StandardThe

Vol. 11 | Issue 3 | Winter 2014

In November, USP announced its call for candidates for the 2015–2020 Council of Experts—USP’s scientific decision-making body.

“The USP Council of Experts drives the creation of public standards that help ensure the quality and safety of medicines and foods, not only for the U.S., but also for those other countries that recognize and use USP standards,” said Dr. Roger L. Williams, USP’s chief executive officer and chair of the Council of Experts. “The foundation of USP’s standards-setting responsibility is a strong network of global experts who represent many scientific disciplines and a broad range of expertise, including pharmaceutical, bio-logic, dietary supplement, and food scien-tists, academicians, healthcare practitioners, regulators and industry professionals.”

USP’s Council of Experts is responsible for developing and revising standards in USP’s seven compendia: the United States Pharmacopeia and the National Formulary; Medicines Compendium; USP on Compounding; Herbal Medicines Compendium; USP Dietary Supplements Compendium; and Food Chemicals Codex.

The USP Council of Experts is global in nature, reflecting the inter-national commerce of pharmaceuticals and foods and worldwide recognition of USP’s standards. Currently more than 30 percent of the Council’s members comprise experts from outside of the U.S. The 2015–2020 Council of Experts includes 26 Expert Committees, six of which will meet outside of the U.S. All Expert Committees are supported by USP’s international sites and Rockville, Maryland, headquarters staff. The 2015–2020 Council of Experts will fully benefit from USP’s network of state-of-the-art laboratories, which includes more than 170,000 square feet of laboratory resources and a global staff located in the U.S., India, China and Brazil.

The Council of Experts is elected every five years at the meeting of the USP Convention, with the next meeting to take place in April 2015. New experts will begin their five-year tenure on July 1, 2015. Members of the Council of Experts serve as chairs of USP’s Expert Committees, each of which addresses a specific standards-setting

Candidates Sought for 2015–2020 Council of Experts

In This Issue CEO Column Science and Standards Global Health Impact Programs Inside USP

area within USP. These areas include chemical medicines, biologic medicines, excipients, compounded preparations, dietary supple-ments and food ingredients. USP is also seeking candidates to serve as members of Expert Committees.

Applications for the 2015–2020 Council of Experts will be accepted until January 1, 2015. For 2015–2020 Expert Committee members, applications will be accepted until May 15, 2015. Candidates may nominate themselves or colleagues.

For more information on requirements, duties and the application process, visit http://uspgo.to/call-candidates or send email to USPVolunteers@usp.org. g

Dr. Maria Ines Santoro, Chair, Medicines Compendium—Latin America Expert Committee, is featured in USP’s call for candidates video.

Dr. Maria Ines Santoro, Chair, Medicines Compendium—Latin America Expert Committee, is featured in USP’s call for candidates video.

Upcoming EventsIn This IssueCEO Column

3 Message from the CEO Sometimes, Imagination and Hope Are Enough

4 USP Board of Trustees Thomas Temple Elected Chair of USP Board of Trustees

Pediatric Research Leader Named to USP Board

Science and Standards

5 New DNA-Based Methods May Help Confirm Authenticity and Identify Adulterated Botanicals

6 First Probiotic Monograph and a New Standard for Skim Milk Powder Proposed for the FCC

7 USP Revises Medicare Model Guidelines

7 Workshop Focuses on Dissolution of Capsules

8 New Reference Standard for Erythropoietin Bioassay Presents Novel Resource

8 General Chapter <1> Injections Highlighted in USP Webinar

9 Workshop Focuses on Standardizing Quality of Cutting-Edge Regenerative Medicine Products

9 Chapter Revision Centers on Physical Environments That Promote Accurate Medication Use

10 Labeling Standards for Ferrules and Cap Overseals Now Official

10 Workshop on Extractables and Leachables in Plastic Packaging Systems

11 Detection of Irradiated Dietary Supplements Proposed for New General Chapter

11 Standards for Good Distribution Practices to be Published in Pharmacopeial Forum

Global Health Impact Programs

12 Strategic Alliance Formed Between GPHF and USP to Fight Counterfeit Drugs

12 Boston University, USP Technology Recognized by Scientific American as “World Changing Idea”

13 Global Fund Approves Indonesian Quality Control Lab

13 USP Joins International “Fight the Fakes” Campaign

Inside USP

14 USP’s New Year Resolutions and Calls

WOrkSHOPS

USP Headquarters – Rockville, MD

4 Dissolution Testing of Capsules March 24–25, 2014

4 6th Bioassay Workshop June 2–3, 2014

4 Alternative Microbiological Methods September 8–9, 2014

4 Synthetic Therapeutic Peptide Drugs October 1, 2014

4 Contaminants in Foods–Compendial Approaches to Protect Public Health November 5–6, 2014

SyMPOSIa

Hyderabad, India

4 Science & Standards Symposium February 25–27, 2014

São Paulo, Brazil

4 Science & Standards Symposium July 29–31, 2014

Visit www.usp.org/meetings-courses/calendar for more information on these events.

Stories in this issue of The Standard were contributed by:

Claudia Costabile, Marilyn Foster, Lauren Hochman, Theresa Laranang-Mutlu and Cassandra Pean.

Message from the CEO roger L. Williams, M.D.

usp.org | 3

One thing a departing USP CEO quickly learns is that a lot of farewells need to be said, especially given that USP has so many activities going on in all parts of the world. For this reason, and many others as well, I started to indicate the end of my tenure beginning about a year ago. So now, in this column, it is time for me

to say farewell to readers of The Standard.

In saying farewell to you, the readers of The Standard, I looked at paper (yes paper!) files in my office and found that they go back to Volume 1/Issue 4 of the USP Press dated April 2004. The headline on this issue says: USP’s SemiHemiquinquennial Meeting—A Sesqui-pedalian* Convocation. The article summarizes a meeting of USP’s volunteers and staff at Lansdowne, Va., March 21–23, 2004. For readers who may be confused about the headline, I can say that at a certain point, USP gave up on Latin to describe its major meetings (“semi-“, “hemi-“ and “quin-”) and went to more modern terms, using for example the term “mid-cycle” to describe the meeting of volunteers held in February 2013 in Phoenix, Ariz.

For the Winter 2008 issue, USP changed the name of USP Press to The Standard, which is presented four times a year and named according to the seasons. In editions of USP Press and now The Standard, I have been privileged to write about 40 CEO columns. In the April 2004 edition of USP Press, I wrote on the “Spirit of Volunteerism,” evoked by the S-H-Q meeting in Lansdowne—the “who” of USP, if you will. In this, my last column, for the Winter edition of The Standard (2013–2014), I could focus on that topic again, because surely one of USP’s great hallmarks and strengths is the continuing commitment of its volunteer com-munities. But then as now, this would be incomplete. There is so much more “why, when, where and how,” as well as “who,” at USP now compared to April 2004.

