the standard - fall-winter 2012

7/29/2019 The Standard - Fall-Winter 2012

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USP Headquarters

Maryland, USA

Europe/Middle East/Africa

Basel, Switzerland

USPIndia Private Ltd.

Hyderabad, India

USPChina

Shanghai, China

USPBrazil

So Paulo, Brazil

QUALITY STANDARDS for Medicines, Dietary Supplements,and Food Ingredients WORLDWIDE

ISO 9001:2008 Certified

CEO Column2 Message from the CEO

The Importance of Public DocumStandards and Reference Materia

USP Science

4 USP Workshop Focuseson Excipient Performance

5 USP Advancing Standardsfor Tablet Scoring

6 General Chapter TransformeFocus on Product Quality Tests foParenteral Medicines

7 USP Releases Standards to GuidContent, Appearance of PrescriptContainer Labels

8 Workshop Focuses on Qualityof Global Heparin Supply

International

12 Global Pharmacopoeias ExplorePotential Collaborations on MedQuality Standards

12 USP Welcomes Guests fromthe Jiangsu Province

Global Health Impact Program

14 African Labs Work towardEstablishing an IndependentProfessional Association

Inside USP

16 USP Awards Recognize VolunteeExperts

17 USP Achieves Continued ISO9001:2008 Certication

In This Issue

VOL. 10 | ISSUE 2 | FALL/WIN

USP Symposium Explores NewStandards for Functional Foodsand Dietary SupplementsThe choices for consumers are nearly endless, as are the promises: Improved bone health. Increased

energy. Enhanced focus. Better digestion. So-called functional ingredients represent not just a

passing fad, but a fast- (and by some accounts, the fastest-) growing segment of the food and di-

etary supplement industries as consumers increasingly seek products that they consider beneficial

to their health, appearance, athletic performance and more. The science behind many popular

ingredients, however, is still emerging, with little consensus on the validity of claims amongindustry, regulators, consumer representatives and other key parties. With this premise, more

than 200 attendees gathered

in Boston September 1820

for the 2012 USP Science and

Standards Symposium, to

consider opportunities and

challenges posed by func-

tional ingredientsand the

future direction for public

standards in this area.

The symposium opened with

an evening keynote addressfrom Dr. Paul Coates, direc-

tor of the Office of Dietary

Supplements (ODS) at the

National Institutes of Health.

Dr. Coates explained the

regulatory landscape governing dietary supplements in the United States as laid out in the 1994

Dietary Supplement Health and Education Act (DSHEA), in which dietary supplements are

regulated as foods. Since DSHEAs passage, supplement sales rose from $8.6 billion in 1994 to

$28.1 billion in 2010. Dr. Coates noted that roughly 50 percent of the domestic population uses

these products. He spoke about ODS work on evidence-based reviews of dietary supplements

such as ephedra (now banned in the U.S.), omega-3 fatty acids, soy, probiotics, vitamin D and cal-

cium; concerns about and current limitations of research in this area; and other ODS initiatives,

including its Analytical Reference Chemicals program with the National Institute of Standards

and Technology and consumer education programs.

In a morning plenary session on the second day of the symposium, Dr. Robert Buchanan of the

University of Maryland and a member of the USP Board of Trustees spoke about the science

behind regulation of functional foods. He explained three intersecting activities: science, science

policy and food law. Dr. Buchanan presented dictionary definitions of a functional food, but noted

that there is no current legal definition, nor is there likely to be. He said that the U.S. Food andContinued on page 19.See Symposium

(From left to right): Drs. Gorecki, Ebert, Buchanan and Susana Socolovsky of

Argentinas Pentachem answer audience questions during a plenary session.


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n This Issue Continued

The Standard Fall/Winter 20122

SP Science

USP Announces Change in LabelingRequirement for Total Strength of

Heparin

New Monograph Naming Policy BringsClarity, Consistency to Drug Names

USP Initiates Spectral Library Project

New Reference Material Offerings for

Novel, Natural Sweeteners

ternational

WHOFIP Meeting Focuses on Future of

International World of Pharmacopoeias

Brazil Conference Provides Opportunity

to Educate on USP Food Standards

obal Health Impact Programs

Voice of America Television Features

USP in Discussion on Counterfeit

Medicines

New PQM Initiative Looks to Build a

Pool of Experts to Improve Regional

Regulatory Enforcement

side USP

USP Granted Observer Status by Codex

Alimentarius Commission

USP Receives National Recognition

for Employee Benefits Program

Three Students Receive 20122013

Global Fellowship Awards from USP

Message from the CEO

The Importance of Public

Documentary Standards and

Reference Materials

Roger L. Williams, M.D. I have written before about the importance of science-based,widely available public standards to help ensure good-quality

medicines, foods and their ingredients. I reprise this themenow, driven by the fragmented state of global public health

measuresparticularly regarding compendial standards. Tothis end, USP posted public statements on its standards-setting

activities atwww.usp.org/about-usp/our-impact/statements-

usp-standards. A more detailed vision is advanced in a Stimuliarticle to be published in Pharmacopeial Forum in January

2013. In this smaller space, I offer a brief overview.

In the world of public monographs for drugs, foods and their

reference materials, the policy elements and opportunities are

clear. A USP article in Pharmaceutical Research explains:For medicines and foods, a national or regional or evenglobal goal might be a comprehensive collection of

public documentary and reference material standards

that can be usedto test for quality. An even moreambitious goal might be a single collection of documen-

tary standards and reference materials to support testingof medicines and foods. (1)

Attempts at harmonization among world pharmacopoeias

have moved slowly, but a new approach has emerged that

offers a path forward. Again, from USPs PharmaceuticalResearch article:

With availability of monographs where multiple accept-able procedures might be allowed (and one reference

procedure designated for purposes of compliance),

coupled with certified reference materials (CRMs)and other reference materials as needed, it is possible

to imagine that a full cohort of public procedures andreference materials may become availableto help

ensure the quality and benefit of medicines and foods.

The importance of this vision is underscored when one considers

USPNF, the most comprehensive of the worlds pharmacopoeias.

USP estimates there are a total of 11,477 medicines, excipients,

dietary supplements, food ingredients and their components

marketed in the U.S. Of this universe, half are missing from USPcompendia. Despite the efforts of dedicated scientists, the growing

demands of global public health need to be better served.

Barriers and Challenges to Public StandardsHistorically, USPs documentary standards and reference ma-

terials have come from donations by manufacturers, and these

are greatly valued. But too many times manufacturers concernsabout intellectual property issues or perceived lack of cost/bene-
http://www.usp.org/about-usp/our-impact/statements-usp-standardshttp://www.usp.org/about-usp/our-impact/statements-usp-standardshttp://www.usp.org/about-usp/our-impact/statements-usp-standardshttp://www.usp.org/about-usp/our-impact/statements-usp-standardshttp://www.usp.org/about-usp/our-impact/statements-usp-standardshttp://www.usp.org/about-usp/our-impact/statements-usp-standards


3/20www.usp.org

fit justification prevent donations. Additionally, it is argued thatthere is no need for a public standard until generic entry, with

multiple companies manufacturing a product. Recently, there

also has been an increased focus on current Good Manufactur-ing Practices (cGMPs) approaches (e.g., Quality by Design) and

a correspondingly decreased emphasis on end-product testing

requiring monographs and reference materials.

Rationale for a Public MonographDuring the 1930s, USP leader James Beal observed that Congress

had chosen to recognize the USP as a standard of measurementagainst which to compare drug products, making the USPno

different from the legal system of weights and measures. (2) Thisperspective remains compelling today. USP has advocated for

a global system of public weights and measures for medicines

beyond the extent that it already does through World HealthOrganization (WHO) initiatives, e.g., International Unit and

Systme International dUnits.

Public monographs and reference materials remain part of thecomplex and imperfectly integrated actions needed to ensure amedicines quality, safety and efficacy. For example, cGMPs are

critical, as are many other manufacturer, regulatory and com-pendial standards. These standards are subject to conformity

assessments by first (sellers), second (buyers) and third parties

(those independent of buyer and sellerregulatory agencies,compendia and others). The role of third parties on behalf of

the practitioner and patient (or consumer) is especially impor-tant, because they are not ordinarily part of the manufacturing

process. While one cannot test quality into a product, better

design processes andproduct testing are essential. It is perhapseasier to recognize this when looking at developing countries

where well-designed products are too often degraded by adul-teration or poor storage and shipment conditions. In such cases,

post-market surveillance and testing are essential.

