a generic drug.

           Background
           
           Biological products and biologics  .  Biological products are  
          generally derived from living material, human, animal, or  
          microorganism and FDA regulations specify that biological  
          products include blood-derived products, vaccines, in vivo  
          diagnostic allergenic products, immunoglobulin products,  
          products containing cells or microorganisms, and most protein  
          products.  These treatments are not widespread but rather used  
          as specialty drugs to treat very ill patients; according to  
          information provided by the author from a MarketScan report,  
          there were almost 380 million pills dispensed in California in  
          2011, with only 1.7 biologic prescriptions dispensed per week  
          from the over 5,000 retail pharmacies in California,  
          representing just .13% of all prescriptions dispensed by retail  
          pharmacies.

          According to the FDA, biologics are regulated under the federal  
          PHSA while drugs, including insulin and other hormone therapies,  
          are regulated under the FDCA.  Both the FDA's Center for Drug  
          Evaluation and Research and Center for Biologics Evaluation and  
          Research have regulatory responsibility for therapeutic  
          biological products, including premarket review and oversight.   
          Following initial laboratory and animal testing that show the  
          use of a particular biological product in humans is reasonably  
          safe, biological products (like other drugs), can be studied in  
          clinical trials in humans under an investigational new drug  
          application.  If trials and studies demonstrate that a product  

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          is safe and effective for its intended use, the FDA may then  
          approve the market of a biologic by granting a biologics  
          license.

          According to background information provided by the author's  
          office and stakeholders, both in opposition to and support of  
          this bill, biologics are large, complex protein molecules used  
          in the treatment, diagnosis or prevention of disease.  These are  
          quite different from small molecule drugs, pills, which are not  
          as structurally complex and are instead relatively simple,  
          organic substances produced by chemical methods.  Biologic  
          medicines, on the other hand, are made in living organisms to  
          produce proteins by genetically modifying cell constructs or  
          cell lines.  Biologics are grown, cultivated and purified and  
          are typically administered as injectables.

           Biosimilars  .  Biosimilars are similar but not identical versions  
          of the original biologic.  The active ingredient of a biosimilar  
          is expected to closely resemble that of the original biologic  
          and unlike generic pills which require the active ingredient to  
          be identical, the exact manufacturing process of an original  
          biologic cannot be exactly duplicated.  Biosimilars are not  
          clinically identical to their reference products.  Biosimilars  
          have been defined by the World Health Organization as "a  
          biotherapeutic product which is similar in terms of quality,  
          safety and efficacy to an already licensed biotherapeutic  
          product," by the European Medicines Agency as a "copy version of  
          an already authorized biological medicine product with  
          demonstrated similarity in physiochemical characteristics,  
          efficacy and safety, based on a comprehensive comparability  
          exercise," and by the FDA as a biological product which is  
          "highly similar to the reference product notwithstanding minor  
          differences in clinically inactive components and for which  
          there are no clinically meaningful differences between the  
          biological product and the reference product in terms of safety,  
          purity and potency of the product."

          In response to increases in an aging population and larger  
          numbers of patients suffering from chronic disease, there has  
          been a rise in use of biologics, and accordingly, a rise in the  
          production efforts of biosimilars.  Biosimilars go through an  
          extensive review process and manufacturers are required to  
          submit immense studies and data demonstrating a products'  
          efficacy and ensuring it is safe for use by consumers.   

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          Manufacturers also have to establish ongoing monitoring programs  
          to ensure the safety of biosimilars.  While biosimilars are  
          currently available in the European Unions, and other nations  
          are in the process of adopting guidelines and regulatory  
          processes, biosimilars are still a relatively new option in the  
          larger health care delivery and treatment conversation.

          A pathway for biosimilar regulation in the U.S. was established  
          as a provision of the Patient Protection and Affordable Care Act  
          (ACA) and, in 2012, the FDA issued draft guidelines for  
          biosimilars.  The guidance included which types of studies  
          manufacturers should undertake in order to ensure product  
          safety, potency and purity.  However, there is no definitive  
          timeline or date by which biosimilars will be available and on  
          the market in the U.S. due to the complexity involved in their  
          development and production. 

