Angie Drakulich was editorial director of Pharmaceutical Technology.

Angie Drakulich

 to advance regulatory science on Aug. 17, 2011, in an effort to “keep pace with and utilize…new scientific advances” and to promote public health. The plan is based on the agency’s five-year strategic goals (see “

FDA Releases Strategic Priorities for 2011–2015

) and its October 2010 report on advancing regulatory science (see “

FDA Reports on Advancing Regulatory Science

“As new discoveries yield increasingly complex products, this strategic plan ensures that our experts are equipped to make science-based decisions resulting in sound regulatory policy. It positions us to foster innovation through better science without compromising our high safety standard,” stated FDA Commissioner Margaret A. Hamburg in a press release about the report.

The plan outlines eight priority areas that describe how FDA intends to gather and communicate information and advance tools and product quality. Of the eight priorities, six focus on pharmaceutical development and manufacturing—the other two address food safety and communication. Each priority area has a public-health component. Below are some highlights.

Priority 1 is to modernize toxicology to enhance product safety. Because nonclinical safety assessment tends to be exposure-based and conducted in healthy test systems, says the plan, certain responses are not addressed, such as those tied to genetic background or progression of a disease. They agency would like to close these gaps by investing in and implementing better models of human adverse responses, biomarkers, and computational methods as well as 

Priority 3 is to support new approaches to improve product manufacturing and quality. The agency notes in the report that it needs to foster innovations by doing more research with industry and academia. It would like to develop and evaluate novel and improved manufacturing methods by looking into the effects of continuous manufacturing on product quality, how innovative approaches affect product failure rates, and the role of excipient ingredients and complex dosage forms on final products. The role of excipients in drug performance has been a large area of discussion in recent months, especially with regard to atypical actives, which are addressed in PharmTech’s September 2011 special issue on ingredients. 

Under this same priority area, the need for new analytical methods and statistical approaches, including testing their feasibility and value, is noted, as is the risk reduction of microbial contamination. Quality by design and process analytical technology are highlighted in this regard. (FDA is publishing a review of its QbD program in PharmTech’s September issue).

Priority 4 is to ensure FDA readiness to evaluate innovative emerging technologies such as nanotechnology. To accomplish this goal, the agency intends to develop additional expertise and infrastructure to establish assessment tools for novel therapies, stimulate and ensure safe innovative development, and enhance information-technology applications.

Priority 5 is aimed at harnessing diverse data using information sciences. The idea is to integrate and analyze data from various sources, including by “unlocking” data from product applications reviewed by FDA. Simulation models for product life cycles and risk assessment are also envisioned. Because the agency has so much information at its fingertips, including toxicology data, FDA would like to incorporate that information into a single database to facilitate the use of predictive toxicology models and model validation, for example.

Priority 7 focuses on facilitating the development of medical countermeasures. These countermeasures are meant to respond to potential chemical or biological threats, infectious disease, and so forth. The agency launched an 

 in 2010 to facilitate the development and approval of medical countermeasures. The use of animal models, modernized tools, and biomarkers are part of the plan.

Priority 8 is to strengthen social and behavioral science to help consumers and professionals make informed decisions about regulated products. Over the past few years, FDA has been more transparent (see “

”) about its work and is trying to better educate the public and collaborate more with industry and academia. This strategic goal builds on those past efforts and aims to improve understanding of consumer decision-making and evaluate the effectiveness of FDA’s communications.

Of note, Priority 2 addresses ways to improve innovation in personalized medicine and clinical evaluations, and Priority 6 addresses food safety.

The final portion of the FDA strategic plan discusses its partnerships with government agencies and the private sector, staff training and professional development, and direct-funding mechanisms. Each area is directly tied to achieving the plan and advancing regulatory science. Overall, notes the report’s concluding section, FDA intends to use the plan to enable the best available resources and tools to keep pace with current science and technology and to promote public health.

 featuring Dr. Vicki L. Seyfert-Margolis, the senior advisor for Science Innovation and Policy in the FDA Commissioner’s office.

Articles

FDA released a strategic plan to advance regulatory science on Aug. 17, 2011, in an effort to "keep pace with and utilize...new scientific advances," and to promote public health. The plan is based on the agency's five-year strategic goals and its October 2010 report on advancing regulatory science.

