NEWS OF THE WEEK
RANBAXY IMPORTS HIT A WALL GENERIC DRUGS: Products from plant in India are banned by U.S.
banned imports of all pharmaceuticals made by a Ranbaxy Laboratories facility in Mohali, India, where the company recently initiated new qualitycontrol systems. FDA’s action will further set back the Indian firm’s struggle to project itself as a global supplier of generic drugs. In May, the company agreed to pay a record fine of $500 million to the U.S. Department of Justice for knowingly manufacturing substandard drugs at its facilities in Paonta Sahib and Dewas, India. And last November, Ranbaxy recalled batches of generic Lipitor in the U.S. after finding they possibly contained glass particles. An import alert issued by FDA said agency inspections in NEWSCOM
Ranbaxy Laboratories’ headquarters outside of New Delhi.
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HE U.S. FOOD & DRUG ADMINISTRATION has
GRAVITY DRAGS DOWN CELL SIZE CELL BIOLOGY: Frog egg cells use
actin to counteract the force
COURTESY OF CLIFFORD P. BRANGWYNNE
Upon disrupting actin, liquidlike RNA/protein bodies (red, green) settle to the bottom of a frog egg nucleus, roughly 400 μm across.
E
UKARYOTIC CELLS, which are defined by hav-
ing a nucleus, rarely grow larger than 10 µm in diameter. Scientists know a few reasons why this is so. For example, cells with a larger volume have a harder time obtaining nutrients from their surroundings. A new study suggests another reason—gravity (Nat. Cell Biol. 2013, DOI: 10.1038/ncb2830). Scientists had thought gravity’s effects at the cellular scale were negligible. Yet Princeton University researchers Marina Feric and Clifford P. Brangwynne observed gravity at work in egg cells from the African clawed frog Xenopus laevis. The frog eggs can reach up to 1 mm across, and they are commonly used in research. The duo made the surprising discovery in a seemingly unrelated experiment studying why organelles seem held in place within frog egg nuclei. They injected microscale polymer beads CEN.ACS.ORG
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September and December 2012 found significant current Good Manufacturing Practices (cGMP) violations at Ranbaxy’s Mohali facility, including failure to adequately investigate manufacturing problems and failure to establish adequate procedures to ensure quality. FDA maintains and updates manufacturing standards that all drugs sold in the U.S. must meet. Ranbaxy responded that it will cooperate with FDA and “take all steps necessary” to address the agency’s concerns. In its 2012 annual report, Ranbaxy claimed that it had recently installed several systems to improve quality at the Mohali plant. A desire by some Ranbaxy managers to cut costs at the expense of quality may explain the manufacturing problems discovered in Mohali, speculates Peter Saxon, president of Saxon International, a New Jerseybased manufacturing consulting firm that has advised dozens of companies in China, India, and other countries on FDA compliance. According to Saxon, Indian pharmaceutical managers often market themselves to potential employers as being able to save money by skirting cGMP rules. Piyush Nahar, a stock analyst at the investment firm Jefferies & Co., told clients that FDA’s latest action will affect Ranbaxy’s profit margins and its ability to gain regulatory approvals for its products. Investors fled Ranbaxy’s stock on news of the FDA ban, pushing it down 29%. Shares of Japan’s Daiichi Sankyo, Ranbaxy’s majority owner, slumped 6%.—JEAN-FRANÇOIS TREMBLAY
into the eggs and tracked their motion. Small beads easily diffused throughout the nucleus, but larger ones were trapped, suggesting an elastic meshwork constrains things. They suspected the mesh contained the protein actin, known for its structural role in the cytoplasm but whose role in the nucleus is unclear. When the team treated the eggs with drugs that disrupt actin, the organelles in the nucleus not only diffused freely but settled to the bottom of the nucleus within a few minutes—clear evidence of the effect of gravity. “We hadn’t thought about gravity at all,” Brangwynne says. “We were just doing our thing, but when we destabilized this actin network it became apparent gravity was at play.” Calculations based on the motion of the microbeads and the organelles showed that gravity starts becoming important around the 10-µm scale. The researchers put forth an intriguing possibility: “Cells are typically no greater than ~10 µm, because beyond this size gravity is increasingly disruptive and additional stabilization mechanisms become necessary,” according to their paper. “This is a very important finding,” says František Baluška of the University of Bonn, in Germany, who has studied the cytoskeleton in plants and its role in responding to gravity. “Gravity is a very weak force, and it is still enigmatic how gravity is perceived by living organisms.”—CARMEN DRAHL
SEPTEMBER 23, 2013
