Amy Ritter was Scientific Editor, BioPharm International.

Amy Ritter, PhD

FDA and Genentech, a member of the Roche Group, have issued warnings about counterfeit versions of the injectable cancer drug, Avastin, circulating in the US. According to the FDA 

,  the counterfeit version of Avastin does not contain the medicine’s active ingredient, bevacizumab, which may have resulted in patients not receiving needed therapy. FDA issued letters to 19 medical practices that purchased unapproved cancer medications from Quality Specialty Products (QSP), a foreign supplier that may also be known as Montana Health Care Solutions. Volunteer Distribution in Gainesboro, Tennessee is a distributor of QSP’s products.

, Genentech provides information that can be used to differentiate real product from counterfeit. Genentech says that all cartons and vials approved for use in the US have “Genentech” or “Genentech, a member of the Roche Group” printed on the labels, the lot number on the carton and vial should be 6 digits with no letters, the expiry date is formatted as a 3-letter month and 4-digit year, the date of manufacture is not printed on the carton or vial, and all the text on the vial labels, cartons, and package inserts is English. Genentech adds, “Patient safety is Roche and Genentech’s primary concern. We are working with the U.S. Food and Drug Administration (FDA) and law enforcement to aid their evaluations, determine the source of the counterfeit drug, and prevent its further distribution.”

 to health care providers about the risks of purchasing unapproved injectable cancer medications from unlicensed sources. The impetus for the notice was the 

 of some injectable cancer drugs that might prompt health care providers to shop unapproved sources to obtain necessary drugs. FDA said in its notice that it may authorize limited importation of a drug in short supply, but that such medications would distributed in the US through a controlled network, and would not be available to practitioners through direct-to-clinic solicitations.

		In this case, FDA says that none of the unapproved cancer medications purchased from Volunteer Distribution are in shortage in the US. Nor have other products including Faslodex (fulvestrant), Neupogen (filgrastim), Rituxan (rituximab), and Herceptin (trastuzumab) available from unapproved suppliers been in short supply. The identification of a counterfeit cancer drug (probably purchased at a less-than-retail price) underscores the old saying that if it seems too good to be true, it probably isn’t.

Articles

FDA and Genentech, a member of the Roche Group, have issued warnings about counterfeit versions of the injectable cancer drug, Avastin, circulating in the US. According to the FDA safety alert, the counterfeit version of Avastin does not contain the medicine’s active ingredient, bevacizumab, which may have resulted in patients not receiving needed therapy.

FDA and Roche Warn of Counterfeit Avastin

GlaxoSmithKline (GSK) released its fourth quarter and full year 2011 earnings 

 on Feb. 7, 2012. In the report, the company tracks its R&D performance, and calculated the return on R&D to be 12%, up from 11% in 2010, and closing in on the company’s goal of a 14% return.

In 2008, GSK reorganized its basic research effort to make it more focused and more competitive, mimicking the environment in the biotechnology industry. At that time, GSK created Discovery Performance Units (DPUs) within its Centers of Excellence for Drug Discovery. These units are small, comprising between 5–70 scientists, with each group focusing on one particular disease or pathway. Funding for the groups is competitive, with reviews every three years by a panel containing senior GSK R&D leaders and individuals from outside of the company operating in venture-capital, biotechnology, or pharmaceutical investment. The panel allocates funding according to assessments of potential returns on investment, scientific quality, and opportunity.

This year marks the first of the three-year review cycles for the DPUs. According to the earnings report, four new DPUs have been created and three have been closed. Of the remaining DPUs, six have received increased investment, and five have had investment decreased. Information about exactly which DPUs were affected was not included in the report. More information on the DPUs will be provided in an in-depth meeting for investors and analysts on Mar. 29, 2012.

GlaxoSmithKline released its fourth quarter and full year 2011 earnings report, which showed its return on R&D to be 12%-up from 11% in 2010, and closing in on the company's goal of a 14% return.

GlaxoSmithKline Tracks R&D Performance

 released on Feb. 8, 2012 from the California Healthcare Institute, BayBio and PwC shows that the shrinking economy, changes in investment strategies, and pressures on the pharmaceutical market have put the brakes on one of the US’s most robust biotechnology centers. California had enjoyed steady growth in its biotech sector for the past two decades, and according to the report, is the source of 28% of the country’s biomedical pipeline. More recently, as with the rest of the world, the slowdown in the global economy has taken its toll on this area. The industry lost approximately 6,300 jobs, or about 2.3% of its life-sciences workforce since 2008, returning employment levels to those seen in 2006.

		The report defines the biomedical sector as consisting of basic research, biopharmaceuticals, diagnostics, medical technology, research tools, laboratory services, and wholesale trade companies. When broken down by area, the employment news is not uniformly bad. Most of the job losses were from academia and from the device industry, and were partially offset by gains in the biopharmaceutical sector. CEOs within the industry were surveyed as to the reasons for reducing their company’s operations within the state. The top three reasons given were cost cutting, the overall business climate, and expanding new operations outside of California. Most CEOs were optimistic about the future, the majority indicating that they expected to either hold steady or increase operations inside and outside of California.

		The investment climate has been affected by the economic slowdown, which in turn, affects the operations of companies in California. According to the report, more than 74% of respondents said that their company had delayed a research or development project in the past year, up from 69% in 2010. The overriding reason, at just over 40% of respondents, was cited as “funding not available.” In an accompanying 

, Tracy Lefteroff, national life sciences partner at PwC US offers this analysis. He says, “The life cycle of biomedical startup companies has changed as challenges to raising capital have increased. Whereas their greatest challenge in years past was in validating the science, these companies now need to validate getting funding by lowering costs and improving returns. The strength of California’s life sciences industry remains closely tied to the level of confidence that the investment community has in the industry’s ability to develop innovative products while effectively managing the challenges associated with clinical and regulatory risk.”

