Erik Greb

The European Public Health Alliance (EPHA) has published its comments about the Falsified Medicines Directive, which is currently under debate by the European Parliament and Council. The EPHA welcomed the Directive because of the growing threat of counterfeit medicines and supported many of the Directive’s measures. However, it also listed several concerns and proposed improvements. 

The EPHA’s primary concern was what it called the need for a clear and internationally agreed-upon definition of the term “counterfeit medicines.” The organization argued that the phrase “falsified medicinal products,” which currently appears in the draft Directive, does not sufficiently encompass the “criminal relevance” of counterfeiting. EPHA proposed that the Directive refer to the World Health Organization’s definition of counterfeit medicinal products, which describes them as products that are “deliberately and fraudulently mislabeled with respect to identity and/or source”.

The EPHA also said that patients must not bear the costs of improved safety measures alone as this arrangement would increase health inequalities. The organization claimed that the effect of the draft legislation’s proposed actions on the price of medicines had not been measured fully and argued that increased costs should not limit patients’ access to medicines. The EPHA proposed that the costs of the new safety measures be borne throughout the supply chain.

Another concern was the need to ensure that the Directive’s measures do not hinder competition or impose barriers to trade. The organization noted that the enforcement regulation has resulted in the seizures of legitimate generic medicines in transit and suggested that applying the proposed measures to medicines that will not be introduced into the EU would be problematic. The EPHA also proposed that the Directive explicitly distinguish between counterfeiting, compliance with GMP, and compliance with good distribution practice to maintain the appropriate scope for counterfeit regulation. The EPHA also said that patent infringements should be explicitly excluded from the definition and the regulation.

In addition, EPHA said it supported pharmacy-level authentication of medicines and called safety features such as barcodes and mass serialization of individual medicine packs “a strong line of attack against the counterfeiters” in its comments. The organization argued against a risk-based approach to authentication, claiming that it was not justified by arguments based on cost and was inconsistent with the idea of pre-emptive action on the basis of precaution. Categorizing medicines as high or low risk of being counterfeited could be counterproductive, according to the EPHA. “As long as opportunity costs remain sufficiently low for any medicine, including over the counter medicines, that medicine is at risk of being counterfeited,” said the organization in its 

Finally, the EPHA said that the Directive failed to mention the internet as a source of counterfeit medicines, and also ignored the fact that the worldwide web is the main distribution channel for them. Thus, it called the proposed initiatives “insufficient to protect consumers and patients from this source of danger” and called for European and international cooperation on regulating sales of drugs on the internet. The EPHA proposed measures such as the following:

A ban on sponsored advertising of illegal pharmacies online

The creation of certification systems for authorized online pharmacies in countries where online sales are legal

Special initiatives to alert consumers of the risks of purchasing online medicines from unknown sources on the internet

Education of consumers and patients about the dangers of counterfeit medicines and the hazards of buying prescription medicines from unregulated sources. 

Articles

The European Public Health Alliance (EPHA) has published its comments about the Falsified Medicines Directive, which is currently under debate by the European Parliament and Council.

EPHA proposes improvements to medicines directive

The Congressional Budget Office (CBO) has released a report titled 

Promotional Spending for Prescription Drugs

 that analyses the pharmaceutical industry’s advertising strategies. The report reviews the industry’s promotional activities from 1989 to 2008 for drugs in the classes of medication that include most outpatient drugs produced in tablets or capsules. More than 2000 drugs were included in the CBO’s analysis, and companies reported promotional spending for 700800 of them in any given year.

Revised advertising guidelines that the FDA introduced in the late 1990s spurred direct-to-consumer (DTC) advertising, which has significantly changed the way companies promote their prescription drugs, the report notes. Companies that had marketed largely to physicians and other healthcare providers began buying print and television advertisements in an effort to reach patients.

Despite the introduction of a new advertising strategy, total promotional expenditures remained consistent. In 2008, promotional expenditures accounted for 10.8% of the US sales reported by the Pharmaceutical Research and Manufacturers of America. During most years since the early 1990s, promotional expenditures have remained at 1012% of total US sales. 

Pharmaceutical manufacturers spent roughly $20.5 billion on promotional activities targeted to consumers and physicians in 2008. Companies spent $12 billion, more than half of that promotional spending, on detailing (i.e., sales representatives’ meetings with physicians, nurse practitioners and physicians’ assistants). The second largest part of the industry’s promotional budgets, $4.7 billion, was allocated to DTC advertising in 2008. Manufacturers spent $3.4 billion to sponsor professional meetings and events, and $0.4 billion to buy advertisements in professional journals.

Companies mainly pursued DTC advertising for treatments for common conditions that affect a large portion of the population, such as high cholesterol, insomnia or reduced bone density. DTC advertising has also been a popular strategy for drugs with large potential markets that are also approved to treat chronic or long-term conditions. DTC advertising has been less common for drugs that address acute conditions  perhaps because individuals are more likely to seek care for an acute condition or because such drugs are typically prescribed for a short time, according to the report. 