Indeed, scanning briefly through the pages from the April 2004 USP Press and continuing to the most recent Standard (Fall edition), I’m struck by the depth and breadth of change. Programs have come and gone, people have come and gone. New programs and people have arrived and changed, as USP charts a stronger international presence and a deeper and broader commitment to public standards—the monographs and general chapters that form the basis for seven compendia. Over my career, the organization has increasingly focused on these documents, with allied reference materials, which are its core public health activity. The goal of achieving a complete cohort of up-to-date, relevant monographs for these several compendia, particularly for USP’s national compendia in law, USP–NF, is daunting. For most of my tenure at USP, I had no hope of realistically achieving anything close to this goal. But now at its close, I do have this hope, which arises out of the considerable capability of USP’s staff working in its own laboratories and partnering with an equally capable cadre of volun-teers and stakeholders.

And beyond the confines of USP, I see hope that pharmacopoeias and their national medicines and food laboratories can work collaboratively to produce and maintain a globally harmonized set of monographs for all food and drug articles of commerce. This won’t be readily achieved and perhaps not even in my lifetime, but it is possible now to imagine the possibility, based on advances in modern science and strengthening synergies between USP and corresponding organizations around the globe. Sometimes, hope and imagination are enough, and with these words, I will say farewell to the readers of The Standard. g

Sometimes, Imagination and Hope Are Enough

I’m struck by the depth and breadth of change. Programs have come and gone, people have come and gone. New programs and people have arrived and changed, as USP charts a stronger international presence and a deeper and broader commitment to public standards.

roger L. Williams, Chief Executive Officer, USP

* Sesquipedalian: having many syllables (literally: foot-and-a-half long)

| The Standard | Winter 20144

Thomas Temple Elected Chair of USP Board of TrusteesOn November 4, 2013, USP announced that Thomas R. Temple, R.Ph., M.S., was elected as the new chairman of its Board of Trustees. Under Mr. Temple’s leadership, the Board will guide the global health organi-zation as it expands the creation and use of science-based standards. He succeeds Duane Kirking, Pharm.D., Ph.D., who has served as chairman of the Board since January 2009.

“The quality of medicines and foods world-wide is the focus of USP, and my focus as chair will be working with our management, Convention membership, the Council of Experts and other USP volunteers, along with the Board of Trustees, to continue that vital mission,” said Mr. Temple. “I am honored to be elected by my colleagues to this position. I look forward to continu-ing this important work. I would also like to thank my predecessor, Dr. Kirking, for his outstanding leadership.”

“The importance and relevance of our standards for medicines and foods are increasingly critical in today’s global marketplace,” said Dr. Roger L. Williams, USP’s chief executive officer. “Our work developing those standards and raising the quality of products

wherever possible will be our continued charge under Mr. Temple as we move forward.”

Mr. Temple has served as a trustee of the Board since 2010. He recently created his own consulting firm after retiring as executive vice president and CEO of the Iowa Pharmacy Association (IPA), a position held since 1980. Today he serves as president of Tom Temple Consulting Inc. and as director of strategic communications for the University of Iowa College of Pharmacy.

Mr. Temple is a member of several professional organizations including the IPA, the American Pharmacists Association (APhA), the National Alliance of State Pharmacy Associations (NASPA) and the American Society of Association Executives. A past president of NASPA, he has also served as a board member for the APhA Foundation, the University of Iowa Alumni Association, the Alliance for Patient Medication Safety, the Pharmacy Marketing Group and the Iowa Initiative to Reduce Unintended Pregnancies.

Mr. Temple received a B.S. degree in biology from Northern Illinois University, a B.S. degree in pharmacy from the University of Illinois and an M.S. degree in pharmacy administration from the University of Iowa. g

Thomas r. Temple r.Ph., M.S.

Pediatric research Leader Named to USP BoardJoining a notable group of industry, healthcare and regulatory experts, Stephen P. Spielberg, M.D., Ph.D., has recently been named as a medical sciences trustee of the USP Board of Trustees. To-gether with USP’s president, past-president and treasurer and 10 other board members, Dr. Spielberg will help guide USP’s policies, finances and strategic direction.

According to Dr. Roger L. Williams, CEO of USP, “Stephen’s broad knowledge of medical research, his back-ground in drug discovery and development for pediatric care and his academic and regulatory leadership experience make him a welcome addition to USP’s board.”

Dr. Spielberg currently is editor-in-chief of Therapeutic Innovation & Regulatory Science (TIRS), the official journal of the Drug Infor-mation Association. Prior to assuming the position of TIRS editor, Dr. Spielberg served as deputy commissioner for medical products and tobacco at the U.S. Food and Drug Administration.

Dr. Spielberg served as dean of Dartmouth Medical School and vice president of Health Affairs at Dartmouth College. He was also

the Marion Merrell Dow Chair in Pediatric Pharmacogenomics and director of the Center for Personalized Medicine and Therapeutic Innovation at Children’s Mercy Hospital in Kansas City, Mo. He has held a wide range of faculty and director positions at the Johns Hopkins University School of Medicine; the University of Toronto, Hospital for Sick Children; Thomas Jefferson University Medical College; and the UMDNJ–Robert Wood Johnson Medical School. Dr. Spielberg was executive director of exploratory biochemical tox-icology and clinical and regulatory development at Merck Research Laboratories and vice president of pediatric drug development at Johnson & Johnson Pharmaceutical Research and Development.

Dr. Spielberg received an A.B. degree in biology at Princeton Uni-versity and Ph.D. and M.D. degrees at the University of Chicago. He completed postgraduate training at Children’s Hospital Medical Cen-ter in Boston, Harvard Medical School and the National Institute of Child Health and Human Development, National Institutes of Health.

Having served on the editorial boards of several journals as well as organizational advisory boards, Dr. Spielberg was president of the American Society for Clinical Pharmacology and Therapeutics. He has published more than 130 papers in adverse drug reactions, human pharmacogenetics and personalized medicine and pediatric clinical pharmacology, and is the recipient of several prestigious awards. g

Stephen P. Spielberg M.D., Ph.D.

USP Board of Trustees

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New DNa-Based Methods May Help Confirm authenticity and Identify adulterated Botanicals

USP’s General Chapter <563> Identification of Articles of Botani-cal Origin describes the methods for identification of articles of botanical origin, which may be used in analysis of botanical dietary supplements or herbal medicines. In September 2013,

USP proposed the inclusion of DNA-based methods as an added measure to confirm the authenticity of botanicals.

