Jennifer Markarian is manufacturing reporter for Pharmaceutical Technology.

Jennifer Markarian

Zoetis, a subsidiary of Pfizer, filed a registration statement with the US Securities and Exchange Commission for a potential initial public offering (IPO) of Class A common stock, Pfizer announced in an Aug. 13, 2012

Details of the IPO, including the price and number of shares, have not yet been determined. The offering, however, is expected to represent an ownership stake of up to 20%.

Prior to the IPO completion, which is targeted for the first half of 2013, Pfizer will transfer its animal health business to Zoetis. The Pfizer Animal Health business unit works to discover, develop, manufacture, and commercialize animal health medicines and vaccines for both livestock and companion animals. 

Articles

Zoetis, a subsidiary of Pfizer, filed a registration statement with the US Securities and Exchange Commission for a potential initial public offering of Class A common stock.

Pfizer's Zoetis Subsidiary Files IPO

		The news that the London 2012 Olympic Games aims to be the first Olympics to be “zero waste to landfill” is an indication of the growing importance of finding new ways to fulfill the old mantra of “reduce, reuse, and recycle”.  Recycling is even finding new applications in the pharmaceutical and healthcare industries as more companies seek to reduce waste.

		A new technology from National Bulk Equipment (NBE), the ProductSaver system, separates powdered or liquid package contents, such as over-the-counter medications, from the packaging material at the manufacturer or packager’s facility. The contents are then disposed of, but the packaging can be recovered for recycling.

		Garments and gloves from cleanrooms and laboratories can also be collected and recycled.  Kimberly-Clark Professional, which specializes in contamination control for cleanrooms and laboratories, started a recycling program with recycling expert TerraCycle last fall.  Life-sciences manufacturer Life Technologies Corporation, for example, is piloting a program to recycle nitrile gloves. 

, “Path to Zero Landfill: Learn How One Company is Leading the Way”, on Tuesday, August 21, in which these three companies will discuss their program.

		TerraCycle, an entrepreneurial New Jersey-based company founded in 2001, has a unique method of achieving their mission to prove that there is no such thing as “waste” but that everything can be recycled or reused.  To collect difficult-to-recycle, post-consumer, consumer-goods waste, such as drink pouches or single-serving coffee containers, TerraCycle organizes brigades of individuals or consumer groups that collect the used packages; the brigades are sponsored by the packaged goods companies whose packages are being collected.  TerraCycle converts the recycled material into new products or sells it to other companies for conversion.  The garments and gloves from cleanrooms and laboratries, for example, can be used to make plastic lumber for park benches and picnic tables.  A little creativity goes a long way.

The news that the London 2012 Olympic Games aims to be the first Olympics to be “zero waste to landfill” is an indication of the growing importance of finding new ways to fulfill the old mantra of “reduce, reuse, and recycle”.

Creative Solutions for Healthcare Recycling

Pharmaceutical industry leaders Pfizer, Novartis, and Merck—among others—released second-quarter 2012 results, emphasizing growth of new products and strength in emerging markets. 

Pfizer’s second-quarter 2012 revenues were $15.1 billion, down 9% from the second-quarter 2011, the company stated in a recent 

. US revenues were down 15% compared with the year-ago quarter, primarily due to the loss of exclusivity of Lipitor on Nov. 30, 2011. International revenues, which represented 62% of total revenues for the quarter, were down 5% compared to the year-ago quarter, primarily due to the unfavorable impact of foreign exchange, said the release. Emerging market unit revenues grew 14% compared with the year-ago quarter, primarily due to volume growth in China and Russia. Pfizer reaffirmed its 2012 financial guidance, noting its continued confidence, financial flexibility, and significant cost savings generated by cost-reduction and productivity initiatives, said Frank D’Amelio, Pfizer CFO, in the release.

Novartis’ group net sales, including its Pharmaceuticals division and Alcon eye care division, were $14.3 billion in the second-quarter 2012, down 4% from second-quarter 2011, stated the company in a

. Currency had a negative impact of 5%, resulting in 1% growth on a constant-currency basis, said the release. Growth from recently launched products more than offset the loss associated with the Diovan patent expiration. Recently launched products now represent 29% of the company’s group net sales compared with 25% last year, demonstrating Novartis’ continued focus on portfolio rejuvenation. The group secured eight significant regulatory milestones in the second quarter as well, which included European CHMP recommendations for Afinitor in breast cancer, Jakavi in myelofibrosis, and Seebri Breezhaler in COPD, commented Novartis CEO Joseph Jimenez. 

Merck’s global sales were $12.3 billion in second-quarter 2012, up 1%, or 5% excluding foreign exchange, from second-quarter 2011, said the company in a

. Second-quarter pharmaceutical sales grew 5% after excluding 2011 sales of Remicade and Simponi transferred to Johnson & Johnson through a settlement agreement. Emerging markets accounted for 18% of pharmaceutical sales in the second quarter. China, in particular, grew 27% in the second quarter, including 4% from foreign exchange. 

Pharmaceutical industry leaders Pfizer, Novartis, Merck, and other companies released second-quarter 2012 results, emphasizing growth of new products and strength in emerging markets.