           Comments
           
          According to the author, "SB 598 updates existing law so when  
          the FDA approves interchangeable biosimilars, California  
          pharmacists can substitute the lower cost biosimilars for brand  
          name biologics."  The author believes this bill is necessary  
          because biosimilars are not defined in California law and  
          existing definitions for generic pills do not apply to these  
          unique medicines.  The author's office states that this bill  
          mirrors patient protections for substitutions of generic pills  
          and that adverse reactions with biologic medicines, which occur  
          when a patient's body rejects a biologic medicine, will be more  
          easily tracked through accountability measures like notifying a  
          physician when a biosimilar is substituted for a biologic,  
          requiring that records of substitutions are kept and requiring  
          the Board of Pharmacy to keep a list on of interchangeable  
          biosimilars on its Internet Web site.  According to the author's  
          office, notifying the prescribing physician, after dispensing,  
          does not alter the policy goal of offering alternative, lower  
          cost options for patients.  The author's office believes that  
          this notification provides a record of the substitution, so that  
          in the event of an adverse reaction, which may not manifest  
          until many months after the biosimilar was administered, health  
          records can reflect these contraindications.  The author  
          intended to allow flexibility in how notification is provided  
          and as such, this bill does not specify how a notification must  
          be transmitted or noted in a patient's record.

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           FISCAL EFFECT :    Appropriation:  No   Fiscal Com.:  Yes    
          Local:  Yes

           SUPPORT  :   (Verified  5/20/13)

          Abbvie, Inc.
          AIDS Institute
          AIM Melanoma
          Alliance for Patient Access
          Alliance for Safe Biologic Medicines
          Alliance of Specialty Medicine
          American Academy of Facial Plastic & Reconstructive Surgery
          American Association of Neurological Surgeons
          American Association of People with Disabilities
          American Autoimmune Related Diseases Association
          American College of Mohs Surgery
          American Council on Science and Health
          American Gastroenterological Association
          American Society of Cataract and Refractive Surgery
          American Society of Echocardiography
          American Society of Plastic Surgeons
          American Urological Association
          Amgen
          Association of Black Cardiologists
          Association of Clinical Research Organizations
          Association of Gastrointestinal Motility Disorders, Inc.
          BayBio
          BIOCOM
          Biotechnology Industry Organization
          Blue Ribbon Advocacy Alliance
          California Healthcare Institute
          California Medical Association
          California Prostate Cancer Coalition Advocates
          California State Association of Electrical Workers
          California State Pipe Trades Council
          Coalition of State Rheumatology Organizations
          Colon Cancer Alliance
          Colorectal Cancer Coalition
          Congress of Neurological Surgeons
          CONNECT
          Genentech
          Global Healthy Living Foundation
          HealthHIV

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          Interamerican College of Physicians and Surgeons
          International Cancer Advocacy Network
          International Myeloma Foundation
          International Union of Operating Engineers
          Jenny's Quest-Cure for Pediatric Brain Stem Cancer
          Kidney Cancer Association
          MANA
          MedImmune
          Merck & Co., Inc.
          National Alliance on Mental Illness
          National Kidney Foundation
          National Physicians Biologics Working Group
          North American Spine Society
          Pharmaceutical Research and Manufacturers of America
          RetireSafe
          Society for Cardiovascular Angiography and Interventions
          Society for Excellence in Eyecare
          State Building and Construction Trades Council
          TechNet
          UCB, Inc.
          Western States Council of Sheet Metal Workers

           OPPOSITION  :    (Verified  5/20/13)

          Anthem Blue Cross
          Boehringer Ingelheim
          California Association of Health Plans
          California Conference Board of the Amalgamated Transit Union
          California Conference of Machinists
          California Retailers Association
          California Teamsters Public Affairs Council
          CVS Caremark
          Engineers and Scientists of California, IFPTE Local 20
          Express Scripts
          Generic Pharmaceutical Association
          International Longshore and Warehouse Union
          Kaiser Permanente
          Mylan Labs
          National Association of Chain Drug Stores
          Novartis Pharmaceuticals
          Professional and Technical Engineers, IFPTE Local 21
          Teva Pharmaceutical Industries, Ltd.
          United Food and Commercial Workers Western States Council
          UNITE-HERE, AFL-CIO