“DNA testing complements traditional identification and is considered more reliable, especially when applied to specimens that are difficult to distinguish among closely related or morphologically similar species,” says Dr. Nandakumara Sarma, director of dietary supplements at USP. “DNA analysis has also been efficient in distinguishing genuine plant materials from adulterants in complex botanical matrixes.”

For example, black cohosh (Actaea racemosa) has been marketed as a dietary supplement, but other varieties of this plant have been used to mimic black cohosh. With DNA identification, it becomes easier to identify each species to make sure products contain black cohosh and not any other variety.

Current identification methods in the general chapter include examina-tion of morphological and histological features of botanicals, as well as chemical identification based on active or marker principles. Mor-phological identification of botanicals is often not possible because the original material may be dried, cut or processed. Chemical identification of botanicals typically employs comparisons of chromatographic profiles against that of a reference material. Collectively, these methods help ensure the authenticity of the article.

With the increasing demand for high quality botanical products, the need for DNA authenti-cation is likely to increase and the revision of General Chapter <563> reflects USP’s desire to provide new scientific methods to meet this demand. This revision is intended to help ensure fair trade of botanicals in the marketplace and raise consumer confidence.

The revision of General Chapter <563> focuses on DNA bar coding, which is a DNA sequence-based identification method that uses short sequences of specific DNA loci for identification of plant species. It relies on the comparison of nucleotide sequences from a specific stretch of DNA. The method involves marker selection, DNA extraction, polymerase chain reaction primers and amplification, DNA sequencing and comparison with reference materials, with cross-references to methods described in other USP–NF general chapters.

The proposed changes to General Chapter <563>, which were open for public comment in Pharmacopeial Forum (PF) until November 30, 2013, complement the current methods in USP–NF monographs. A Stimuli article on the topic was also available in the same edition of PF, and USP is developing a USP Global Education and Training course on the topic for January 2014.

As with all USP–NF general chapters, the inclusion of DNA-based authentication for botani-cals is a work in progress, and stakeholders are invited to participate in the process of making this general chapter a valuable compendial tool that may be used to confirm the identity of botanical ingredients and detect adulteration where it is present. g

With the increasing demand for high quality botanical products, the need for DNA authentication is likely to increase, and the revision of General Chapter <563> reflects USP’s desire to provide new scientific methods to meet this demand.

Science and Standards

| The Standard | Winter 20146

Science and Standards

• Non-Protein Nitrogen Determination for Skim Milk Powder — This new proposed standard is a simple identifica-tion tool that selectively measures and tightly defines the amount of non-protein nitrogen that authentic skim milk pow-ders should contain, thereby excluding materials that are intentionally adulter-ated with nitrogen-rich chemicals like melamine.

The method is supported by new USP Reference Standards in development, including USP Skim Milk Powder and USP Skim Milk Powder with Melamine–Level D. These USP Reference Standards will be employed in system suitability tests to verify that the method is performing correctly. USP Reference Standards for food ingredients are closely tied to the documentary standards pub-lished in the FCC.

These Reference Standards for skim milk are the first in a series of new tools that are being developed by USP’s Skim Milk Powder Advisory Group aimed at protecting the food supply from economically-motivated adulteration, not only with melamine and other known milk adulterants, but also with new, yet unknown adulterants.

USP Skim Milk Powder with Melamine–Level D is the first Reference Standard in the history of USP that has been produced by intentionally spiking an authentic product with a specific level of a known adulterant. In this case, melamine was added to liquid skim milk before spray-drying to produce a skim milk powder contain-ing a specified amount of melamine. The production process was designed to mimic as closely as possible the way skim milk powder is expected to be adulter-ated with melamine.

USP is proposing new monographs and introducing a new standard for authentication of skim milk powder to be included in the

Food Chemicals Codex (FCC), First Supple-ment to the Ninth Edition.

The proposed FCC standards are available for public review in the most recent FCC Forum—the free, online vehicle for public comment–—for a 90-day period, which ends on March 31, 2014.

“The food ingredients industry is constantly developing new products and USP proposes new FCC standards in an effort to keep pace with new ingredients and modern technologies,” said Dr. Gabriel Giancaspro, vice president for food ingredients, dietary supplements and herbal medicines at USP. “USP is seeking comments on these proposals from all interested stakeholders and the comments we receive in the FCC Forum are invaluable to guide our work. Our ultimate goal is to offer standards to help assure consumer confidence in the food supply.”

Highlights of the FCC Forum include:

• Bacillus coagulans GBI-30, 6086 — This is the first proposed FCC monograph for a probiotic type of microbial food culture. Bacillus coagulans GBI-30, 6086 is a Gram-positive, spore-forming bacterium, classified as a probiotic for its purported support to good digestive and immune health. It was the first bacillus to receive a GRAS (Generally Recognized as Safe) notification in 2012, and it can be used in a variety of foods, including baked goods and baking mixes, breakfast cereals, coffee and tea, dairy products, grain prod-ucts and pastas, among others.

Because of the unique characteristics of food ingredients comprised of live micro-organisms, the proposed monograph is specific to the strain level and represents only food ingredients that are labeled as this specific strain of Bacillus coagulans.

First Probiotic Monograph and a New Standard for Skim Milk Powder Proposed for the FCC

• Chromium Picolinate and Chromic Chloride Monographs Modernization — Chromium is a metal that humans re-quire in trace amounts to process certain sugars, proteins and fats. Chromium’s most common forms are Chromium (III) and Chromium (VI), and both are used for industrial applications such chrome plat-ing, dyes and pigments, leather tanning and wood preserving.

Chromium (III) Picolinate and Chromium (III) Chloride are commonly used in foods as nutritional supplements and can be found in a large amount of food products, including infant formulas and nutritional beverages.

Human health concerns are being raised by the possible contamination of these foods ingredients with Chromium (VI), which is classified as a carcinogen (IARC Group 1– the strongest statement made for carcinogenic compounds). Due to the production processes, Chromium (VI) can occur as an impurity in all Chromium (III)-containing substances.

The public health risk associated with a contamination of Chromium (III)-containing food ingredients with Chromium (VI) prompted USP to introduce a limit test for Chromium (VI) in Chromium Picolinate and Chromic Chloride. Comments including additional data or alternative limits are specifically encouraged. g

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Workshop Focuses on Dissolution of Capsules

Capsules are a simple way to dis-pense the desired dose of drugs in an appropriate formulation. They are easy-to-swallow containers that effectively mask the unpleasant taste of drugs. As an example, gelatin capsules are widely used for drug products and dietary supplements. They can be made of hard or soft gelatin, and are filled with solids, liquids or semisolid formulations.

