BILL ANALYSIS                                                                                                                                                                                                    �



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          Date of Hearing:   June 25, 2013

              ASSEMBLY COMMITTEE ON BUSINESS, PROFESSIONS AND CONSUMER  
                                     PROTECTION
                              Richard S. Gordon, Chair
                      SB 598 (Hill) - As Amended:  June 20, 2013

           SENATE VOTE  :   29-4
           
          SUBJECT  :   Biosimilars

           SUMMARY  :   Permits a pharmacist to substitute a biological  
          pharmaceutical with a "biosimilar" pharmaceutical in the same  
          manner as generic drugs are substituted, and for prescriptions  
          filled prior to January 1, 2017, requires the pharmacist to  
          notify the prescriber.  Specifically,  this bill  :   

          1)Permits a pharmacist to substitute a biosimilar for a  
            prescribed biological product only if all of the following  
            conditions are met:

             a)   The product selected as a biosimilar has been approved  
               by the federal Food and Drug Administration (FDA) and has  
               been determined to be interchangeable with the prescribed  
               biological product;

             b)   The prescriber does not personally indicate, either  
               orally or in his or her own handwriting, "Do not  
               substitute," or words of similar meaning, as specified;  
               and,

             c)   For prescriptions filled prior to January 1, 2017, the  
               pharmacy notifies the prescriber or enters the appropriate  
               information in a patient record system shared by the  
               prescriber within five business days of the selection.

          2)Prohibits a biosimilar substitution if the prescriber  
            personally indicates, orally or in writing, "Do not  
            substitute," as specified. 

          3)States that substitution is within the discretion of the  
            pharmacist, unless the prescriber indicates otherwise.  

          4)States that the pharmacist who selects the biosimilar to be  
            dispensed according to this bill shall assume the same  








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            responsibility for substituting the biosimilar as he or she  
            would incur by filling a prescription for a biosimilar  
            prescribed by name.

          5)States that there shall be no liability on the prescriber for  
            an act or omission by a pharmacist in selecting, preparing, or  
            dispensing a biological product pursuant to this bill. 

          6)Prohibits the pharmacist from substituting a biosimilar unless  
            the biosimilar costs the patient the same or less than the  
            prescribed biological product, as specified. 

          7)States that the provisions of this bill shall apply to all  
            prescriptions, including those presented by or on behalf of  
            persons receiving assistance from the federal government or  
            pursuant to the Medi-Cal Act.

          8)Requires the substitution of a biosimilar to be communicated  
            to the patient.

          9)Requires the Board of Pharmacy (BOP) to maintain on its public  
            Internet Web site a link to the current list, if available, of  
            biosimilar products determined by the FDA to be  
            interchangeable.

          10)States that nothing in this bill prohibits the administration  
            of immunizations, as specified.

          11)States that nothing in this bill shall be interpreted to  
            prohibit a disability insurer or health care service plan from  
            requiring prior authorization or imposing other appropriate  
            utilization controls in approving coverage for any biological  
            product.

          12)Defines the following:

             a)   "Biological product," "biosimilar," and  
               "interchangeable" have the same meanings that apply to  
               those terms under the federal Public Health Service Act, as  
               specified;

             b)   "Prescription," with respect to a biological product,  
               has the same meaning as used in the Federal Food, Drug, and  
               Cosmetic Act, as specified; and,









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             c)   "351(k) pathway" refers to the licensure of a biological  
               product as a biosimilar or an interchangeable biosimilar by  
               the FDA pursuant to the federal Public Health Service Act,  
               as specified. 

          13)States that no reimbursement is required by this act pursuant  
            to Section 6 of Article XIIIB of the California Constitution  
            because the only costs that may be incurred by a local agency  
            or school district will be incurred because this act creates a  
            new crime or infraction, eliminates a crime or infraction, or  
            changes the penalty for a crime or infraction, within the  
            meaning of Section 17556 of the Government Code, or changes  
            the definition of a crime within the meaning of Section 6 of  
            Article XIIIB of the California Constitution.

           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.  (Health and  
            Safety Code (HSC) Section  1600.1)  

          2)Defines "drug" to include articles intended for use in the  
            diagnosis, cure, mitigation, treatment, or prevention of  
            disease in human beings or other animals. (Business and  
            Professions Code (BPC) Section 4025)

          3)Creates the California Board of Pharmacy (BOP), which  
            regulates the practice of pharmacy. (BPC 4000 et seq.)