Even in developed countries, public standards help stakeholders

maintain confidence in the quality of medicines. Regulatorshave their greatest influence at the time of the market-access

decision, when manufacturers agree to many regulatory

controls. After this, regulatory oversight can diminish rapidly.Based on this, USP believes public compendial monographs and

reference materials should be available from the time of marketentry for all medicines, innovator and generic.

Lessons from the USP Medicines CompendiumThe initial motivation for the USPMedicines Compendium(MC) was to expand the availability of public monographs and

reference materials in view of the challenges that face USPNF

in having a full complement of current monographs with al-lied reference materials. USP had no expectation that the MC

would solve the deficiencies ofUSPNF. It simply was a way tocreate standards for articles approved in any country. But USPs

experience since theMClaunch in July 2011 provided compel-

ling insights. USP learned (or re-learned) how to create and/ormodernize a monograph on its own. To do this, USP can create

a monograph based on research and development activities in

its own laboratories. These are termed Reference Proceduresthat are multi-source, i.e., they are suitable to control many

articles under the same name. A set of Reference Procedures in

a monograph synergize with a more optimized manufacturer-specific procedures, which are termed Acceptable Procedures.

Together, the dual approach allows a single set of procedures ina monograph that can support a single global control standard

for all articles under the same name. As a further opportunity,the performance-based monograph creates a framework for

this testing standard. Beyond these document approaches, USP

can independently identify impurity reference materials neededto support a monograph and can create these materials in USP

laboratoriesa departure from USPs reliance on manufactur-ers or other laboratories for donated materials to support the

procedures of a monograph.

Toward a Global System, Working CollaborativelyDespite progress by international bodies, we still lack a globalsolution. Instead, there are many non-harmonized monographs,

supplemented at times by the WHO International Pharmacopoeia.USPsMCmay be seen as complementary to all pharmacopoeias,

and this is enhanced byMCs open-access character and rapid,

web-based approach to allow public comment. Relevant tomanufacturers, theMCapproach suggests that a pioneers

donation of a drug substance could be used across all proceduresin any pharmacopoeia. Ultimately, this leads to global har-

monization. In some ways,MCaccords with the notion of the

ideal pharmacopoeia as articulated by the pioneer industry,because it can provide a single ICH-based global standard that

can apply across markets and manufacturers. For ministries ofhealth, regulatory bodies and pharmacopoeias, the value of a

good monograph with reference material rarely needs defense

in resource-poor countries where borders are porous, regulatorycontrol is weak and capacity is limited. Even where regulatory

resources and market control are strong, however, argumentsin favor of public standards gain traction with rising concerns

about counterfeit and substandard medicines. For patients and

consumers, while concepts discussed here might be unfamiliar,these parties might benefit from clear statements about the

value of independent standards.

Moving forward, USP is well positioned to work with all stake-

holders. Our present vision embraces the concepts embodied byJames Beals arguments many decades ago, while extending them

to the globalized world in which we find ourselves today.

REFERENCES

(1) USP Council of Experts, USP Reference Standards Committee, Hauck WW. Primary andsecondary reference materials for procedures to test the quality of medicines and foods.Pharm Res. 2012; 29(4):922931. doi: 10.1007/s11095-012-0687-7.

(2) Anderson L, Higby GJ. The Spirit of Voluntarism: A Legacy of Commitment and Contribution:The United States Pharmacopeia 18201995. Rockville, MD: USP; 1995:275276.

Note: Modified from original CEO Column on January21, 2013.
http://www.usp.org/http://www.usp.org/


4/20The Standard Fall/Winter 20124

USP Science

USP Workshop Focuses on Excipient PerformanceUSP held its first

Workshop on Food

Ingredient Functional-

ity and its Correlationswith Pharmaceutical

Excipient Perfor-

mance in conjunction

with its Science and

Standards Symposium

in Boston, Mass. It is

the first workshop to

highlight the paral-

lels and contrasts

between pharmaceuti-

cal excipient and food

ingredient quality. A

consistent workshoptheme was variabil-

ityits inevitability

in excipients and food ingredients, how to detect and measure it,

why and when it matters, and how to manage it. While excipi-

ents are sometimes called the inert ingredients in a regulated

product, such as flavors, fillers, binders, colors, preservatives,

etc., in reality no ingredient added to a medicine or food is fully

inert. This is a complex environment that can be altered by, for

example, a change of suppliers, equipment, processes, or even

personnel or their training regimens.

With the traditionally disparate worlds of pharmaceutical, food

ingredient and dietary supplement manufacturing increas-

ingly overlapping, the use of excipients and the need for shared

understanding of how to define and asses their quality provided

the impetus for the workshop. While each industry is regu-

lated differently in the United States, a single pharmaceutical

excipient supplier might have all three types of manufacturers

as customers. This makes common understanding increas-

ingly necessary in a time of global markets, multiple regulatory

requirements, limited resources and the growing adoption of

Quality by Design (QbD) as well as compendial approaches.

The workshop was intended, stated opening speaker Dr. Gregory

Amidon, chair of USPs Physical Analysis Expert Committee,

to provide an overview of food ingredient functionality, rawmaterial variability, the role of USPs General Chapter

Excipient Performance and the Food and Drug Administration

(FDA)s views, and to facilitate discussion among all parties.

Dr. Amidon observed that the food ingredients and pharmaceu-

tical industries have much to learn from each other in dealing

with excipients. Excipient manufacturers and suppliers most

accustomed to supplying food processors must become familiar

with how pharmaceuticals are regulated, and with current Good

Manufacturing Practices (cGMPs) applied by FDA to excipi-

ents intended for use in medicines. On the pharmaceuticals

side, manufacturers could benefit from the food ingredients

industrys familiarity with ingredient variation in composition,process efficiencies and flexibility in materials sourcing.

There was much discussion about functions in foods, in the

contexts of chemistry, regulation andimportantlymarket

expectations and economics. Dr. Grady Chism, vice chair

of USPs Food Ingredients Expert Committee, noted that

functional foods is a term gaining popularity but not well

understood. Dr. Chism observed that, from industrys perspec-

tive, the two most important functions of food ingredients are

lower cost and improved accessibility/acceptance by consumers.

In contrast, pharmaceutical manufacturers emphasis is on

excipient variability and how that impacts drug product perfor-

mance (i.e., safety and efficacy as well as cost).

Functions in foods are generally complex and are products

of an ingredients interactions with water, air, lipids, carbohy-

drates, ions, proteinsor with nothing. While most ingredients

have more than one function, manufacturers may not always

know what those are or how they affect the finished product.

Food functions include appearance, nutrition, stabilizers, pre-

servatives, texture and flavor (economically the most important,

and the most diverse in terms of the number of compounds

and structure)and many others. Dealing with such a range of

variables inevitably involves trade-offs. For instance, consumers

are demanding foods that are natural, and without preserva-

tivesbut they also want products to last in the refrigerator

and taste good. In the pharmaceutical world, there is a greater

emphasis on excipient ingredient performance and what ingredi-

ent variations in composition are appropriate to achieve required

performance (functionality). Functionality in an excipient is a

broad, qualitative and descriptive term for the purpose an excipi-

ent serves in a formulation. Of greater importance, however, are

the quantitative performance requirements (e.g., critical material

attributes) of excipients that must be evaluated and controlled to

ensure consistent performance throughout the product life cycle

(General Chapter ). Properties such as quality and safety

are important to both industries, but where food manufactur-

ers are focused on rapidly shifting consumer trends and are lesstightly regulated, pharmaceutical manufacturers are concerned

with medical efficacy and side effects, multiple regulatory agen-

cies and oversight, and ICH QbD principles.

An overarching consideration for both is a robust approach to

risk management. Drs. Brian Carlin (MonographsExcipients

Expert Committee) and Bruno Hancock (General Chapters

Physical Analysis Expert Committee) in particular addressed the

Dr. Bruno Hancock, a member of USPs

General ChaptersPhysical Analysis ExpertCommittee, speaks about critical material

attributes for excipients in formulations.

Continued on page 15.See Excipient Workshop


5/20www.usp.org

USP Advancing Standards for Tablet ScoringAs pharmaceutical tablet splitting has become more common

among patients, often on the recommendation of practitioners

or manufacturers, the U.S. Food and Drug Administration

(FDA), USP and others are collaborating to bring consistencyand clarity to this practice.

There are a number of reasons patients subdivide tabletsto

adjust (halve) the dose, to ease swallowing and to save money.

Tablets intended for oral use are the most common dosage form

in the United States and many bear score marks. There is an

expectation on the part of some patients that if tablets have score

marks, they will get a proportionate

dose when tablets are split.

