Angie Drakulich was editorial director of Pharmaceutical Technology.

Angie Drakulich

The US Pharmacopeia released a statement this week that explains in more detail last January’s recall of the 

 28). The statement also discusses steps to ensure the quality of future 

 28 volume was made after errors were discovered in the publication (See 

, “USP Recalls Latest Monographs”. “These errors occurred as a result of an initiative known as the Monograph Redesign Project, in which all of the monographs in the compendia were redesigned to streamline presentation, improve the ease of use, and update and harmonize terminology,” according to the USP 

  Since the recall, USP’s management, a Board-appointed task force (consisting of Board, USP Convention, and USP Council of Experts volunteers), and an independent law firm have performed three separate evaluations to examine factors that led to the errors, including the role of the Monograph Redesign Project. The three teams reached similar conclusions, some of which are highlighted below.

 -“The Monograph Redesign Project proved to be far more complicated than originally thought…. At the outset, a decision not to include experienced scientific liaisons in the redesign project for USP–NF, as was done with the redesign of USP's Food Chemicals Codex (FCC) standards, precluded a full understanding of the magnitude of the task.”        

“The Project was not handled through USP's normal systems and management processes. As a result, typical quality assurance protections and controls were not utilized.”   

“USP senior management was not adequately involved in supervising the Project and there was a lack of clear accountability and responsibility. The Project lacked a strong, cross-functional management team to ensure organization-wide oversight.”

  The evaluation teams proposed several corrective and preventative actions to ensure the future success of the Monograph Redesign Project, which will continue. Among the recommendations are: to include scientific liaisons who have intimate knowledge of the monographs in the redesign work (USP plans to add new staff to ensure adequate resources); to make division chiefs ultimately responsible and accountable for the redesign work; to implement a new automated workflow system that will track the monographs; to make the staff aware of the project’s importance; and to establish a quality assurance group that will perform regular process audits to the project before republication of the 

 volumes. In addition, rather than redesigning all of the monographs at once, they will be redesigned based on priority over several years. The overall project completion target is 2015.

  The full conclusions and recommendations can be reviewed on the USP 

. In the USP statement, Board Chair Duane Kirking, PhD, said he is “convinced that the redesign project remains vital to improved usability of these important compendia-and that USP management and staff are ready, willing, and able to move this project forward with assurance of accuracy.”
 

Articles

The US Pharmacopeia released a statement this week that explains in more detail last January's recall of the United States Pharmacopeia 33–National Formulary 28 (USP 33–NF 28).

USP Issues Explanatory Statement Regarding Recall of USP 33–NF 28

 will be featuring occasional reports on bio/pharmaceutical companies, organizations, foundations, and governmental bodies engaged in improving access to medicines and healthcare in the developing world. Industry work in this area has been on the rise during the past few years, according to the Access to Medicine Index, which ranks pharmaceutical companies on their efforts to provide access to medicines, vaccines, and diagnostic tests to people living in 88 countries. The index is published by the Access to Medicine Foundation (AMF), an international nonprofit based in Haarlem, The Netherlands, that is dedicated to improving access to medicine to societies in need. The 2010 index reports significant increases since 2008 in the sharing of intellectual property (e.g., compound libraries) for research purposes, collaborations targeting areas of need—including increased innovator–generic company partnerships, and innovative approaches to providing access to medicines (e.g., new funding mechanisms). 			

In July, the World Health Organization (WHO), World Trade Organization, and World Intellectual Property Organization gathered in Geneva to discuss the challenges involved in increasing the availability and affordability of medicines for those who need it most. While the problem is "nothing new, the context today is strikingly different than in the past," said WHO Director-General Margaret Chan during the symposium. "A quest for greater fairness, in income levels, in opportunities, in access to medicines and health services, has become a strategy for coping with the unique pressures of a globalizing world." 

Many groups are determined to overcome these growing challenges, paying special attention to the United Nation's call to achieve the Millennium Development Goals (MDGs) by 2015. In fact, a Millennium Goal Summit was held last month at UN headquarters in New York to discuss progress on the goals, which aim to end poverty and advance sustainable development. MDG 4, 5, and 6 specifically focus on improving child and maternal health, and combating HIV/AIDS, turberculosis, and malaria.  