FDA Publishes Strategy for Advancing Regulatory Science

Since China’s State Food and Drug Administration (SFDA) revised its GMPs last year (they became effective Mar. 1, 2011), the agency has been making other improvements to enhance the quality of its pharmaceutical manufacturing industry. Many improvements are tied to the 2015 deadline SFDA has placed on existing domestic drug manufacturers to implement the revised guidelines. Newly created companies are expected to meet the new GMPs from the start.

 note ongoing changes and requirements. For example, SFDA is working to strengthen the way it manages drug GMP inspections by standardizing its inspection and certification procedures and requirements. Along these lines, the agency revised its requirements for appointing and evaluating drug GMP inspectors.

In July, SFDA issued specific requirements regarding contract-manufacturing assignments from foreign pharmaceutical companies. The agency says it will monitor the acceptance of these contracts and regulate them more strictly.

Anticounterfeiting measures also seem to be high on China’s list. To ensure drug safety for the public, SFDA says it is cracking down on Internet and mail-order sales of counterfeit drugs. “Since the establishment of SFDA’s leading group of the special operation against IPR [intellectual property rights] infringement and counterfeiting in November 2010, the SFDA has organized the nationwide food and drug regulatory departments involved in this special operation and has made stage achievements with the support and cooperation from the departments of public security, departments of industry and information technology and other relevant departments,” says a 

 about the agency’s efforts. Previously, the agency had increased the agency’s technical capacity as well as routine inspections and sampling.

When China released its new GMPs in February of this year, an SFDA press release noted that the revised guidelines borrow from “advanced international experiences” and that they incorporate “the concepts of quality risk management and whole process control of drug manufacturing, [thereby attaching] more importance to the scientific nature, instruction function and maneuverability, so as to [be] consistent with the [World Health Organization] WHO GMP.” It seems that the agency is working to meet these goals.

Of note, INTERPHEX China is taking place Nov. 9-11, 2011, in Nanjing, and will feature a unique program put together by 

 on buying and validating GMP-compliant equipment.

The Chinese government’s mandate to improve the quality of the country’s pharmaceutical industry includes manufacturing supplies, from raw materials to equipment. The program is aimed at helping pharmaceutical manufacturers understand the new quality requirements for equipment and offer some information on how to evaluate equipment to determine whether it’s compliant. This program will bring together regulators, equipment vendors, and procurement officers, all offering their perspectives and advice on purchasing and validating quality equipment.

China’s State Food and Drug Administration Discusses Drug Applications

Since China's State Food and Drug Administration revised its GMPs last year, the agency has been making other improvements as well to improve the quality of its pharmaceutical manufacturing industry.

China's SFDA Following Through on GMP Efforts

Rare diseases are those that affect populations of 200,000 or less in the United States.  Approximately 7000 such diseases, including certain congenital conditions and rare cancers, exist in the US, and they affect nearly 25 million Americans. New drug applications for these diseases can be submitted simultaneously to FDA and EMA and receive priority review under orphan-drug provisions, and multiple grant programs exist for rare-disease research. For years, many bio/pharmaceutical companies have turned a blind eye to developing products for rare diseases because such medicines have a small consumer base, and thus fall short of meeting desired revenues. Efforts to pay attention to these conditions and find cures for them, however, are  gaining momentum.  

Why now? According to Steve Groft, director of the National Institutes of Health (NIH) Office of Rare Diseases Research, industry and regulators have reached a point where guidance can be provided in this area. "There has not been tremendous interest in rare disease research and treatments until the past 5 to 8 years," he explains. "There was some interest in the 1980s after the Orphan Drug Act was passed in the US, but then we had the consolidation of the pharma industry, which led to an emphasis on larger blockbuster drugs. In 2000, Europe developed its orphan-drug legislation, and that stimulated more product development in this area. Today, industry realizes there are niche markets available for rare-disease treatments and that it can be a profitable market. There is increased interaction between the scientific and the patient-advocacy communities. And, most important, we are now able to look at results of years of basic research on rare diseases and better understand them," he says. 

Groft is part of a unique project that began in October 2010 to develop a diagnostic tool for most known rare diseases. Known as the International Rare Disease Research Consortium, NIH and the European Commission are leading the global scientific community to find treatments for the world's most disregarded medical syndromes and conditions.  

The consortium's first target is no drop in the bucket—the goal is to find new therapies for 200 rare diseases by the year 2020. "There is no list of targeted diseases yet," says Groft. "This is the master goal. We're just beginning to identify possible compounds and diseases that may be considered—some may be used for multiple diseases—and to enter them into clinical studies." The project involves research and development into new molecular entities as well as looking at already approved drugs to see whether they can be repurposed for rare diseases and made available to new populations. "Currently, only 10 to 20 products are approved per year for all diseases, and we feel there is a need to do better than that," adds Groft. 