At present, there are no standards for

the performance of subdivisions of

scored tablets. However, this has beena long-term concern for USP. At an

August 9, 2012, FDA meeting of the

Advisory Committee for Pharmaceutical

Science and Clinical Pharmacology

addressing the topic, Dr. Anthony

DeStefano, senior vice president of

general chapters and healthcare quality

standards for USP, provided background on this issue from the

organizations perspective. USP first discussed this publicly in

the March/April 2002Journal of the APhA, publishing a piece

titled Lack of Medication Dose Uniformity in Commonly Split

Tablets, in which a trained analyst used a single-edge razor blade

to split tablets from 11 products and the resulting uniformity was

studied. USP concluded that there was a strong suggestion that

split tablets (scored or unscored) generally fail to meet expecta-

tions for weight variation.

A more recent discussion of the topic occurred in Pharmaco-

peial Forum 35(6) [NovemberDecember 2009] with the Stimuli

article, Pharmacopeial Standards for the Subdivision Character-

istics of Scored Tablets. Among the top-line observations from

this piece was that scored tablets can be difficult to break and

often display large variations in the mass of subdivided parts,

as shown in extensive literature. Additionally, USP noted that

in a Dutch study, 39 percent of patients dissatisfied withsubdivision characteristics and poorly functioning score lines

perceived these as quality defectswhich could lead to reduced

patient compliance with the medication.

FDA proposed a draft guidance for industryTablet Scoring:

Nomenclature, Labeling and Data for Evaluationin August

2011. This was a focus of the August 2012 advisory commit-

tee meeting. The document provides guidance and criteria for

assessing characteristics of scored tablets during development;

proposes the nomenclature functional score for tablets meet-

ing the criteria; and provides a pathway for manufacturers to

demonstrate functionality of scoring. At the committee meet-

ing, FDAs Russell Wesdyk explained that the agency is using aQuality by Design (QbD) approach. Mr. Wesdyk also stated that

FDA is working with USP on a general chapter that builds on

other compendia such as the European Pharmacopoeia (EP).

As explained by Dr. DeStefano, USPs role is to develop post-

release testing requirements for tablets labeled as having a

functional score to show they perform as expected throughout

their shelf life. This would include pro-

viding a means to confirm the quality

of functional scoring via specific tests

and acceptance criteria. USPs standards

will align with FDAs guidance, and will

look to the existing resources from EP,which presents standards for accuracy

of subdivision but not ease of subdivi-

sion or loss of mass.

The new standards are being developed

under the USP General Chapters

Dosage Forms Expert Committee.

The Expert Committee is considering some key questions as it

develops the new general chapter, such as whether the standard

should address all subdivided tablets (including those that are

not scored); whether it would be a general chapter intended to

be applied, or for information only; and whether the full mono-

graph standard is applied to the split tablets.

The importance of accuracy in scoring tablets depends in large

part on the individual tablet, according to Dr. DeStefano. For

a drug with a wide therapeutic index, like a statin, considerable

variation in daily dosage can be tolerated without seriously im-

pacting the therapeutic effect. This is in stark contrast to a drug

like warfarin, which has a narrow therapeutic index. If someone

gets that wrong, the consequences could be severe or perhaps

even life threatening.

He further noted, Patients and practitioners assume that a

split tablet will behave like two halves, and that it will be ofthe same quality, safety and efficacy of the whole tablet of the

equivalent dose. FDAs draft guidance says in a drugs develop-

ment phase, a manufacturer should demonstrate that is true if

the tablet is scored.

The FDA guidance, as well as new USP standards, are anticipat-

ed to apply to new products that are labeled functionally scored,

and not those already on the market. It is anticipated that draft

USP standards will be proposed in the first half of 2013. u



USP Science

General Chapter Transformed to Focus onProduct Quality Tests for Parenteral Medicines

As part of a larger effort

to develop overall productquality chapters based on

the five routes of adminis-tration for medicines, USP

recently proposed a revisedGeneral Chapter

Injections and Implanted

Drug Products (Parenter-als)Product Quality Tests.

Parenteral drug productsencompass both injections

and implants, and allow the

direct administration of the

active drug substance(s)into blood vessels, organs,tissues or lesions.

USP groups all dosage forms based on five routes of admin-istration: injection, oral, topical-transdermal, mucosal and

inhalation. To support individual drug product monographs,USP has divided the tests of a monograph into two categories:

product quality tests and product performance tests. Product

quality tests assess product quality attributes, which for paren-teral products include identification, sterility and particulate

matter, among others. Product performance tests assess, forexample, in vitro release of the drug substance (active phar-

maceutical ingredient) from the drug product. For each routeof administration, USP intends to or has created two generalchaptersone that provides product quality tests and one that

provides one or more product performance tests. The approachwas detailed in a Stimuli article in Pharmacopeial Forum (PF)

29(5) [SeptemberOctober 2003].

Based on these considerations, General Chapter has been

completely revised. The revised general chapter groups testsinto three categories. The first is universal tests, which apply

to all parenteral dosage forms. These tests include descrip-

tion, identification, assay, impurities, foreign and particulatematter and sterility, among others. The next category of tests is

specific tests, which may be considered on a case-by-case basisand are referenced in particular monographs. These include

physiochemical properties, container content, water content

and residual solvents. The third category is product quality tests

for specific dosage forms. Dosage forms covered include sterile

powders for injection, suspensions, in situ gels, implants, drug-eluting stents and more.

A new informational General Chapter Product Perfor-mance Tests for Injections and Implanted Drug Products, will

be prepared to provide information on potential product per-formance tests.

According to Dr. Desmond Hunt, senior scientific liaison forUSP, We are looking at this general chapter as a road map for

parenteral drug products. It provides the fundamentals to helpensure product quality, and then points the user to the appro-

priate locations within USPNFfor more detail on the required

testing. Since this is a major revision of a frequently referencedchapter, we encourage people to pay close attention to the

structure, dosage form grouping and methodology, and provide

comments. USP has already rolled out the product quality chap-ter model with General Chapter Topical and Transdermal

Drug Products: Quality Tests, which is already official, and thisis similar. When finalized, we anticipate these general chapters

will allow for clearer understanding of expectations regarding

potential testing and specifications for these products.

Standards previously in General Chapter that do notpertain to product quality tests have been removed from the

revised general chapter and relocated to other general chapters.

This information falls into the areas of 1) nomenclature anddefinitions, 2) labeling and 3) container content and packag-

ing and storage. References to this material remain in GeneralChapter to minimize the impact that changes to this general

chapter will have on previously submitted regulatory filings.

No new tests have been incorporated into the revised general

chapter for dosage forms currently in the pharmacopeia. Dosageforms for which monographs do not currently exist in USPNF

(e.g., implants) have been added, clarifying compendial expecta-

tions for such products. Methods and procedures specific tothese dosage forms but not yet established as compendial tests

remain to be developed.

The revised general chapter was published in PF38(6) [Novem-

berDecember 2012], which is accessible at www.usp.org/usp-

nf/pharmacopeial-forum.u

Join the Conversation. Follow USP on
http://www.usp.org/usp-nf/pharmacopeial-forumhttp://www.usp.org/usp-nf/pharmacopeial-forumhttp://www.youtube.com/user/USPharmacopeiahttp://us.linkedin.com/company/u.s.-pharmacopeiahttps://twitter.com/USPharmacopeiahttps://www.facebook.com/USPharmacopeiahttp://www.usp.org/usp-nf/pharmacopeial-forumhttp://www.usp.org/usp-nf/pharmacopeial-forum


7/20www.usp.org

With medication misuse resulting in more than one million

adverse drug events per year in the United States, new standardspublished in November 2012 in USP36NF 31 for the first

time provide a universal approach to the format, appearance,

content and language of instructions for medicines in containers

dispensed by pharma-

cists. Wide variabil-

ity in prescription

container labels exists

today across indi-

vidual prescriptions,

pharmacies, retail

chains and states. The

USP standards provide

specific directionon how to organize

labels in a patient-

centered manner that

best reflects how most

patients seek out and

understand medica-

tion instructions.

Lack of universal

standards for labeling

on dispensed pre-

scription containers is a root cause for patient misunderstand-

ing, non-adherence and medication errors, said Dr. Joanne

G. Schwartzberg, director, aging and community health for

the American Medical Association and a member of the USP

Nomenclature, Safety and Labeling Expert Committee, which is

responsible for the new standard. With an aging and increas-

ingly diverse population, and people utilizing a growing number

of medications, the risks are more pronounced today than

ever. These USP standards will promote patient understanding

of their medication instructions, which is absolutely essential

to preventing potentially dangerous mistakes and helping to

ensure patient health and safety.

