Category Archives: US FDA


The Indian generic drug industry is the largest supplier of medicines worldwide and US is the largest consumer of the same. One of the leading companies, a leading generic manufacturer which is also the leading supplier of generic medicines to the US has come under the FDA scanner since the last 12 months.  The trigger to the Ranbaxy problems came when Dinesh Thakur , ex-Ranbaxy employee, acted as the whistleblower. The same came out as an action from the FDA when Ranbaxy’s key manufacturing plants in India went on a spree of Imports alerts and 483’s. To add to the problems, even Ranbaxy’s’ US based plants came under the FDA lens.

 The problems were many:

  • Response from the Indian regulated DCGI to the Ranbaxy fiasco came only after the FDA warnings to Ranbaxy
  •  Internal conflict within Ranbaxy between the ex-owners, Malvinder Singh and Diachii Sankyo occupied the front pages of the media Continue reading

Excessive Scrutiny

The US FDA has issued an import alert to Ranbaxy for non compliance. Is this justified considering that the US is the largest consumer of Indian made medicines since many years?

A recent fact sheet on generic drugs says:

  •  Around three-quarters of prescription medication in the U.S. are generics. Some reports put that number at 84%, with predictions as high as 87% for the near future. Meanwhile, research firm IMS Health found that, in 2012, money spent on prescription drugs decreased by 1%. It was the first such drop since IMS started tracking numbers in 1957. Continue reading

After a banner year in 2009 in which OOPD surpassed the 2,000 orphan drug designation mark and designated a near-record 160 products for orphan (i.e., rare) diseases and conditions, in 2010, the Office saw a record 323 orphan drug designation requests come through the door and granted 192 designations (for a grand total of 2308). Despite the intense interest in orphan drugs, however, FDA approved only 14 orphan products in 2010, according to data taken from OOPD’s recently updated orphan drug designation database. That figure is down from 17 approvals in 2009, and from a 1996 high of 25 approvals.

A new analysis finds that so-called first-cycle approval rates for new drugs, particularly for those that are given priority status, are slipping. And there is also a significant and ongoing decline in so-called priority designation rates.

Overall, there was a 25 percent decline in first-cycle approval rates for priority-rated new drugs and a 17 percent decrease in priority designations for new drug applications, or NDAs. First-cycle reviews for priority NDAs were 47 percent in fiscal year 2003 and continued to climb to 70 percent in fiscal year 2007, but have since slipped back to 53 percent in fiscal year 2009. Among standard NDAs, however, the rate has bounced around 40 percent, give or take a couple of percentage points during the same period. And for NDAs overall, the rate was 42 percent in fiscal year 2009, the lowest in four years.

These trends can be attributed to the FDA’s Safety First Initiative as well as the demands late in the NDA review process caused by a growing number of risk management strategies known as REMS.

As for priority designations for original NDAs, fiscal year 2005 marked a high of 30 percent after running as low as 10 percent four years earlier. However, that fell back to 13 percent in fiscal year 2009. Sources says the decline has been “most stunning” in for antiviral and oncology NDAs, which are the two therapeutic areas that have driven overall rates at the FDA’s Center for Drug Evaluation and Research in previous years. Priority designation rates for cancer NDAs have been declining consistently for several years, from 65 percent of the NDAs submitted between fiscal year 2003 and fiscal year 2005, to 18 percent in fiscal year 2009. The decline in AIDS and other antiviral therapies fell from 95 percent in fiscal year 2006 and fiscal year 2007 timeframe to just 8 percent among NDAs submitted in fiscal year 2009.

”Some side effects will make a medicine too dangerous to keep around. But the decade-long age of mass-market drug recalls – in which an average of one medicine a year has been withdrawn from the U.S. market – looks to be ending thanks to new powers the FDA was granted by a 2007 law, the Food and Drug Administration Amendments Act (FDAAA).

The USFDA can exercise its ability to forcibly change drug labeling and compelling drug companies to publicly register clinical trials. But the most effective new power has been the risk evaluation and mitigation system (REMS).

Statistical outlook
The FDA says there are currently REMS approved for 146 products. Ninety-six of these include only a medication guide, which warns patients about the risks and benefits of a drug. Thirty-three include a communication plan that takes additional steps to approve the drug. Fifteen have what the FDA calls “elements to assure safe use,” which includes much more extreme steps to make sure that the medicine is used properly. As the Avandia case seems likely to show, these requirements can almost eliminate a drug from the market without withdrawing it.”

”The US FDA is authorised to perform inspections under the Federal Food, Drug, and Cosmetic Act. The FDA Form 483 is a form used by the FDA to document and communicate concerns discovered during these inspections and to list items that deviate from Good Manufacturing Practices.

