Role of Industry in USP Monograph Modernization. ExcipientFest Americas 2015 APRIL 29, Agenda

Transcription

1 Role of Industry in USP Monograph Modernization ExcipientFest Americas 2015 APRIL 29, 2015 John S. Punzi, Ph.D. 1 Agenda Impact of OTC s + Complexity Monograph Modernization Industry Approaches Acetaminophen Drug Substance Acetaminophen Drug Products Cough and Cold products Future 2 1

2 OUR COMMITMENT CHPA is committed to promoting the increasingly vital role of OTCs and dietary supplements in America's healthcare system through science, education, and advocacy. Committed to promoting the role of OTC and Dietary Supplement products through Science, Education and Advocacy serving the self-medication industry since 1881 CHPA S MEMBERS 4 2

3 IMPACT OF OUR MEDICINES 5 How Many OTC s are Marketed? 6 3

4 Active Ingredients OTC precondition for active ingredient monograph [21 CFR (a)(2) VII] An official United States Pharmacopeia (USP)-National Formulary (NF) drug monograph for the active ingredient(s) or botanical drug substance(s), or a proposed standard for inclusion in an article to be recognized in an official USP-NF drug monograph for the active ingredient(s) or botanical drug substance(s). 7 USP OTC Monograph Modernization History Mid-2010 USP Resolutions 2 (Strengthen Focus on Core Compendial Activities) and 3 (Strengthen Relationship with FDA). Oct 2010 Correspondence from Dr. Woodcock to USP on the importance of monograph modernization. Nov 2010 FDA task group formed. First priority list (APAP, diphenhydramine, etc). Aug 2011, Second FDA list. Additional priority monographs. And by the way include products including the ai s 4

5 Modernization of Monographs Achieved by: Replacing outdated procedures (e.g., packed column GC, TLC, wet chemistry tests, etc) Adding critical tests to the monograph (e.g., impurities/degradants) Deleting non-value added tests, as needed (e.g., odor test, melting point) Modernization proposals published in PF for a 90-day comment period 9 Wants and Needs for USP Monograph Modernization Public Safety Unambiguous enforceable specifications Referee method(s) / surveillance U.S. scope, participate globally Public Standard Align w/ FDA as much as possible Broad brush approach Worldly impact High Quality Products Practical, meaningful, balanced Requirement clarity, but flexibility U.S. focused, but worldly scope 5

6 FDA on USP s Monograph Modernization Program: The direct participation of the pharmaceutical industry. is encouraged to assist in providing updated public standards.. the submission of updated analytical methodology as well as materials which could be used for independent validation. FDA encourages all stakeholders to fully support this effort. 11 USP on USP s Monograph Modernization Program USP s greatest challenge is obtaining updated procedures and acceptance criteria manufacturers are encouraged to submit proposals to USP 12 6

7 USP OTC Monograph Modernization Substance monographs are relatively easy 140 are in need of modernization Separate task force for priority substance updates Ex-US USP laboratories HPLC / UPLC methods USP OTC Monograph Modernization Much of the industry sentiment from 2010 persists today The FDA OTC monograph system accommodates a large variety of products USP activities need to keep-up with OTC industry (flexible and fast to keep pace with seasonal and market driven needs) Alternatives needed for publishing methods, updating monographs Establish primary USP method and publish additional methods from industry 7

8 USP OTC Monograph Modernization It s still big (2600+ monographs to address to begin) It s still complex (grouping like APIs/DPs and using general chapters is part of the solution but is that enough?) It s still wanted by all, but especially the FDA Keep pushing, do it within <the next> 5-year cycle Benefits accrue with stakeholder input (3-legged stool, et.al.) USP OTC Monograph Modernization Industry Approaches Acetaminophen Acetaminophen combination products Cough and Cold products 16 8

9 Industry Approach Acetaminophen CHPA Impurities Breakout Group (2010) Sub team for APAP Evaluated methods for the API monograph Agreed on 4-aminophenol limits with supporting tox and product data Members Invited to Acetaminophen Expert Panel (EP) USP General Chapter <227> Capable of assaying for 4AP in a variety of complex products 17 Repeated Industry Approach CHPA Monograph Modernization (2013) Sub team for Diphenhydramine Evaluated methods for the API monograph Proposed Impurity Limits 18 9

10 USP OTC Monograph Modernization Cycle Time OTC DP Formula 1 OTC DP Formula 2 OTC DP Formula 3 OTC DP Formula 4 USP process 2 years USP monograph is potentially obsolete before it s official. Industry Approach Acetaminophen Existing Monographs 4050 products containing Acetaminophen 47% (1899) fall under 18 USP monographs 20 10

11 USP OTC Monograph Modernization APAP Capsules APAP Solution APAP Effervescent for Solution APAP Suppositories APAP Suspension APAP Tablets APAP, ASP Tablets APAP, ASP, CAF Tablets APAP, PSE Tablets APAP, CAF Tablets Capsules with APAP and at least 3 CPM, DEX, PSE Powders with APAP and at least 3 CPM, DEX, PSE Solutions with APAP and at least 3 CPM, DEX, PSE Tablets with APAP and at least 3 CPM, DEX, PSE APAP, CPM, DEX Tablets APAP, DOX, DEX, PSE Solution APAP, DPH (citrate) Tablets APAP, DPH, PSE Tablets 21 USP OTC Monograph Modernization Industry Role is staffing USP expert panels and using committees to test products