We start our on-the-ground global healthcare coverage by looking at the PATH Malaria Vaccine Initiative (MVI), which provides funding and technical support to partners worldwide to accelerate the development of and access to malaria vaccines. Each year, approximately 250 million people contract malaria, and 900,000 die from the disease. The majority of deaths are among children under age 5 living in Africa. The parasitic infection, transmitted by mosquitoes, accounts for 40% of Africa's public health expenditures, or nearly $12 billion a year. 

MVI is an international nonprofit organization established as part of PATH in 1999 through a grant from the Bill & Melinda Gates Foundation. PATH is a global nonprofit that works to create sustainable, culturally relevant solutions that enable communities worldwide to break longstanding cycles of poor health. 

The organization identifies promising malaria vaccine approaches that target the most dangerous malaria parasite, 

, and works with partners in private industry, government, and academia to move these approaches through the development process. MVI also works to ensure that any successful malaria vaccine will be available and accessible in the countries that need it most. 

PATH support has provided Zambia with 5.3 million insecticide-treated bednets and more than 60% of pregnant women in the country now take malaria-prevention medication. In Ethiopia, 20 million bednets have been distributed. 

Last year, MVI, along with GlaxoSmithKline Biologicals (Brussels, Belgium) and scientists in Africa, launched an efficacy trial of RTS,S, the world's most clinically advanced malaria vaccine candidate to date. The trial is underway in seven African countries and will involve as many as 16,000 children. MVI is also now collaborating with the US Agency for International Development's Malaria Vaccine Development Program and biopharmaceutical firm Crucell N.V. (Leiden, The Netherlands) to determine the effectiveness of Crucell's prime-boost vaccine approach against 

. This approach uses Crucell's proprietary recombinant adenoviruses to deliver a malaria antigen to the immune system. 

), MVI Press Office information, PATH MVI (

A look at MVI's malaria work in developing countries.

Global Healthcare on the Ground: The PATH Malaria Vaccine Initiative

 last week  of certain lots of Epogen and Procrit (epoetin alfa) vials. The injectable products, used to treat anemia related to HIV therapy, chronic renal failure, and chemotherapy, may contain “extremely thin glass flakes (lamellae) that are barely visible,” says the press release. The lamellae, says the release, resulted from the interaction of the formulation with glass vials over the shelf life of the product. Approximately 200 lots of Epogen are being recalled, and 155 of Procrit are being recalled. Potential financial implications have not been released.

  The company, along with Centocor Ortho Biotech Products, the authorized distributor of Procrit in the United States, found that the glass flakes have low potential for affecting patients. Although there have been no adverse event reports or complaints [as of Sept. 24, 2010], “potential serious adverse events resulting from the use of a sterile injectable product with particulates by the intravenous route include embolic, thrombotic, and other vascular events (e.g., phlebitis), and by the subcutaneous route include foreign body granuloma, local injection site reactions, and increased immunogenicity,” according to the Amgen release. 

  The recall is being conducted in cooperation with the US Food and Drug Administration. Of note, Amgen is the manufacturer of both Epoetin alfa products, which are manufactured in Puerto Rico, but Johnson & Johnson licenses and markets the product under the Procrit brand. 

Amgen (Thousand Oaks, CA) issued a voluntary recall last week of certain lots of Epogen(R) and Procrit(R) (Epoetin alfa) vials.

Amgen Recalls Products for Glass Flakes

US Food and Drug Administration Commissioner Margaret A. Hamburg 

 at the Generic Drug User Fees Public Meeting last Friday, Sept. 17, 2010, about enacting user fees for the generic-drug sector. The agency called the meeting to gather public input on the development of such a program.

  Although more than 70% of the prescriptions written in the United States are for generic drugs, the approval process for these drugs faces many challenges, she told the audience. For example, there has been a significant increase in abbreviated new drug applications (ANDAs) submitted to the agency for review. The number of new and foreign ANDA applicants has grown as well, and generic-drug applications are increasingly including “more complex dosage forms.”

  The generic-drug sector’s growth has potential to strain the agency’s review system, and there is a chance that the agency will not be able “ to assure that generic versions of drugs are ready to be distributed to American consumers on the first day that they may legally be marketed,” said Hamburg at the meeting. “I want to be clear: we are not in crisis now. But we may soon be…. We need the resources to promote the health and well-being of all Americans. And we need them as soon as possible.”

  The solution proposed is generic-drug user fees. User fees are already collected for innovator prescription drugs, medical devices, and veterinary drugs (including generic versions). Hamburg noted that Congress provided the agency with $10 million to address the ANDA backlog (50 additional scientists were or are being hired), but more resources are still needed.

