Angie Drakulich was editorial director of Pharmaceutical Technology.

Angie Drakulich

The steering committee of the International Conference on Harmonization and its expert working groups adopted Quality Guideline Q10 “Quality Systems” last week at a meeting in Portland, Oregon. The adoption represents the final stage of the harmonization process, which means that all parties to ICH (the US, Europe, and Japan) have reached scientific consensus on the technical issues of the guideline’s text and agreed to fully implement  the guideline through their individual regulatory bodies.

 Q10 was in Step 3 (the consultation and comment period) from May 2007 until  last week, the ICH parties finalized the guideline’s concept in late 2005.

Q10 incorporates the concepts behind ICH Q8 “Pharmaceutical Development” and ICH Q9 “Quality Risk Management” by providing a model for a pharmaceutical quality system that can be implemented throughout  a product life cycle. Q10 is meant to complement and add to current good manufacturing practices but, as a guideline, is not enforceable. The overall goal, according to the Q10 business plan, is to facilitate innovation and continual improvement and strengthen the link between pharmaceutical development and manufacturing activities. 

 and SGS will host a web seminar titled “Quality Systems in the Global Marketplace” on June 12. Some of the panelists in the webcast participated in the ICH meeting in Portland last week and will be answering questions from industry. Log on to the 

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The steering committee of the International Conference on Harmonization and its expert working groups adopted Quality Guideline Q10 "Quality Systems" last week at a meeting in Portland, Oregon.

ICH Q10 Moves to Final Stage: International Adoption

The US Food and Drug Administration issued a new guidance this week on indexing structured product labeling (SPL). The 

Center for Biologics Evaluation and Research

 (CDER) will begin indexing SPL in the product labeling for human drug and biologic products.

SPL became a requirement in October 2005 when FDA stated that SPL in extensible markup language (XML) was the only electronic format for content of labeling that CDER could process, review, and archive, according to the guidance. The agency is now recommending that content be submitted in SPL. 

SPL enables the electronic exchange of the content of labeling and other regulated product information. It also enables the inclusion of indexing elements with product labeling. Indexing is made possible by machine-readable tags that are inserted into the label, but that do not appear on the actual printed label (consumers cannot see them). With these tags, individuals using clinical-decision support tools and electronic prescribing systems can more easily and rapidly search and sort product information in product labeling. 

“Being able to electronically access labeling information and to search and sort that information is an important step toward the creation of a fully automated health information exchange system,” states the guidance.

The change also will help to decrease prescribing errors and enhance the safe use of medical products. For example, says the guidance, a full-text search of the content of labeling for 

. New indexing elements based on standards adopted for use in the healthcare setting will address this problem. 

The new guidance comes upon the completion of a six-month FDA pilot project that evaluted how best to add indexing elements to products. It also comes approximately two months after FDA issued a draft guidance on structured product labeling. The new guidance addresses some of the suggestions received from industry based on the draft, including more concrete advice on how applicants can recommend indexing terms to the agency and how indexed terms will be identified and shared.

Applicants are advised to suggest indexing terms with the SPL file in their regulatory submission. Because the SPL indexing process is independent from the labeling review process, FDA states that SPL indexing will not affect review times or delay approvals. Moreover, the applicant’s SPL file will remain unchanged by the indexing process. However, says the guidance, indexing considerations may be incorporated in the standard labeling review discussions. 

The guidance notes that the labeling process will apply to all products, not just those subject to 21 

 201.57. FDA will index SPL using a phased approach, starting with pharmacological class, and is seeking public input about future phases.

. Comments on the guidance can be submitted electronically 

The US Food and Drug Administration issued a new guidance Monday on indexing structured product labeling. The Center for Biologics Evaluation and Research and the Center for Drug Evaluation and Research will begin indexing structured product labeling in the product labeling for human drug and biologic products.

FDA Issues Structured Product Labeling Guidance; Says Delays Will Not Occur

Last week, 2704 delegates representing 190 nations met in Geneva for the 61st World Health Assembly to set a global course for tackling new as well as longstanding threats to public health worldwide. The assembly’s biggest breakthrough focused on adopting a resolution that encourages research and development (R&D) as well as access to medicines for people living in developing countries, according to a World Health Organization (WHO) release. 

In early May, an intergovernmental working group agreed on approximately 200 paragraphs of a global strategy and plan of action aimed at essential R&D for diseases that disproportionately affect developing nations. The working group began two years ago when WHO member states decided to address shortfalls in R&D for noncommunicable diseases and to overcome the rich nation–poor nation arguments over patent laws, which developing countries claim prevent their populations from accessing affordable, life-saving drugs. 

Last week, assembly delegates tackled the remaining 20 unresolved paragraphs of the global strategy, working into the weekend to finally agree upon the Public Health, Innovation, and Intellectual Property Strategy. Aimed at removing intellectual property barriers so that essential R&D for public health can move forward, the globally strategy, which is part of the adopted overall resolution, is designed “to promote new approaches to pharmaceutical R&D…to enhance access to medicines…[and] to provide a medium-term framework for enhancing and making sustainable essential R&D relevant to diseases impacting developing countries.”

