USP Monographs
Roger L. Williams, M.D.CEO/Chair, Council of Experts
6th Annual Science and Standards SymposiumJanuary 16, 2013Istanbul
The Basics Management The Future—Science The Future—Putting It Together
Topics
Assignments
Documentary Standards-setting Process
Expert Committee Participation by Compendium
Expert Committee Participation
Public Review and Comment
Forum Frequency and Terminology
CompendiumPublication
USP−NF Involves the
majority of the Expert Committees
Pharmacopeial Forum (PF)
90 daysFree, Web access
only to start in January 2011
Includes new and revised standards
6 times per year (Jan, Mar, May, July, Sep, and Nov)
In Process Revision (IPR)
Official, legally enforceable text
Book and 2 Supplements published annually
Food Chemicals Codex (FCC)
Food Ingredients Nomenclature,
Safety and Labeling
FCC Forum (FF)90 daysFree, Web access
only Includes new and
revised standards
2 times per year(June and Dec)
Proposed Changes and Additions (PCA)
Effective text Published every
2 years with three intervening Supplements
Expert Committee Participation by Monograph Initiative
Expert Committee Participation
ScopePublic Review and Comment
Terminology
Pending Monographs
Primarily Small Molecules
Possibly Excipient Monographs
Nomenclature, Safety and Labeling
Monographs based on generic applications awaiting FDA approval
Not legally enforceablePending can become official
USP−NF monograph via Revision Bulletin (separate EC approval needed)
90 daysWeb onlyContent
updated monthly
Proposals are “Draft”
EC-approved content is “Authorized”
Non-US Monographs
Small Molecules Expert Committees, possibly others
Articles approved outside the U.S.Voluntary public standardRemains on Web site--not intended
to become official USP−NF monograph
90 daysWeb onlyContent
updated monthly
Proposals are “Draft”
EC-approved content is “Authorized”
Accelerated Revisions by Compendium
Accelerated Revision Type
USP–NF Revision Bulletin Revision Interim Announcement Errata
FCC Immediate Standard Expedited Standard Errata
EC Approval Required Required Not required
Notice and Comment
None 60 days (will be 90 days as of Jan 2011)
None
Uses Compliance, urgent safety issues, correction of substantive broad-impact errors
Non-urgent safety issue, non-working procedures
Correction of minor, low-impact errors and errors that do not reflect intended requirement as approved by the EC decision
Publication Monthly on Web site
6 times per year on Web site
Official or Effective Date
As of the date indicated in the posting
As of the date indicated Immediate
The Basics Management The Future—Science The Future—Putting It Together
Topics
Key Elements of Science & Standards Division: Organization Flow
Compendial Research
- Standards Acquisition- Analytical Reseach
Compendial Science
- Small Molecules- Biologics
- General Chapters- Excipients
- Dietary Supplements- Foods
- Healthcare Quality
Reference Material Operations
- Reference Standards Lab
- Reference Standards Production
- Production Planning - Technical Servcies
PrioritiesProject & Portfolio
Management
Publishing Monograph
Expert Committees
Quality Assurance
Reference Material
Released for Sale
Drivers for Change
Increase/improve interface between different parts of USP
Increase efficiency on work flow within SSD
– External to USP– Internal within USP
Expert Committees were recently restructured to manage monographs and reference standards
To make project ownership for each product clear (single point of accountability in the context of the team)
Maximize capacity of our work load (identify constraints and provide solutions)
Products (monographs, reference materials) to our customers are synchronized and reference standards are available as early as possible
There is a portfolio owner for each segment of the portfolio for Small Molecules, Biologics, Excipients, Dietary Supplements, Food Ingredients, General Chapters/Pharmacists’ Pharmacopeia, Healthcare Quality Standards
A uniform criteria for priority setting.
