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)

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CompendialGlobalization

Patient Benefit

Pioneers and Harmonization