Studies have found that 46 percent of patients misunderstoodone or more dosage instructions on prescription labels. The

problem is particularly troublesome in patients with marginal

literacy, and in patients receiving multiple medications that

are scheduled for administration using unnecessarily complex,

non-standardized time periods. However, even patients with

adequate literacy often misunderstand common prescription

directions and warnings.

USP Releases Standards to Guide Content,Appearance of Prescription Container Labels

USPs efforts to create these new standards emanated from an

Institute of Medicine (IOM)-led initiative to improve healthliteracy, which is defined as the degree to which people can

obtain, process and understand the basic health information

and services they need to make appropriate health decisions.

According to IOM, 77 million

Americans have limited health

literacy, and a majority of Ameri-

cans have difficulty understanding

and using currently available health

information and services.

Elements of the new standards,

contained in General Chapter

Prescription ContainerLabeling, include:

4Emphasize instructions and

other information important to

patients. Prominently display infor-

mation that is critical for patients

safe and effective use of the medi-

cine. At the top of the label specify

patient name, drug name (spell

out full nonproprietary and brand

name) and strength, and clear direc-

tions for use in simple language.

Less critical information (e.g., pharmacy name, drugquantity) should not supersede critical information and

should be placed away from dosing instructions.

4 Improve readability. Labels should be designed and

formatted so they are easy to read. Typography should be

optimized by using high-contrast print; adequate white

space between lines of text (i.e., 2530 percent of the point

size); simple uncondensed familiar fonts (Times Roman

or Arial are specifically recommended); and large font size

(e.g., minimum 12-point Times Roman or 11-point Arial)

for critical information. Older adults, in particular, have

difficulty reading small print.

4 Give explicit instructions. Instructions for use should

clearly separate the dose itself from the timing of eachdose. Do not use alphabetic characters for numbers. For

example, write, Take 2 tablets in the morning and 2

tablets in the evening rather than Take 2 tablets twice

daily. Dosing intervals such as twice daily, 3 times

Continued on page9. See Labeling Standards4

Dr. Thomas Reinders, chair of the USP Nomenclature, Safety and Labeling

Expert Committee, explains the impetus for and aspects of the new standards.

Video with Dr. Reinders is available atwww.youtube.com/uspharmacopeia .
http://www.usp.org/http://www.youtube.com/uspharmacopeiahttp://www.youtube.com/uspharmacopeiahttp://www.youtube.com/uspharmacopeiahttp://www.youtube.com/uspharmacopeiahttp://www.usp.org/



USP Science

Workshop Focuses on Quality of Global Heparin SupplyUSP co-hosted the Fifth Workshop on the Characterization

of Heparin Products at its U.S. headquarters in Rockville,

Md., August 1415, 2012. Since 2008, USPs workshop on

heparin products has provided a forum for manufacturers,regulators and other stakeholders dedicated to disseminat-

ing information on methods and practices for testing heparin

quality and analyzing its components. Co-organized by the

National Institute for Biological Standards and Control (NIB-

SC) and the European Directorate for the Quality of Medicines

and Healthcare (Council of Europe)which publishes the

European Pharmacopoeia (EP)the workshop brought together

participants from around the world.

In 2008, the U.S. heparin supply came under close scrutiny

from the Centers for Disease Control and Prevention (CDC)

and the U.S. Food and Drug Administration (FDA) when

adverse health events in 2007 and 2008including more than200 deathsassociated with the use of adulterated or coun-

terfeit heparin prompted an investigation of this commonly

used blood thinner. The investigation led to the discovery of an

adulterant, oversulfated chondroitin sulfate (OSCS), in heparin

sourced from China. OSCS is a less costly substance than

heparin, and was used for economically motivated adulteration

because it can mimic properties of heparin when using older,

less-sensitive quality tests.

In response to the immediate public health crisis, USP worked

with FDA and manufacturers to develop more sophisticated test

methods related to its heparin standards, which were further

strengthened in a second stage of revisions. A third stage,

including new proposed methods for molecular weight determi-

nations and nucleotidic impurities detection as well as improved

tests for identification and protein impurities, was a featured

topic at the workshop, along with updates on upcoming revi-

sions to labeling requirements for heparin (see associated article

on page 9). USPs revised monographs with the new methods

and improved tests will become official on May 1, 2014. Updates

to heparin standards in the EPand theJapanese Pharmacopoeia

also were presented.

A session on the sourcing and production of unfractionated

heparin active pharmaceutical ingredients (APIs) featured per-spectives from industry, regulatory and international speakers.

Dr. Christopher Bryant of Fresenius-Kabi North America,

who is a member of USPs Low Molecular Weight Heparins

(LMWHs) Expert Panel, discussed the complexities of global

supply chains and the need for more integrated supplier

quality oversight into drug product manufacturers quality

systems. Providing input from the regulatory realm, Dr. Ali

Al-Hakim of FDA described how the use of risk assessment

management within a Quality

by Design (QbD) ap-

proach can play a role

in the developmentof control strategies

and the identification

of critical quality at-

tributes, which can

ultimately lead to

higher quality prod-

ucts. Dr. Patricia Aprea

of the Administracin Nacional

de Medicamentos Alimentos y Tecnologa Mdica (ANMAT)

in Argentina discussed the split between bovine and porcine

sources of heparin in the Latin American marketplace and

Argentinas efforts to create separate standards for each.

With a focus on good manufacturing practices related tocrude heparin manufacturing in China, Ms. Xiaoxia Wang of

Changzhou Qianhong Bio-pharma gave an overview of her

companys integrated approach of requiring good manufacturing

practices throughout all stages of crude heparin manufacturing

and supporting all stages of upstream and downstream manu-

facturing within one enterprise.

Presentations by representatives from NIBSC, Sanofi-Aventis

(France), Baxter, Kings College London, Fresenius Kabi

(USA), Gland Pharma (India) and Momenta Pharmaceuticals

(USA) were featured in a session dedicated to the implementa-

tion of new and revised monographs for heparin and lessons

learned. Assessments of validity, potency bioassays, molecular

weight determination, nucleotidic impurities determina-

tion and analytical methods related to impurities in heparin

sodium were among the topics addressed.

A session focused on LMWHs included presentations on the use

of proton nuclear magnetic resonance (1H NMR) for heparin

product identification and control; NIBSCs efforts to identify a

replacement for the international standard for LMWH potency;

structure-function relationships for LMWHs; and other modern

approaches for analyzing LMWHs.

The workshop concluded with a final session on regulatoryand dossier requirements, which featured industry feedback to

FDAs draft guidance on heparin and as well Europes evolv-

ing regulatory requirements related to unfractionated heparin.

Overviews were also presented by the Institute for Public Health

and the Environment (the Netherlands); the Brazilian Phar-

macopeia Commission; the National Administration of Drugs,

Foods, and Medical Devices (Argentina); the Pharmaceutical

and Medical Devices Agency (Japan); and FDA. u


9/20www.usp.org

USP Announces Change in LabelingRequirement for Total Strength of HeparinTo address safety concerns about the expression of drug strength

on labels for heparin sodium injections and heparin lock flushsolutions, USP has revised its current standards for these prod-

ucts. Heparin is a widely used anti-coagulant agent, or blood

thinner. Medication errors related to misunderstanding of the

expression of total strength on multi-dose product labels have

the potential to result in serious consequences to patients. The

revised standards will become official on May 1, 2013.

The labeling sections of the currently official Heparin Sodium

Injection and Heparin Lock Flush Solution monographs in

USPNFare being revised to ensure that labels comply with

General Chapter Injections. General Chapter requires

that the label reflect strength per total volume as the primary

expression of strength, followed in close proximity by strengthper milliliter (mL). An example of an expression of prod-

uct strength as articulated in General Chapter would be

30,000 USP Units/30 mL (1000 USP Units/mL).

In a July 2010 letter from the U.S. Food and Drug Adminis-

tration (FDA) to USP, the agency referred to data indicating

that containers labeled only with product strength statements

written as mg per mL are often misunderstood by healthcare

practitioners as total drug content statements. Such errors could

result in improper dosing with serious outcomes, including

death. FDAs concerns were evaluated by the 20052010 USP

Safe Medication Use Expert Committee, composed of 18 patient

safety experts representing multiple health professions including

medicine, nursing and pharmacy (now part of the USP Nomen-

clature, Safety and Labeling Expert Committee). FDA was also

represented by liaisons to USPs Expert Committee.

USP is committed to developing standards that help to ad-

vance public health, said Dr. Roger L. Williams, USPs chiefexecutive officer. It is our goal to ensure that USP standards

aid practitioners in their delivery of quality care to patients.

