Angie Drakulich was editorial director of Pharmaceutical Technology.

Angie Drakulich

Articles

Today begins the two-day public hearing being held at FDA headquarters in Rockville, MD, to gain public in put on how to implement and regulate the follow-on biologics pathway that was cleared via President Obama's Biologics Price Competition and Innovation Act of 2009, which falls under the 2010 approved healthcare reform legislation.

Biosimilars Hearing Begins Today

launched this series to cover the ways in which pharmaceutical companies, nonprofit and nongovernmental organizations, charities, and others are working to increase access to needed drugs in the developing world. Here, we highlight the efforts of two of the world's largest pharmaceutical companies, Merck and AstraZeneca, in this area. 

From its home base in Whitehouse Station, New Jersey, Merck is working with the government of Bhutan and the Australian Cervical Cancer Foundation to implement a national cervical cancer vaccination program for girls aged 12 to 18. Bhutan, which borders India and Tibet, will be the first developing nation to have such a program in place.  

The six-year program, which began in 2010, is intended to reduce cervical cancer in the country. Currently, cervical cancer affects more women in Bhutan than any other cancer—about 200 women are diagnosed each year, and one-half of them die. Merck's Gardasil (human papillomavirus [HPV] quadrivalent [Types 6, 11, 16, and 18] vaccine, recombinant) vaccine will be administered. As part of the program, Bhutan's Ministry of Health will also provide educational materials regarding HPV to girls who receive the vaccine at local schools and through routine vaccination services in basic health units.  

The Bhutan program is part of a larger Merck effort to improve access to cervical cancer vaccines in the developing world Through the company's Gardasil Access Program, Merck is donating at least 3 million doses of its HPV vaccine to low-income countries, including: Bolivia, Cambodia, Cameroon, Georgia, Ghana, Haiti, India, Kenya, Lesotho, Moldova, Nepal, Nicaragua, Papua New Guinea, Tanzania, Uganda, and Uzbekistan.  

More recently, the company launched a joint venture with United Kingdom's Wellcome Trust, a global charity based in London, to create the MSD Wellcome Trust Hilleman Laboratories, which will use a nonprofit operating model to develop and deliver vaccines to low-income countries. While an initial portfolio of projects will be selected after a technical assessment and consultation with the international community, an example of the kind of program being considered is developing vaccines that do not require refrigeration, according to the company. The laboratory, to be based in India, will help to advance projects to proof of concept and help to ensure that production can be scaled up. 

Overall, Merck believes it has an important role to play in helping to improve access to medicines, vaccines, and quality healthcare worldwide, says Brenda Colatrella, executive director of Merck's Office of Corporate Responsibility. "Barriers to quality care and medical treatment such as lack of trained healthcare professionals, weak infrastructure, and civil strife in many parts of the world make even basic healthcare delivery difficult at best," she said. "[Although] substantial progress is being made to address these challenges and future technological advances portend even greater opportunities for the world's population and growing economies,... more progress and more partnerships are needed to ensure everyone worldwide has access to the same level of quality medicines, vaccines, and healthcare." 

With headquarters in London, this pharmaceutical company is the only one in the world with a research program dedicated specifically to finding a new, improved treatment for tuberculosis. The disease affects 2 billion people globally,  according to the 2009 TB fact sheet from the World Health Organization (WHO), and 5% of those infected have a multidrug resistant form of the disease, which means that standard first-line drugs do not work. In fact, last month, the US Food and Drug Administration announced nearly $3 million in grants for TB research, including research on the resistant forms of the disease, as part of its Critical Path Initiative. 

In 2003, AstraZeneca opened a purpose-built TB research center in Bangalore, India, focused on multidrug resistant strains. Today, more than 80 scientists work there in collaboration with AstraZeneca's infection research center in Boston. And in May 2010, AstraZeneca joined forces with the Global Alliance for TB Drug Development to accelerate the discovery, development and clinical use of drugs to treat TB, including drug-resistant strains of the disease. 

