BILL ANALYSIS                                                                                                                                                                                                    �






                             SENATE COMMITTEE ON HEALTH
                          Senator Ed Hernandez, O.D., Chair

          BILL NO:       AB 1277
          AUTHOR:        Hill
          AMENDED:       June 20, 2012
          HEARING DATE:  June 27, 2012
          CONSULTANT:    Marchand

           SUBJECT  :  Sherman Food, Drug, and Cosmetic Law.
           
          SUMMARY  :  Eliminates licensing inspections by the Department of 
          Public Health (DPH) for drug and medical device manufacturers, 
          as specified. Limits DPH's authority to make investigations or 
          inspections of manufacturers to situations where DPH has 
          determined the health and safety of the public is at serious 
          risk, or when the U.S. Food and Drug Administration (FDA) has 
          requested assistance for enforcement activities.

          Existing 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.

          2.Establishes the Sherman Law, administered by DPH, which, among 
            other things, regulates the packaging, labeling, and 
            advertising of drugs and medical devices in California.

          3.Prohibits, in the Sherman Law, the sale, delivery, or giving 
            away of any new drug or new device unless it is either: 
             a.   A new drug, and a new drug application has been approved 
               for it by the FDA, pursuant to federal law, or it is a new 
               device for which a premarket approval application has been 
               approved, and that approval has not been withdrawn, 
               terminated, or suspended under the FDA; or
             b.   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               new drug or device application, and has not withdrawn, 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.

          4.Requires DPH to adopt regulations to establish the application 
            form and set the fee for licensure and renewal of a drug or 
            device license. 

          5.Requires DPH to inspect the place of business of each licensed 
            manufacturer of a drug or medical device prior to issuing a 
            license, to determine ownership, adequacy of facilities, 
                                                         Continued---



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            personnel qualifications, and compliance with current law.

          6.Requires DPH to perform subsequent inspections once every two 
            years, unless the FDA has inspected the place of business 
            within the previous two years. Requires DPH to use the 
            information in the FDA inspection's written documents, rather 
            than conducting its own inspection.  

          7.Allows DPH, if necessary, to conduct an inspection to obtain 
            information not included or not sufficiently clear in the FDA 
            written documentation, as specified.

          8.Permits a DPH-authorized agent to enter and inspect specified 
            locations, as specified, to enforce the Sherman Law.
          
          This bill:
          1.Clarifies that biologic products are included in provisions of 
            existing law prohibiting anyone from selling, delivering, or 
            giving away any new drug or new device unless it has been 
            approved under specified provisions of federal law.

          2.Repeals the requirement that DPH inspect each place of 
            business prior to issuing a new license to a drug or device 
            manufacturer, and instead requires DPH to receive from the 
            place of business documentation that evidences any of the 
            following:
             a.   The place of business is operating pursuant to a valid 
               biologics license issued by the United States Food and Drug 
               Administration (FDA), as specified, requiring the 
               documentation to include an attestation from the place of 
               business that a federal inspection was completed within the 
               past two years from the date of the attestation;
             b.   The place of business is operating with a valid federal 
               establishment registration, as specified;
             c.   The place of business is operating in compliance with 
               audits conducted pursuant to the International Standards 
               Organization standards, as specified; or
             d.   The place of business is operating pursuant to an 
               approved investigational new drug issued by the FDA, or 
               pursuant to an approved investigational device exemption 
               issued by the FDA, as specified.

          3.Prohibits DPH from inspecting the place of business prior to 
            issuing a license if DPH receives documentation that satisfies 
            the requirements in 2) above; if this documentation is not 
            received, DPH is required to inspect the place of business 




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            prior to issuing a license.

          4.Requires DPH to provide an official copy of the valid license 
            upon request of the place of business.

          5.Repeals the requirement that DPH inspect a licensed drug or 
            device manufacturer once every two years following initial 
            licensure to determine ownership, adequacy of facilities, and 
            personnel qualifications.

          6.Limits the ability of DPH to make investigations or 
            inspections of licensed drug or device manufacturers to only 
            when any of the following occur:
             a.   DPH makes a determination that the health and safety of 
               the public is at serious risk;
             b.   A complaint has been registered with DPH, and DPH makes 
               a determination that the public health and safety is at 
               serious risk;
             c.   A notification has been sent by the FDA to DPH that 
               requests assistance regarding certain recall actions; or
             d.   The FDA has requested assistance for enforcement 
               activities, including, but not limited to, embargoes, 
               seizures, or injunctions.