Second-Quarter 2012 Financial Reports Show Pfizer, Novartis Down; Merck Up

The continuous process of hot-melt extrusion (HME), which is useful for making solid dispersions of poorly-soluble drugs and controlled-release dosage forms, lends itself well to quality-by-design (QbD) principles such as defining a process design space. Design space, by ICH Q8 definition, is the “multidimensional combination and interaction of input variables (e.g., material attributes) and process parameters that have been demonstrated to provide assurance of quality” (1). Because HME is a well-understood industrial process, it has the sound body of data needed to establish the critical process parameters (CPPs). HME, by nature of being continuous, is run at steady state, which allows multiple, steady-state iterations to be tested while minimizing material use during the process of establishing a design space, notes James DiNunzio, PhD., principal scientist at Hoffman-La Roche.  “A structured approach to process design can greatly increase your chances of success,” said Josh Shockey, P.E. and principal at Green Ridge Consulting, in a presentation at last month’s Pharmaceutical Extrusion Seminar organized by Leistritz (2). The TSE incorporates a series of unit operations (e.g., feed, convey, mix, melt, devolatilize). In designing the HME process, one should understand the overall goal, the goals of each of the unit operations, and how these operations interact, Shockey explained.

When producing an amorphous solid dispersion using HME, the overall goals, or critical quality attributes (CQAs), are acceptable levels of degradation and acceptable levels of residual crystallinity. The CPPs in the extruder can be said to be residence time, melt temperature, and an energy component that can be defined as shear rate, shear stress, or specific energy input. These CPPs are not easily defined during extrusion, however, because shear, temperature, and time are distributional in nature, says DiNunzio. “Development scientists need to define these behaviors based on controllable inputs to the process, such as screw speed, screw design, feed rate and process section temperature.” An advantage of a twin-screw extruder is that these inputs have a wide range that can be easily adjusted to get the desired output. Because the extruder is modular, even screw design can be relatively easily modified by changing the segments of the screw. 

Since the extruder is operated at steady state, materials that enter the extruder at a given feedport experience a certain residence time distribution and shear distribution within the control volume. Both residence time and shear rate are functions of mass flow, screw speed, and screw design, explained DiNunzio in a presentation (3). Melt temperature is a function of melt pressure, barrel temperature, and viscous heat dissipation. CQAs are affected by a complex interaction of these process parameters. Too low a level of temperature, residence time, or shear will not produce enough mixing to create a stable amorphous dispersion, but too high a level will result in degradation. 

The design space becomes further refined as developers move through the development process from early development to optimization. If the process is designed such that the operational space can accommodate normal perturbations, the system parameters can be adjusted to support processing with different material properties (e.g., different API particle size) while remaining in the design space, concludes DiNunzio.

J. Shockey, presentation at the Leistritz Pharmaceutical Extrusion Seminar (Clinton, NJ, 2012).

J. DiNunzio, presentation at the Leistritz Pharmaceutical Extrusion Seminar (Clinton, NJ, 2012).

Continuous manufacturing of amorphous solid dispersions in a twin-screw extruder is well-suited to quality by design processes such as defining design space.

Defining Design Space in Hot-Melt Extrusion

	The pharmerging nations are expected to nearly double their spending on medicine by 2016, according to an IMS Institute for Healthcare Informatics report, The Global Use of Medicines: Outlook through 2016, the Institute said in a 

. The report lists the pharmerging nations as: China, Brazil, India, Russia, Mexico, Turkey, Poland, Venezuela, Argentina, Indonesia, South Africa, Thailand, Romania, Egypt, Ukraine, Pakistan and Vietnam.  Increased medicine spending comes from the increasing purchasing power of the growing middle class in these countries, as well as government efforts to improve healthcare access.  For example, the Brazilian government’s 2011 Programa Brasil Sem Miseria (Brazil Without Poverty) aims to bring social services like healthcare to an estimated 16 million Brazilians, a 

 with Brazil’s Development Bank Leader explained.  The Brazilian government has also been encouraging the pharmaceutical industry to grow in Brazil by improving the health system and the regulatory regime.  But increased spending does not necessarily mean branded pharma company growth, since this spending is mostly on generics, over-the-counter medicines, diagnostics, and non-therapeutics, said the IMS report.  The government in India plans to increase healthcare spending, and in February proposed an initiative called “free medicine for all through public health facilities”, stated a Feb. 29, 2012 

 gave an update on this Indian government program, which is expected to spend nearly $5 million to provide generic drugs to patients at government-run facilities over the next five years.  While big pharma may not find much demand for branded drugs in these government spending programs, the generics industry should benefit, and can all agree the programs should benefit the poorest of the poor?

The pharmerging nations are expected to nearly double their spending on medicine by 2016, according to an IMS Institute for Healthcare Informatics report, The Global Use of Medicines:

Increased Generics Spending in Pharmerging Markets Predicted

A report from the IMS Institute for Healthcare Informatics, 

The Global Use of Medicines: Outlook through 2016

, found that annual global spending on medicines will rise from $956 billion in 2011 to nearly $1.2 trillion in 2016, the Institute said in a July 12, 2012, 

. According to the study, growth is expected to rebound from a low of 3–4% in 2012 to 5–7% in 2016, driven by volume increases in pharmerging markets and  spending increases in developed nations. 

In developed nations, the high level of patent expiries will limit branded medicine growth, but this will be offset by increased generics spending. In the US, medicine use is predicted to grow at an average annual rate of 1–4% over the next 5 years, driven by expanded patient access expected from the implementation of the Affordable Care Act in 2014 and by new medicines for currently unmet needs. Globally, 160–185 new molecular entities are expected to launch between 2011 and 2016, compared to 142 launches between 2007 and 2011, according to the report. 

Medicine spending in emerging pharmaceutical markets is expected to double in the next five years due to rising incomes, low drug costs, and government-sponsored programs to increase access. Over 80% of this increase, however, will come from generics, OTC medicines, diagnostics, and nontherapeutics, estimated the IMS Institute. 

“The trillion-dollar spending on medicines we forecast for 2016 represents a rebound in growth that will accentuate the challenges of access and affordability facing those who consume and pay for healthcare around the world,” said Murray Aitken, executive director of the IMS Institute, in the release.

Global spending on medicines is estimated to reach nearly $1.2 trillion by 2016.