Under the agreement, the TB Alliance and AstraZeneca will contribute promising TB drug-discovery projects into a joint portfolio that will be codeveloped. Potentially successful compounds will be tested  in combination with other therapies as part of the program, which is being called Critical Path to TB Drug Regimens. 

The European drug manufacturer also has programs focused on finding treatments for malaria, including collaboration with the Medicines for Malaria Venture (MMV), a nonprofit Switzerland-based public–private partnership established in 1999 to reduce the burden of malaria in disease-endemic countries. The MMV project involves the use of AstraZeneca's compound library to search for novel drug candidates to treat malaria. And last year, AstraZeneca agreed to provide at least 3 million doses of its H1N1 attenuated intranasal vaccine to WHO for distribution. 

Looking ahead, AstraZeneca believes industry needs to work together with other groups to keep up momentum for finding new treatments for diseases that largely affect developing and neglected populations. "The challenge for pharmaceutical companies is to balance downward pressures on the price of medicines with the cost of the continued innovation that is required to address the unmet medical needs and bring benefit for patients and society," says AstraZeneca R&D's Aileen Allsop, vice-president of science policy. "Just as there is no single source to the issues related to improving health outcomes, there is no single solution. We need to foster a collaborative, multistakeholder approach to ensure strong partnerships between pharmaceutical companies, other industries, governments and NGOs." 

Merck and AstraZeneca Tackle Cervical Cancer and Tuberculosis.

Global Healthcare on the Ground: Merck and AstraZeneca Tackle Cervical Cancer and Tuberculosis

In late September, the US House of Representatives' Research and Science Education Subcommittee held a hearing on the science of science and innovation policy to discuss various federal initiatives in the science and technology field.  

One such initiative, the Science of Science and Innovation Policy program (SciSIP), was established in 2005 by the National Science Foundation (NSF) to gain an understanding of how policy decisions affect innovation and science and engineering research. The interdisciplinary program includes outreach and education as well as research investment and has three major goals: advancing evidence based science and innovation policy decision making; building a scientific community to study science and innovation policy; and leveraging the experience of other countries. 

Earlier this year, the Obama Administration launched a similar program, called the Science and Technology for America's Reinvestment: Measuring the Effect on Innovation, Competitiveness and Science program, better known as STAR METRICS. This federal–academic partnership is aimed at developing a system to track and quantify the effect of federal science investments on economic growth, workforce outcomes, scientific knowledge, and social outcomes. The latter project includes collaboration with the European Union. 

"Federally funded basic and applied scientific research has had a significant impact on innovation, economic growth, and America's social well-being," Julia Lane, MD, program director of SciSIP for NSF, told the Congressional subcommittee at the September meeting.  

"We have little information about the impact of individual projects and programs, whether federally or privately funded. We have little information about the impact of science agencies....," she added. "A deeper understanding of the changing framework in which scientific and technical innovation occurs would help policymakers decide how best to make and manage limited public R&D investments to exploit the most promising and important opportunities." 

To start gathering and making use of this type of information, the White House National Science and Technology Council interagency group for the science of science policy is meeting in December in Washington, DC, to identify a joint agenda for federal agencies and the research community. Their work and that of SciSIP can be followed online at 

www.whitehouse.gov/administration/eop/ostp

www.scienceofsciencepolicy.net/scisipcentral.aspx

In the pharmaceutical sector, the American Association of Pharmaceutical Scientists (AAPS) is also celebrating innovation through their awards programs. At this month's Annual Meeting & Exposition in New Orleans, AAPS,  in conjunction with the International Pharmaceutical Federation's Pharmaceutical Sciences World Congress (see the AAPS Guest Editorial on page 12, and the FIP Viewpoint article on page 146), will be honoring innovators young and old for their work in the pharmaceutical sciences. Awards identify outstanding work in research and development, education, authorship, service, and other areas.  

During the conference, Editor-in-Chief Michelle Hoffman and I will be talking to many of the award recipients about their research and inspirations. We hope you will have a chance to meet some of these bright individuals during the show. If you are unable to attend, plesae visit 

 in early December to listen to the podcast interviews. 

