Agnes Shanley is senior editor of Pharmaceutical Technology.

Agnes Shanley

As developing nations grow their pharmaceutical and biopharmaceutical industries, awareness is growing of the fact that some economies have two tracks for quality, one for domestic consumption and the other for exports to nations with stricter regulations. 

This came to a head last year, with reports of widespread cGMP noncompliance at various Indian pharmaceutical companies. An FDA inspector’s repeated questions led some staffers at one company (you know the one) to tear up documents and try to hide them and even throw samples down the drain. There was the rampant backdating and fictionalizing of lab notebooks. And then there was the indelible image of the reused plastic gloves in an aseptic environment. And that other company, whose European owners simply fired, or threatened to fire, everyone involved in the inspection snafu.  

Sometimes wires are crossed, and exported materials aren’t up to snuff, either.

As we all know, it takes time to build the kind of quality culture needed to make patient safety the real priority. And that can be difficult when there is tension, or if there are gaps in authority between central and local regulatory offices. We saw that with the compounding tragedy in the US. 

Then there is the problem of quanxi, or its equivalent, which has led to serious lapses in ethics at so many companies operating in emerging markets. 

Some Indian companies that were hit with import bans and warning letters last year took serious actions, hiring former FDA experts and others to help them establish stronger quality and compliance cultures. But that was just the larger companies. 

Historically, it is stark and terrible events, such as death, that lead to change and to tighter regulations. Will the recent deaths in India, which may be connected to the use of contaminated antibiotics at the Bilaspur sterilization camp, be a wakeup call to India’s regulatory authorities to enforce stricter standards and exact stiff penalties?  

So far, executives of two manufacturing companies have been held for questioning. One of the companies had its manufacturing license revoked two years ago for quality problems, but was then quietly allowed to get back into business. The company has denied any wrongdoing and insists that the medications were not contaminated, reported Fox News.  

We’ll see how the story unfolds, but it has raised questions about how India regulates its drug manufacturers. In the recent past, we had heard that India’s central regulatory body would be assuming more authority.  In reality, some see a very different picture.  What is clear is the fact that India’s growing middle class is demanding quality and will expect it from drug suppliers. Will suppliers be ready? 

Dinesh Thakur, now chairman of Medassure Global Compliance Corp., who blew the whistle against Ranbaxy’s questionable quality practices in the landmark US Department of Justice case, recently wrote 

 in India’s newspaper, The Hindu. He calls for a more proactive approach to enforcement at the top level, a Cabinet-level appointment to head India’s drug authority, and more enforcement power. 

Articles

Reports of widespread cGMP noncompliance at various Indian pharmaceutical companies raise awareness on the need for one quality standard for both developing nations and those with stricter regulations.

Death in Bilaspur: Must Tragedy Drive Change?

The Tufts University Center for the Study of Drug Development (CSDD) released its 

 on the costs and timeframes required for launching a new drug.  Although the study acknowledges that it still takes about 10 years to launch a new brand-name pharmaceutical, this year, the costs required were estimated at $2.6 billion (in 2013 dollars), $1.4 billion of that for out-of-pocket costs and another $1.2 billion in time costs (i.e., the cost of missed opportunities, when resources are channeled from other potential activities to the development of a specific drug). In 2003, CSDD put the figure at $802 million (in 2000 dollars, which would be $1044 in 2013 dollars), so the latest figures reflect an increase of 145%, or a compound annual growth rate of 8.5%.

Factors leading to higher costs, researchers say, include more extensive and complex clinical trials and high failure rates for other drugs in testing. Only 12% of new candidate drugs entering clinical trials wind up being approved for use, according to CSDD. After a drug has been approved, there is the need to test new indications, new formulations, new dosage strengths and regimens, and to monitor safety and long-term side effects in patients, as required by FDA. CSDD estimates that these post-approval costs run to $312 million, increasing the full product lifecycle cost per approved drug to $2870 million (in 2013 dollars).

Tufts based its new data on information provided by 10 pharmaceutical companies on 106 randomly selected drugs first tested in human subjects between 1995 and 2007, including 87 small molecule drugs and 19 biopharmaceuticals.  “Drug development remains a costly undertaking despite ongoing efforts across the full spectrum of pharmaceutical and biotech companies to rein in growing R&D costs,” said Joseph A. DiMasi, director of economic analysis at Tufts CSDD and principal investigator for the study, in a 

. The study was authored by DiMasi, Henry G. Grabowski of the Duke University Department of Economics, and Ronald W. Hansen at the Simon Business School at the University of Rochester. 

“Because the R&D process is marked by substantial technical risks," DiMasi added, “with expenditures incurred for many development projects that fail to result in a marketed product, our estimate links the costs of unsuccessful projects to those that are successful in obtaining marketing approval from regulatory authorities.”

Rising drug development costs have been driven mainly by increases in out-of-pocket costs for individual drugs and higher failure rates for drugs tested in human subjects, according to the study. Factors that likely have boosted out-of-pocket clinical costs include increased clinical trial complexity, larger clinical trial sizes, higher cost of inputs from the medical sector used for development, greater focus on targeting chronic and degenerative diseases, changes in protocol design to include efforts to gather health technology assessment information, and testing on comparator drugs to accommodate payer demands for comparative effectiveness data. Lengthening development and approval times were not responsible for driving up development costs, DiMasi said.

These latest figures have provoked strong response from those on both sides of this issue. The Pharmaceutical Research and Manufacturer's Association (PhRMA; Washington, DC) noted the challenges faced by cancer drugs, citing a recent PhRMA study on failure rates for melanoma, lung and brain cancer therapy candidates. “In the past 16 years, there have been 96 unsuccessful attempts to develop drugs to treat melanoma, 167 for lung cancer, and 75 for brain cancer. In this same period, there were some medicines that beat the odds and advanced care: 7 to treat melanoma, 10 for lung cancer, and 3 for brain cancer were approved by the Food and Drug Administration,” noted the 

“These findings underscore the ongoing challenges the biopharmaceutical industry faces as R&D efforts focus on some of the most costly and challenging diseases, where the science is more complex and the failure risks are compounded," said a PhRMA spokesperson in a press release. 

  However, some industry observers question CSDD’s figures. 

Indiana University Medical school professor and 

 blogger Aaron Carroll has questioned the study’s objectivity and its failure to account for public funding in industry R&D in a 

, Doctors Without Borders’ director of policy and analysis Rohit Malpandi puts it bluntly. “If you believe [the study numbers], you probably also believe the earth is flat.” 

Malpani cites Andrew Witty’s reaction to CSDD’s previous estimates, when he called the 2003 figure “one of the great myths of the industry” 

As drug pricing and increased access to medicine remains a sensitive issue, for both payers and the public, the debate promises to continue. If nothing else, CSDD’s figures suggest a need for pharma companies to “fail fast,” or to take an approach to early development that considers all possible risks and points of failure very closely for its new candidate drugs.  

Tufts research suggests costs to launch a new drug have doubled since 2003, but some question conclusions.