To meet its goal, the consortium would like to see harmonization of clinical trials for small patient populations and the standardization of trial-data collection.  "We need global acceptance of how to do the trials, and we need patients from many different countries to have enough to complete a study more quickly. We're trying to develop a plan and process that people can use to coordinate efforts to better minimize redundant research," explains Groft. If research-data collection efforts can be standardized in a common protocol, drug-product developers will be able to use and submit that data to regulatory agencies in a much easier way—and the regulatory authorities will receive better research results to evaluate.  

Common data elements can also provide a framework for patient registries to be developed and, looking ahead, says Groft, scientists may be able to use that information for natural-history studies and to develop biomarkers for clinical trials. "We should be able to do the same thing for rare diseases that is being done for cancers and for HIV/AIDS products," he says. Public communication and distribution of the information are also part of the plan. 

The consortium plans to build on already existing models for some rare diseases that have received more attention than others over the years, such as certain muscular dystrophy conditions and cystic fibrosis. "These discovery and development efforts have taken a global approach, and we can use those as examples and build on those successes," says Groft.  For example, the consortium would like to have the same analytical tools available on all project-relevant clinical-trial sites and the services of a data-coordination center.  

NIH is also working with FDA to create a national policy for rare-disease research and related drug regulation. FDA boosted its own rare-disease efforts this past year with a newly created position in the Center for Drug Evaluation and Research, an Associate Director for Rare Diseases, and the launch of a free searchable database that lists approved compounds and products that may help researchers in their search for treatments for rare diseases. "Overall, this is an opportunity to facilitate partnerships," says Groft. "We've been talking about rare diseases for years. Individuals have been developing many of these pieces, and now is the appropriate time to put all those pieces together. The result should be a larger number of products available for the rare-disease community." 

For more information, contact NIH's Dr. Groft (

). To listen to a podcast interview about NIH's global health efforts with Director Francis S. Collins, visit 

NIH leads new international consortium to develop a diagnostic tool for most known rare diseases by the year 2020.

Global Healthcare on the Ground: NIH Aims to Help Treat 200 Rare Diseases

FDA released this week a report from its Center for Drug Evaluation and Research (CDER) that identifies regulatory science needs that will guide CDER’s strategic planning in the years ahead and allow it to fulfill its regulatory mission. The report, 

Identifying CDER’s Science and Research Needs

, discusses internal research initiatives and goals for contributing to the agency’s overall regulatory science efforts.

Behind the report is the agency’s Critical Path 

, which was launched in 2004 to transform the way FDA-regulated medical products are developed, evaluated, and manufactured. More than 200 representatives from various offices within FDA were interviewed to help identify the areas of greatest need. The report notes that computational infrastructure needs and data standards are not addressed because efforts are already underway to in these areas. “Communicating our science and research needs represents an important step in stimulating research and fostering collaborations with our external partners,” said CDER director Janet Woodcock, MD, in a release about the report. 

The 24-page report, put together by the CDER Science Prioritization 
 and Review Committee, goes into detail about how to address key science and research needs, which are broken down into seven areas:

To improve access to postmarket data sources and explore feasibility of their use in different types of analyses;

To improve risk assessment and management strategies to reinforce the safe use of drugs;

To evaluate the effectiveness and impact of different types of regulatory communications to the public and other stakeholders;

To evaluate the link among product quality attributes, manufacturing processes, and product performance;

To develop and improve predictive models of safety and efficacy in humans;

To improve clinical trial design, analysis and conduct; and

To enhance individualization of patient treatment (including biomarkets and drug product behavior in specific populations).

The first four bulletpoints may be of most importance to pharmaceutical manufacturers. For example, the first point about postmarket data calls for determining the accuracy of available postmarket data sources and to use that data, along with premarket data, in safety analyses. The second point, improving risk assessment and management strategies, notes that regulators need to better characterize the risks associated with drugs that have not gone through the FDA approval process and to enhance risk-mitigation strategies for those drugs that have. For example, the report notes that, “to ensure the safe use of drugs, we need to evaluate whether our regulatory activities are resulting in improved outcomes for patients…. This will necessitate identification of additional appropriate outcome measures, methodologies, and accompanying metrics.” A more in-depth look at counterfeit and subquality products is also called for in the report.