Along the same lines that Dr. Lane explained to Congress, the more we get to know the people innovating in the lab and how their work might affect science and healthcare, the better we'll be able to support their research and the scientific community at large. As we all  know, no one becomes successful without a little help. We all can be advocates for innovation. 

Connecting science and policy might increase support for innovation.

Innovation In Depth

The US Food and Drug Administration issued a 

Qualification Process for Drug Development Tools

. According to the document, drug-development tools (DDTs) include biomarkers and patient-reported outcome instruments, among other things. Specifically, the guidance offers a framework for DDT submitters to interact with officials at FDA’s Center for Drug Evaluation and Research (CDER) regarding data needed to support qualification of a DDT. The draft guidance also offers a mechanism for formal review by CDER to qualify the DDT. 

“Qualification” in the document is defined as “a conclusion that within the stated context of use, the results of assessment with a DDT can be relied upon to have a specific interpretation and application in drug development and regulatory decision-making.” 

FDA is issuing the draft guidance now because it has recognized that “the process of drug development and the availability of new therapies have not been as strongly affected by recent advances in biomedical science as might be possible,” states the document. Furthermore, “CDER anticipates that this guidance will encourage individuals and companies with an interest in these tools to advance their development.”

CDER has not had a qualification process for DDTs in the past. Instead, DDTs have been reviewed on a case-by-case basis, which, says the draft guidance, can inhibit the DDTs' development and potentially delay a drug-development program. A new process may provide “some degree of generalizability for use of the tool, such as use across multiple clinical disorders, multiple drugs, or drug classes. Having a qualified DDT that many sponsors will be able to use will aid in advancing therapy development and evaluation in multiple cases, and can more widely benefit patients.”

In the draft guidance, FDA proposes stages for the qualification process, including consultation and advice with CDER (e.g., letter of intent, briefing, meeting, investigation), and review for the qualification decision. The agency intends to make public its information regarding qualified DDTs.

The US Food and Drug Administration issued a draft guidance last week on the Qualification Process for Drug Development Tools.

FDA Issues Draft Guidance for Qualifying Drug-Development Tools

The US Food and Drug Administration has posted on its website the minutes of the Prescription Drug User Fee Act (PDUFA) V reauthorizaton stakeholder meeting. Held in late September, the meeting focused on proposals from the agency and from stakeholders for renewing the  Act. Also on the agenda were FDA’s regulatory oversight with regard to direct-to-consumer advertising and an update to the Reagan-Udall Foundation’s work. 

Participants at the meeting including officials from key FDA centers, including the Center for Drug Evaluation and Research (CDER), the US Department of Health and Human Services, and various nonprofit and nongovernmental healthcare organizations.

FDA presented its proposals for improving PDUFA. The fourth version of PDUFA expires in Sept. 2012. FDA has been and will continue to hold meetings with industry and other patient and consumer groups until its final recommendations are due to Congress on Jan. 15, 2012. FDA’s proposals, according to the minutes, include the following:

1. Reduce multiple review cycles 
 2. Enable greater review predictability by standardizing drug application data 
 3. Ensure consideration of patient-focused drug development 
 4. Test the Sentinel project as a tool for evaluating safety signals 
 5. Expand capacity for scientific advice to address complex manufacturing issues
 6. Ensure quality in non-inferiority and adaptive trial designs 
 7. Ensure quality in meta-analysis 
 8. Improve human subject protection by building quality into clinical trial oversight
 9. Standardize and integrate risk evaluation and mitigation strategies (REMS) into the healthcare system 
 10. Ensure the quality of patient-reported outcomes and other endpoint assessment tools  
 11. Better plan for optimal dose selection
 12. Advance biomarkers and pharmacogenomics 
 13. Advance development of drugs for rare diseases 
 14. Improve the prediction of drug safety before and during development 
 15. Clarify small business waiver procedures 
 16. Issue product fees for discontinued products 
 17. Set expiration date for appeals for waivers, refunds, and reductions 

In turn, the consumer stakeholder groups asked to be included in premarket discussions regarding REMS development and in any advisory committee planning meetings. Stakeholders expressed concern about the Sentinel Initiative’s progress. (The initiative aims to implement a system to help the agency track adverse-event reports.) Additional comments were related to the resources and/or authority FDA might need to ensure that manufacturers meet their postapproval study commitments. And patient groups proposed to continue the FDA Amendments Act of 2007 annual drug-safety user-fee funding increases throughout PDUFA V.  