Of concern to USP is that gelatin, in the presence of certain compounds such as aldehydes, or when exposed to high humidity and temperature, can cross-link, rendering it insoluble in aqueous solvents that are the primary medium in dissolution tests. As a consequence, products will fail the test, but that does not necessarily reflect a possible failure to dissolve in the human body.

USP’s General Chapter <711> Dissolution allows the inclusion of enzymes in the dissolution medium where gelatin capsules experience dissolution failure. The general chap-ter recommends the use of pepsin or pancreatin depending on the pH of the dissolution medium.

To discuss manufacturing, formula-tion, storage and packaging conditions that could have an impact in the dissolution testing of capsules, USP is holding a workshop on March 24, 2014.

Stakeholders will present their perspectives on the subject and offer feedback on the revision of General Chapter <711>, as well as General Chapters <1094> Capsules —Dissolution Testing and Related Quality Attributes and <2040> Disintegration and Dissolution of Dietary Supplements.

For a preliminary agenda and to register, visit http://uspgo.to/dissolution-workshop. g

7

F rom October 1 to 31, 2013, USP posted for public comment its recommended revisions to the USP Medicare Model Guidelines, a listing of categories and classes of medicines that Medicare Part D plan sponsors can use when developing their Part D formularies.

Under the Medicare Prescription Drug Improvement and Modernization Act of 2003, USP was charged with developing the Medicare Model Guidelines, which are periodically re-vised by request of the Centers for Medicare & Medicaid Services (CMS). In March 2013, USP received a request from CMS to conduct a clinically based review of Part D drugs approved since version 5.0 and to update the USP Medicare Model Guidelines to accom-modate changes in therapeutic uses and the additions of new Part D drugs.

“The USP Medicare Model Guidelines are developed through a transparent and inclusive process, as has been consistently done with previous revisions. In doing so, USP helps to contribute to Part D beneficiaries’ access to safe and effective drugs while providing the flexibility that plans need to develop affordable and effective outpatient drug benefits,” said Angela Long, senior vice president and principal investigator for the USP Medicare Model Guidelines project.

A USP Category (e.g., Antibacterials) is the broadest classification of the USP Medicare Model Guidelines and provides a high-level formulary structure designed to include all potential therapeutic agents for diseases and conditions of Part D beneficiaries. A USP Class (e.g., Quinolones) is a subset of a category and provides therapeutic classification of medicines approved by the U.S. Food and Drug Administration (FDA), consistent with current U.S. healthcare practices and standards of care.

The draft USP Medicare Model Guidelines v6.0 comprises 50 categories and 154 classes, which includes nine new class designations. The increased number of classes represents a greater breadth of medicines approved by the FDA and potentially covered by Part D plans.

In addition to accepting written public comments via its website, USP conducted open micro-phone web meetings to solicit specific feedback on the content and organization of the draft guidelines from beneficiaries, drug plans, pharmaceutical manufacturers and providers.

The USP Therapeutic Information and Formulary Support Expert Committee is responsible for developing and drafting the USP Medicare Model Guidelines v6.0 as well as reviewing input received during the public comment period. The final USP Medicare Model Guidelines v6.0 underwent approval in December 2013 and will be presented to CMS in January 2014. The members of the Expert Committee comprise a range of expertise, including pharmacolo-gists, clinical pharmacists, other healthcare practitioners, academicians, formulary specialists, providers, beneficiaries, drug information experts, healthcare policy experts and others.

The USP Medicare Model Guidelines v6.0 will be available for utilization by prescription drug plans for the plan years 2015–2017.

For more information about the proposed USP Medicare Model Guidelines v6.0, please visit http://uspgo.to/usp-mmgv6. Questions may be directed to modelguidelines@usp.org. g

USP revises Medicare Model Guidelines

| The Standard | Winter 20148

Science and Standards

New reference Standard for Erythropoietin Bioassay Presents Novel resource

In September 2013, USP’s Monographs—Biologics and Bio-technology 1 Expert Committee (BB1 EC) posted for public comment new General Chapter <124> Erythropoietin Bioassays in Pharmacopeial Forum (PF). The general chapter provides an

assay for the measurement of activity in erythropoietin—commonly referred to as “epo.” USP also recently released a USP Reference Standard (RS) to be used with the assay included in General Chapter <124>. The deadline for receiving comments to General Chapter <124> was November 30, 2013.

Erythropoietin is a therapeutic agent that increases red blood cell levels and is used to treat anemia, most commonly in cases of chronic renal failure and cancer chemotherapy. Today, there are two approved erythropoietin products in the U.S. and an applicable USP–NF monograph is currently still under development. In Europe, two biosimilars are already available in the market. In the absence of a USP–NF monograph, USP initiated the development of a general chapter and an RS to measure product potency or activity; it is possible the new general chapter could be referenced in the forth-coming monograph(s) and become a component of an applicable compendial quality standard.

Several factors make USP’s new RS and its associated general chapter unique. Typically, when a pharmacopoeia develops a standard for which a World Health Organization (WHO) international standard (IS) already exists, that standard is calibrated against the IS and thus recognized as a secondary standard. When USP initiated development of its RS, the National Institute for Biological Standards and Control (NIBSC)—a national government institution—was in the process of replacing WHO’s Erythropoietin IS. NIBSC and USP

agreed to use a common source for the development of each or-ganization’s standard, making USP’s Reference Standard, in effect, the same material as the primary IS and eliminating the need for calibration.

General Chapter <124> provides procedures for an animal-based (in vivo) assay used to measure activity in an erythropoietin sample. In spite of a general trend toward greater use of cell-based (in vitro) assays in lieu of animal-based assays as a demonstration of activity, in vitro assays differ greatly from one another, making traceability a challenge. Since the unitage of USP’s Bioassay RS is assigned by animal-based assays, it can be used to calibrate an animal-based assay of any process-specific erythropoietin mixture. However, if a manufacturer intends to use a cell-based assay for product release and transfer unitage from the USP RS to its own erythropoietin preparation, it will be necessary first to establish that the USP RS and the material in question exhibit equivalent ra-tios for both in vitro and in vivo potency. In cases where the ratios are not equivalent, General Chapter <124> does provide guidance on how to establish a correlation based on a ratio between the in vivo and in vitro assays and use that ratio to transfer unitage from the USP Bioassay RS to the material being tested. Thus, General Chapter <124> and USP’s RS have utility for measuring activity of any erythropoietin mixture.