          3)Permits a pharmacist filling a prescription order for a drug  
            prescribed by its brand name to substitute a generic version  
            or a different form of medication with the same active  
            chemical ingredient, unless the prescriber personally  
            indicates, either orally or in his or her own handwriting, not  
            to substitute.  (BPC 4052.5, 4073)

          4)Absolves the prescriber from any liability for an act or  
            omission by a pharmacist in selecting, preparing, or  
            dispensing an alternate generic drug or a different form of  
            medication with the same active chemical ingredient. (BPC  








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            4073)

          5)Prohibits a pharmacist from substituting a generic drug or a  
            drug with the same active chemical ingredient unless the drug  
            costs the patient less than the prescribed drug. (BPC 4073)

          6)Permits pharmacists to administer immunizations pursuant to a  
            protocol with a prescriber. (BPC 4052)

          7)Requires all records or other documentation of the acquisition  
            and disposition of dangerous drugs by any entity licensed by  
            the Board of Pharmacy to be retained on the licensed premises  
            in a readily retrievable form for a period of three years from  
            the date of making. (BPC 4105)
             
           EXISTING FEDERAL LAW  :

         1)The Food, Drug and Cosmetics Act requires drug manufacturers to  
            obtain approval of new drugs from the FDA.  (21 United States  
            Code (USC) Section 355)

         2)Prohibits a person from delivering for introduction into  
            interstate commerce any biological product unless a license is  
            issued pursuant to the Public Health Service Act.  (42 USC  
            262)

         3)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  (BPCI).  (42 USC 262 (k))

         4)Requires that, for a biological product to be considered  
            biosimilar to a reference product, data must be derived from  
            analytical, animal and clinical studies, as specified.  (42  
            USC 262 (k)(2))

         5)Clarifies that a product is biosimilar to a reference product  
            under the BPCI 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.  (42 USC 262(i)(2)(a) and (b))
           
           FISCAL EFFECT  :   Unknown








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           COMMENTS  :   

           1)Purpose of this bill  .  This bill will allow pharmacists to  
            substitute FDA-approved interchangeable biosimilar  
            pharmaceuticals for biological pharmaceuticals in the same way  
            that pharmacists currently substitute generic drugs for name  
            brand drugs.  SB 598 will also require pharmacists to notify  
            prescribers of the change until 2017.  This bill is  
            author-sponsored.    

           2)Author's statement  .  According to the author's office, "SB 598  
            updates the law so when the FDA approves interchangeable  
            biosimilars, California pharmacists can substitute the lower  
            cost biosimilars for brand name biologics.

            "SB 598 proposes a 'don't ask, just tell' policy and it does  
            not restrict a physician's prescribing choices.  Notification  
            to the prescribing physician AFTER dispensing does not alter  
            the policy goal of offering alternative, lower cost options  
            for patients.  The purpose of a prescriber notification  
            provision is to provide a record of the substitution, in the  
            event of an adverse reaction, or other clinical responses to  
            the biologic."

           3)Understanding biologic and biosimilar drugs  .  A "biologic"  
            drug is one that is created by biological rather than chemical  
            processes.  Biologics have been available for more than 20  
            years and include enzymes, human growth hormones, human  
            insulins, interleukins, and vaccines.  Many biologics are  
            among the most costly medicines available, ranging from $1,000  
            to $50,000 per treatment.  

            Biologic drugs represent a fast-growing segment of the  
            pharmaceutical market, constituting 32% of products in the  
            development pipeline and accounting for around 10% of  
            pharmaceutical expenditures (as of 2011).  The biologic market  
            is expected to grow more than 20% per year.

            A "biosimilar" is a biologic drug that is designed to be  
            comparable to a particular existing biologic drug, known as  
            the biologic "reference" drug.  Some manufacturers will seek  
            "interchangeable" status for their biosimilar, a designation  
            granted by the FDA that means those biosimilar drugs may be  
            substituted for the biologic reference drug without any  








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            expected change in clinical outcomes.   

            There are currently no biosimilars approved by the FDA for use  
            in the United States, and FDA has not yet received any  
            applications for a biosimilar.  However, as of February 6,  
            2013, FDA's Center for Drug Evaluation and Research had  
            received 50 requests for an initial meeting to discuss  
            biosimilar development programs for 12 different reference  
            products, held 37 initial meetings with sponsors, and received  
            14 Investigational New Drug applications for biosimilar  
            development programs.  