Although pharmaceutical manufacturers use DTC advertising only for a small group of drugs, they spend a lot on that advertising. The 10 drugs in the CBO’s dataset with the highest DTC expenditures in 2008 accounted for 30% of DTC advertising expenditures industry wide. In contrast, the drugs with the highest expenditures on detailing totaled 16% of the industry’s detailing expenditures.

When pharmaceutical manufacturers promoted drugs to consumers, they also spent more, on average, promoting those drugs to physicians, according to the CBO’s analysis. For drugs with reported spending on DTC advertising, manufacturers spent an average of $40.5 million per drug in 2008 on promotional activities directed to physicians, which is 14 times the average amount they spent when promoting drugs exclusively to physicians. The difference may indicate that manufacturers use promotional activities directed to physicians and DTC advertising to reinforce each other.

The efficacy of drug advertising remains a subject of debate. Studies that analysed the effects of DTC advertising for various drugs or classes of drugs have shown mixed results, according to the report. The writing and filling of prescriptions increased for some advertised drugs, but not for others. Similarly, some analyses of detailing found positive effects on the number of prescriptions written for the targeted drugs, but others suggest that the effects of detailing are unclear.

The Congressional Budget Office (CBO) has released a report titled Promotional Spending for Prescription Drugsthat analyses the pharmaceutical industry?s advertising strategies.

Report examines spending on drug advertising

The US Pharmacopeial Convention (USP) has posted a 

 for what should and should not appear on the ferrules and cap overseals of medication vials. The revision, which is designed to prevent medication errors, states that these areas must not contain any markings except those intended to prevent an imminent life-threatening situation. If the revision were accepted, nurses, physicians and pharmacists would be expected to know that such warnings must be observed and acted upon before administering a drug to a patient. 

USP previously adopted and postponed a similar revision, but the new revision clarifies its intent. The revised standard explains why labeling on ferrules and cap overseals is limited to the warnings necessary to prevent imminent life-threatening situations and provides examples of warnings (e.g., “Warning: Paralyzing Agent” or “Dilute Before Using”). To ensure that the warnings are heeded, the proposed standard requires that they be printed in a contrasting color and be clearly visible under ordinary conditions of use. 

The revised standard also contains other requirements, including restricting the location of important, but less urgent information (e.g., lot numbers, product names, company names, and logos) to other parts of the vial. If no urgent warning is necessary, the top surface must remain blank to ensure that urgent warnings on other injectable medications are readily noticed.USP carefully reviewed the current standard and consulted with medical, nursing, and pharmacy practitioners; the pharmaceutical industry; and US Food and Drug Administration officials and representatives before it drafted the proposed revision. Industry representatives suggested liberal rules for labeling, but a USP standards-setting expert committee concluded that additional messages would distract practitioners from critical safety messages. 

The proposed standard will be published in USP’s 

 in January 2010 for a 90-day public comment period. The posting on the USP website is intended to allow stakeholders additional time to review the proposal and provide  comments, which will be accepted through April 15, 2010. 

The US Pharmacopeial Convention (USP) has posted a proposed revised standard for what should and should not appear on the ferrules and cap overseals of medication vials.

USP revises standard to prevent medication errors

The FDA is using prescription data from Wolters Kluwer Pharma Solutions to track the treatment of influenza A (H1N1) and other influenza viruses. Wolters Kluwer, a market research firm, is providing the agency with weekly updates so that the latter can track groups of patients throughout the US who are being treated with the four most popular oral antiviral prescriptions.

The data show agency officials where prescriptions for oral antivirals are being filled and help the FDA identify areas of high concentrations of antiviral use. The information sorts oral antiviral use by location and provides the FDA with demographic information about patients.

"The FDA is using our prescription data as a means of tracking the treatment of populations affected by flu outbreaks, including the H1N1 virus, and the specific medications being used to treat them," said Mark Spiers, President and CEO of Wolters Kluwer Pharma Solutions, in a 

. "The data are typically not more than 5 days old upon delivery. This near real-time picture provides the FDA an ability to act quickly in the event of a public-health crisis."

Wolters Kluwer's updates provide details about the four antivirals and permit the agency to track use nationally, regionally and by state. The data also reveal antiviral use at core-based statistical area and combined statistical area levels.

The FDA contracted Wolters Kluwer to provide 2 years of prescribing data for each drug to help the agency evaluate historical norms of use and identify spikes in prescriptions. The weekly flu tracking began in early September 2009 and will continue for at least 1 year, according to the company.

"We’ve already been successful at identifying clusters of antiviral prescriptions in various geographic pockets," said Joe Markmann, the company’s director for healthcare policy, in the press release. "One of them recently shows clear spikes within regions of Alabama, a finding that reflects what the Centers for Disease Control and Prevention (CDC) is reporting and further reinforces the reliability of the data.”

The CDC recommends that all people with suspected or confirmed influenza who require hospitalization be treated with oseltamivir or zanamivir. Roche (Switzerland) sells oseltamivir under the trade name Tamiflu, and GlaxoSmithKline (UK) sells zanamivir under the trade name Relenza. Rimantadine and amantadine are also used to treat influenza A, but currently circulating influenza A viruses resist these drugs, according to the CDC.