           FISCAL EFFECT  :  According to the Assembly Appropriations 
          Committee:
          1.Reduced cost pressure to the Drug and Device Safety special 
            fund within DPH, associated with reduced frequency of 
            inspections.

          2.It is unclear whether the reduction in inspection frequency 
            will result in decreased expenditures for drug and device 
            regulation, as there is an existing and ongoing backlog in 
            initial licensure inspections. DPH indicates initial licensure 
            of manufacturers requires significantly more time than renewal 
            inspections, and the number of new manufacturers continues to 
            exceed DPH projections

           PRIOR VOTES  :  
          Assembly Health:                             17- 0
          Assembly Business, Professions and Consumer Protection:9- 0
          Assembly Appropriations:                     16- 0
          Assembly Floor:                              78- 0
           
          COMMENTS  :  




          AB 1277 | Page 4




           1.Author's statement.  Under existing law, biotechnology and 
            medical device companies undergo inspections from the FDA 
            every two years and DPH's Food and Drug Branch (FDB) every two 
            years. This is in addition to inspections performed by the FDB 
            prior to clinical trials and potential follow-up inspections 
            the state performs within weeks following FDA inspections. 

            The state inspections are duplicative of federal inspections 
            since both use the same compliance standards contained in the 
            Current Good Manufacturing Practices (GMP), as spelled out in 
            Title 21 of the US Code of Regulations, which mandates 
            compliance on issues ranging from Organization/Personnel, 
            Equipment, Building Lighting, Plumbing, Sewage &Ventilation, 
            Product & Process Controls, Package & Labeling Controls and 
            Records & Reports, among other things.

            AB 1277 reduces redundant inspections between the state and 
            federal government by clarifying that the FDA shall be 
            responsible for initial and biennial inspections and the state 
            FDB shall be responsible for taking action against companies 
            in instances where the public's health and safety may be at 
            risk. The state FDB would continue to conduct enforcement 
            activities including injunctions, embargoes & seizures and 
            conduct "for cause" inspections.  Companies would still be 
            responsible for paying biennial fees to the state FDB.
          
          2.DPH licensure of drug and device manufacturers. FDB in DPH is 
            responsible for licensing and inspecting all manufacturers of 
            pharmaceutical drug products and medical devices in 
            California, unless the manufacturer is specifically exempted. 
            DPH currently licenses and inspects 1,673 drug and medical 
            device manufacturing firms in California. FDB is required to 
            inspect the place of manufacture before issuing or denying a 
            license; firms cannot legally manufacture in California 
            without a valid license.  In addition to issuing a license, 
            DPH has the authority to revoke or suspend a license for any 
            violation of the Sherman Law. Current law also requires FDB to 
            conduct license renewal inspections of these companies once 
            every two years, and permits additional follow-up inspections 
            to be conducted "for cause" (e.g., to investigate injuries and 
            deaths or following product recalls).  
            
            According to DPH, its inspections are aimed at preventing the 
            sale and distribution of drugs and medical devices that have 
            been improperly manufactured; are adulterated, misbranded or 
            falsely advertised; have not been shown to be safe or 




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            effective; or in the case of medical devices, fail to meet 
            design verification requirements. As these products are being 
            used to treat life-threatening diseases or are necessary for 
            life support, early regulation by DPH prevents product 
            contamination, misbranding, and a variety of formulation, 
            fabrication, and labeling problems.  

          3.FDA regulation of drug and device manufacturers. Before a new 
            drug even gets to the manufacturing stage, it must undergo 
            preclinical testing, followed by clinical testing. The FDA is 
            involved in each stage of testing, ensuring the tests conform 
            to FDA's Good Laboratory Practices. After three phases of 
            clinical trials, and if the FDA does not require additional 
            information about the drug's efficacy, safety and side 
            effects, the sponsor of the new drug may submit a New Drug 
            Application, which contains all relevant and necessary 
            information about how the drug will be manufactured. According 
            to the FDA, "Manufacturing issues are also among the reasons 
            that approval �of a New Drug Application] may be delayed or 
            denied. Drugs must be manufactured in accordance with 
            standards called good manufacturing practices, and the FDA 
            inspects manufacturing facilities before a drug can be 
            approved. If a facility isn't ready for inspection, approval 
            can be delayed. Any manufacturing deficiencies found would 
            need to be corrected before approval. 
            