            It is anticipated that biosimilars will substantially reduce  
            pharmaceutical costs once they are introduced.  Industry  
            studies and academic articles indicate a potential cost  
            savings of 10-40% for a biosimilar compared to a biologic  
            reference drug, which would potentially expand access to these  
            important but expensive medications.   

            This bill will require BOP to maintain on its Web site a link  
            to the current list, if available, of biosimilar products  
            determined by the FDA to be interchangeable.  
           
          4)Current law on generic substitutions  .  In practice, this bill  
            would allow a pharmacist to substitute an interchangeable  
            biosimilar for a prescribed biologic to save money, in the  
            same way a pharmacist may currently substitute a generic for a  
            brand name drug.   

             Currently, a pharmacist filling a prescription order for a  
            drug prescribed by its brand name may substitute a generic  
            drug instead, unless the prescriber personally indicates  
            verbally or in writing not to substitute.  The prescriber is  
            not liable for the pharmacist selecting, preparing, or  
            dispensing a generic drug, and a pharmacist may not substitute  
            a generic drug unless it results in cost savings for the  
            patient. 

            These existing provisions of law would apply to the  
            substitution of interchangeable biosimilars as well, except  
            that a biosimilar may be substituted which costs the patient  
            the same or less than the prescribed biological product. 

           5)Prescriber notification  .  This bill would require a pharmacist  
            to inform the prescriber of the interchangeable biosimilar  








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            substitution within five business days of the selection, until  
            January 1, 2017.  The pharmacist has the option of notifying  
            the prescriber by entering the information in a patient record  
            system shared by the prescriber.   

            The three-year sunset on the notification provision was added  
            in the Senate Business, Professions, and Economic Development  
            Committee with the understanding that "accountability for  
            biosimilars may be achieved when California's e-pedigree law,  
            creating a track and trace system for drugs in this state, is  
            implemented, or in the event that Congress creates a national  
            track and trace system.  Accountability may also be heightened  
            through processes created by the FDA for biosimilars and  
            through natural market channels once biosimilars are utilized  
            more frequently."    

           6)Comparing biosimilars with generic drugs  . According to the  
            FDA, a generic drug is identical -- or bioequivalent -- to a  
            brand name drug.  However, a biosimilar is not, and cannot be,  
            the exact bioequivalent of a biologic reference drug because  
            of minor variations in the product caused by the high level of  
            complexity involved in making it. 
             
             According to the Biotechnology Industry Organization, "a drug  
            is typically manufactured through chemical synthesis, which  
            means that it is made by combining specific chemical  
            ingredients in an ordered process."  In contrast, "[a]  
            biologic is manufactured in a living system such as a  
            microorganism, or plant or animal cells.

            "The living systems used to produce biologics [and  
            biosimilars] can be sensitive to very minor changes in the  
            manufacturing process. Small process differences can  
            significantly affect the nature of the finished biologic and,  
            most importantly, the way it functions in the body. To ensure  
            that a manufacturing process remains the same over time,  
            biologics manufacturers must tightly control the source and  
            nature of starting materials, and consistently employ hundreds  
            of process controls that assure predictable manufacturing  
            outcomes.

            "Process controls for biologics are established separately for  
            each unique manufacturing process/product, and are not  
            applicable to a manufacturing process/product created by  
            another manufacturer. These process controls may also be  








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            confidential to the original manufacturer. Therefore, it would  
            be difficult or impossible for a second manufacturer to make  
            the 'same' biologic without intimate knowledge of and  
            experience with the innovator's process."

            Because of these complexities, the FDA has established a new  
            pathway to approve biosimilar drugs. 

           7)Biologics Price Competition and Innovation Act  .  The Biologics  
            Price Competition and Innovation Act (Act) was enacted as part  
            of the federal Affordable Care Act on March 23, 2010.  The Act  
            created an abbreviated licensure pathway for biosimilars.   

             The Act defines "biosimilarity" to mean that "the biological  
            product is highly similar to the reference product  
            notwithstanding minor differences in clinically inactive  
            components" and that "there are no clinically meaningful  
            differences between the biological product in terms of the  
            safety, purity, and potency of the product."    