The FDA is using prescription data from Wolters Kluwer Pharma Solutions to track the treatment of influenza A (H1N1) and other influenza viruses.

FDA tracks influenza A treatment with prescription data

 for industry about Risk Evaluation and Mitigation Strategies (REMS). “With this new guidance, manufacturers will have a useful blueprint for how to develop these important safety strategies,” said Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, in a press release.

The document describes the format and content of a proposed REMS, including supporting documentation, the content of assessments and proposed modifications of an approved REMS, which identifiers should be used on REMS documents, and how to communicate with the FDA about a REMS. The guidance also provides an example of what an approved REMS might look like.

According to the draft guidance, a proposed REMS submission to the FDA should include a proposed REMS, which concisely describes the proposed goals and elements of the REMS, and a REMS supporting document that provides additional information such as a thorough explanation of the rationale for, and supporting information about, the content of the proposed REMS. All proposed materials that are included in the REMS (e.g., proposed communication and education materials, Medication Guide, elements to assure safe use, patient package insert, enrollment forms, and prescriber and patient agreements) should be appended to the proposed REMS. A 

 for the proposed REMS is available on FDA’s website.

The REMS supporting document should thoroughly explain the rationale for and supporting information about the content of the proposed REMS, according to the draft guidance. The REMS supporting document should describe how and when each REMS element will be implemented and specify the rationale for the timelines and milestones. If any REMS activity will not be implemented at the time of REMS approval, the REMS supporting document should describe the reason for the implementation schedule. “For example, the document should address the rationale for whether a communication plan would be implemented before, or concurrently with, other elements,” the draft guidance says. A 

template for the REMS supporting document

In addition, the draft guidance describes REMS policies for certain regulatory situations. The draft lists FDA websites where documents about approved REMS will be posted.

The FDA Amendments Act of 2007 granted FDA the authority to require the submission and implementation of a REMS if the agency determines that it is necessary to ensure that a drug’s benefits outweigh its risks. Future draft guidance will address additional REMS topics. 

The FDA has published its first draft guidance for industry about Risk Evaluation and Mitigation Strategies (REMS).

FDA guidance offers blueprint for safety strategies

Eli Lilly and Co. is undergoing a company-wide reorganization intended to accelerate the progress of the company’s pipeline. As part of the reorganization, Lilly will establish a Development Center of Excellence to speed the launch of important molecules during the next decade and bring medicines to patients sooner. The center will use a common operating system and a common set of priorities to streamline and accelerate the late-stage development of new medicines.

Tim Garnett and Tom Verhoeven will lead the Development Center of Excellence within Lilly Research Laboratories. Garnett will be responsible for medical affairs, regulatory affairs, global product safety, translational medicine, and global health outcomes. Verhoeven will oversee the clinical-development organization, product research and development, toxicology, and project management.

In addition, Lilly will reorganize the company around five global business units, including oncology, diabetes, established markets (which encompasses neuroscience, osteoporosis, and cardiovascular health), emerging markets, and Elanco animal health. The reorganization represents a shift from a functionally oriented structure to a business-unit structure.

John H. Johnson, currently the Chief Executive Officer of ImClone Systems, a wholly-owned subsidiary of Lilly, will lead the oncology business unit. Enrique A. Conterno, President of Lilly USA, will lead the diabetes business unit. Bryce D. Carmine, Lilly’s Executive Vice President of global marketing and sales, will lead the established-markets business unit. Jacques Tapiero, Lilly’s President of the intercontinental region, will lead the emerging-markets business unit. Jeffrey N. Simmons will continue to lead Elanco, the animal-health business unit. The leadership appointments will become effective on 1 November 2009.

Lilly’s reorganization includes a plan to cut $1 billion in costs by the end of 2011. The company will accomplish this goal in part by eliminating 5500 jobs. At the end of 2008, Lilly employed 40,500, but the company plans to reduce its headcount to 35,000 by the end of 2011. Strategic sales additions in high-growth emerging markets and Japan will be exempt from the reduction.

“While our structure and approach served us well in the past, we must take measures now that will make us leaner, more focused, more customer-oriented, and more competitive,” said John C. Lechleiter, Lilly’s Chairman and Chief Executive Officer, in a press release. “The changes we’re making will simplify our organization, clarify accountability and authority, and speed decision making.”

In his statement, Lechleiter cited patent expirations for key products as reasons for the reorganization. The patent for Zyprexa, Lilly’s best-selling drug, will expire in 2011. Zyprexa earned $4.7 billion in sales in 2008, which was 23% of the company’s revenue. Likewise, Cymbalta earned $2.7 billion in sales in 2008 and faces patent expiration in the next few years. Lechleiter observed that the reorganization had also been prompted by challenges that the global pharmaceutical industry is facing such as slowing innovation, rising costs, healthcare reform, and increased generic competition.

Lilly plans to have its new organizational structure in place by 1 January 2010. The company will offer further details of the changes taking place at its annual investment community day in New York (US) on 10 December 2009.

Eli Lilly and Co. is undergoing a companywide reorganization intended to accelerate the progress of the company?s pipeline.