As part of the resolution, delegates also endorsed a six-year action plan for fighting noncommunicable diseases, which caused 60% of all deaths globally in 2005 (approximately 35 million deaths), according to WHO. 

“This is a contribution to fairness in health and this is proactive public health at its very best,” said WHO Director-General Dr. Margaret Chan, at the close of the assembly on Saturday.

Chan is tasked with finalizing the outstanding components of the intellectual property resolution, including timeframes, progress indications, and estimated funding needs. She is also to finalize a plan of action to boost incentives for pharmaceutical companies to tackle diseases that mainly afflict the poor, according to 

The assembly will review both plans at its May 2009 session. 

Among other issues discussed at the assembly were climate change, including commitments from nations to scale up adaptation projects that would limit the impacts of climate change on health; the eradication of polio; preparation for an influenza pandemic; migrant health; progress on the Millennium Development Goals; and a global immunization strategy that involves encouraging nations to develop new vaccines.


Pharma Impacted by UN Agency's Public Health Debates

Last week, 2704 delegates representing 190 nations met in Geneva for the 61st World Health Assembly to set a global course for tackling new as well as longstanding threats to public health worldwide. The assembly?s biggest breakthrough focused on adopting a resolution that encourages research and development (R&D) as well as access to medicines for people living in developing countries, according to a World Health Organization (WHO) release.

World Health Assembly Tackles Intellectual Property, Noncommunicable Diseases, and More

The World Health Organization’s World Health Assembly is holding its 61st annual session this week to discuss a number of public health issues, many of which are tied directly to pharmaceutical manufacturing. Approximately 193 assembly delegates attending the five-day meeting in Geneva have come together from all corners of the world to debate and, hopefully, decide on some critical action points impacting pharma, including intellectual property reform, anti-counterfeiting of drug products, pandemic influenza preparedness, and the control of noncommunicable diseases.

Below is a brief look at some of the issues on the assembly’s agenda. A follow-up report will be included in next week’s 

Developing countries claim that current patent      laws still prevent them from getting life-saving medicines at affordable      prices, despite the World Trade Organization’s Trade-Related Aspects of      Intellectual Property Rights (TRIPS) agreement which makes allowances for      developing nations to create or buy copycat versions of patented drugs.      WHO has been working on the issue for some time-its most recent attempt      carried out earlier this month by an 

  that was unable to reach consensus on all points. Industry leaders,      represented by the International Federation of Pharmaceutical      Manufacturers and Associations, and many industrialized nations, including      the United States, have argued that current intellectual property rules      protect against counterfeits and offers pharmaceutical companies a return      on their large investments into developing new drugs; they are leery of      major patent reform. Assembly delegates are discussing how to move      forward.

In 2006, WHO launched the International Medical      Products Anti-Counterfeiting Taskforce (IMPACT) to coordinate action      across and between countries to halt the production, movement, and      commerce of counterfeit medical products around the globe. The taskforce      incorporates, among others, representatives from national and      international organizations, health professionals, enforcement      authorities, and drug regulatory bodies such as the US Food and Drug      Administration. The taskforce has come up with recommendations to      strengthen WHO’s good distribution practices (GDP) for pharmaceutical      products. GDPs are 

 due to recent contamination in some      drug product’s supply-chains. Assembly delegates are expected to comment on IMPACT’s achievements and      other anti-counterfeiting approaches.

  in April that outlines an action plan for      controlling and preventing noncommunicable diseases. The action plan      specifically calls for national governments, including the US, to      incorporate more government departments and sectors-including the      pharmaceutical production sector-in its approach to combating these      diseases. The assembly asks governments to go beyond “health policy      alone.” According to WHO, noncommunicable diseases, including      cardiovascular diseases, diabetes, cancers, and chronic respiratory      diseases, caused approximately 35 million deaths in 2005, or 60% of all      deaths globally. This statistic is expected to increase another 17% over      the next 10 years. If approved, the WHO action plan is to be rolled out      over the next six years, from 2008-2013. 

Last but not least, the assembly is discussing      the sharing of influenza virus information and access to vaccines.      Specifically, delegates may comment on the new traceability mechanism for      all influenza A (H5N1) viruses submitted to the Global Influenza      Surveillance Network and other methods to best prepare for and fight the      virus. Last month, Sanofi Pasteur, the vaccines division of 

      (Paris), received a US order      for 38.5 million doses (worth $192.5 million) of vaccine against a new      strain of avian influenza.

The World Health Organization's World Health Assembly is holding its 61st annual session this week to discuss a number of public health issues, many of which are tied directly to pharmaceutical manufacturing.

Once again, the US Food and Drug Administration is under fire for not doing its job. This time the issue is direct-to-consumer (DTC) advertising. According to a new Government Accountability Office (GAO) report, FDA only issued two regulatory or warning letters regarding DTC violations in 2007. Compare this with the 15–25 letters the agency sent each year between 1997 and 2001.