Particularly in light of the public health emergency involving

adulterated heparin in 2008, USP and FDA are continuing to

work closely together to help ensure that drug delivery is as

safe and accurate as possible.

The process to change the labeling requirement began with

posted Interim Revision Announcements for Heparin Sodium

Injection and for Heparin Lock Flush Solution on May 1, 2012,

and September 4, 2012, respectively, for public comment in

Pharmacopeial Forum. The revised monographs will become

official on May 1, 2013, at which time all drug products affectedby this change will need to be in compliance with the standard.

Posting of the official monographs in the Official Text section

of USPs website (www.usp.org/usp-nf/official-text) will occur

on January 25, 2013.

Healthcare professionals must be vigilant during the transition

period when old labels and revised labels for heparin sodium in-

jections and heparin lock flush solutions both may appear in the

marketplace. Old heparin labels may only display strength per

mL, whereas the revised heparin labels will display both total

drug content as strength per total volume (total mL) followed

in close proximity by strength per mL.

For additional information, go to http://uspgo.to/heparin-

labeling-revisions.u

daily, or hourly intervals such as every 12 hours should

be avoided because such instructions are implicit rather

than explicit, may involve numeracy skills, and patient

interpretation may vary from prescriber intent. Ambiguous

directions such as take as directed should be avoidedwithout clear supplemental information.

Include purpose for use. If the purpose of the medication

is included on the prescription, it should be included on

the label unless a patient prefers that it not appear. Confi-

dentiality and FDA approval for intended use (i.e., labeled

vs. off-label use) may cause some to constrain its inclusion

on labels. Current evidence supports inclusion of purpose-

Labeling StandardsContinued from page7.

for-use language in clear, simple terms (e.g., for high blood

pressure rather than for hypertension).

Other elements of the standards include addressing limited

English proficiency and visual impairment.

Enforcement of the standard will be the decision of individual

state boards of pharmacy, which may choose to adopt it into

their regulations. At its 2012 annual meeting, the National

Association of Boards of Pharmacy passed a resolution sup-

porting state boards in requiring a standardized prescription

container label. u
http://www.usp.org/http://www.usp.org/usp-nf/official-texthttp://uspgo.to/heparin-labeling-revisionshttp://uspgo.to/heparin-labeling-revisionshttp://www.usp.org/http://www.usp.org/usp-nf/official-texthttp://uspgo.to/heparin-labeling-revisionshttp://uspgo.to/heparin-labeling-revisions



USP Science

New Monograph Naming Policy Brings Clarity,Consistency to Drug NamesTo provide greater clarity and consistency in naming practices

for medicines, a new drug naming policy established by USPwill become official on May 1, 2013. The policy will apply

prospectively to drug product and compounded preparation

monographs that appear in USPNF. USP has worked closely

with the U.S. Food and Drug Administration (FDA) and

industry stakeholders over a number of years to develop the

new policy.

According to theMonograph Naming Policy for Salt Drug

Substances in Drug Products and Compounded Preparations

(Monograph Naming Policy), a drug product or compounded

preparation formulated with a salt of an acid or base will use

the active moietythe portion of the molecule responsible for

clinical activityin the title of a monograph. The MonographNaming Policy also stipulates that the strength of the product

or preparation will be expressed in terms of the active moiety.

This means that the name of the drug and its strength should

be based on the active moiety, not its salt form.

The development of USPs Monograph Naming Policy is

designed to provide concise and consistent names for drug

products, said Dr. Roger L. Williams, chief executive officer

of USP. This consistency in drug product names ultimately

will benefit manufacturers, regulators, practitioners and, most

importantly, patients.

Under the Federal Food, Drug and Cosmetic Act, if there is

a USP monograph for a drug product, the monograph title

must be used as the nonproprietary name of that product. If a

monograph does not exist at the time the product is approved,then FDA can designate an Interim name that may be used

unless USP later designates a different name. USP monographs

are often developed years after the product approval, which

along with other factors has led at times to inconsistencies in

naming, including mismatches of the name and strength of the

drug product.

The Monograph Naming Policy was posted to USPs website

in 2007 as a revision to General Chapter Nomenclature,

so that stakeholders would have time to prepare for the May

2013 official date. The USP Nomenclature, Safety and Label-ing Expert Committeethe Expert Committee responsible for

monograph title approvalswill generally apply the following

implementation principles:

For products with an existing USP monograph, the policy

will not be retroactively applied unless there is

a justifiable need.

Prior to May 1, 2013, FDA-approved products with no

existing USP monographs will be considered on a case-by-

case basis. USP generally will accept Interim drug names

approved by FDA for USP dosage form monograph titles

that are proposed or implemented before May 1, 2013. The

Expert Committee will work to avoid retrospective changes

to approved product names, and will consider input fromindustry and other stakeholders regarding retrospective

application of the policy.

After May 1, 2013,the policy will apply to FDA-approved

products with no existing USP monographs. Deviations

from the policy may continue to occur, and will be consid-

ered on a case-by-case basis.

With regard to products not yet approved by the FDA,

applicants are encouraged to contact the FDA early in the

application process to consider implications of the policy.

Exceptions to the policy will include:

Cases in which the strength of the drug product isexpressed for historical reasons in terms of the salt;

When the inclusion of the specific salt form of the active

moiety provides vital information from a clinical perspective

(e.g., when the salt form affects the absorption, distribution,

metabolism and/or excretion [ADME] of the drug in a man-

ner that influences a clinicians product selection); and

Attempts to maintain consistency with other dosage form

monographs in a particular monograph family (e.g., new

approval for an additional dosage form of an existing

product line).

Because of the prospective nature of the policy, said Dr.

Williams, we do not anticipate many changes in the namesof existing products, which would be confusing to patients

and practitioners. Rather, the changes will occur prospectively

over time.

A proposed revision to General Chapter describing

the monograph naming policy appears in the November

December 2012 issue ofPharmacopeial Forum. To access

additional information on USPs monograph naming policy,

go to http://uspgo.to/monograph-naming. u

This consistency in drug product names

ultimately will benefit manufacturers,

regulators, practitioners and, most

importantly, patients.

Dr. Roger L. Williams, chief executive officer, USP
http://uspgo.to/monograph-naminghttp://uspgo.to/monograph-naming


11/20www.usp.org

USP Initiates Spectral Library ProjectIn recent years, USP has been exploring the feasibility of building

an authoritative and comprehensive food and drug informat-

ics database, known as the USP Spectral Library. Once fully

developed, such a library would have the potential to be usednot only in the development of quality standards, but as a tool

for material identification and rapid screening for counterfeit

and substandard food and drugs in the field.

Every food and pharmaceutical ingredient and formulated

product, together with its packaging materials, has a set of

unique physical and chemical properties, and generates charac-

teristic signals or leaves a fingerprint within various regions

of the electromagnetic spectrum of wavelengths that can be

probed and captured using appropriate analytical instrumen-

tation and advanced informatics. A vast collection of spectral

fingerprints, also called a spectral library, can aid regulatory

authorities, law enforcement agencies, hospitals, pharmacies,manufacturers and distributors worldwide to screen for poten-

tial counterfeit and substandard food and drug substances and

products in any part of the world via Internet access.

An authoritative spectral library of reference standards can

also help compendial laboratory scientists and quality control

personnel in food and drug industries confirm the identity of a

substance in question by providing access to reference spectra of

any global pharmacopoeia that is available through the library.

As a scientific and independent standards-setting organiza-

tion, USP is well positioned to serve the role of being a central

repository of reference spectra from sources throughout the

world, also making the library potentially useful in global efforts

related to the harmonization of standards.

USP has begun working with stakeholders to explore the

feasibility of establishing such a spectral library with a goal of

providing the public with the most authoritative and compre-

hensive spectral information for material identification. USP

envisions that the spectral library also will capture any knownor likely adulterants for drugs and contaminants for foods.

To fully characterize a substance, USP has adopted an orthogo-

nal methodology for the development of the library. This uses

multiple analytical technologies including, but not limited to,

gas chromatography-mass spectrometry (GC-MS); near infrared

spectroscopy (NIR), nuclear magnetic resonance (NMR) spec-

troscopy, X-ray fluorescence (XRF) and X-ray diffraction (XRD),

and Raman technology to gather spectral information. Advances

in many of these technological areas have enabled the develop-

ment of hand-held or portable versions of these instruments.

USP has engaged several global scientific instrumentation

companies that are market leaders in hand-held and portabledevices, and is incorporating their expertise on these instruments

in the spectral library project. One concept being explored is

the creation of a USP SmartLab, a portable lab in the field,

which would include key analytical devices needed to con-

duct orthogonal analysis and to access the database. Through

wireless connection, one could conceivably employ the relevant

hand-held devices and be able to perform real-time data search

and analysis from anywhere in the world.

