Patricia Van Arnum was executive editor of Pharmaceutical Technology.

Patricia Van Arnum

FDA issued a new report this week that details the activities that the agency is using to address the increased globalization of the industries that it regulates, including pharmaceuticals. 

“As our world transforms and becomes increasingly globalized, we must come together in new, unprecedented, even unexpected, ways to build a public health safety net for consumers around the world,” said FDA Commissioner Margaret A. Hamburg, MD, in an Apr. 23, 2012, 

Since 2002, imports of pharmaceuticals products and biologics have more than doubled, according to the FDA report, 

. Foreign-sourced pharmaceuticals now account for approximately 40% of the drugs consumed in the United States, and 80% of APIs in US-consumed drugs are sourced from abroad. 

The report outlines a variety of engagement strategies FDA is using in partnership with other agencies, organizations, and coalitions around the world to strengthen global regulatory capacity-building efforts, develop and harmonize science-based regulatory standards, increase awareness about the importance of regulatory systems, and share information and data globally to facilitate rapid identification of and response to public health emergencies.

Part of FDA’s strategy has been to open international offices to increase the agency’s overseas presence. As of 2011, FDA has posts in China (Beijing, Shanghai, and Guangzhou), India (New Delhi and Mumbai), Latin America (San Jose, Costa Rica; Santiago, Chile; and Mexico City, Mexico), Europe (Brussels, London, and Parma, Italy), South Africa (Pretoria), and the Middle East and North Africa (Amman, Jordan).

Articles

A new report by FDA details the strategies, programs, and other activities the agency is using to address the rise of imported pharmaceutical products and APIs.

FDA Details Strategies for Addressing Globalization

	Last week Human Genome Sciences (HGS) rejected GlaxoSmithKline’s (GSK) unsolicited $2.59 billion bid for HGS or $13 per share.  Although rejecting GSK’s initial bid, HGS kept the door open for other suitors, including again GSK.

	HGS has authorized its board of directors to explore strategic alternatives for the company, including a potential sale. HGS has invited GSK to participate in this process and has requested additional information regarding investigational products in GSK’s clinical pipeline to which HGS has substantial financial rights, including darapladib, in Phase III development for treating cardiovascular disease, and albiglutide, in Phase III development for treating Type 2 diabetes.

	HGS posted a net loss of $381.1 million in 2011 on revenues of $131 million and also posted a loss in 2010 of $233 million. Last year, HGS received FDA approval for Benlysta (belimumab), a drug to treat lupus. The drug was approved by FDA in March 2011 and posted 2011 revenues of $52.3 million. In 2006, HGS and GSK entered into a codevelopment and commercialization agreement under which HGS conducted the Benlysta Phase II trials, with assistance from GSK. The companies share equally in Phase III/IV development costs, sales, and marketing expenses, and profits of any product commercialized under the agreement.

	Although HGS rejected GSK’s $13.00-per-share bid, the companies’ mutual interest in Benlysta and in the late-stage candidates darapladib and albiglutide make them possible suitors. Some analysts say it is unlikely that another company would be interested in HGS given its stake in the GSK-shared drugs.

	Analysts say the deal would be favorable to GSK for it would secure full ownership of Benlysta and the late-stage candidates darapladib and albiglutide. When approved last year, Benlysta became the first new drug to treat lupus in 50 years, and although it has gotten off to a slow start in terms of sales, some analysts are bullish on its prospects as well as the other HGS/GSK late-stage candidates.

	So time will tell if a marriage of GSK and HGS will be realized.

Last week Human Genome Sciences (HGS) rejected GlaxoSmithKline’s (GSK) unsolicited $2.59 billion bid for HGS or $13 per share.

GlaxoSmithKline: A Rebuffed Suitor for the Moment

Takeda Pharmaceutical has agreed to acquire URL Pharma for an upfront payment of $800 million and future performance-based, contingent, earn-out payments. The company announced the deal last week. 

URL Pharma’s lead product is Colcrys (colchicine), a drug used to treat and prevent gout flares. Net sales for Colcrys in calendar year 2011 were more than $430 million, accounting for a major portion of URL’s 2011 revenues of $600 million. The drug complements Takeda’s position in the gout marketplace with Uloric (febuxostat), which is used to lower blood uric acid levels in adults with gout.