USP’s Bioassay RS for erythropoietin is now available in the USP Reference Standard Catalog. The BB1 EC currently is reviewing feed-back on General Chapter <124> received during the public comment period. Questions about General Chapter <124> and USP Bioassay RS may be addressed to Dr. Fouad Atouf at fa@usp.org. g

On November 22, 2013, USP held a webinar to inform stakeholders and solicit comment about proposed changes to General Chapter <1> Injections. The general chapter was revised to contain only product quality tests for injections and implanted drug products (parenterals). The revision was published for public comment in Pharmacopeial Forum (PF) 39(5) [September–October 2013].

For each route of administration for medi-cines—injection, oral, topical-transdermal,

General Chapter <1> Injections Highlighted in USP Webinar

mucosal and inhalation—USP intends to create two separate general chap-ters: one that provides product quality tests and one that provides product performance tests.

Topics covered in the webinar included an overview of USP’s dosage forms taxonomy; a discussion about the con-tent and structure of General Chapter <1>; and a presentation of the industry perspective on the subject. g

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Chapter revision Centers on Physical Environments That Promote accurate Medication Use

Data on medication errors reported to the USP Medication Error Reporting Program (2008) show that various physical attributes of the workplace affect human performance on the job. These characteristics may help or hinder health-

care providers as they strive to deliver safe, high quality care to every patient. As noted by the Institute of Medicine in its landmark 2001 report, Quality Chasm, “Health care today harms too frequently and routinely fails to deliver its potential benefits.”

USP General Chapter <1066> Physical Environments That Promote Safe Medication Use is proposed for revision to include advance-ments in research regarding physical environments that promote safe medication use. The proposed revisions include a partial reorganization of the content to present the Medication Safety Zone section earlier in the general chapter for greater emphasis. In addition, the proposed revisions provide greater detail on the human factors that affect safe medication use. New sections

include recent research on multi-tasking, the home environment, odors, temperature and humidity and evidence-based design of the workplace.

The process of safe medication use involves multiple aspects or stages: procurement, prescribing, transcribing, order entry, prepara-tion, dispensing, administration and monitoring the medication’s effects on the patient. A better understanding of these processes can form a solid foundation for improvement, allowing healthcare providers to reach optimal performance within the medication use system in various practice settings.

The proposed revisions to General Chapter <1066> Physical Environments That Promote Safe Medication Use are available for comment in Pharmacopeial Forum 40(1) [January–February 2014]. USP will accept comments until March 31, 2014. g

Workshop Focuses on Standardizing Quality of Cutting-Edge regenerative Medicine Products

T he field of cell- and tissue-based regenerative medicine products has generated as a wide range of therapies that include stem cells,

tissues for organ reconstruction and even cancer treatments based on the use of a patient’s own cells. Regenerative medicine based therapies have been proposed as alternatives to conventional treatments.

On November 7–8, USP and the Interna-tional Society for Cellular Therapy (ISCT) co-hosted a two-day workshop, “Cell and Tissue-based Regenerative Medicine Products: From Characterization to Com-pendial Assays.” The workshop highlighted challenges and opportunities associated with this maturing field and how the creation of public standards can support and further the development of regenerative medicines. As described by workshop chair Dr. Nicole Provost, member of USP Monographs—Biologics and Biotechnology 2 Expert Committee, the meeting was about “how to validate assays, how to gain consistency and how to achieve quality” in these products.

Unlike other modern therapies being developed for commercial-ization, many regenerative medicine products are developed in

investigational settings. As such, regenera-tive products are challenging some existing paradigms for drug development and their role in clinical care. Keynote speaker Dr. Carl June of the University of Pennsylvania discussed the growing role of combinatorial cancer immunotherapy, in which oncology treatments are based on immune-mediated destruction of tumors, and how these thera-peutic approaches are pushing oncologists to also become immunotherapists in their practice. Dr. June also discussed how the cell and gene therapy fields are currently driven by cooperative groups within aca-demic research settings that lack a history of manufacturing experience as well as a

deep understanding of liability issues associated with these products. By transferring these initiatives out of the research space into the pharma sector, Dr. June discussed the potential for successfully inte-grating regenerative products into the broader healthcare community.

The first session of the workshop focused on the promise of new therapies. Discussions included T-cell safety and efficacy; esophagus reconstruction; a regenerative patch for age-related macular degen-eration; and cardiovascular repair and regeneration. The following

Continued on page 15. See regenerative Medicine Products

| The Standard | Winter 201410

Science and Standards

Workshop on Extractables and Leachables in Plastic Packaging Systems

USP is revising existing quality standards and developing new standards for plastic packaging systems. These changes are likely to have a significant impact on drug manufacturers and packaging-material suppliers, and USP

held a December 2013 workshop, “Suitability and Compatibility for Packaging and Delivery Systems: Extractables and Leachables,” designed to inform stakeholders. The workshop was co-sponsored by the Product Quality Research Institute (PQRI). Packaging systems must protect and be compatible with drug prod-ucts and not compromise their stability, efficacy or safety. In turn, the ingredients of a drug product should not be absorbed onto the surface or migrate into the body of the plastic packaging system.

Extractables are chemical compounds that can be extracted from a material under laboratory conditions. Leachables are extractables that may migrate into the drug product over the course of a drug product’s shelf life. Drug-product leachables can affect the stabil-ity and efficacy of the product, and in some extreme cases, pose significant patient safety risks.

Among the workshop’s introductory presentations was a key- note delivered by Dr. Don Klein of the U.S. Food and Drug Administration (FDA) on the agency’s approach to revising the 1999 Packaging Guidance.

The first workshop session focused on USP’s strategy for establish-ing suitability and compatibility of packaging and delivery systems. Subsequent presentations included general goals and overviews of relevant USP general chapter standards:

The next session elaborated on revisions to General Chapter <661> and the goals of new General Chapters <661.1> and <661.2>. <661> will provide a testing rationale for materials of construction and packaging systems. New General Chapter <661.1> is intended to provide tests, procedures and acceptance criteria for plastic materials of construction used in pharmaceutical packaging systems, and General Chapter <661.2> addresses the testing of packaging systems to establish that they are suitable for their intended use.

Labeling Standards for Ferrules and Cap Overseals Now Official

In USP 36–NF 31 General Chapter <1> Injections, USP published standards for labeling of ferrules and cap overseals, with a delayed official date of December 1, 2013. Strategically placed messages on ferrules and cap overseals can provide an addition-

al layer of protection for healthcare practitioners as they determine a medications dosage prior to administering an injectable drug.

The Packaging section of General Chapter <1> was revised to include a labeling subsection intended to deter medication errors related to misinterpreting messages on ferrules and cap overseals. Specifically, ferrules and cap overseals subject to <1> must remain clear of any markings, including logos, except those intended to prevent an imminent life-threatening situation. Products that do not require cautionary statements should be free of information so those with cautionary statements are immediately apparent.

