Amy Ritter was Scientific Editor, BioPharm International.

Amy Ritter, PhD

 that the US pharmaceutical company Merck & Co. has agreed to pay $950 million to resolve criminal charges and civil claims related to its promotion and marketing of the painkiller Vioxx.

The criminal charges relate to off-label marketing of Vioxx. Under the agreement, Merck will plead guilty to a misdemeanor for its illegal promotional activity and will pay a $321,636,000 criminal fine. Vioxx was approved for three indications in 1999, but not approved for use in rheumatoid arthritis patients until 2002. However, Merck marketed the painkiller for use in rheumatoid arthritis patients between 1999 and 2002 and received a Warning Letter from FDA in November 2001, for the practice.

Merck has also agreed to a civil settlement under which it will pay $628,364,000 to resolve additional allegations regarding off-label marketing of Vioxx and false statements about the drug’s cardiovascular safety. The settlement resolves allegations that Merck representatives made inaccurate, unsupported, or misleading statements about Vioxx’s cardiovascular safety in order to increase sales of the drug, resulting in payments by the federal government. According to a 

 from Merck, as a result of the settlement, the US and the participating states have released Merck from civil liability related to the government’s allegations regarding the sale and marketing of Vioxx in the US, They also state that the civil settlement does not constitute any admission by Merck of any liability or wrongdoing. However, previously disclosed litigation with seven states remains outstanding.

Finally, as part of the settlement, Merck has also agreed to enter into an expansive corporate integrity agreement with the Office of Inspector General of the Department of Health and Human Services (HHS-OIG), which will strengthen the system of reviews and oversight procedures imposed on the company. Although Vioxx was voluntarily withdrawn from the market in 2004, this ongoing monitoring of Merck’s conduct is aimed to deter and detect similar conduct in the future.

Bruce N. Kuhlik, executive vice-president and general counsel of Merck, said in the company press release, “Merck recognizes the importance of robust compliance programs and is committed to adhering to the law and to our fundamental values and standards. We believe that the settlement of this lengthy investigation is in the best interests of our stakeholders, and we look forward to focusing on our mission to save and improve lives around the world.”

GlaxoSmithKline Agrees in Principle to $3-Billion Settlement with the US Government

AstraZeneca Fined $520 Million for Off-Label Marketing

Articles

The justice department announced that Merck has agreed to pay $950 million to resolve criminal charges and civil claims related to its promotion and marketing of the painkiller Vioxx.

Merck Resolves Claims Related to Vioxx for $950 Million

 that would increase penalties for those convicted of trafficking in counterfeit drugs was introduced in the House of Representatives. The Counterfeit Drug Penalty Enhancement Act of 2011, cosponsored by Senators Patrick Leahy (D-VT), Chuck Grassley (R-IA), Michael Bennet (D-CO), and Richard Blumenthal (D-CT) and Representatives Patrick Meehan (R-PA) and Linda Sánchez (D-CA), would set maximum fines of $4 million for an individual and $10 million for a “person other than an individual,” and a maximum jail sentence of life imprisonment for an individual convicted of counterfeit drug trafficking.

Under current law, no distinction is made between counterfeit drugs and other counterfeit consumer items, such as clothing or electronics. The amendment is intended to address the severity of the crime and the potential for harm to the public. “These drugs present a serious threat to the health and safety of people around the world. It’s important we address this threat by imposing harsher penalties on criminals who counterfeit these medicines,” said Senator Grassley in a 

 in support of the bill. The company has confirmed counterfeit versions of more than 50 of its medicines in at least 101 countries, according to the statement. Pfizer supports the tougher penalties, saying that they will afford patients greater safety. The proposed legislation “demonstrates that the US is prepared to lead in ensuring safety of the global drugs supply—both by putting a very tough anticounterfeiting law into effect in the world’s largest drugs market and by encouraging partner nations to put similar laws into effect,” according to the statement.

On Nov. 17, 2011, a bill that would increase penalties for those convicted of trafficking in counterfeit drugs was introduced in the House of Representatives. The Counterfeit Drug Penalty Enhancement Act of 2011, cosponsored by four US Senators and two US Representatives.