The third regulatory-science need regarding regulatory communication suggests that CDER “determine whether current approaches (content, media, and format) are effective in conveying important medical information, and whether they are having an impact on patient and health care provider behavior and patient outcomes.” And the fourth point regarding product process and performance suggests that CDER officials need to “better understand the impact of variability in the drug components and manufacturing process parameters on product quality and performance.” Combination products and biologics are specifically called out in this section of the report. Achieving this goal, according to the report, may require implementation of advanced analytical technology as well as quality risk-management principles and quality-by-design approaches.

Looking ahead, CDER intends to explore the ideas and opportunities noted within the report with other groups such as industry, academia, and nonprofit organizations. “The intent is to enable priorities to be established among the categories and identify gaps that could be addressed through targeted research projects,” states the report. Public comments on the report are due within 60 days of the report’s publication in the 

FDA released this week a report from its Center for Drug Evaluation and Research (CDER) that identifies regulatory science needs that will guide CDER's strategic planning in the years ahead and allow it to fulfill its regulatory mission.

CDER Identifies Key Regulatory Science Needs and Strategies

FDA issued a draft guidance for industry comment that contains proposed policy for diagnostic tests used with targeted drug therapies (i.e., personalized medicine). Companion diagnostics are used to help healthcare professionals determine whether a patient with a particular disease or condition should receive a particular drug therapy or how much of the drug to give, according to the press release about the 

. The draft guidance discusses the agency’s plans for how it will review a companion diagnostic and its corresponding therapy.

The draft guidance defines a companion diagnostic and its use. According to the release, for example, looking for a specific gene amplicfication in a patient that may predict whether a drug would benefit that patient. Herceptin (trastuzumab), approved in 1998, for instance, targets HER2 gene amplification or HER2 protein over-expression in potential breast cancer patients. Herceptin “was approved with a companion test and today testing is routinely performed on women diagnosed with breast cancer to help health care professionals determine whether or not the patient should receive” it, says the release.

The draft guidance calls for early engagement between FDA and manufacturers so that the agency’s expectations can be included in development plans, and states that FDA will aim to conduct simultaneous reviews of a drug or biologic therapy and its corresponding companion diagnostic. The document also notes instances in which the agency may approve a targeted medicine in the absence of a cleared or approved companion diagnostic (e.g., in cases where the therapy is intended to treat a serious or life-threatening disease or condition for which there is no available or satisfactory treatment and when the potential benefits outweigh the risks of not having a cleared or approved companion diagnostic, states the release).

Comments on the draft guidance are due Sept. 12, 2011.

FDA issued a draft guidance for industry comment on proposed policy for diagnostic tests used with targeted drug therapies, that is personalized medicine.

FDA Issues Draft Guidance on Targeted Drug Therapies

In early July 2011, FDA provided an update in which the agency said that it has made progress toward implementing the US Food Safety Modernization Act (FSMA), which was enacted in January 2011. In addition to clarifying expectations for new dietary ingredients through new draft guidance, the agency has issued an antismuggling strategy.

FDA worked with the US Department of Homeland Security to create the strategy, which aims to “identify and prevent smuggled foods from entering the United States and posing a threat to national security and consumer safety,” according to an agency 

. Although the strategy, like many portions of FSMA, focuses on food safety, many components and directives within the act also pertain to pharmaceuticals. Food-safety actions taken now may provide guidance for drug-safety issues in the future (see “

FDA Gains Food Recall Authority, Drugs Could be Next

“This new system, overall, will better leverage the resources of federal agencies and it will make industry an important partner in safeguarding the health of US consumers,” said Deputy Commissioner for Foods Michael R. Taylor in the press release.

As part of the strategy, FDA will work with US Customs and Border Protection (CBP) to review historical data and better identify products, firms, and countries of origin to target potential food smuggling and smugglers. FDA and CBP also will share information on import shipments and conduct joint examinations to identify shipments that may contain smuggled food. FDA has been increasing its focus on drug imports at the borders as well with its Predictive Risk-Based Evaluation for Dynamic Import Compliance Targeting (PREDICT) 

The agency also issued draft guidance regarding new dietary ingredients as part of FSMA implementation. The document aims to prevent consumers from being exposed to “unnecessary public-health risks from new ingredients with unknown safety profiles,” says the press release. Specifically, dietary-supplement manufacturers are required to notify FDA before adding a new dietary ingredient to their products, except when the ingredient has been part of the food supply and has not been chemically altered for use in supplements.

 devoted to FSMA implementation and updates for more information.

FDA announced in early July 2011 that it has made progress toward implementing the US Food Safety Modernization Act, which was enacted in January of this year.