USP has recently completed a proof-of-concept activity for the

spectral library with a European-based informatics group and

continues to build its consortium of partners for the project.

Industries, pharmacopoeias, government agencies and other

stakeholders interested in learning more about USPs spectral

library project may contact Ms. Bei Ma at [email protected]

+1-301-230-6356.u

New Reference Material Offerings for Novel, Natural Sweeteners

As USPs standards-setting activities for food ingredients evolve via the Food Chemicals Codex (FCC), a major focus area is novel

ingredients that are of high interest to consumers and manufacturers. These include a number of plant-derived sweeteners, which

are now being used increasingly in beverages and a variety of other foods as more consumers seek out natural products. Many of

these sweeteners also fall into the low-, or no-, calorie categorymaking them particularly attractive in product formulation.

Such plant-derived ingredients, however, are often difficult to characterize and present unique quality challenges. Additionally,

as with all ingredients du jour, they command a higher priceputting them at a potentially higher risk for economically motivated

adulteration and making standards particularly important in the global supply chain. USP has published a number ofFCC

monographs for ingredients falling into this category, and now has reference standards available for ingredients including Monk

Fruit, Stevia (high-purity Rebaudioside A as well as a mixture of Steviol Glycosides) and Mogroside V. These can serve as an

invaluable tool for finished-product manufacturers as they source their ingredients, ingredient suppliers who want to demonstrate

the quality of their substances and regulatory agencies worldwide. For a full list of food ingredient reference standards available

from USP, visit http://www.usp.org/sites/default/files/usp_pdf/EN/fccRefStandards.pdf.
http://www.usp.org/mailto:[email protected]://www.usp.org/sites/default/files/usp_pdf/EN/fccRefStandards.pdfhttp://www.usp.org/mailto:[email protected]://www.usp.org/sites/default/files/usp_pdf/EN/fccRefStandards.pdf



USP International

Global Pharmacopoeias Explore PotentialCollaborations on Medicines Quality Standards

Representatives of pharmacopoeias from around the world par-

ticipated in the Second Global Summit of the Pharmacopoeias

on September 7, 2012, in Xian, China. Hosted by the Chinese

Pharmacopoeial Commission (ChP) and USP, the Global

Summit is a forum for participating national, regional, and

international pharmacopoeias to share information about their

standards-setting activities and to discuss the potential for

harmonized standards for medicines. At this years summit,

pharmacopoeial representatives from 11 countries participated,

including Brazil, China, Germany, Indonesia, Japan, Kazakh-

stan, Russian Federation, Thailand, the United Kingdom and

the United States.

We hope this Global Summit promotes understanding and pro-

vides a long-term platform for exchanges of mutual experiences

and information in terms of standards for medicines, said Mr.

Wang Lifeng, director general of the ChP, in his opening state-

ment. Our shared mission is international collaboration that

will ultimately benefit the health of patients in the world.

Dr. Roger L. Williams, USP chief executive officer, noted that

USP is pleased to be a part of this important initiative. The

globalization of medicines requires global solutions, he said.

It is critical to learn and share experiences with each other and

to pool our expertise to create globally harmonized standards.

Because pharmacopoeial standards can differ from country to

country, one aim of the Global Summit is to explore ways in

which pharmacopoeial standards can be more broadly harmo-

nized. An outcome from the first Global Summit was a proposal

from the ChP to develop an index of pharmacopoeias, and the

initial work was presented at this meeting. This index coalesces

information about standards from seven pharmacopoeias, and

shows the similarities and differences in those standards, said

Mr. Wang Ping, deputy director general of the ChP. We hope

this index becomes an important technical reference on the

development and revision of drug standards to achieve more

globally harmonized standards.

USP Welcomes Guests from the Jiangsu ProvinceIn September 2012, USP welcomed to its Rockville, Md., head-quarters a delegation of 23 leaders from the Jiangsu Province

in China. The delegation was led by Ms. Zhang Mei, deputy

director-general of the Jiangsu Institute for Food and Drug

Control, and had representatives from the Jiangsu Food and

Drug Administration, Jiangsu Province Medical Instrument

Testing Institute, Xuzhou Pharmaceutical Vocational College,

Nanjing Institute for Food and Drug Control, Wuxi Institute for

Drug Control, Changzhou Institute for Drug Control, Suzhou

Institute for Drug Control, Nantong Institute for Drug Control,

Lianyungang Institute for Drug Control, Yangzhou Institute forDrug Control, and Taizhou Institute for Food and Drug Control.

The delegation was in the United States to learn more about the

U.S. food and drug market and to establish a relationship with

USP. The delegation was provided with an overview of USP and

its activities in China, and conversations focused on USP refer-

ence standards and their importance in promoting the safety of

foods and medicines. The delegation was taken on a tour of the

USP facilities.u

Continued on back cover. See Global Pharmacopoeias

Pharmacopoeial officials from 11 countries participated in the Second Global Summit of the Pharmacopoeias.


13/20www.usp.org

Brazil Conference Provides Opportunityto Educate on USP Food StandardsAt a So Paulo conference titled U.S. & Brazil: Navigating

New Frontiers in Pharmaceutical, Medical Device & Food Law

& Regulation held September 1011, 2012, and organized by

the Food and Drug Law Institute (FDLI), Mr. Luiz Rogerio M.

Silva, laboratory director for USPBrazil, presented on Brazil-

ian regulations governing the food industry and USPs role and

relevance as publisher of the Food Chemicals Codex (FCC).

As noted by FDLI, Brazil, which is the sixth largest economy in

the world, is experiencing unprecedented growth and regula-tion in the pharmaceutical, medical device and food industries,

dramatically affecting the operations of both multinational and

Brazilian companies. USP opened its site in Brazil in 2008. The

September event featured top U.S. Food and Drug Administra-

tion (FDA) and Brazil National Health Surveillance Agency

(ANVISA) officials, multinational and Brazilian manufacturers,

legal experts, and international trade and import experts.

FCCalong with the Joint FAO/WHO Expert Committee on

Food Additivess Codex Alimentariusis recognized as an of-

ficial compendium under Brazilian law, and according to Dr.

Silva, We have seen increasing awareness ofFCCin the past few

years in the country. People want to know more about it, and

how they can utilize it to test materials and check specifications.

Mr. Silvas presentation encompassed the definition of food

in Brazil; the relevant governmental organizations overseeing

the industry; the main regulations, including microbiological

standards and food additives; the history and scope ofFCC; andthe value of an FCCmonograph.

The USPBrazil site organizes speaking and other outreach

opportunities to generate broader understanding of USPs

standards and how they can be a resource in the area of food

ingredients, as well as pharmaceuticals and dietary supple-

ments. USP staff from the Brazil site and U.S. headquarters

have spoken at various conferences, academic institutions and

in other forums in the country. u

Continued on page back cover. See WHOFIP Meeting

WHOFIP Meeting Focuses on Futureof International World of PharmacopoeiasAs a next step following the World Health Organization

(WHO)-organized International Meeting of World Pharma-copoeiaswhich was held in March 2012 and brought together

representatives from 23 pharmacopoeias for the first time in

a decadeofficials from pharmacopoeial bodies, regulatory

agencies, industry groups and WHO convened October 78,

2012, in Amsterdam to discuss the future role of international

pharmacopoeias and a path forward for global collaboration.

The meeting occurred in conjunction with the International

Pharmaceutical Federation (FIP) World Centennial Congress

of Pharmacy and Pharmaceutical Sciences.

The meeting opened with an overview of WHOs International

Pharmacopoeia from Dr. Sabine Kopp. Professor Alan Nich-

ols of the French Pharmacopeia followed with a summary ofconclusions from the March 2012 meeting, which included an

emphasis on modern monographs, new analytical methods

and interchangeability of reference materials. Dr. Mike Morris,

representing the International Conference on Harmonisation

(ICH), presented on the topic of multinational harmonization

of compendia. A spirited discussion among participants about

what has worked well and what has not in this area followed.

Industry participants noted their support for harmonization

through the Pharmacopoeial Discussion Group, but suggested

including all of the pharmacopoeias and focusing on prospectiveharmonization rather than retrospective harmonization, which

has proven to be a slow process.

In a session on good pharmacopoeial practices, each of the

individual pharmacopoeias provided updates on current initia-

tives and suggestions for international cooperation. Dr. Roger

L. Williams, USPs chief executive officer, emphasized the need

for the pharmacopoeias to work together, and explained the

science behind the innovative approaches advanced by the new

USPMedicines Compendium (a performance-based monograph

with a Reference Procedure). He also spoke about the efforts to

harmonize pharmacopoeias, which began in 1865 and continue

to this day.