The standards are the result of careful reviews and consultation between USP and medical, nursing and pharmacy practitioners,

the pharmaceutical industry and U.S. Food and Drug Administration representatives. Some industry stakeholders proposed revisions to the standard that would have permitted more liberal labeling on ferrules and cap overseals of vials containing injectable medicines. After careful consideration, USP’s Nomenclature, Safety and Label-ing Expert Committee—comprised of independent experts from a variety of backgrounds including healthcare practitioners (physicians, pharmacists and nurses), safety experts, nomenclature experts and the pharmaceutical industry—concluded that allowing additional messages on ferrules and cap overseals would make it more difficult for practitioners to notice the most critical safety information. Under the standards, if a nurse, physician or pharmacist sees a warning on a ferrule or cap overseal, he or she will know immediately that it is a vital, possibly life-saving piece of information that must be observed and acted upon before administering the drug to the patient.

The standards explicitly state why labeling on the ferrules and cap Continued on page 15. See Standards for Labeling

<661> Plastic Packaging Systems and Their Materials of Construction

<661.1> Plastic Materials of Construction

<661.2> Plastic Packaging Systems for Pharmaceutical Use

<1663> Assessment of Extractables Associated with Pharmaceutical Packaging/Delivery Systems

<1664> Assessment of Drug Product Leachables Associated with Pharmaceutical Packaging/Delivery Systems

<1664.1> Orally Inhaled and Nasal Drug Products

Continued on back cover. See Packaging Systems

usp.org | 11

Standards for Good Distribution Practices to be Published in Pharmacopeial Forum

USP is developing a series of new informational general chapters focused on good distribution practices in the global manufacturing environment. The proposed general chapters will be posted for public comment in Pharmacopeial Forum (PF) 40(2) [March–April 2014], and will address four main areas:

• Quality Management System—documentation control and resource management; nonconformances, complaints and corrective actions; and continuous improvements.

• Environmental Control Manage-ment—building/facility (storage) and transportation (shipping).

• Good Importation and Exporta-tion Practices—audits and supply agreements; container seals, cargo inspections, customs and brokers; and verifying product and firm compliance with regulations.

• Supply Chain Integrity and Security—adulteration and

counterfeiting; diversion and theft; and production recalls.

For more information about USP’s general chapters on good distribution practices, contact Dr. Desmond Hunt at dgh@usp.org. g

Detection of Irradiated Dietary Supplements Proposed for New General Chapter

Irradiation of fresh foods and food ingredients has been permitted in the U.S. for growth and maturation inhibition of fresh foods, as well as for microbial disinfection of culinary herbs and spices, but current federal regulations do not permit irradiation of dietary supplements.

“Irradiation of dietary supplements could potentially influence the quality of products,” says Dr. Nandakumara Sarma, director of dietary supplements at USP. “Another problem is that irradiation may potentially mask degradation of products through microbial growth, which could be a marker for poor processing and handling practices.”

Federal regulations (21 CFR 179.26) define the kind of foods and the limitations for irradia-tion where permitted (1 kGy for fresh foods and 30 kGy for herbs and spices). Such irradiated foods should be labeled as such with statements like “Treated with Irradiation” or “Treated by Irradiation,” and carry the irradiation logo on the label.

Several methods, which are validated and recognized worldwide, are used to detect irradia-tion in dietary supplements. USP proposed two procedures in General Chapter <2250> Detection of Irradiated Dietary Supplements: photostimulated luminescence (PSL), which is a rapid and simple screening method to detect irradiation, and thermoluminescence (TL) to confirm irradiation.

Most natural dietary supplements contain silicate minerals. Exposure to radiation from gamma rays, electron beams or x-rays stimulates electrons in those compounds. When stimulated with light or controlled heat, those electrons are released and their energy is captured as luminescence. The intensity of the luminescence is proportional to the initial radiation absorbed.

PSL is a nondestructive method because it does not require separation of the inorganic materials and organic compounds of the samples being tested. Two light intensity thresh-olds are initially set up to classify the samples and, after being tested, those samples result into either negative, or not irradiated (if photon count per minute for the sample is below the lower threshold), intermediate (if the photon count per minute for the sample is between the two set thresholds) or positive (if the photon count per minute for the sample is above the higher threshold).

TL analysis is based on physical changes in the silicate minerals that are present in the samples. These minerals are able to store absorbed radiation energy. The amount of light emitted during controlled heating is compared to the light emission of the same sample irradiated at 1 kGy. If the ratio between the two measures is greater than 0.1, the sample is considered to be irradiated.

“The newly proposed general chapter provides tools for manufacturers and suppliers to detect undeclared irradiation,” says Dr. Sarma. “The chapter could also serve as a compli-ance tool for the industry and regulators.” g

usp.org | 11

| The Standard | Winter 201412

Global Health Impact Programs

Strategic alliance Formed Between GPHF and USP to Fight Counterfeit Drugs

On October 29, 2013, a new partnership to improve access to good quality, safe and

beneficial medicines was formal-ized between the Global Pharma Health Fund (GPHF) and the Center for Pharmaceutical Advancement and Training (CePAT) in Ghana. GPHF is a charitable organization initiated and funded exclusively by donations from Merck KGaA, Darmstadt, Germany. CePAT was launched in Ghana by USP in May 2013, to help build local and region-al capacity in pharmaceutical quality assurance and quality control.

“CePAT is one of the most important initiatives to ever be implemented in this part of the world. It goes deep into the root problem of lack of quality medicines in Africa, which is insufficient human resource capacity,” said Dr. Stephen K. Opuni, chief executive officer of the Ghana Food and Drugs Authority.

“We at GPHF are excited about this opportunity to partner with CePAT on this important initiative to combat the scourge of coun-terfeit drugs. Substandard and fake medicines pose a true public

health threat,” said Frank Got-thardt, chairman of the GPHF.

Counterfeit medications are a major challenge in developing countries, where there are limited resources for screening and quality assurance.

The collaboration between CePAT and GPHF outlines a strong plan to improve local capacity to detect substandard and counterfeit drugs through training at CePAT’s facility in Ghana and the use of the GPHF-Minilab®, a mobile mini-laboratory for rapid drug quality verification and counterfeit medicines detection.

Both the GPHF and CePAT believe that this strengthened cooperation

will contribute to realizing their common vision, which is of a world in which all citizens have access to good quality, safe and benefi-cial medicines.

