Stephanie Sutton was an assistant editor at Pharmaceutical Technology Europe.

Stephanie Sutton

GlaxoSmithKline has responded to a recently aired 

 program about the whistleblower lawsuit that resulted in GSK paying $750 million to settle civil and criminal charges. GSK was accused of manufacturing and selling adulterated drug products to Medicaid and other government health plans. The products were manufactured at the company’s Cidra plant in Puerto Rico, which was closed in 2009 due to declining demand. The plant is no longer owned by GSK. 

The 60 Minutes program interviewed Cheryl Eckard, a former GSK Quality Assurance Manager about the violations at the Cidra facility, which was GSK’s top facility in 2002, making more than 20 products worth $5.5 billion annually, including Avandia and Paxil.

 from Getnick & Getnick law firm, Eckard learned of “serious and systemic violations of manufacturing standards” at the Cidra factory in 2002 and urged managers to take action. "All the systems were broken, the facility was broken, the equipment was broken, the processes were broken. It was the worst thing I had run across in my career," said Eckhard on the 60 Minutes program.

Eckhard claimed that no action was taken and then in 2003 she was made redundant. She filed the whistleblower suit in February 2004 and the FDA subsequently seized all stocks of Avandamet and Paxil CR manufactured at Cidra — the largest seizure in FDA history. The FDA also placed the Cidra plant under a Consent Decree, requiring that all products released to the market be approved by an independent monitor.

The 60 Minutes program provides a rare, detailed look at a whistleblower case, but is also a harsh blow to GSK’s reputation, with claims being made that some medicines may have been contaminated with bacteria or mislabeled, while others may have been too strong or not strong enough. Additionally, claims were made that GSK tried to cover up the problems after a pharmacist called to report a mix up with an antidepressant medicine. 

“They [GSK] filed a report with the FDA that said that the mix-up was not real. And did not happen at the factory,” said Eckhard. “We all knew, they all knew it was real."

In its response to the program, GSK says that it regrets the manufacturing issues at the Cidra facility and “strongly disagrees with 60 Minutes’ implication that patients suffered harm as a result”. GSK also emphasized that the issues outlined in the 60 Minutes story occurred between 2001 and early 2005 and related to one manufacturing facility. “GSK had been working with the FDA to improve the plant’s performance as early as 2001, before Cheryl Eckard was sent in 2002 as part of the team to address issues cited by the FDA,” said a 

GSK also rejected claims made by Eckard in the 60 Minutes interview that she was terminated for bringing the manufacturing problems to light. “The company strongly rejects any claim of retaliation for whistle-blowing. In fact, employees are encouraged to report any concerns that they may have to management or through a confidential compliance hotline. Issues raised are investigated, and company policy prohibits any retaliation against employees.”

The company added: “The FDA; the US Department of Justice; and Neil Getnick, Cheryl Eckard’s attorney, all stated that there was no indication that patients were harmed as a result of the production issues.”

Under the agreement reached in October 2010, GSK agreed to pay a criminal fine of $150 million and an additional $600 million to the federal government and states to resolve the claims. As part of the resolution, Eckard was to receive approximately $96 million from the federal share of the settlement amount, according to a statement from the US Department of Justice. 

“This settlement resolves a significant and long-standing legal issue facing the company,” said PD Villarreal, GSK’s senior vice president and head of global litigation, in a 

 issued by GSK in October. "We regret that we operated the Cidra facility in a manner that was inconsistent with current Good Manufacturing Practice (cGMP) requirements and with GSK's commitment to manufacturing quality. GSK worked hard to resolve fully the manufacturing issues at the Cidra facility prior to its closure in 2009, and we are committed to continuous improvement in our manufacturing processes. Our commitment to compliance with cGMP is demonstrated by the fact that we have not received an FDA warning letter at any plant since the Cidra facility was cited in July 2002.”

Articles

GlaxoSmithKline has responded to a recently aired 60 Minutes program about the whistleblower lawsuit that resulted in GSK paying $750 million to settle civil and criminal charges.