In addition to discussing PDUFA’s reauthorization, meeting participants reviewed FDA’s drug-promotion oversight efforts. FDA pointed out that it places higher priority on new drugs and indications and on products that contain new safety information. Also given priority are drugs that have first-time television promotions. The agency noted that it reached agreement with industry on a user-fee program for the review of direct-to-consumer ads during last year’s PDUFA IV discussions but that Congress had decided the review funding should come from appropriated dollars instead. 

Finally, as part of the meeting agenda, the executive director of the Reagan-Udall Foundation offered an updated on the Foundation’s activities. The Foundation was established as part of the FDA Amendments Act of 2007 to “aid in the discovery of new, applied scientific knowledge to evaluate products and enhance the FDA’s ability to protect and promote the health of the American public,” according to the minutes.  The Foundation’s projects include a tuberculosis program aimed at accelerating the development of treatments, harmonization of science-based food standards, and an effort to mine aggregated patient data for use in subgroup labeling and special population analyses in breast cancer trials. The  Foundation, according to the minutes, has been concerned about the perceived influence of regulated industry on its and is therefore building stronger policies regarding conflicts-of-interest and transparency. 

The US Food and Drug Administration has posted on its website the minutes of the PDUFA V reauthorizaton stakeholder meeting.

FDA Posts Minutes to PDUFA V Discussion Meeting

 The US Food and Drug Administration  released an implementation 

 on its Regulatory Science Initiative. The report outlines the agency’s plans to advance regulatory science through new tools, standards, and approaches for assessing the safety, efficacy, quality, and performance of FDA-regulated products, according to an agency press release.

Last February, FDA launched the Regulatory Science Initiative to fast-track drug product  innovations to the public. The strategy builds upon the agency’s Critical Path Initiative (See 

, “FDA and NIH Collaborate to Speed the Introduction of New Medicines”). 

  Included in the new report are examples of FDA activities in regulatory science as well as recommendations for helping to deliver better and safer products to the market. The following seven public-health areas are addressed:

Accelerating the delivery of new medical treatments to patients 

Protecting against emerging infectious diseases and terrorism 

Enhancing safety and health through informatics 

 Meeting the challenges for regulating tobacco

For scientific advances to reach their full potential, FDA “must play an increasingly integral role as an agency not just dedicated to ensuring safe and effective products, but also to promote public health and participate more actively in the scientific-research enterprise directed towards new treatments and interventions,” according to the report’s executive summary.  “We must also modernize our evaluation and approval processes to ensure that innovative products reach the patients who need them, when they need them.”

  The initiative, based on President Obama’s $25-million budget request for fiscal year 2011, includes a new office of regulatory science within FDA, and focuses on the following:

 Leadership, coordination, strategic planning, and transparency to support science and innovation

 Support for mission-critical applied research, both at FDA and collaboratively

 Support for scientific excellence, professional development and a learning organization

 Recruitment and retention of outstanding scientists.

In FY2011, according to the report, the agency will support research in transforming product development for patients(e.g., methods for modernizing toxicology, biomarkers, stem-cell initiatives, and drug-review standard updates), science to address emerging technologies in FDA-regulated products    (e.g., nanotechnology and new animal biotechnology products), information sciences for health outcomes (e.g., a medical device registry), addressing unmet public health needs
(e.g., nutrition). 

FY2011 activities will also work toward the opening of a network of Centers of Excellence in Regulatory Science “to be integrated with expanded intramural FDA research and with other clinical research networks,” says the summary. 

 the initiative at the National Press Club last week.  

The US Food and Drug Administration has released an implementation report on its Regulatory Science Initiative. The report outlines the agency's plans to advance regulatory science through new tools, standards, and approaches for assessing the safety, efficacy, quality and performance of FDA-regulated products, according to an agency press release.