URL is headquartered in Philadelphia and has approximately 500 employees. In addition, URL Pharma has a contracted sales force consisting of approximately 350 individuals. The deal is expected to close in 60 days.

Company makes bolt-on acquisition to enhance position in gout marketplace.

Takeda to Acquire URL Pharma for $800 Million

	Researchers at the Massachusetts Institute of Technology (MIT) recently developed nanoparticles that can be controllably triggered to synthesize proteins. The hope is that particles could be used to deliver small proteins that kill cancer cells and eventually larger proteins such as antibodies that trigger the immune system to destroy tumors.

	The nanoparticles consist of lipid vesicles filled with the cellular machinery responsible for transcription and translation, including amino acids, ribosomes, and DNA caged with a photo-labile protecting group. These particles served as nanofactories capable of producing proteins including green fluorescent protein (GFP) and enzymatically active luciferase. 

 protein synthesis was spatially and temporally controllable and could be initiated by irradiating micron-scale regions on the timescale of milliseconds. (1).

	The researchers designed the new nanoparticles to self-assemble from a mixture that includes lipids, which form the particles’ outer shells, plus a mixture of ribosomes, amino acids, and the enzymes needed for protein synthesis. Also included in the mixture are DNA sequences for the desired proteins. The DNA is trapped by DMNPE, which reversibly binds to it. This compound releases the DNA when exposed to ultraviolet light. In this study, particles were programmed to produce either GFP or luciferase. Tests in mice showed that the particles were successfully prompted to produce protein when UV light shone on them, according to an Apr. 9, 2012, 

	Although more testing must be done to show that the nanoparticles can reach their intended destination in humans and that they can be used to produce therapeutic proteins, the research is an interesting start. The researchers are working on particles that can synthesize potential cancer drugs by targeting protein production that could be turned on only in the tumor, thereby avoiding side effects in healthy cells. The team also is working on new ways to activate the nanoparticles. Possible approaches include production triggered by acidity level or other biological conditions specific to certain body regions or cells, according to the MIT release.


	1. A. Schroeder et al, ” Remotely Activated Protein-Producing Nanoparticles,” 

., online, DOI: 10.1021/nl2036047, Mar. 20, 2012.

Researchers at the Massachusetts Institute of Technology (MIT) recently developed nanoparticles that can be controllably triggered to synthesize proteins.

Nanofactories: The next frontier in protein synthesis?

US spending on prescription drugs increased moderately in 2011 reflecting increased generic-drug incursion and lower spending on prescription drugs. Pfizer retained its number one position of the top company of US prescription drug sales, and the generic-drug company Teva Pharmaceutical moved into the top-five companies of US prescription drug sales. 

Total healthcare system spending on medicines in the US reached $320 billion in 2011, up 3.7% in nominal terms or 0.5% on a real-per-capita basis, according to a recent report by the IMS Institute for Healthcare Informatics. Branded medicines spending grew 2.2% on a nominal basis and reflected the impact of $14.9 billion lower spending on products that lost their patent exclusivity. In 2011, spending for brands launched within the past two years was $12.2 billion, compared with $8.5 billion in the year-earlier period. Spending on generic drugs, which now account for 80% percent of dispensed prescriptions, increased $5.6 billion in 2011, according to IMS. Overall spending on medicines continued to be concentrated on traditional small-molecule oral pills dispensed through retail pharmacies, even as specialty drugs and biologics experienced higher growth.

Overall per-capita-use of medicines in the US declined slightly in 2011, as physician office visits and nonemergency-room hospital admissions dropped, and older Americans reduced their retail drug use, according to IMS. The number of office visits declined 4.7% while emergency-room admissions, which are relatively small in number, rose 7.4%. Retail prescription usage declined on average 1.1% in 2011 and fell by more than 3% in ten states, reflecting variations in demographics, epidemiology, clinical practice, and payer dynamics. Seniors age 65 and over reduced their use of prescription drugs by 3.1% last year, most notably in the antihypertensive class. Individuals age 19 to 25 increased their use of medicines by 2.0%, notably for attention deficit hyperactivity disorder treatments and antidepressants. This was the only age group that increased drug utilization in 2011.