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          Utility Workers Union of America, Local 132
          Walgreens

           ARGUMENTS IN SUPPORT  :    Supporters include biologic and  
          biosimilar manufacturers, representatives of chronically ill  
          patients, alliances of physician and research groups, as well as  
          organizations for California's life sciences community who  
          believe that it is a common sense measure which will ensure  
          patient safety without delaying the introduction of biosimilars  
          to the California market.  Supporters highlight the differences  
          between biosimilars and other generic drugs, resulting in a need  
          for prescriber notification to ensure accurate patient records  
          are maintained.  Supporters believe that substitution of  
          biosimilars for biological products will improve patient access  
          to these often life-saving medicines, but note that there need  
          to be certain accountability measures taken, given the unique  
          and very sensitive nature of these drugs.  Supporters agree that  
          the prescriber notification guarantees that physicians maintain  
          knowledge about what medication their patients receive.   
          Supporters note that the physician notification provision is  
          identical to that contained in SB 1301 (Hernandez, Chapter 455,  
          Statutes of 2012) which passed the Legislature with unanimous  
          bipartisan support and was signed by the Governor.  That bill  
          required physician notification if a pharmacist extended a  
          prescription from 30 days to 90 days.

          The California State Pipe Trades Council, California State  
          Association of Electrical Workers, and Western States Council of  
          Sheet Metal Workers write, "For many of [the] working men and  
          women in our industry, including their families and our retired  
          members - who suffer from one or more chronic illnesses,  
          biologic medicines represent life-changing, and often  
          lifesaving, therapies.  This new generation of treatments has  
          transformed the health and lives of our patients and has given  
          them hope for recovery.  In the next couple of years, biosimilar  
          medications are expected to enter the U.S. healthcare market.   
          They are copies of an original biologic medicine and hold the  
          promise of providing similar results as the original biologic at  
          a lower price.  However, unlike generic drugs, biosimilars are  
          not structurally identical to the biologic products they seek to  
          copy; thus the name biosimilar.  Due to the sensitive nature of  
          biologics, the slightest variation from the original biologic  
          medicine can result in an immune response or other patient side  
          effects.  As important as these new therapies are to patients in  

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          California, it is just as important that public policy ensures  
          the safety of the patients who rely upon them."

           ARGUMENTS IN OPPOSITION  :    Opponents, including manufacturers  
          of generic drugs, health plans and retailers, argue that this  
          bill creates barriers to biosimilars entering the California  
          market, will restrict insurers' ability to provide affordable  
          options to patients and that California is unnecessarily making  
          changes before the FDA has weighed in on the issue of  
          substituting biosimilars.  Hospira, Teva Pharmaceuticals, Inc.,  
          Boehringer Ingelheim and the Generic Pharmaceutical Association  
          believe that SB 598 is premature and is intended to create doubt  
          about the safety and effectiveness of affordable biosimilar  
          drugs and will prevent patients from accessing more  
          cost-effective, lifesaving medications.  Kaiser Permanente notes  
          that the organization would be able to comply with the  
          provisions of this bill but that it does not support public  
          policy which provides artificial and unnecessary barriers to  
          safe and low cost alternatives for patients.  Health Access  
          California writes that the use of generics has helped to control  
          health costs even as prescription drugs have become an even  
          bigger share of health care costs and that there is no reason to  
          create additional barriers to the prescribing of biosimilar  
          drugs beyond those in place for generic drugs.  The California  
          Retailers Association and CVS Caremark are concerned that there  
          is not a clear public policy rationale for pharmacies being  
          required to keep records of biosimilars dispensed and that  
          physician notification increases pharmacist workload.  Blue  
          Shield, states that this bill contains a provision that only  
          allows for substitution if the biosimilar product costs the  
          patient less, which wile seemingly pro-consumer, would be a de  
          facto ban on biosimilar substitution because there are not  
          separate cost sharing rules in the standardized benefit designs  
          established by the California Health Benefit Exchange.

          MW:ej  5/20/13   Senate Floor Analyses 

                           SUPPORT/OPPOSITION:  SEE ABOVE

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