BILL ANALYSIS                                                                                                                                                                                                    Ó



                                                                  AB 1139
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          Date of Hearing:   April 30, 2013

              ASSEMBLY COMMITTEE ON BUSINESS, PROFESSIONS AND CONSUMER  
                                     PROTECTION
                              Richard S. Gordon, Chair
               AB 1139 (Lowenthal) - As Introduced:  February 22, 2013
           
          SUBJECT  :   Prescription: biosimilar products.

           SUMMARY  :   Permits a pharmacist to substitute a biological  
          pharmaceutical product with a comparable 'biosimilar' product,  
          provided that biosimilar product is deemed by the federal Food  
          and Drug Administration (FDA) to be interchangeable with the  
          prescribed biological product.  

           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 Sections 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  








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            medication with the same active chemical ingredient. (BPC  
            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)

           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  :   None.  This bill is keyed non-fiscal by the  
          Legislative Counsel. 

           COMMENTS  :   

           1)Purpose of this bill  .  This bill would allow a pharmacist to  
            substitute a biosimilar pharmaceutical product, deemed  
            interchangeable by the FDA, for a prescribed biologic product,  
            mirroring the current process for generic drug substitutions.   








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            Opponents contend that this measure does not contain  
            sufficient safeguards for patients because biosimilar drugs  
            are relatively new.  This bill is sponsored by the Generic  
            Pharmaceutical Manufacturers Association.     


            2)Author's statement  .  According to the author, "In the coming  
            years, when the FDA has determined that safety and efficacy  
            standards have been met, these less-costly biosimilars will  
            become available to patients.  In order for biosimilars to be  
            prescribed in California, state law needs to allow for their  
            distribution and substitution.


            "AB 1139 allows pharmacists to select and dispense at a lower  
            cost, equivalent biosimilar drug products, once they are  
            approved for use by the FDA.

            "Physicians will use the same process for prescribing  
            biosimilars as they do for other drugs, including the option  
            to prohibit the substitution [of] the prescribed drug, by  
            simply checking the 'dispense as written' box on the  
            prescription itself, the same specification that's allowed for  
            the prescribing of name brand or generic medication."
             
          3)Understanding biologic 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  
            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 or interchangeable 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 present a considerable  
            cost savings 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.   
           
          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. 

           5)Biosimilars v 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  
            bioequivalent of a biologic reference drug because of the high  
            level of complexity involved in producing it. 
             
             According to the Biotechnology Industry Organization, "a drug  
            is typically manufactured through chemical synthesis, which  








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            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  
            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. 

           6)Biologics Price Competition and Innovation Act  .  The Biologics  
            Price Competition and Innovation Act (Act) was enacted as part  
            of the 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  








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            [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."  

            A patient should not be able to tell the 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)Arguments in support  .  Express Scripts writes, "For far too  
            long, thousands of Californians have paid far too much for  
            biologic medicines.  These are the most costly medicines  
            available, ranging in price from $1,000 to more than $50,000  
            per treatment.  These drugs aren't 'experimental,' - they  
            treat very real chronic conditions that touch all of us and  
            the people around us:  cancer, rheumatoid arthritis, multiple  
            sclerosis, and others.  
                 
             "?By 2016, six of the top ten pharmaceuticals worldwide will  
            be biologics.  As such, it is critical that we not create  
            barriers to the availability and use of biosimilars when they  
            become available for patients in the United States.

            "As with generics today, the availability of biosimilars will  
            give patients greater access to life-saving medications and  
            reducing [sic] their costs by and [sic] estimated 10-40%.  It  
            is in the interests of the opponents of this legislation to  
            up-end the FDA's role and expertise in this area and to  
            intentionally create confusion and fear around the use of  
            biosimilars by requiring physician notification.  

            "In fact, FDA Commissioner Hamburg has spoken specifically to  
            that issue in comments regarding pending legislation in the  
            states regarding physician notification.  She stated, 'The  
            high standard for approval of biosimilar and interchangeable  
            products mean? they will meet the standards of safety,  
            efficacy and high quality that everyone expects and can count  
            on.  Efforts to undermine trust in these products are  
            worrisome and represent a disservice to patients who could  








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            benefit from these lower-cost treatments.'" [These remarks  
            were presented in a February 2013 speech to the Generic  
            Pharmaceutical Manufacturers Association, and FDA has not  
            contacted the Committee regarding this legislation.] 
                
            9)Arguments in opposition  .  The Alliance of Specialty Medicine  
            writes that they have "closely followed the development of  
            federal policy related to biosimilars and the safety  
            considerations that should be taken into account as biosimilar  
            versions of existing biologic medicines become a new treatment  
            option for our patients.  Importantly, AB 1139 fails to  
            address key policy issues to ensure patient safety is  
            preserved, including assurance that once biosimilars come to  
            market the treating physician is notified if another version  
            of the biologic medicine is substituted for the version  
            prescribed by the doctor.  The practice of automatic  
            substitution that is seen with generic drugs is not entirely  
            appropriate for biosimilar products given that they are not  
            simply 'generic' versions of biologics.  Physicians need to  
            know what medicine their patient receives and therefore, the  
            prescribing physician should be notified whenever a patient's  
            biologic medicine is substituted."  
                 
            10)Related legislation  .  SB 598 (Hill) is nearly identical to AB  
            1139, but requires a pharmacist who substitutes a biosimilar  
            product to notify the prescriber or enter the appropriate  
            information in a patient record system shared by the  
            prescriber within five business days, until January 1, 2017.   
            SB 598 also requires BOP to maintain a link on its Web site to  
            the FDA's list of interchangeable biosimilar products, if  
            available.  SB 598 is currently pending in the Senate Health  
            Committee.       
                 
           11)Double-referral  .  This bill is double-referred, and if passed  
            by this Committee, it will be referred to the Assembly Health  
            Committee.  
           
           REGISTERED SUPPORT / OPPOSITION  :   

          Support 
           
          Generic Pharmaceutical Manufacturers Association (sponsor)
          California Retailers Association
          Express Scripts
          Mylan Inc. 








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          Pharmaceutical Research and Manufacturers of America 
          Pharmacy Choice and Access Now
          Teva Pharmaceutical Industries, Ltd.
          Walgreens

           Opposition 
           
          Alliance for Patient Access
          Alliance of Specialty Medicine
          Amgen
          BayBio
          California Healthcare Institute
          Coalition of State Rheumatology Organizations
          Global Healthy Living Foundation
          UCB, Inc.
           
          Analysis Prepared by  :    Sarah Huchel / B.,P. & C.P. / (916)  
          319-3301