Nearly one-third of total healthcare spending was concentrated in five therapy areas: oncology, asthma and chronic obstructive pulmonary disease, dyslipidemia, diabetes, and mental health, according to IMS. Each of these therapy areas grew faster than the overall market and exhibited a range of dynamics related to new treatment option usage and growing diagnosis of the related disease.


 On a product basis, Pfizer’s anticholesterol drug Lipitor (atorvastatin) retained its position as the top-selling drug in the United States in 2011 with sales of $7.7 billion, according to data from IMS. Bristol-Myers Squibb’s and Sanofi’s antiplatelet drug Plavix (clopidogrel) was second with US sales of $6.8 billion. AstraZeneca’s Nexium (esomeprazol), a drug to treat gastroesophageal reflux disease, was third with US sales of $6.2 billion. Bristol-Myers Squibb’s Abilify (aripiprazole), an antipsychotic and antidepressant, came in fourth with US sales of $5.2 billion, and GlaxoSmithKine’s Advair Diskus (fluticasone and salmeterol), a drug to treat asthma, was fifth with US sales of $4.6 billion. Rounding out the 10 top-selling prescription drugs in the US were AstraZeneca’s antidepressant Seroquel (quetiapine), Merck & Co’s anti-asthma drug Singulair (montelukast), AstraZenenca’s anticholesterol drug Crestor (rosuvastatin), Eli Lilly’s antidepressant Cymbalta (duloxetine), and Abbott’s Humira (adalimumab), a drug to treat rheumatoid arthritis. 

On a company basis, Pfizer retained its top position of US prescription drug sales in 2011, with sales of $25.1 billion followed by AstraZeneca with US sales of $19.9 billion, according to data from IMS. Merck & Co and Novartis closely followed with respective US sales of $19.3 billion and $19.2 billion. Teva Pharmaceutical took the fifth slot with US sales of $15.1 billion. Rounding out the top 10 companies of US prescription sales were Eli Lilly ($14.9 billion), Roche ($14.5 billion), GlaxoSmithKline ($14.2 billion), Amgen ($13.1 billion), and Johnson & Johnson ($12.1 billion). Sanofi, Abbott, Bristol-Myers Squibb, Boehringer Ingelheim, and Takeda, respectively, completed the top 15 companies of US prescription drug sales. 

Generic-drug incursion and reduced demand contribute to modest gains.

US Spending on Prescription Drugs Increased Moderately in 2011

	Sterility assurance is a critical component in the planning and manufacturing of pharmaceutical products. Good risk management consists of identifying and assessing risks prior to the manufacturing process as well as taking measures during the production process to control, mitigate, or eliminate risks. An upcoming educational webcast by 

, will examine best practices for risk management in sterile manufacturing.

	Risk management and its tools are crucial for capturing product and process knowledge, understanding criticality, and creating a plan of action to evaluate and mitigate risk. A three-member panel will examine these issues in further detail. Dr. Mike Long, MBB and director and senior consultant with ConcordiaValSource LLC, will speak on quality-by-design principles in sterile manufacturing. He is also co-chair of the Parenteral Drug Association’s (PDA) Risk Management Task Force and member of PDA’s Science Advisory Board. Hal Baseman, chief operating officer and principal at ValSource LLC, will examine FDA’s recent process validation guidance and its implications with respect to sterile manufacturing. He is also chair-elect of PDA’s board of directors, vice-chair of the PDA Science Advisory Board, and co-leader of the PDA Process Validation Interest Group. Michael Curry, director of operations at the DPT Lakewood Center of Excellence for Aseptic and Specialty Products, will discuss ways to identify, assess, and mitigate risk in a sterile manufacturing environment.

, will be held this Thursday Apr. 12 from 2:00–3:00 PM EST. Additional information, including how to register to view this webcast both live and on-demand, may be found

Sterility assurance is a critical component in the planning and manufacturing of pharmaceutical products.