In the closing session, Professor Saleh Bawazir, chair of the 47th

meeting of the WHO Expert Committee on Specifications for

Pharmaceutical Preparations and vice president of the Saudi

Food and Drug Regulatory Authority, presented his perspec-

tives of the future role of WHO in international pharmacopoeial

harmonization. He began with a quote from Dr. Williams on



Global Health Impact Programs

African Labs Work toward Establishingan Independent Professional Association

In September 2012, 11 countries of sub-Saharan Africa joined

together to establish the Network of Official Medicine Control

Laboratories-Africa (NOMCOL-Africa) with the goal of be-

coming an independent association. What began as an activity

supported by USPs Promoting the Quality of Medicines (PQM)

program is moving forward to become a self-sustaining profes-

sional organization. At a three-day meeting held at the recently

opened Laboratrio Nacional de Controle de Qualidade dos

Medicamentos in Maputo, Mozambique, the NOMCOL-Africa

representatives and facilitators developed a mission statement,

vision and objectives, and drafted a charter to guide the net-

works future.

To facilitate south-south collaboration on common issues and

to provide a forum for sharing best practices, the directors of

the national quality control laboratories of Ethiopia, Ghana,

Mali, Senegal and Uganda originally

formed the Network of African Medi-cines Control Laboratories (NAMCOL)

in 2009. PQM provided the group with

hands-on training in Good Laboratory

Practices and proper use of compendial

analytical methodstools that can be

used to detect substandard and coun-

terfeit medicinesand supervised their

participation in inter-laboratory testing

to improve the labs operations.

Due to the success of the network,

invitations were extended to six addi-

tional countriesKenya, Nigeria, SierraLeone, Tanzania, Zambia and Zimbabweto participate in the

meeting and join the network. The meeting in Mozambique

provided an opportunity for NAMCOL members to renew their

commitment to advancing medicines quality control, welcome

new ideas and learn from the experience of the countries

represented. One goal of the meeting was for the network to

determine how it could become a professional organization;

subsequently, the expanded membership voted to change their

designation from NAMCOL to NOMCOL-Africa.

The PQM team will play only an advisory role in the

coming year, guiding the newly formed secretariat of NOM-

COL and supervising the drafting of bylaws. PQM expects

to hand over operations of the network to the African coun-

tries involved, ensuring better long-term sustainability of

the program. u

Representatives from 11 countries came together to advance medicines quality control.

Voice of America Television Features USPin Discussion on Counterfeit Medicines

Dr. Patrick Lukulay, vice president of global health impact programs for USP and

director of USPs Promoting the Quality of Medicines (PQM) program, spoke to

Voice of America health reporter Ms. Linord Moudou about counterfeit medicines

on the TV2Africa daily magazine In Focus on October 4, 2012. Voice of America is amultimedia broadcaster funded by the U.S. government that reaches an international

audience. While in the studio, Dr. Lukulay discussed what constitutes a good-quality

medicine; the scope of the problem of substandard/counterfeit medicines; and how

developing countries in particular can combat this problem, with the need for a multi-

faceted approach encompassing policy, technology and public education. Earlier that

week, Dr. Lukulay was a panelist addressing the public health and economic aspects

of poor-quality medicines at the conference Counterfeit Medicines: Impact and

Potential Solutions, hosted by The World Bank. u

Video of Dr. Lukulays VOA appearance is available

at http://uspgo.to/YS6twp.
http://uspgo.to/YS6twphttp://www.youtube.com/watch?v=-bPoU7bcMYE&list=PL432199D1C9EE2643&index=1http://uspgo.to/YS6twp


15/20www.usp.org

New PQM Initiative Looks to Build a Pool of Expertsto Improve Regional Regulatory EnforcementUSPs Promoting the Quality of Medicines (PQM)

program convened a regional meeting to kick offits new initiative, Building Regional Expertise in

Medicines Regulation, Information-sharing, Joint

Investigation and Enforcement (BREMERE).

Held in Bangkok, Thailand, on August 2829,

2012, BREMERE aims to strengthen regional

cooperation between and among the medicines

regulatory authorities and law enforcement agen-

cies in the Greater Mekong Subregion to improve

the quality of medicines in the area.

Representatives of the relevant authorities (medi-

cines authorities, police, enforcement agencies

and customs) from Cambodia, Laos, Thailand,Vietnam, Philippines and Indonesia as well

as a wide range of international and scientific

organizations and academia participated in the

meeting. During two days of discussions, the group drafted the

Terms of Reference (TOR) that would encompass BREMEREs

governance, coordination, implementation and complementary

activities with other similar efforts. By the end of the meeting,

participants successfully reached a consensus on the TOR

and leadership of the initiative, and prepared a timeline for

future activities.

The BREMERE initiative aims to build capacity in all member

countries by sharing regional expertise, and providing training

and technical/financial support. In the long term, it will

create a regional pool of experts who will share information

and expertise in medicines regulation, registration, post-

marketing surveillance and enforcement. In order to reach the

objectives included in the TOR, support and collaboration will

need to be strengthened between political bodies in the field

of medicines quality and regulation, and improvements will

need to be made in the processes among regulatory/technical

agencies and other sectors, such as customs and INTERPOL,

at national and regional levels. u

At the first BREMERE initiative meeting in Bangkok, groundwork was laid for future collaboration.

Excipient WorkshopContinued from page4.

topic. Dr. Carlin provided an overview of ICH Q9 risk assess-

ment and its application to excipients, noting that collaboration

among suppliers, industry, academia, and regulators is essential

to identifying and understanding the impact of raw materials

variability and approaches to eliminating failures. Dr. Hancock

outlined a systematic risk management strategy, noting that

comprehensive studies of excipient properties are needed only

when they are expected to impact the drug products criticalquality attributes. While there are challenges to a systematic risk

management approache.g., it takes time to do it properly

benefits are tangible and extend to the manufacturer as well as

to patients.

Discussions of risk management raised several key ideas, all tied

to the variability of excipients. First, it is essential to know your

suppliers, without which quality cannot be assured. Second,

while compendial approaches are necessary, they are often not

sufficientpharmacopeial compliance is not a guarantee of

fitness-for-purpose. The emergence of QbD approaches is an

essential next step beyond adherence to a monograph (elaborated

on by keynote speaker Dr. Robert Iser from FDA). General

Chapter draws a more direct link between excipient

properties not necessarily identified in compendial monographsand product performance. (A recent revision appearing in

Pharmacopeial Forum 38(5) provides a framework for apply-

ing QbD principles to excipient quality and performance.) And

finally, attendees were urged to beware the unknowns, which

abound and are often not recognized. Continual monitoring

is essential to tracking unforeseen changes in the variable realm

of excipients.u



nside USP

USP Awards Recognize Volunteer ExpertsAt its annual Science & Standards Symposium held in Boston,USP recognized the exceptional contributions of two of itsvolunteer bodies to improving the health of people worldwide

through public standards as part of its Awards and RecognitionProgram for USP Expert Volunteers. The 2012 USP awardswere presented to its Food Ingredients Expert Committee andJoint Expert Panel on General Chap-ter Excipient Performance ina ceremony on September 18, 2012.

These two groups embody thevolunteer spirit that has guided USPsince its founding nearly 200 yearsago, said Dr. Roger L. Williams, chiefexecutive officer of USP. Their com-mitment and creativity in developing

standards that address the complexchallenges facing the global pharma-ceutical and food industries benefitsmanufacturers, regulators, and aboveall, patients and consumers.

The Food Ingredients Expert Com-mittee, chaired by Dr. Andrew Ebert,received the 2012 USP Award foran Innovative Response to Public

Health Challenges. It was selectedfor its outstanding work and lead-ership in transitioning the FoodChemicals Codex (FCC) from theInstitute of Medicine to USP (USPacquired the compendium of foodingredients in 2006) as well as spe-cifically addressing the public healthchallenge of food adulteration. The Expert Committee not onlyprovided its expertise and guidance for the transition ofFCCtoUSP, but ensured its growth and continuity as an internationalcompendium of food ingredients standards. Further, the ExpertCommittee guided USP staff in a significant expansion of thescope ofFCCto include new and novel ingredients essential tokeeping FCCrelevant to parties worldwide.