A memorandum of understanding formalizing the alliance was signed during a ceremony hosted by the H.E. Peter Ammon, the German ambassador to the U.S., at his residence in Washington, DC. g

Boston University, USP Technology recognized by Scientific American as “World Changing Idea”

PharmaCheck, a new inexpensive and portable tool with the potential to revolutionize detection of poor-quality medi-cines around the world, was featured in the December 2013 issue of Scientific American as one of the magazine’s “World

Changing Ideas of 2013—Ten ways science may jazz up our gadgets, help to solve our most intractable problems and save lives.” In collaboration with USP’s Promoting the Quality of Medicines (PQM) program, researchers from Boston University (BU) developed PharmaCheck, which is scheduled for field-testing in early 2014 in sub-Saharan Africa, a region heavily threatened by poor quality medicines. Addressing this global threat is a key goal of PQM, which is funded by the U.S. Agency for International Development.

Since 2009, USP has been providing technical assistance to regula-tory, quality control and healthcare personnel in developing countries via PQM as a central strategy in the fight against substandard and counterfeit medicines. Poor quality medicines—especially those drugs used to treat malaria, tuberculosis and HIV—are an insidious threat to patients and public health around the world.

BU and USP scientists have spent the past two years honing the technology behind PharmaCheck. While other methods to screen for substandard or counterfeit products in the field are currently available, they are limited in their ability to quickly quantify the actual amount of active ingredient in a medicine sample as well

Susan de Mars, USP’s executive vice president and chief legal officer, and Frank Gotthardt, chairman, GPHF, sign an agreement to collaborate in Africa.

Continued on back cover. See Scientific American

usp.org | 13

Indonesia’s National Agency for Food and Drug Control (NA-FDC) quality control laborato-ry was recently recognized by the Global Fund for AIDS, Tuberculosis and Malaria (GFATM)

as an official ISO/IEC 17025-accredited laboratory to conduct quality testing on GFATM-procured medicines used for the treatment of HIV, tubercu-losis (TB) and malaria. The Promoting the Quality of Medicines (PQM) program has been providing the agency with technical assistance to support the country’s goal of increasing access to quality-assured anti-TB medicines. PQM is implemented by USP and funded by the U.S. Agency for Interna-tional Development.

The NA-FDC’s quality control laboratory, the Pusat Pengujian Obat dan Makanan Nasional (PPOMN), is one of only five laboratories in the ASEAN region of Southeast Asia listed as an officially accepted laboratory to conduct testing of GFATM-procured medicines for HIV, TB and malaria (either being ISO/IEC-17025 accredited or World Health Organization (WHO) Prequalified). This recognition qualifies the PPOMN to conduct advanced testing on HIV, TB and malaria medicines in Indonesia, as well as for other GFATM recipients worldwide. Testing GFATM medicines at PPOMN, instead of sending samples abroad for testing at other quality control laboratories, ensures that funds are being used to build capacity in Indonesia both at the laboratory and within the disease programs the Fund supports. Because the GFATM sets strict poli-cies on quality assurance of medicines, local testing in Indonesia

guarantees that the principal recipients of funding will be compliant with these policies, translating to better quality medicines for the people of Indonesia and a more robust quality assurance system that is locally implemented and overseen. g

PQM trainer Sanford Bradby explains how to use basic testing apparatus and the importance of good laboratory practices.

Global Fund approves Indonesian Quality Control Lab

USP Joins International “Fight the Fakes” CampaignCounterfeit and substandard medi-cines are a global health crisis, spread across an international marketplace for pharmaceuticals and their ingredients, which demands a cooperative solution. In a concerted effort to help protect people from fake medicines, USP has joined other global health organizations in a campaign to raise awareness and mobilize strategic partners to address the growing problem of counterfeit and substandard medicines.

Fight the Fakes encourages organizations and individuals around the world to help spread the word about this vital public health issue: • Counterfeit and substandard

medicines constitute a $431 billion markets—a 300% increase since 2000—according to the World Health Organization (WHO).

• Fake medicines put patients and the public at risk, offering potentially

dangerous products that can increase resistance to real treatments or cause further illness, disability or even death.

• An estimated 25–60% of the medicine supply in developing countries is either substandard or counterfeit (WHO).

USP is pleased to join the international Fight the Fakes campaign as part of its ongoing initiatives to help ensure the quality of medicines. g

| The Standard | Winter 201414

Inside USP

USP’s New year resolutions and Calls

While its fiscal year begins each July, the start of 2014 marks an important time for USP. Our bylaws require that every five years USP’s primary govern-ing body, the Convention, sets the path for the next

five years—from resolutions to elections. Right now, USP is begin-ning the process of determining which people and which issues may drive its work from 2015 to 2020. At USP, governance by the Convention defines the future! Q. How is USP governed? (Who are USP’s decision makers?)A. USP has three key volunteer bodies:

1) Convention Membership, which includes almost 450 member organizations, elect the other two decision-making bodies; the USP Convention officers (the president and treasurer) and trustees (see #2), and the Council of Experts (see #3). They vote on resolutions that guide USP’s strategic direction. And the Convention is the only body that can amend USP’s Bylaws.

2) Board of Trustees, members of which (including the

president and treasurer) are elected every five years by the Convention membership, make decisions about USP’s policies, finances and strategic direction.

3) Council of Experts, each member of which (other than the

Chair of the Council of Experts) serves as the chair of an Expert Committee for a five-year term. The chairs then elect members of the Expert Committees who also serve five-year terms. The Council of Experts and the Expert Committees make USP’s scientific and standards-setting decisions and provide the scientific foundation for USP’s public health products and programs.

Q. Why is Convention Membership important?A. By making decisions about what USP’s priorities should be and

who serves as its decision makers (resolutions and elections), Convention Members influence not only the operations of USP but also impact world health for every consumer of food, dietary supplements and medicines here in the U.S. and in other coun-tries that use USP standards.

Q. Why is this important now when the Convention doesn’t meet until April 2015?

A. Because if you are a USP volunteer or your work intersects with USP’s, it is important to know where USP is in its current cycle and to start thinking about the future. Here are three activities taking place now or in the near future:

1) Currently, there is a Call for Candidates for the Council of Experts.

2) In an April 2014 meeting of Convention Members, there will be an update on the resolutions passed in 2010, which cover a wide range of important initiatives. For instance: “Continue and Expand Commitment to Quality Standards for Food Ingredients”; “Promote Availability, Use and Recognition of Quality Standards for Dietary Supplements”; “Support and Advance Global Public Health Initiatives”; and “Develop, Maintain and Promote Adoption of Quality Standards for Compounded Medicines.”

3) At that same April meeting, the Council of the Convention

will put out the Call for Resolutions for the 2015 Membership Meeting.

