United States Pharmacopeial Convention Inc

PROMOTING THE QUALITY OF MEDICINES PLUS (PQM+) PROGRAM

PROMOTING QUALITY OF MEDICINES PROGRAM TO ASSIST IN EFFICACY AND SAFETY OF MEDICINES IN USAID AREAS OF INTEREST

THE PURPOSE OF THIS MODIFICATION IS TO PROVIED INCREMENTAL FUNDING IN THE AMOUNT OF $150,000.00 UNDER A MAARD FROM THE PHILIPPINES.

ASSESSMENT OF THE PERFORMANCE OF MAM VS CONVENTIONAL QC METHODS FOR EVALUATION OF PRODUCT QUALITY ATTRIBUTES OF ADALIMUMAB AND ETANERCEPT - ABSTRACT MONOCLONAL ANTIBODIES AND OTHER BIOTHERAPEUTICS ARE SUBJECT TO A VARIETY OF MODIFICATIONS THAT CAN IMPACT ACTIVITY AND STABILITY AND THEREFORE MUST BE ANALYZED AS PART OF QC AND COMPARABILITY. MASS SPECTROMETRY (MS) HAS BECOME A WORKHORSE FOR BIOPHARMACEUTICAL ANALYTICAL LABORATORIES DUE TO ITS ABILITY TO DETECT PROTEIN MODIFICATIONS AT A MOLECULAR LEVEL. OVER THE PAST FEW YEARS, THE MULTI-ATTRIBUTE METHOD (MAM) HAS GAINED TRACTION THROUGHOUT PHARMACEUTICAL DEVELOPMENT AND QC LABS, WITH SEVERAL DEVELOPERS IMPLEMENTING SOME FORM OF MAM IN CHARACTERIZATION OR RELEASE. WHILE REPLACING MULTIPLE QC TESTS PROVIDES AN OPPORTUNITY TO STREAMLINE LAB WORK AND DECREASE DEVELOPMENT TIME AND POST-APPROVAL COSTS, SEVERAL CHALLENGES REMAIN. WHILE SOME LARGE BIOPHARMA COMPANIES ARE IMPLEMENTING MAM IN QC, MAM IS NOT AS COMMONLY USED IN BIOSIMILAR AND SMALL BIOPHARMA COMPANIES. THIS PROPOSAL ADDRESSES ONE OF THE KEY AREAS OF CONSIDERATION FOR IMPLEMENTATION OF MAM IN QC AS OUTLINED IN A 2019 PUBLICATION FROM FDA STAFF: THE PERFORMANCE OF MAM VS CONVENTIONAL METHODS. COLLECTING DATA TO SUPPORT TRANSITIONING FROM CONVENTIONAL TECHNIQUES TO MAM IS A SIGNIFICANT INVESTMENT THAT CAN PREVENT OR DELAY DEVELOPMENT OF BIOSIMILARS. THE OBJECTIVE OF THIS WORK IS TO ASSESS THE PERFORMANCE OF THE MS-BASED MAM VERSUS CONVENTIONAL QC METHODS TO IDENTIFY CHANGES IN PRODUCT QUALITY ATTRIBUTES (PQAS) UPON FORCED DEGRADATION AND TO CORRELATE CHANGES IN THOSE PQAS WITH BIOACTIVITY, BINDING AFFINITY, AND STRUCTURE. RESULTS OF THIS STUDY WILL HELP SUPPORT TRANSITIONING FROM CONVENTIONAL TECHNIQUES TO MAM BY CREATING A KNOWLEDGE BASE THAT CAN LOWER THE BARRIER TO ADOPTION OF MAM AND ENABLE WIDER USE OF MAM BY BIOSIMILAR MANUFACTURERS. THE WORK PROPOSED HERE WILL ASSESS AND COMPARE PQAS OF A MONOCLONAL ANTIBODY (ADALIMUMAB) AND FC FUSION PROTEIN (ETANERCEPT) ACQUIRED FROM THREE DIFFERENT SOURCES USING BOTH CONVENTIONAL QC METHODS AND MAM-BASED APPROACHES. SENSITIVITY OF EACH TECHNIQUE TO CHANGES DURING FORCED DEGRADATION WILL BE EVALUATED AND COMPARED TO FUNCTIONAL AND STRUCTURAL CHANGES DETECTED USING CELL-BASED ASSAYS, BINDING ASSAYS AND CIRCULAR DICHROISM. WE PROPOSE TO FIRST CONDUCT FORCED DEGRADATION STUDIES OF ADALIMUMAB AND ETANERCEPT FROM MULTIPLE SOURCES (SPECIFIC AIM 1). PQAS WILL BE EVALUATED USING CONVENTIONAL METHODS TO ASSESS CHARGE VARIANTS, GLYCOSYLATION, AND SIZE VARIANTS, (SPECIFIC AIM 2) AND COMPARED TO THE SPECIFIC MOLECULAR MODIFICATIONS DETECTED USING AN MS-BASED MAM WORKFLOW (SPECIFIC AIM 3) TO ASSESS COMPARABILITY AND SENSITIVITY TO CHANGES IN PQAS. LASTLY, UNDER SPECIFIC AIM 4, WE WILL ASSESS THE BIOACTIVITY AND STRUCTURE OF BIOTHERAPEUTIC PRODUCTS EXHIBITING SIGNIFICANT DIFFERENCES IN PQAS TO CORRELATE MOLECULAR CHANGES TO CHANGES IN STRUCTURE AND FUNCTION.