As noted in the awards ceremony, the Expert Committee

faced serious challenges soon after it was formed by USP towork on FCCin 2006. As it was becoming acquainted withUSPs standards-setting processes and transitioning FCCtoa regular publication cycle of every two years with interven-ing supplements, a number of food and drug crises occurredworldwide and increased the urgency and broadened the scopeof the Expert Committees work. Specific to foods, episodesof economically motivated adulteration involving pet food (inwhich wheat gluten was replaced with melamine) and infantformula and other milk powder products (in which melamine

was used as a low-cost replacement for protein) led to adversehealth events and deaths in humans and companion animals,and demanded development of new, more specific analytical

methods that could not be tricked by such replacements. TheExpert Committee worked to identify at-risk ingredients andpotential adulterants, and developed a USP Food Fraud Data-

base to serve as a free resource andrisk management tool globally. Inaddition, USP held an AdulterationWorkshop at USPs headquartersin Rockville, Md., to consider newtesting strategies and future direc-tions for standards, with follow-upworkshops now planned in Chile,China and Israel.

The Joint Expert Panel on GeneralChapter Excipient Perfor-mance, a collaboration between theGeneral ChaptersPhysical Analysisand MonographsExcipients ExpertCommittees that is co-chaired byDrs. Gregory Amidon and EricSchmitt, received the 2012 USPAward for an Outstanding Con-

tribution to the Standards-setting

Process. Due to the Expert Panelsefforts, General Chapter provides an overview of criticalmaterial attributes for many excipi-ent functional categories along witha toolbox of procedures that may beuseful in evaluating and controllingexcipient critical material attributes

that are not typically included in compendial monographs. Thegeneral chapter also provides a framework for applying Qualityby Design principles to excipient quality and performance. USPExpert Panels are formed to provide additional expertise withadvisory input on a particular scientific topic, thereby supple-menting Expert Committee expertise.

As detailed in the awards ceremony, this general chapter hasa long historywith talk about such a resource beginning

more than 20 years ago at a USP-convened meeting in 1991 inOrlando, Fla. At this meeting, the International PharmaceuticalExcipients Council was formed, and discussions about the needfor standards focused on excipient functionality first took place.USP has advanced many general chapters addressing excipientquality in the intervening years, but General Chapter isthe first focused on excipient function and performance.

Video interviews with Drs. Ebert and Amidon may be viewed athttp://youtu.be/gyUMykO5h4M.u

Ms. Angela Long, with Drs. Williams and Duane Kirking,present USPs volunteer awards to Drs. Amidon (top) and

Ebert on behalf of their Expert Panel and Expert Committee,

respectively.
http://youtu.be/gyUMykO5h4Mhttp://youtu.be/gyUMykO5h4M


17/20www.usp.org

USP Achieves Continued ISO 9001:2008 CertificationReflective of the organizations continued commitment to

the highest standards of quality, USP headquarters was recom-

mended for continued certification of its quality management

system in accordance with ISO 9001:2008 based on a successfulsurveillance audit by the BSI Group in August 2012. The ISO

9001:2008 certification demonstrates that USPs quality man-

agement system is evident under the standard and provides

effective management of internal processes to meet interna-

tional quality requirements.

USP first achieved ISO 9001 certification in 2004 for its

quality management system. It also first achieved ISO 17025

accreditation in 2004 for competence in laboratory testing

and calibration. All USPs global sites are audited against ISO

standards.

USPs ISO 9001:2008 accrediting body is the independentregistrar, the BSI Group. Additionally, USPs ISO 17025:2005

accrediting body is ACLASS, one of three ANSI-ASQ National

Accreditation Boards.

As an organization that sets quality standards for use aroundthe world, we feel it is imperative that we, too, adhere to the

highest quality of standards in all the work that we do, said

Dr. Roger L. Williams, USPs chief executive officer. I com-

mend the staff for their diligence in helping to ensure USPs

internal processes are up to par with this rigorous interna-

tional standard.

To achieve this accreditation, auditors looked at USPs informa-

tion technology security plan, the implementation of tools for

improved reporting in finance/accounting and organizational

operation manuals, among others. USP headquarters passed

the ISO 9001:2008 continued accreditation with zero non-con-

formities and zero opportunities for improvement, which are thebest results that can be achieved from the surveillance audit.u

USP Granted Observer Status by CodexAlimentarius Commission

Joining an international community dedicated to protecting

the health of consumers and ensuring fair practices in the food

trade, USP was granted observer status by the Codex Alimen-tarius Commission in August 2012. In this capacity, USP will

provide expert information, advice and guidance to the Com-

mission, along with other international governmental and non-

governmental organizations (NGOs).

The Commission was established by the Food and AgricultureOrganization of the United Nations (FAO) and the World

Health Organization (WHO) in 1963. Today, it has more than

180 members, and more than 200 inter-governmental and

international non-governmental organizations are accredited as

observers. The Commissions main work is the development of

international food standards, guidelines and codes of practice.

The Commission also promotes the coordination of all food

standards work undertaken by international governmental and

non-governmental organizations.

The increasingly globalized food industry, the associated

supply chain complexities, consumer interest in new, complex

ingredients with purported health and nutritional benefits,

economic pressures to keep food costs lowall call for strong

international standards, said Dr. Roger L. Williams, chief ex-

ecutive officer for USP. USPs mission and work in the area of

food standards align closely with those of the Commission, and

we are honored to now serve in an accredited NGO capacity.

Food ingredients, which represent a key component of the food

supply, are particularly important and remain our focus.

Through its Food Chemicals Codex (FCC), USP develops inter-

nationally used standards for the identity, quality and purity offood ingredients including colorings, flavorings, emulsifiers,

nutrients, preservatives and processing aids. FCCstandards are

developed by the Food Ingredients Expert Committee (FIEC),

chaired by Dr. Andy Ebert. The work of the FIEC aligns closely

with manufacturers innovating and marketing foods throughout

the world and with the work of the U.S. Food and Drug Admin-

istrations Center for Food Safety and Applied Nutrition. u

The Commissions main work is the

development of international food

standards, guidelines and codes

of practice.



Inside USP

USP Receives National Recognition for EmployeeBenefits ProgramIllustrating its strong commitment to the long-term

well-being of its employees, USP recently earned nationalacclaim for its benefits program. An independent judging

panel of employee benefits experts named USP as one of

the 2012 winners ofThe Principal 10 Best Companies for

Employee Financial Securityin August 2012.

Judges selected USP because of its dedication to its

employees through a focus on employee benefits, such as

retirement and wellness programs, designed to improve

both physical health and financial security.

USP and other Principal 10 Best winners continue to set

the standard for improving employee financial security;

they realize an investment in their employees constitutesan investment in their own future well-being, said Mr. Luke

Vandermillen, vice president at the Principal Financial Group.

Winning companies offer a number of ways to impact the

long-term physical and financial health of their employees and

understand the direct connection between well-rounded ben-

efits, a healthier workforce and a better bottom line.

The Principal Financial Group sponsors the national program,

which is now in its 11th year. It honors growing companies

(five1,000 employees) for their commitment to their employ-

ees financial security.

USP offers a core basket of fully paid benefits, with numer-

ous options for upgrades at minimal employee expense. These

benefits include a three-tiered healthcare plan offering compre-

hensive coverage, with the organization paying the total cost of

its base silver plan for employees and their families; a 401(k)

retirement savings plan in which the organization contributes

10 percent of the employees total cash compensation (including

salary and bonus) per year after one year of service; and tuition

assistance of up to $10,000 per calendar year, among others.

We are proud and gratified to receive the tremendous honor

of being named to Principals 10 Best list, said Ms. Susan Bach,

vice president of human resources for USP. In keeping true to

our mission of improving the health of people worldwide, we

seek to provide the best-possible benefits to our own employees

as they work to advance our mission.u

As part ofThe Principal10 Best Companies award, USP received a $2,500 donationto a charity of its choice. Here, USP and Principal representatives deliver a check toThe Reginald S. Lourie Center.

Three Students Receive 20122013Global Fellowship Awards from USPFor the 20122013 academic year, USP awarded three global

fellowships that focus on various detection methods of

counterfeit and substandard drugs, analysis of pharmacopeial

reference standards, and methods of excipient identification

and adulteration detection. The goal of the USP Global

Fellowships is to advance new research that contributes toinnovative or updated quality standards for medicines, food

ingredients and dietary supplements, and to support the work

of early career scientists in these fields. The $50,000 Global

Fellowship Awards recognize research that directly address a

specific USP scientific or research need. All Global Fellows will

present their work at a future USP event. Since the programs

inception in 1981, USP has invested nearly $4 million in 235

Fellowship awards.

Recipients of the 20122013 USP Global Fellowships are:

Darash Desai, Ph.D. candidate, Boston University,

Department of Biomedical Engineering. His area of research is

Pharmacheck:

the standard - fall-winter 2012

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