Drivers For Change: Outcomes
Current Status for US Compendia
Compendium Expert CommitteeMissing from
Compendia (Estimate) Total Monograph
Universe (Estimate)Small Molecules 1513 5042
Biologics 297 415Pharmacy 105 204
1937 566134%
Excipients 163 56329%
Dietary Supplements 1091 150073%
Food Ingredients 2535 367569%
Total 5726 11399
New Monographs
Compendium Expert Committee NeededWork in Process Work in Process
Small Molecules 2600 419 214Biologics 44 0 61
Pharmacy 0 0 46
2644 419 32470% 11% 17%
Excipients 96 62 3624% 16% 22%
Dietary Supplements 100 24 8324% 6% 8%
Food Ingredients 250 34 5422% 3% 2%
Total 3090 539 608
USP Total
NF
DS
FCC
5695
Modernization
USP
DS 40927%
FCC 114031%
USP Total 374666%
NF 40071%
In Compendia
USP3529
11899
Current Status: OTC Modernization (Focus for FY’13)
Substances Dosage Forms Total
Official in USP-NF 240 500 740
Modernization Required 141 325 466
% of OTC Monographs 59% 65% 63%
4128%
21%
64%
3221%10
7%
4832%
107%
New Monograph Breakdown(As of April 30, 2012)
Small Molecules (USP)
Biologics (USP)
Pharmacy (USP)
Excipients (NF)
Foods (FCC)
Dietary Supplements (DSC)
Medicines Compendium
Pending
Monographs Received by Portfolio Category
Reference Standards: Pipeline vs. Process
Collaborative Testing
SamplingTest Protocol Bulk procurement ShippingOracle Input
Data Analysis andScientific Review Packaging
Q/A and Q/C Released to Inventory
Reference Standard Lot Releases
Note: This information is updated from what appeared in briefing materials.
The Basics Management The Future—Science The Future—Putting It Together
Topics
Drug Product Monographs and General Chapters
A PBM can include:– Specified tests
• Identification, Assay, others
– Specific acceptance criteria • 97%-103%, NMT 0.1%, others
– Criteria-based procedures with:• Procedure Performance Measures (Precision,
accuracy, others)• Procedure Performance Acceptance Criteria (% RSD,
Bias, R2, others)
Performance Based Monograph
Glutathione Example: Assay
USP General Chapter Validation of Compendial Procedures <1225> defines the critical validation parameters necessary to validate a procedure.
Pre-set criteria assure that an acceptable procedure will reliably assess whether an article meets acceptance criteria of its Tests.
USP now terms these criteria as Procedure Performance Measures (PPM) and the Procedure Performance Acceptance Criteria (PPAC).
PPM and PPAC may be used to determine suitability of multiple acceptable procedures.
PPMs and PPACs
Small Molecules Collaborative Group, Williams RL, Abernethy DR, Koch WF, Hauck WW, Cecil TL. Performance-based monographs. Pharm Forum. 2009;35(3):765-771.
Hauck WW, DeStefano AJ, Cecil TL, Abernethy DR, Koch WF, Williams RL. Acceptable, equivalent, or better: approaches for alternatives to official compendial procedures. Pharm Forum. 2009;35(3):772-778.
Koch WF, Hauck WW, de Mars SS, Williams RL. Measurement science for food and drug monographs: toward a global system. Pharm Res. 2010;27:1203-1207.
Williams RL, de Mars S, Koch WF, Hauck WW, Cecil TL. USP responses to comments on Stimuli article: performance-based monographs. Pharm Forum. 2010;36(4):1074-1079.
References
USP Medicines Compendium: www.usp-mc.org
Key Points About the Medicines Compendium
MC is applicable to medicines legally marketed outside of the US; USP-NF covers articles legally marketed in the US
Science based
Authoritative, not official; the approval by the Council of Experts makes it authoritative
Supplements donor model
Helps modernize USP-NF
Experimental, unique, and innovative
USP Medicines Compendium Process
The Basics Management The Future—Science The Future—Putting It Together
Topics
Compendial Globalization (Merck)
Sta
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Pra
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Co
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Re
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CompendialGlobalization
Patient Benefit
Pioneers and Harmonization