A report released on Feb. 8, 2012 from the California Healthcare Institute, BayBio and PwC shows that the shrinking economy, changes in investment strategies, and pressures on the pharmaceutical market have put the brakes on one of the US’s most robust biotechnology centers.

Shrinking Economy Hits California Biotech Sector

The Pharmaceutical Research and Manufacturers of America (PhRMA) announced that it will transition the management of its benefit–risk action team (BRAT) to the Centre for Innovation in Regulatory Science (CIRS), according to a 

. CIRS is a neutral, independent UK-based subsidiary company, forming part of the Intellectual Property and Science business of Thomson Reuters. This transition is being made to further the program’s technical development and broaden input from the scientific community.

The BRAT framework is a structured framework and methodology for benefit–risk assessment that has been developed over the last six years. In 2011, a voluntary pilot program was conducted among PhRMA member companies to gain practical industry experience with the framework, process, and tools and to help facilitate adoption of a more structured approach to benefit–risk assessment by industry and regulators. According to PhRMA’s press release, progress beyond a pilot program will require increased stakeholder input, improved incorporation of pilot program results, and further development of benefit–risk assessment principles.

To that end, CIRS will incorporate the BRAT Framework into its new Unified Methodologies for Benefit–Risk Assessment (UMBRA) initiative. The goal of UMBRA is to improve benefit–risk assessments during the drug development and regulatory approval process and increase the transparency, predictability, and consistency with which benefit–risk assessments are conducted. UMBRA will be expanded to incorporate the BRAT Framework and other CIRS benefit–risk activities, which have focused on the development of an internationally accepted approach for the systematic, routine, and standardized documentation of decision making in the benefit–risk assessment of medicines.

PhRMA announced that it will transition the management of its benefit–risk action team to the Centre for Innovation in Regulatory Science (CIRS). CIRS is a neutral, independent UK-based subsidiary company, forming part of the Intellectual Property and Science business of Thomson Reuters.

PhRMA Transitions Management of its Benefit–Risk Action Team

 consent decree, the company is required to set up a program whereby whistleblowers can come forward with information related to potential violations of the Food, Drug, and  Cosmetic Act. According to the decree, available through 

 post, Ranbaxy must, within 75 days, establish a phone line and a system to receive and maintain submissions from individuals wishing to report suspected violations. The submissions are required to be confidential, there should be no retaliation, and a good-faith effort must be made to investigate any allegations.

		But what’s good for Ranbaxy has been causing some discomfort for FDA. Whistleblowers from FDA’s Center for Devices and Radiological Health have sued the agency over allegedly being harassed and dismissed after publicly questioning the agency’s approval methods for devices. The suit brought by the whistleblowers alleges, among other things, that FDA improperly read private emails to support a case for dismissing the plaintiffs. This prompted a 

 to FDA commissioner Margaret A. Hamburg from Senator Charles Grassley, in which he castigates the agency for perceived mistreatment of the whistleblowers, and includes a series of questions for the agency to answer to clarify their actions with respect to email monitoring.

		Among the questions to the agency, Grassley asks “What steps have you taken to reassure employees that they have a right to direct communications with Congress?” The answer to that question is an important one. FDA should expect no less from itself with respect to whistleblower protection than it demands of others.

As part of Ranbaxy’s recently announced consent decree, the company is required to set up a program whereby whistleblowers can come forward with information related to potential violations of the Food, Drug, and Cosmetic Act. According to the decree, available through Pharmalot’s post, Ranbaxy must, within 75 days, establish a phone line and a system to receive and maintain submissions from individuals wishing to report suspected violations

FDA Encourages Whistleblowers, Just Not Its Own

Genzyme, a unit of Sanofi, announced in a 

 that FDA had approved its manufacturing facility in Framingham, Massachusetts, for production of Fabrazyme (agalsidase beta). Fabrazyme is used in the treatment of Fabry’s disease, a rare genetic disorder for which it is the only FDA-approved treatment. The company 

 EMA approval for the plant on Jan. 18, 2012.

According to the press release, the company expects all patients in the US currently on therapy to be returned to full dosing beginning in March. Globally, the company expects a complete return to normal supply levels of Fabrazyme to begin in the second quarter and continue throughout the year. Genzyme will begin the process of moving the most severely affected patients in Europe to full doses of Fabrazyme in the first quarter of 2012.

Shortages of Fabrazyme have been ongoing for the past two years. Problems began in 2009 with GMP deficiencies found during an inspection of its Allston, Massachusetts, plant that culminated in a 

 in May of 2010. Since that time, Fabrazyme has been in short supply, leading to rationing of the drug and frustration among patients.

Genzyme’s President and CEO David Meeker said in the release, “We are very pleased with the FDA approval of our Framingham plant as we continue our manufacturing recovery and path forward to serve the Fabry patient community. With this approval, we continue upon our 2012 plan to restore unconstrained supply for all patients globally throughout the course of the year.”

Sanofi's subsidiary Genzyme has received FDA's approval for the production of Fabrazyme (agalsidase beta), used in the treatment of Fabry's disease, at its manufacturing facility in Framingham, Massachusetts. Shortages of Fabrazyme have been ongoing for the past two years.