The reaction of the clinical research community to the issuance of these Form 483s borders on paranoia — paranoia at the prospect of an FDA audit resulting in the issuance of the dreaded Form 483, an action that some liken to the kiss of death for the recipient.
The recipient of a Form 483 should respond to the FDA, addressing each item, indicating agreement and either providing a timeline for correction or requesting clarification. Since September 2009, this response must be submitted within 15 working days, regardless of the number of observations. While a response is not compulsory, a good response can usually help a company avoid receiving a warning letter from the FDA, which may mean withholding of product approval, or plant shut-down.
The original intent of the Form 483 is to be an instrument of prompt notification to allow the inspected entity an opportunity for correction and improvement, not an instrument of punishment.
The US FDA has jurisdiction only within the US. However, the supply chain for pharmaceuticals often extends far beyond borders. The agency therefore performs foreign inspections and observations, which are also captured on a Form 483. Although they have no legal authority outside of the US they can restrict imports into the US. ”

At least 2% of all prescription drugs sold in the USA are without approval. There is a growing crackdown by the U.S. Food and Drug Administration on unapproved drugs being sold in the USA.

Recently, a federal judge denied a request by Cody Labs to block an FDA enforcement action requiring the company to halt production of a specific formulation of morphine sulfate, a powerful painkiller.

Though morphine has been used since the Civil War, the exact dosages and formulation for the orally administered version of the narcotic made by Cody Labs had never been formally approved by the FDA.

But the FDA has long allowed the sale of many such “unapproved” drugs that are generally considered safe and effective after decades of widespread use. The agency estimates that about 2 percent of all prescription drugs sold lack approval.

Over the last four years, however, the agency has been clamping down on unapproved versions of some drugs under a law that allows the first manufacturer that gains agency approval to continue production, while forcing unapproved versions off the market.

“Some of the world’s most popular blood pressure pills may slightly increase your risk of getting cancer, but doctors say it’s too soon to ditch the drugs, according to new research. In an analysis of five previous studies following about 60,000 patients, experts found a link between people taking medicines known as angiotensin-receptor blockers, or ARBs, and cancer. The drugs are taken by millions of people worldwide for conditions like high blood pressure, heart problems and diabetic kidney disease. In the analysis, researchers found that people who took the drugs had about a 1 percent higher risk of getting cancer than people who weren’t on the drugs. This included a whole range of cancers – prostate, breast and a noticeable spike in lung cancer. About 85 percent of those people were on telmisartan, sold as Micardis, made by Boehringer Ingelheim Corp. There was no difference in the rate of cancer deaths in people on the drugs compared to those not on them.
The study was published Monday in the medical journal, Lancet Oncology. No funding was provided for the study, but Dr. Ilke Sipahi, the study’s lead author, has received past payments from drug makers Pfizer Inc., AstraZeneca PLC and Ranbaxy Pharmaceuticals Inc., which all make blood pressure drugs. Other authors reported similar grants from other pharmaceuticals.”

“In a bid to strengthen safety and project a tougher image, the FDA may soon require drugmakers to conduct on-site audits at manufacturing facilities run by outside contractors, The Wall Street Journal reports. Right now, drugmakers may review data about quality control and product testing, but this new requirement is all about doing a hands-on inspection.
The move comes following the Heparin scandal and increasing use of contract manufacturing operations in far-flung locales where costs are lower but supervision may be minimal. However, the effort would also include contractors in the US. In taking such a step, the plan was discussed at a recent conference at Xavier University’s Med-Xu by FDA consumer safety officer Brian Hasselbalch.
The FDA would put more onus on drugmakers to vouch for their goods and certify contractors have followed FDA drug-making standards, according to Marla Phillips, who runs Xavier’s Med-XU program, which includes people from industry, regulators, medical researchers and corporate risk managers.
In the past three years, the FDA tripled the number of warning letters sent to contractors for violations, the Journal reports, while citations against drug makers remained stable. During the conference yesterday, FDA officials mentioned the possibility of sending more warning letters for contractor actions. ”

“The FDA Dilemma – Industry and FDA Brace for Change Things are going to change and everyone must step up or get trampled. We are going to have to change, but we have no idea how or how much it will cost. Drug development is in crisis, and there is a demand for better evidence. The FDA is at the same point in Comparative effectiveness as they were with drug efficacy in 1960. FDA did not know how to do it and there was a lot of resistance to it. There was a battle over efficacy that almost died. In 2010 there is no requirement for comparative evaluation pre-market. Effectiveness is something different. Pre-market clinical trials won’t give the kind of expected effectiveness, because they aren’t done in a ‘real world’ setting. The FDA Amendments Act explicitly calls for additional evidence regarding safety when new safety questions come up after marketing. Comparative effectiveness is a call for more outcomes data to guide practice. It’s a trajectory that industry needs to recognize. ”