The reason for the change, says GAO, is an FDA-initiated protocol that went into effect in 2002. At that time, FDA decided to start sending all draft warning letters regarding DTC violations through legal review before sending the letters out to companies. 

In November 2006, GAO issued a report noting that FDA’s new protocol was leading to delays in issuing regulatory letters for DTC violations. What took two weeks from 1997 to 2001, took an average of four months between 2002 and 2005, and last year, took an average of five months. In 2006, GAO recommended that FDA issue letters more quickly and also implement a better tracking system for prioritizing DTC materials upon receipt. 

DTC advertising materials have been on the rise over the past few years. According to GAO, FDA received approximately 6000 such submissions in 1999, and 21,000 in 2007. It’s FDA’s role to oversee that such materials, whether on TV, in print or on the Internet, are truthful and nonmisleading. 

But, states the new GAO report, the agency “still does not systematically apply its criteria to all of the DTC materials it receives.” 

GAO Director of Health Care Marcia Crosse 

 to the House Subcommittee on Oversight and Investigations, part of the Committee on Energy and Commerce, on May 8, regarding the study’s findings. Overall, she said that not much has improved since GAO offered recommendations in late 2006. 

 “The amount of time it takes to draft and issue letters has continued to lengthen,” said Crosse. “We believe that delays in issuing regulatory letters limit FDA’s effectiveness in overseeing DTC advertising and in reducing consumers’ exposure to false and misleading advertising.”

The fact that FDA has been unable to regulate DTC advertising effectively has brought up many questions, including whether or not DTC advertising should continue to be allowed. The United States is one of only two countries (New Zealand is the other) that still allow the practice. 

Furthermore, FDA’s letters have not been very effective. According to the GAO report, for the six warning letters FDA issued in 2004 and 2005, the corrective advertising materials were initially disseminated more than 5 to almost 12 months after FDA issued the letter. One violative advertisement for an allergy medication ran from April through October 2004 before FDA issued a regulatory letter in April 2005; even then, the corrective ad was not released until January 2006. 

Current law authorizes FDA to require companies to submit draft television ads up to 45 days before they are aired and to charge civil fines for violations of prescription drug DTC advertising. The agency, however, has not implemented such rules.

House Oversight and Investigations Subcommittee Chairman Bart Stupak

 (D-Mich) said  that if the US continues to allow DTC materials, additional limits on companies’ ads may need to be required. 

Once again, the US Food and Drug Administration is under fire for not doing its job. This time the issue is direct-to-consumer (DTC) advertising.

Direct-to-Consumer Oversight Faltering, Says GAO

The European Community and European Federation of Pharmaceutical Industries and Associations (

) held its first call for proposals for its five-year, €2 billion ($3.1 billion) initiative to boost biomedical innovation. The 

 (IMI), kicked off in March, is meant to tackle the ongoing decline in biopharmaceutical innovation that has occurred as a result of increasing research and development (R&D) costs, higher regulatory hurdles, and more complex science, according to an EFPIA release.

 (Leverkusen, Germany) Arthur J. Higgins addressed the audience in Brussels. “We as an industry fully accept our responsibility and are ready to play our part in bringing forward medical innovation. At the same time, we have no problem to admit that we cannot solve all these issues by ourselves-but rather, we need to join forces with partners to address the main causes of delays, or ‘bottlenecks,’ in drug discovery,” he said.

Under IMI, innovative patient-centered projects that aim to address such R&D bottlenecks will be eligible for funding. Identified “bottlenecks” include safety evaluation, the prediction of efficacy, knowledge management and gaps in education, and training. Research projects are to focus on five disease areas: cancer, brain disorders, inflammatory diseases, metabolic diseases, and infectious diseases. 

IMI will award research grants to a variety of stakeholders, according to the release. Small and medium-sized enterprises, academia, research centers, patient groups, public authorities (including regulators), and the research-based pharmaceutical industry will all be involved. 

IMI will also work to improve education and training among European scientists. The initiative’s research agenda includes establishing a European Medicines Research Academy (EMRA) by 2013 to educate and train current and future professionals, including regulatory officers, involved in biomedical R&D.  

According to IMI’s Governing Board Chairman Jonathan Knowles, also of EFPIA and member of the Roche executive committee and head of group research at 

 (Basel, Switzerland), “Europe has great potential for innovation because of its excellent science base. However, it is lagging behind other global players such as the US. The Innovative Medicines Initiative will ensure that Europe’s biomedical sciences receive targeted strategic support for the benefit of patients, scientists and citizens. This in turn will help to improve Europe's competitiveness in biopharmaceutical innovation and make it a more attractive place for pharmaceutical R&D.”

The European community and European Federation of Pharmaceutical Industries and Associations (EFPIA) held its first call for proposals for its five-year, €2 billion ($3.1 billion) initiative to boost biomedical innovation.