            FDA sets an even higher standard for biosimilar drugs that a  
            manufacturer wants to deem "interchangeable" with a biologic  
            reference drug.  To attain interchangeability, according to  
            the FDA, "a [manufacturer] must provide sufficient information  
            to demonstrate biosimilarity, and also to demonstrate that the  
            [interchangeable biosimilar] can be expected to produce the  
            same clinical result as the reference product in any given  
            patient and, if the [interchangeable biosimilar] product is  
            administered more than once to an individual, the risk in  
            terms of safety or diminished efficacy of alternating or  
            switching between the use of the biological product and the  
            reference product is not greater than the risk of using the  
            reference product without such alteration or switch."  

            In other words, a patient should not experience a difference  
            between an interchangeable biosimilar and its reference  
            biologic.  The Act expressly states that a pharmacist or other  
            dispenser may substitute an interchangeable biological product  
            for the reference product without consulting the prescribing  
            doctor.  

           8)Questions for the Committee  .  Given that the purpose of  
            prescriber notification and a three year record maintenance  
            requirement is to collect data that may help to identify  
            potential adverse reactions, the Committee may wish to inquire  








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            of the author as to why there is no provision about reporting  
            adverse events to the FDA's MedWatch program.  MedWatch is  
            FDA's voluntary reporting database used to maintain safety and  
            surveillance of drug products.  Adverse drug reports may  
            prompt FDA to order a modification in the use or design of a  
            drug product, which would improve drug safety and lead to  
            increased patient safety. 

            If the FDA deems certain biosimilars to be interchangeable, it  
            will be because those drugs are supposed to have no clinically  
            meaningful differences from the original biological product.   
            If there is sufficient concern regarding adverse reactions to  
            biosimilar drugs that have met the FDA's interchangeability  
            threshold to merit prescriber notification, then it would seem  
            logical to also require that the nation's drug regulator be  
            notified of adverse effects as well. 

            According to the FDA, MedWatch reporting is voluntary.   
            However, the author may wish to consider requiring pharmacists  
            who substitute interchangeable biosimilars to notify MedWatch  
            within 10 days of learning of any adverse effects.    

           9)Related legislation  . AB 1139 (Lowenthal), of 2013, was  
            virtually the same bill as SB 598, but would not have required  
            prescriber notification and did not require BOP to maintain a  
            list on its Web site of interchangeable biologics.  AB 1139  
            was held in the Assembly Business, Professions, and Consumer  
            Protection Committee.  
             
             SB 294 (Emmerson) would revise requirements related to sterile  
            compounding pharmacies and includes a provision requiring that  
            any adverse effects reported or potentially attributable to a  
            pharmacy's sterile drug product be immediately reported to BOP  
            and the MedWatch program.  SB 294 is currently pending in the  
            Assembly Rules Committee.  

           10)Double-referred .  This bill is double-referred to Assembly  
            Health Committee. 

           REGISTERED SUPPORT / OPPOSITION  :

           Support 
           
          AIDS Institute 
          AIM Melanoma 








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          Abbvie, Inc. 
          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 Coalition of State Rheumatology 
          Organizations 
          California Prostate Cancer Coalition Advocates 
          Colon Cancer Alliance 
          Colorectal Cancer Coalition 
          Congress of Neurological Surgeons 
          CONNECT 
          Genentech 
          Global Healthy Living Foundation 
          Health HIV 
          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 








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          National Kidney Foundation 
          National Physicians Biologics Working Group 
          North American Spine Society 
          Pharmaceutical Research and Manufacturers of America 
          RetireSafe 
          Silicon Valley Leadership Group 
          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 
           
          America's Health Insurance Plans
          Anthem Blue Cross
          Association of California life & Health Insurance Companies
          Blue Shield
          Boehringer Ingelheim
          California Association of Health Plans
                   California Board of Pharmacy
          California Conference Board of the Amalgamated Transit Union
          California Conference of Machinists
          California Retailers Association
          California Society of Health System Pharmacists
          California State Board of Pharmacy
          CVS/Caremark
          Engineers & Scientists of California, IFPTE Local 20, AFL-CIO
          Express Scripts
          Generic Pharmaceutical Association
          International Longshore and Warehouse Union
          Kaiser Permanente
          National Association of Chain Drug Stores
          Novartis
          Professional and Technical Engineers, IFPTE Local 21, AFL-CIO
          Teamsters
          Teva Pharmaceuticals
          UNITE HERE, AFL-CIO
          United Food and Commercial Workers Union
          Utility Workers Union of America, AFL-CIO
          Walgreens

           Analysis Prepared by  :    Sarah Huchel / B.,P. & C.P. / (916)  
          319-3301 








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