CONGRESSIONAL EARMARK: VERSION 5 COMPLETION OF THE MODEL GUIDELINES

COMPLETE THE USP MEDICARE MODEL GUIDELINES VERSION 10.0 - THE UNITED STATES PHARMACOPEIAL CONVENTION, INC. (USP), AS STIPULATED BY THE MEDICARE PRESCRIPTION DRUG IMPROVEMENT AND MODERNIZATION ACT OF 2003, WORKS WITH THE CENTERS FOR MEDICARE AND MEDICAID SERVICES (CMS) TO REGULARLY REVISE AND UPDATE THE MEDICARE MODEL GUIDELINE (MMG). USP DEVELOPED MMG VERSION 1.0 IN 2004, AND IN SUBSEQUENT YEARS ENTERED INTO ANNUAL COOPERATIVE AGREEMENTS WITH CMS THAT RESULTED IN MMG VERSIONS 2.0, 3.0, 4.0, 5.0, 6.0, AND 7.0. VERSIONS 2.0, 3.0, AND 4.0 WERE PART OF A CONTINUOUS REVISION PROCESS, WHILE VERSIONS 5.0, 6.0, 7.0, 8.0, AND 9.0 REPRESENT A TRIENNIAL REVIEW PROCESS. USP IS NOW PREPARED TO DEVELOP MMG VERSION 10.0, SUPPORTING CMS EFFORTS TO PROVIDE HIGH-QUALITY, COST-EFFECTIVE CARE TO BENEFICIARIES. PLEASE SEE ATTACHMENT FOR COMPREHENSIVE PROJECT ABSTRACT.

MEDICARE MODEL GUIDELINES (MMG) VERSION 9.0 - THE UNITED STATES PHARMACOPEIA (USP) IS AN INDEPENDENT, SCIENCE-BASED PUBLIC HEALTH ORGANIZATION. USP'S CONTRIBUTIONS TO PUBLIC HEALTH ARE ENRICHED BY THE PARTICIPATION AND OVERSIGHT OF EXPERT VOLUNTEERS REPRESENTING PHARMACY, MEDICINE, AND OTHER HEALTHCARE PROFESSIONS AS WELL AS ACADEMIA, GOVERNMENT, THE PHARMACEUTICAL INDUSTRY, HEALTH PLANS, AND CONSUMER ORGANIZATIONS. IN DECEMBER 2003, THE MEDICARE PRESCRIPTION DRUG IMPROVEMENT AND MODERNIZATION ACT OF 2003 (MMA) WAS SIGNED INTO LAW. UNDER MMA, PART D PLANS ARE REQUIRED TO COVER PRESCRIPTION DRUGS WITHIN EACH THERAPEUTIC CATEGORY AND CLASS OF COVERED PART D DRUGS. PER THE MMA, USP IS TASKED TO DEVELOP, IN CONSULTATION WITH PHARMACEUTICAL BENEFIT MANAGERS AND OTHER INTERESTED PARTIES, A LIST OF CATEGORIES AND CLASSES THAT MAY BE USED BY PRESCRIPTION DRUG PLANS AND TO REVISE SUCH CLASSIFICATION FROM TIME TO TIME TO REFLECT CHANGES IN THERAPEUTIC USES OF COVERED PART D DRUGS AND THE ADDITIONS OF NEW COVERED PART D DRUGS. THE METHODOLOGY FOR THE USP MEDICARE MODEL GUIDELINES REMAINS FOCUSED ON TWO OBJECTIVES: 1. CONDUCTING A CLINICALLY BASED REVIEW AND INCORPORATION OF PART D DRUGS (AS DEFINED IN 42 CFR 423.1001) 2. UPDATING THE USP CATEGORIES AND CLASSES AS NECESSARY TO ACCOMMODATE CHANGES IN THERAPEUTIC USES AND THE ADDITIONS OF NEW PART D DRUGS, AS SPECIFIED IN 1860D-4(B)(3)(C)(II) OF THE SOCIAL SECURITY ACT THE USP CATEGORIES AND CLASSES ARE DEVELOPED UTILIZING CONTEMPORARY SCIENTIFIC INFORMATION AND EXPERT EVALUATION AND AIM TO STRIKE A BALANCE OF ASSURING PART D BENEFICIARY ACCESS TO SAFE AND EFFECTIVE DRUGS THAT THEY NEED WITH THE FLEXIBILITY THAT PLANS NEED TO OFFER AN AFFORDABLE AND EFFECTIVE BENEFIT. THIS BALANCE CREATES THE TAXONOMY OF THE USP MEDICARE MODEL GUIDELINES, WHICH ARE DISTINCTLY DIFFERENT IN PHILOSOPHY AND STRUCTURE THAN OTHER TAXONOMY SYSTEMS CLASSIFYING DRUGS SOLELY BASED UPON EITHER PHARMACOLOGY OR THERAPEUTICS.

COMPLETE THE USP MEDICARE MODEL GUIDELINES V7.0 AS STIPULATED IN SECTION 1860 D-4 (B)(3)(C)(II) OF THE MEDICARE PRESCRIPTION DRUG, IMPROVEMENT, AND M

USP 2013

MEDICARE MODEL GUIDELINES VERSION 8

CO-SPONSORSHIP OF A TWO-DAY WORKSHOP ON #19;DNA FOR QUALITY CONTROL OF BOTANICAL PRODUCTS