12 USP OTC Monograph Modernization Industry Approaches Cough and Cold products 23 Total 2013 OTC Pharmaceutical Sales (Billions) $33 OTC $7.2 Cough and Cold Products $321 Rx 24 12

13 5/11/2015 How Many Cough & Cold Products? Regular Original Citrus Bubblegum Grape Cherry Honey Lemon Pleasant Mixed Berry Licorice Fruit Punch Watermelon Mint 25 How Many Cough & Cold Products? Liquids Drops Exlixer Liquicap Liquigel Liquid Shots Liquid Sprays Suspensions Syrups Solids Balms Capsule Chewable pill Caplets Dissolvable pellets/powders Effervescent Express gel Gel Gelatin caplet Gelcap Gummi Lotion Tablet 26 13

14 5/11/2015 How Many Cough & Cold Products? Other Dosage Forms?? Globule Medicated Swab Medicated Vial Melt Away Oil Packet Pastille Patch Powder Quick Melt Shot Square Stick 27 How Many Cough & Cold Products? ~250 Unique Single Actives and Combinations of Actives ~7200 OTC Products Product sales >10,000 units in past 5 years containing one or more: Acetaminophen, Chlorpheniramine, DEX, Diphenhydramine, Doxylamine, Guaifenesin, Phenylephrine, Pseudoephedrine 28 14

15 CHPA Collaboration Cough/Cold Sub-Team Goal: Develop Industry Consensus for Degradants Legal Agreements by several companies with CHPA put in place (Oct 2014) P&G Perrigo McNeil/J&J Bayer Novartis Pfizer Data Sharing Sessions Started December 4, 2014 The Formula of Everything for Cough/Cold Syrups Actives APAP, GG, PE, DOX, DEX, CPM, DPH PSE Free (want to be on shelves and not behind the counter) Buffer Na Citrate/citric acid ph 4.6 Solvents Ethanol Propylene glycol Glycerin Water Preservatives Na Benzoate Sweeteners HFCS, Sorbitol, Sucralose Na Saccharin, Acesulfame K Dyes Green #3 + Blue #1 + Yellow #6 + Yellow #10 + Red#40 30 Confidential 15

16 PE & AceK Cough and Cold Products are Complex Mixtures APAP DOX DEX & DPH 31 USP OTC Monograph Modernization Industry Approaches Cough and Cold products Agree on degradation products Share the assay and impurities methods and limits 32 16

17 Medicines Marketed Under FDA OTC Regulations: Strategy for Developing USP Standards PF41(1), Jan 2015, Stimuli Article Strategy Individual Drug Product (DP) monographs that reference General Chapters ID + Assay by gradient UPLC-PDA Only certain specified organic impurities deg. product(s) / toxic adducts by gradient UPLC-PDA No unspecified impurities or total impurities Coverage of unspecified, others, the unexpected via proposed <427> and revised <1086> that make clear manufacturer responsibility re ICH Q3B approach to impurities EI, residual solvents, anti-microbial, antioxidants, etc. Stimuli Article DP Monograph Outline Definition IDENTIFICATION A. ID A B. ID B ASSAY Drug Product Assays <321> IMPURITIES Drug Product Impurities <327> Elemental Impurities <232> Residual Solvents <467> SPECIFIC TESTS C. ph <791> D. Alcohol Determination <611> E. Anti microbial agents <341> F. Antioxidants <342> G. Preservatives <343> PERFORMANCE TESTS H Dissolution <711> I. Uniformity of Dosage Units <905> J. Deliverable Volume <698> ADDITIONAL REQUIREMENTS Packaging and Storage Labeling USP Reference Standards <11> <321> Drug Product Assays Acetaminophen Test 01 from USP lab Test 02 from manufacturer xyz Test 03 from manufacturer abc < Aspirin Test 01 from USP lab Test 02 from manufacturer abc Test 03 from manufacturer tty Caffeine Test 01 from manufacturer xyz etc 17

18 OTC Drug Product Monographs Improve the environment for participation Use of technology for publication OTC company direct input according to USP template Compromise Allow multiple ID tests for Products but only require two Let industry be the one to propose UPLC Work toward incremental change Benefits and Advantages Transparency Manufacturer selected compliance route which is easily enforced by FDA, etc. Broad application Flexibility for Manufacturers Assay and Impurities fast adoption, known path, low threshold donor model Easily extended as new actives and products come into the market 18

19 OTC Project Team Charge The purpose is to enhance interaction between stakeholders and USP regarding the process and framework for modernization Consider and provide feedback on the proposed USP OTC monograph and General Chapter approach, and suggest other new or novel approaches (i.e. FDA guidance). Advise USP on strategy for development and prioritization of monograph revisions. Consider communication of OTC-related initiatives to industry, regulatory, and other stakeholders. Work with FDA and counsel to develop a better understanding of the legal requirements, goals and flexibility that the agency is willing to consider while modernizing the USP OTC drug substance and drug product monographs 37 Role of Industry In USP OTC Monograph Modernization Concluding Remarks Acetaminophen Acetaminophen products Cough and Cold products Future 38 19

20 Contact Industry Liaison John S Punzi, Ph.D. Director Quality Assurance and Technical Affairs Consumer Healthcare Products Association 1625 Eye Street NW Washington DC Jpunzi@CHPA.org 39 QUESTIONS? 40 20