GSK Whistleblower Case Gets TV Airing

Looking to 2011, the European Medicines Agency (EMA) has adopted its work program and budget for the year, as well as a new Road Map to 2015. The agency expects a similar number of marketing authorizations this year compared with last, with 43% of those attributable to generics and 41% to new medicines.

, the work program forecasts a stable number of applications for marketing authorizations for human medicines in 2011, with 97 applications expected in total, compared with 95 in 2010. Of these, 40 are expected to be for new medicines, 12 for orphan medicines and 42 for generic applications. The budget for 2011 is 208.9 million Euros, representing an increase of 0.23% compared with 2010, and includes fee revenue of 161 million Euros and an EU contribution of 33.5 million Euros, down from 39.1 Euros in 2010. The special orphan medicines fund given by the EU has also been slashed from 8.2 million Euros to 4.9 million Euros.

The EMA’s management board has also adopted its new 

, which builds on the success of the first road map for 2005 to 2010. The final road map, due to be published later this month, focuses on delivery of the EMA’s core business, as well as three priority areas for future actions to strengthen the EMA’s role in addressing public health needs, facilitating access to medicines an optimizing safe use of medicines. The adoption follows public consultation from the first half of 2010 and takes into account responses from more than 70 stakeholders.

The EMA will face 2011 without Thomas Lönngren, who ended his 10-year mandate as Executive Director of the EMA on 31 December 2010.

Looking to 2011, the European Medicines Agency (EMA) has adopted its work program and budget for the year, as well as a new Road Map to 2015.

EMA prepares for 2011

Following two cases of fatal liver injury, Pfizer has voluntarily withdrawn Thelin from the worldwide market and discontinued all ongoing trials. The drug had been approved in the EU, Canada and Australia for the treatment of pulmonary arterial hypertension (PAH). 

The withdrawal was based on a review of emerging safety information from clinical trials and post-marketing reports. Thelin belongs to a class of drugs of which liver toxicity is a known complication. As such, the treatment has been contraindicated in patients with mild to severe hepatic impairment and elevated aminotransferases prior to initiation of treatment. In a 

, however, Pfizer said: “Given the availability of alternate treatments, Pfizer has concluded that the overall benefit of Thelin no longer outweighs the risk in the general population of PAH patients.”

The company has recommended that no new patients be prescribed Thelin and that current patients be transitioned to alternate therapies as soon as safely possible. In a 

, the EMA also added that patients currently taking Thelin are advised not to stop the treatment and to consult their physician to review their treatment at their next scheduled appointment. 

Pfizer acquired Thelin after buying Encysive Pharmaceuticals in 2008. The treatment has been authorized for use in the EU in 2006. On the other side of the Atlantic, however, the FDA has refused to approve the drug on three different occasions because of safety concerns. Pfizer had been trying to alleviate these with new clinical studies, which have now been discontinued.  

Following two cases of fatal liver injury, Pfizer has voluntarily withdrawn Thelin from the worldwide market and discontinued all ongoing trials.

Pfizer's Thelin Withdrawn Due To Fatalities

 released by the EMA regarding the evaluation of marketing authorization (MA) applications show a significant decline in the number of approved products for 2010 — only 38 positive opinions have been issued as of October 2010 compared with 117 in 2009. The number of negative opinions is also low, with just two issued so far this year compared with 8 in 2009. 

All in all, it seems that there has been a significant decline in both started and finalised MA applications as a whole, reflecting drying industry pipelines. In 2009, the EMA started and finalized 95 and 125 MA applications respectively, compared with only 75 and 41 in 2010. The 2010 figures span January–October 2010 so obviously there’s still time for them to increase, but it seems highly unlikely that they will match those of 2009. 