House Bill Would Stiffen Penalties for Drug Counterfeiters

AstraZeneca, Bayer, Sanofi, Tibotec, TB Alliance, and the World Health Organization agreed to share information on tuberculosis (TB) compounds within their respective drug pipelines, according to the Critical Path to TB Drug Regimens (CPTR). The purpose of the agreement is to promote information sharing around scientific and clinical studies so that partners can identify opportunities to test compounds in combination. Under the agreement, if two or more organizations choose to work together to further develop a regimen, they will enter into a separate arrangement that defines the rights and responsibilities of each party.

“Today’s announcement will accelerate efforts to simplify and improve TB drug regimens,” said Mel Spingleman, president and CEO of TB Alliance, in a 

. “It is critical that we decrease the complexity and duration of treatment, make the treatment of multidrug-resistant TB significantly easier and more tolerable, and make new regimens available to all those who need them as quickly as possible.”

CPTR is working closely with regulatory scientists at FDA, EMA, and other regulatory bodies in China, India, and African countries to develop the tools that will allow testing of new TB drugs in combination. The group’s goal is to shorten the development timeline. Under the leadership of the Critical Path Institute, CPTR’s Regulatory Science Consortium focuses on establishing consensus about preferred standards, methods, and tools for developing new TB drug regimens, and on obtaining official acceptance from international regulatory authorities. CPTR was cofounded by the Bill & Melinda Gates Foundation, the Critical Path Institute, and the TB Alliance with the purpose of fostering collaboration to reduce the time it takes to develop novel TB drug regimens, regardless of sponsor.

AstraZeneca, Bayer, Sanofi, Tibotec, TB Alliance, and the World Health Organization agreed to share information on tuberculosis compounds within their respective drug pipelines, according to the Critical Path to TB Drug Regimens. The purpose of the agreement is to promote information sharing around scientific and clinical studies so that partners can identify opportunities to test compounds in combination.

Alliance Between Pharma and Nonprofits to Speed Development of Tuberculosis Therapies

In response to the increase in drug shortages over the past three years, President Obama issued an 

 on Oct. 31, 2011 that directs FDA to take the following steps to prevent and reduce drug shortages:

Require manufacturers to provide advance notice of manufacturing discontinuities that are likely to lead to shortages

Provide expedited regulatory review of new drug suppliers, manufacturing sites, and manufacturing changes, whenever it determines that expedited review would help to avoid or mitigate existing or potential drug shortages

Report to the Department of Justice any suspected stockpiling of drugs or the sale of drugs in short supply at exorbitant prices by distributors.

FDA sees the requirement for advance notice as crucial to managing shortages, and such notice has been instrumental in averting at least 99 drug shortages, according to the agency. Many drugs in short supply are generics, and the Generic Pharmaceutical Association issued a 

 affirming its commitment to working with FDA to alleviate the problem. “Generic manufacturers have pledged to work with the FDA and healthcare providers to formalize the process for not only manufacturers, but also others in the supply chain, to proactively report drug shortages to the FDA’s drug shortage staff, as many now do voluntarily,” according to the press release.

The Pharmaceutical Research and Manufacturers of America also issued a 

 in support of the executive order, stating “America’s innovative biopharmaceutical companies have long worked to prevent drug shortages in advance, and will continue to work closely with the FDA to prevent manufacturing disruptions.” The organization also stated, “While the majority of drug shortages involve generic drugs, with FDA specifically referring to an increase in shortages among ‘older sterile injectable drugs,’ this problem concerns us all and requires our combined attention.”

, the executive order is one in a series of steps that will help address the shortage of prescription drugs and ensure patients have access to the medicines they need. The Obama Administration also took the following steps:

 to drug manufacturers, reminding them of their legal responsibility to report the discontinuation of certain drugs to FDA. The letter also encourages companies to voluntarily notify FDA about potential prescription-drug shortages when notification is not currently required.

Increased staffing resources for FDA's Drug Shortages Program to address the increased workload that will result from additional early notification of potential shortages by manufacturers.

 from the Department of Health and Human Services, Office of the Assistant Secretary for Planning and Evaluation (ASPE) that assesses the underlying factors that lead to drug shortages. The administration also released an 

 on the agency’s role in monitoring, preventing, and responding to these shortages.