  She also stressed out that generic-drug user fees could help advance regulatory science by providing FDA with the capacity to issue additional guidance and standards for the generic-drug sector.  “Above all, though, there must be commitment and collaboration from both our agency and the generics industry,” concluded Hamburg. “ We hold a joint stake in moving our respective efforts forward and developing a well-constructed Generic Drug User Fee Program.”

  The Generic Pharmaceutical Association (GPhA) presented at the meeting as well and released a 

 in support of a user-fee program. “We are eager to continue working with the agency in developing a user fee program that provides increased certainty in the generic application review process. This includes assuring timely inspections and expanded opportunities for communications between industry and FDA,” said GPhA’s Vice-President for Regulatory Science Gordon Johnston in the statement.

  FDA and industry negotiations about a generic-drug user-fee program are ongoing. Comments on the agency docket are due Oct. 17, 2010.  In related news, the agency and industry are also working on reauthorizing user fees for innovator drugs under the Prescription Drug User Fee Act (PDUFA), version V. PDUFA version IV is set to expire in September 2010.
 


US Food and Drug Administration Commissioner Margaret A. Hamburg spoke at the Generic Drug User Fees Public Meeting last Friday, Sept. 17, 2010, about enacting user fees for the generic-drug sector.

FDA's Hamburg Calls for Generic-Drug User Fees

The US Food and Drug Administration launched last week a performance-management system designed to advance President Obama’s commitment to transparency, public participation, and governmental collaboration. Called FDA-TRACK, the system will monitor more than 100 FDA program offices using data from key performance metrics, according to an agency 

. Data will be gathered monthly, analyzed, and presented each quarter to FDA senior leadership. The system is called FDA-TRACK because the public will be able to view the data on  FDA's website and track the agency’s progress in meeting established goals.
  
“It gives managers and employees a new way to measure their effectiveness in meeting goals to protect the public health and provides a way for the public to monitor agency activities,” said FDA Commissioner Margaret Hamburg in an Aug. 31, 2010, FDA press release.
  
The system will monitor four areas, according to the release:

Common Measures: These are agencywide measures may focus on the agency’s recent priorities such as the number of employees who have been trained in the Incident Command System, which helps the agency respond to emergencies.

Key Center Director Measures: These measures are center-specific and may focus on targets such as increasing the number of technical publications (e.g., guidance) drafted for industry.

 Program Measures: These program/office-specific targets will reflect work important to the public and to FDA’s mission such as monitoring the percentage of 510(k) decisions that meet the 90-day Medical Device User Fee Act goal during a specific time period.

 Key Projects: Finally, these program/office-specific key projects will be measured based on achieving stated milestones within a project plan such as the development of a new risk-based approach for evaluating safety, effectiveness, and quality of new animal drugs.

  On a related note, the agency launched an information-technology 

 to monitor imports coming across US borders last February.

The US Food and Drug Administration launched last week a performance management system designed to advance President Obama's commitment to transparency, public participation, and governmental collaboration.

FDA Launches Public System to Monitor Its Own Performance

 Angie DrakulichWhen our team set out to cover how pharmaceutical companies are addressing issues of global healthcare, including providing access to medicines to those who need it most, we were amazed at the high level of corporate philanthropy. A simple flip through the Developing World Health Partnerships Directory highlights this fact. The International Federation of Pharmaceutical Manufacturers (IFPMA) publishes the directory each year, and the 2010 edition showcases more than 200 programs carried out by pharma, nongovernmental and nonprofit organizations, governments, charities, and global partnerships. The groups are working to develop and deliver treatments that target diseases prevalent within developing nations. Research and development (R&D) efforts, for example, focus on HIV/AIDS, malaria, tuberculosis, and chronic and tropical diseases.   

Much of the work being done also includes educational/awareness programs, capacity building, transportation, infrastructure, and technical support. Most all of the programs correlate directly with the United Nations Millennium Development Goals (MDGs) as well. The MDGs, many of which target health and healthcare, aim to reduce extreme poverty worldwide.  

. Also of interest is the 2010 Access to Medicines Index, a publication put out by the international Access to Medicine Foundation. This index (

) analyzes and ranks access-to-medicines efforts of the world's largest pharmaceutical companies. Check out PharmTech's ongoing coverage of the pharmaceutical industry's efforts to improve global healthcare beginning next month.  

Industry efforts toward global healthcare surpass average expectations.