            In addition to approval of each individual drug, federal law 
            requires every establishment in any state engaged in the 
            manufacture, preparation, propagation, compounding, or 
            processing of a drug to register the name of the business with 
            the FDA. Federal law goes on to require that every such 
            registered establishment be inspected by the FDA at least once 
            in the two-year period beginning with the date of registration 
            and at least once in every successive two-year period 
            thereafter.
             
          4.Prior legislation. AB 764 (Davis), Chapter 516, Statutes of 
            1997, changed the regulatory process between FDA and DPH, 
            including changing the annual inspection frequency of drug and 
            device manufacturers to once every two years; repealing a 
            prohibition on drug and device advertising; and requiring, if 
            the FDA has conducted its own inspection within the previous 
            two years, that DPH use the information contained in the 
            written FDA documentation prior to conducting its own 
            inspection.




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          5.Support.  This bill is supported by the California Healthcare 
            Institute (CHI), which states that the duplicative regulation 
            of drug and medical device manufacturers is a perfect example 
            of onerous state regulations. According to CHI, California is 
            the only state that has duplicate regulations requiring 
            state-level permitting and inspection of drug and medical 
            device facilities. According to CHI, the FDA performs 
            stringent oversight of drug and device manufacturers, with 
            approvals required and inspections taking place throughout the 
            development process and on a regular basis thereafter. CHI 
            states that duplicative state oversight and inspection place 
            an increased financial burden on manufacturers in California.  
            CHI stated that in one example, a company spent more than 
            $200,000 and had more than 40 staff members involved in a FDB 
            inspection that took 8 days to complete. CHI states that this 
            was a routine inspection and did not find any health or safety 
            problems, and was conducted less than six months after a 
            comprehensive FDA inspection.

          The Advanced Medical Technology Association also supports this 
            bill, stating that this bill would relieve companies of the 
            added financial burden from redundant inspections, as well as 
            relieve state staff resources.  The Pharmaceutical Research 
            and Manufacturers of America states in support that 
            California's existing policy has the potential to create 
            unnecessary delays for patient access to medicines, and by 
            streamlining the approval process for medicines in California 
            that have already been approved by FDA will result in improved 
            access to medicines. BIOCOM states in support that although 
            the FDB serves a valuable and necessary role in the drug and 
            device safety chain, there is also some unnecessary and 
            duplicative overlap. BayBio states in support that everything 
            from the sterility of facilities to the quality of final 
            product to the font size used on packaging is scrutinized and 
            approved by the FDA, and that California should do everything 
            it can to remove barriers for its industry.

          6.Policy comment. This bill limits DPH's ability to conduct 
            investigations or inspection of licensed drug or device 
            manufacturers to only certain instances, including when it 
            makes a determination that the health and safety of the public 
            is at  serious  risk. It is unclear what constitutes a risk 
            serious enough to warrant a DPH inspection. Given that the 
            primary thrust of this bill is to eliminate duplicative 
            licensure and periodic inspections, the Committee may wish to 




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            consider whether the ability of DPH to conduct an inspection 
            based on a determination of risk to the public should be 
            limited to only "serious" risks.
               
          7.Technical amendment. As drafted, this bill requires a business 
             operating pursuant to a federal biologics license  to include 
            an attestation that a federal inspection was completed within 
            the two years prior to DPH issuing a license as a drug 
            manufacturer. The author states that this is a drafting error, 
            and the intent was to require businesses  operating pursuant to 
            a federal establishment registration  to include the 
            attestation of a completed federal inspection in order to be 
            licensed by DPH.  The author intends to offer technical 
            amendments in Committee to correct this drafting error.
          
           SUPPORT AND OPPOSITION  :
          Support:  Advanced Medical Technology Association
                    BayBio
                    BIOCOM
                    California Healthcare Institute
                    Pharmaceutical Research and Manufacturers of America
                    Silicon Valley Leadership Group
                    
          Oppose:   None received.
          
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