In response to the increase in drug shortages over the past three years, President Obama issued an executive order on Oct. 31, 2011 that directs FDA to take several steps to prevent and reduce drug shortages.

President Obama Issues Executive Order to Reduce Drug Shortages

Merck, Sharpe, and Dohme (MSD) and Singapore’s Economic Development Board jointly 

 plans for significant investments by MSD to improve its existing manufacturing facilities in Singapore, as well as for new manufacturing, marketing, and research activities. MSD plans to invest more than $250 million over the next 10 years. The investments will go towards site improvements at its existing facilities in Tuas, expansion of its biotech operations, and addition of technology capabilities to support new product launches. In addition, MSD will commit to new expenditures of $700 million for local research activities.

In a press release, Dr. Beh Swan Gin, managing director of the Economic Development Board said, “We are encouraged that this will pave the way for Singapore to continue to enhance our capabilities as an integrated global pharmaceutical site in Asia, across manufacturing, R&D and commercial operations.” 

MSD has a significant presence in Singapore, with approximately 1500 employees in manufacturing, marketing, sales, and the Translational Medicines Research Center. The total value of MSD’s investments in the area is estimated to be $1.5 billion.

GSK and Singapore Partner in Green Manufacturing

Merck, Sharpe, and Dohme (MSD) and Singapore's Economic Development Board jointly announced plans for significant investments by MSD to improve its existing manufacturing facilities in Singapore, as well as for new manufacturing, marketing, and research activities.

Merck, Sharpe, and Dohme Announces New Investments in Singapore

At the request of the US Senate Subcommittee on Federal Financial Management, Government Information, Federal Services, and International Security, the Government Accountability Office (GAO) conducted an 

 into doctor shopping in Medicare Part D. Doctor shopping is the practice in which individuals solicit prescriptions for drugs of abuse from multiple doctors and fill them at multiple pharmacies. The report is a follow-up to a 2009 

 on doctor shopping within the Medicaid program, in which GAO found that doctor shopping resulted in costs of $63 million to the Medicaid program. Because of its size and complexity, Medicare Part D is vulnerable to fraud and abuse. GAO was asked to determine the extent to which Medicare beneficiaries obtained frequently abused drugs from multiple prescribers, identify examples of doctor shopping activity, and determine the actions taken by the Centers for Medicare and Medicaid Services (CMS) to limit access to drugs for known abusers.

GAO looked at claims for 14 commonly abused classes of drugs from the approximately 1 billion Medicare Part D paid claims for the 2008 calendar year. From this subset of claims they determined the number of beneficiaries who saw at least five different doctors for the same class of drugs. They found that 170,000 individuals, or around 1.8% of Medicare Part D beneficiaries that received prescriptions for those classes of drugs saw at least five different doctors. GAO estimates the cost of this activity to be about $148 million (about 5% of the total cost for these drugs).

In its analysis, GAO found that most of the Medicare beneficiaries that obtained drugs from five or more doctors were eligible for Medicare Part D because of a disability. They also found that, of the 14 classes of drug examined, oxycodone and hydrocodone were by far the most frequently obtained drugs, making up 80% of the instances of potential doctor shopping. The report also contains specific examples of individuals engaging in doctor shopping; for instance, over the course of a year, one beneficiary received prescriptions for a total of 3,655 oxycodone pills from 58 practicioners, and filled prescriptions at 45 pharmacies.

According to the report, CMS has systems in place to identify individuals with doctor shopping behavior; however, according to CMS policy officials, federal law may not authorize them to restrict these individuals’ access to drugs, including highly abused drugs, such as hydrocodone and oxycodone. To curb the practice, GAO recommended a restricted recipient program, a practice already in place within Medicaid and some private sector plans. Under such a program, suspected doctor shoppers would be limited to one prescriber, one pharmacy, or both for receiving prescriptions. GAO also recommended that CMS consider facilitating the sharing of information on identified doctor shoppers among the Part D drug plan sponsors so that those beneficiaries cannot circumvent the program by switching prescription drug plans.

At the request of the US Senate Subcommittee on Federal Financial Management, Government Information, Federal Services, and International Security, the Government Accountability Office conducted an investigation into doctor shopping in Medicare Part D.