Now that 2014 is here, it is time to get to work setting the path for USP’s 2015–2020 Cycle through calls for resolutions and for candi-dates. If you are a Trustee, a Member of the Council of Experts or Expert Committees or a constituent of a Member organization of the Convention, NOW is the time to start tuning in. The important role you are already playing will be even more significant between now and spring 2015. In fact, if your work intersects with USP’s and/or you have an interest in USP’s global health work, then we encourage your participation as well. g

usp.org | 15

The Standard

Standards for Labeling Continued from page 10

regenerative Medicine Products Continued from page 9

session addressed specific challenges associated with characteriza-tion of regenerative products. Examples of “neo-organs” gener-ated from tissue matrix grown on a scaffold underscored the need to characterize both matrix and scaffold materials as well as the importance of understanding how to characterize cellular/biomate-rial combinations. A presentation on an investigational cord blood product highlighted the critical role of a rapid release assay in cases of products with very short shelf lives. The most commonly avail-able assay—a colony-forming unit test—requires a 14-day incubation period that is not applicable for product release. According to Dr. Malcolm Moos of the U.S. Food and Drug Administration (FDA), for many cell- and tissue-based prod-ucts, characterization is difficult since the critical quality attributes of these products are often not known. Dr. Moos posited that when engaging in the early stages of clinical translation, investiga-tors should look at how exploratory research into biological control systems can play a role similar to that of characterization studies in identifying critical quality attributes.

A session on chemical and physical testing of products included pre-sentations on a collagen-based human vascular graft for replacement or bypass of diseased vessels in trauma patients, dialysis access or other vascular procedures; characterization, validation and release testing of acellular human tissue matrix; and the testing of human cellular placental-derived repair matrices. Combinations of physical and biochemical tests, as well as the inclusion of mechanical tests, appear to be key in successful characterization approaches for tis-sue-based products. A fourth session on potency testing generated much discussion about the important relationship between mecha-nisms of action (MOAs) and product potency. Dr. Robert Deans of

Athersys emphasized the need for investigators to base their under-standing of product potency on a matrix of MOAs rather than a single mechanism of action. According to Dr. Deans, the first questions often posed to investigators by development partners and regulators are related to MOAs and potency assays, and investigators are well aware that measures of functionality are related to clinical activity. This session also included highlights of potency assay development initiatives by ISCT in conjunction with the Alliance for Regenerative

Medicine. A following session on standards and limiting product variability included perspectives from the National Institute of Sci-ence and Technology, the National Institute for Biologic Standards and Control, the FDA and the American Association of Tissue Banks.

The last technical session of the workshop focused on case studies

of regenerative products in different stages of development as well as regulatory approval paths. These included presentations from Mesoblast, Dendreon, Organogenesis and AxoGen. The workshop concluded with a summary of common themes generated from the sessions and an overview of ways in which interested stakeholders in the cell- and tissue-based regenerative medicine arena can col-laborate with USP. According to Dr. Fouad Atouf, director of biologics and biotechnology at USP, “The measurement of biological activity for cell- and tissue-based products can be challenging, and the de-velopment of relevant compendial assays and associated Reference Standards can create great opportunities for collaboration between USP and stakeholders in this field.”

For information on USP’s ongoing efforts on standards for cell- and tissue-based regenerative medicines, contact Dr. Fouad Atouf at fa@usp.org. g

overseals is limited to the warnings neces-sary to prevent imminent life-threatening situations, and provides examples of warn-ings—such as “Warning–Paralyzing Agent” or “Dilute Before Using.” To further ensure that they are heeded, the standards require such warnings to be printed in a contrast-ing color and be clearly visible under ordi-nary conditions of use. Other requirements include restricting the location of informa-tion that is important but less urgent to be located elsewhere on the vial. This would include, for example, lot numbers, product or company names and logos. If no urgent warning is necessary, the top surface must

remain blank to help ensure that urgent warnings on other injectable medications are readily noticed.

The General Chapter <1> Injections labeling standards for ferrules and cap overseals are now proposed to relocate to General Chapter <7> Labeling, as part of a series of proposed revisions published in Pharma-copeial Forum (PF) 39(6) [November– December 2013]. While the General Chapter <7> proposal was initially published in PF 38(6) [November–December 2012], public comments led to further revision and on the basis of comments received, this general

chapter is being revised to include the section on caps and ferrules and previously proposed revisions such as the general reformatting of the chapter to distinguish labeling for injectible products from other product categories. All labeling requirements from the Preservation, Packaging, Storage and Labeling section in the General Notices and General Chapter <1> Injections have been relocated to create this new chapter. The proposed general chapter provides definitions and standards for labeling of official articles. The deadline for receiving public comments on General Chapter <7> is January 31, 2014. g

Unlike other modern therapies being developed for commercialization, many regenerative medicine products are developed in investigational settings.

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Another session on new General Chapter <1663> addressed best-demonstrated scientific practices for accomplishing an extractables assessment. Due to inclement weather, the second day of the workshop was postponed and will take place in spring 2014. Day two of the workshop will address the focus of new General Chapter <1664> on the design, justification and implementation of assessments for drug-product leachables derived from pharmaceutical packaging and delivery systems. Accompanying <1664> is General Chapter <1664.1>, which will address specific considerations for leachables in metered dose inhalers, nasal sprays, dry powder inhalers and inhalation solutions, suspensions and sprays. General Chapter <1664.1> is intended to incorporate specific best practice recommendations from the Product Quality Research Institute (PQRI) related to leachables in orally inhaled and nasal drug products (OINDP), including the first safety-based thresholds for leachables character-ization and safety qualification.

Following USP’s portion of the workshop will be sessions led by PQRI. Presentations will include overviews of PQRI’s Leachables and Extractables Working Group Initiatives for Parenteral and Ophthalmic Drug Products (PODP), application of PQRI’s OINDP recommen-dations and PQRI’s activities related to toxicology and chemistry PODP best practices.

For additional information on USP’s general chapters related to plastic packaging systems and extractables and leachables, contact Dr. Desmond Hunt at dgh@usp.org. g

Packaging Systems Continued from page 10

Scientific American Continued from page 12

as to determine how quickly that active ingredient dissolves so it can work as intended when taken (known as a medicine’s “dissolution”). PharmaCheck could change all this by employing a unique combination of a fluorescent probe tailored to bind to an active ingredient in a specific drug and a silicon-polymer testing chip that detects the amount of light the probe emits. Software translates that light reading into an estimate of active ingredient concentration. Monitoring that signal over time indicates the ingredient’s dissolution. Within minutes, a doctor, regulatory official or health worker can have critical insight about the quality of a medicine sample. In early 2014, BU researcher Dr. Muhammad Zaman, developer of the technology, will conduct field tests on PharmaCheck through USP’s Center for Pharmaceutical Advancement and Training (CePAT) in Accra, Ghana. g