Despite views that pharma innovation and productivity has been lagging for some time, the figures show that MA applications to the EMA have actually been increasing, or at least remaining relatively stable, over the past few years. In 2007, the EMA started and finalised 90 and 65 MA applications respectively, and this increased in 2008 to 103 and 72 applications. In 2009, there was a slight decline in started MA applications (down to 84), but a major increase in finalized applications (114). 2009 also saw a huge increase in the number of generic MA applications (38 started; 51 finalised).

For 2010, the decline in MA applications stretches across both new products and generics, and is particularly marked in finalized applications. Only 18 applications were finalized for new products (down from 49 in 2009) while generics applications dropped to 15. 

The EMA has said that it will provide monthly updates on its website concerning the volume and evaluation of MA and post-authorization applications. However, we’ll probably have to wait until early next year before we know exactly what the full picture is for 2010. The EMA has also said that it will also provide commentaries and analysis of the figures in its own annual report. 

Figures released by the EMA regarding the evaluation of marketing authorization (MA) applications show a significant decline in the number of approved products for 2010 &#151; only 38 positive opinions have been issued as of October 2010 compared with 117 in 2009.

A Bad Year For Pharma R&D

 released by the European Medicines Agency (EMA) regarding the evaluation of marketing-authorization (MA) applications show a significant decline in the number of approved products for 2010. Only 38 positive opinions were issued as of October 2010, compared with 117 in 2009. The number of negative opinions is also low, with just two issued so far this year compared with eight in 2009. 

All in all, the number of started and finalized MA applications has declined significantly, reflecting drying industry pipelines. In 2009,  EMA started and finalized 95 and 125 MA applications, respectively, compared with only 75 and 41 in 2010. The 2010 figures span the period from January through October 2010. The figures may yet  increase, but it seems unlikely that they will match those of 2009. 

Despite views that pharmaceutical innovation and productivity have been lagging for some time, the figures show that MA applications to  EMA have actually been increasing, or at least remaining relatively stable, over the past few years. In 2007,  EMA started and finalized 90 and 65 MA applications, respectively, and these numbers increased in 2008 to 103 and 72 applications. In 2009, there was a slight decline in started MA applications (down to 84), but a major increase in finalized applications (114). Also in 2009, there was  a huge increase in the number of generic MA applications (38 started and 51 finalized).

For 2010, the decline in MA applications encompasses both new products and generics and is particularly marked in finalized applications. Only 18 applications were finalized for new products (down from 49 in 2009) while generics applications dropped to 15. 

The EMA has said that it will provide monthly updates on its website concerning the volume and evaluation of MA and post-authorization applications. The full picture  for 2010 will not be clear until early next year, however.  EMA also said that it will provide commentaries and analyses of the figures in its own annual report.

Figures released by the European Medicines Agency regarding the evaluation of marketing authorization (MA) applications show a significant decline in the number of approved products for 2010.

A Bad Year for Pharmaceutical R&D

Following two cases of fatal liver injury, Pfizer has voluntarily withdrawn Thelin (sitaxentan) from the worldwide market and discontinued all ongoing trials. The drug had been approved in the European Union (EU) , Canada, and Australia for the treatment of pulmonary arterial hypertension (PAH). 

The withdrawal was based on a review of emerging safety information from clinical trials and post-marketing reports. Thelin belongs to class of drugs of which liver toxicity is a known complication. As such, the treatment has been contra-indicated in patients with mild to severe hepatic impairment and elevated aminotransferases prior to initiation of treatment. In a 

, however, Pfizer said, “Given the availability of alternate treatments, Pfizer has concluded that the overall benefit of Thelin no longer outweighs the risk in the general population of PAH patients.”

,  EMA also added that patients currently taking Thelin are advised not to stop the treatment and to consult their physician to review their treatment at their next scheduled appointment. 

Pfizer acquired Thelin after buying Encysive Pharmaceuticals (Houston, TX) in 2008. The treatment was authorized for use in the EU in 2006. On the other side of the Atlantic, however, the US Food and Drug Administration  refused to approve the drug on three different occasions because of safety concerns. Pfizer had been trying to alleviate these with new clinical studies, which have now been discontinued. 
