Ranbaxy to Shed as Many as 400 Middle and Senior Management Jobs

Posted in BioBusiness

The UK’s Economic Times reported  today that the troubled Indian generic drug manufacturer Ranbaxy may shed as many as 400 jobs from its various divisions. Most of the persons receiving pink slips will be senior and middle management who are likely losing their jobs because of ongoing serious drug manufacturing problems that have plagued the company for over three years.  The drug maker employs about 14, 600 people in 43 countries.

While the job cuts do not represent a significant percentage of Ranbaxy’s workforce, Daiichi Sankyo which owns the company, is likely eliminating members of the management team that have been responsible for the company’s ongoing manufacturing problems. According to the Economic Times article

“On Thursday, some senior executives from the finance department at Ranbaxy were asked to leave. On Friday, some senior executives from the Research & Development wing were given marching orders,” an employee familiar with the job cuts told ET. Another executive said some officials from the API(active pharma ingredient) division have also been handed pink slips.

This past May, Ranbaxy paid the US Department of Justice $500 million to settle criminal and civil charges to resolve the manufacturing problems that prompted the US Food and Drug Administration (FDA) to ban the sale of dozens of drugs manufactured by the company.  More recently, FDA inspectors issued an unsatisfactory inspection report for one of the company’s manufacturing plants in India.

Ranbaxy is one of the world’s leading generic drug manufactures and the company’s ongoing manufacturing problems have certainly hurt Daiichi Sankyo’s image. Also, it has led some analyst to question whether or not Daiichi Sankyo ought to have purchased the troubled generic manufacturer for $4.6 billion in 2008.

Until next time…

Good Luck and Good Job Hunting!!!!!!

Regulatory Affairs Update; FDA 483 and Warning Letters Trends for 2012

Posted in BioEducation

Those of you who manufacture products approved by the US Food and Drug Administration (FDA) are well aware of the importance of complying with Current Good Manufacturing Practices (cGMP) during FDA mandated inspections of your manufacturing facilities. Failure to comply with cGMP requirements during an inspections results in the issuance of 483s. And if you fail to adequately address the concerns of the agency outlined in 483s, it may ultimately result in issuance of warning letter to your company.

FDA is more vigilant and aggressive than ever before with its 483 and warning letter enforcement procedures. In the words of Commissioner Margaret Hamburg, FDA is quick, visible and vigilant.  With this in mind, it may be worthwhile to participate in a webinar offered by Expert Briefings.com entitled “Top Compliance Trends for 483 and Warning Letters for 2012—Based on Rare FDA Data.”

The webinar will be held on March 8, 2012 from 2:00-3:30 PM EST and Dennis Moore, Managing Partner, AUK Technical Services and a 28 year veteran FDA investigator will lead it. 

Topics to be covered include:

  • Top warning letter trends for 2012, such as more 806 enforcement
  • The Top 10 QS 483 Observations for 2010 and 2011
  • Most common quality system failures for drugs for 2010
  • Top drug and device citations in 483s for 2010
  • Top drug and device warning letter citations for 2010
  • Total 2010 BIMO inspections for CDER, CBER, CDRH, and CVM
  • Details on clinical investigator, sponsor/monitor and IRB audits for 2010
  • Most common sponsor deficiencies for 2010
  • The rising trend of ‘cease to market’ letters, one of which hit a NY pharma company in 2011
  • The total number of 483s issued in 2010 and 2011 – an all time high
  • Total CAPA 483 observations in 2010
  • How long to receive a warning letter, based upon which offices issues it
  • 483 inspection targets for drugs and devices for 2010, 2011, and 2012
  • Total warning letters issued by drug and device category in 2010
  • Which district offices write the most warning letters
  • How long to receive a warning letter, based upon issuing office
  • Warning letters issued by QS system for 2010
  • 483s broken down by QS subsystem for 2010
  • Warning letters by CFR section
  • Top device 483 observations for 2010
  • Details on process validation observations for 2010
  • Design control 483 observations by category for 2010
  • Click here to visit Expertbriefings.com.

Click here to visit Expertbriefings.com.

I hope to see (hear ?) you at the webinar!


The Number of Prescription Drug Recalls Continues to Rise

Posted in BioBusiness

Last week, I reported in a post that in 2011 the US Food and Drug Administration (FDA) had approved a near-record of 35 new medicines. Coincidentally, earlier this week, Ed Silverman posted on the Pharmalot blog that prescription drug recalls are rising and nearing historical records. 

According to Ed, “During the third quarter of this year, the number of pharmaceutical recalls jumped to 150, compared with about 90 recalls during each of the first two quarters of 2011, according to FDA Enforcement Reports. Moreover, the recent tally dwarfs the roughly 65 recalls that were made during the last quarter of 2010 and nearly doubled the 80 recalls that were notched during the 2010 third quarter.”

The reason for the spike in drug recalls? Some suggest that FDA is getting tough and still trying to reinvent itself after the 2004 Vioxx debacle and the tainted heparin incident. Also, Congress is putting pressure on the agency to better enforce manufacturing regulation and supply chain management practices. Sadly, the only way for FDA to accomplish this is by increasing the number of inspections that it conducts on both foreign and domestic manufacturing facilities. And, given that the agency’s budget for enforcement activities has not increased much over the past few years; it is unlikely that increased regulatory scrutiny will occur any time soon.

Finally, for those of you who may not know. FDA does not have the authority to recall drugs. Recalls are voluntary and must be orchestrated by the company that manufactures the product in question. Luckily, FDA has many financial and legal methods at its disposal to induce companies to “voluntarily” recall suspect or tainted products from the US market.

Until next time…

Good Luck and Good Job Hunting!!!!!!


Why Transforming FDA Makes Sense

Posted in BioBusiness

During the Bush Administration I, along with many others, was a harsh critic of the US Food and Drug Administration (FDA). The criticisms that I levied against the agency were mainly based on its inability to adequately maintain the safety of the American drug and food supply and Bush’s repeated attempts to politicize the organization and render it useless. That said, it is amazing how much has and will change at the agency during the Obama Administration. To wit, Margaret Hamburg, the current FDA Commissioner yesterday announced plans that would dramatically transform the agency and largely change the way it does business.

In an unusually rare special report entitled “Pathway to Global Product Safety and Quality” Hamburg points out the monitoring problems currently facing the agency and proposes a four-point plan on how to fix them. To understand the importance of this document it is necessary to point out some little know facts about the American food and drug supply.

First, almost two-thirds of all fruits and vegetables and nearly 75 percent of all seafood consumed by Americans is imported. This year the number of these types of food shipments is expected to grow to 24 million through 300 or more ports. A little as a decade ago, the agency was responsible for overseeing and policing six million shipments annually. Second, it is estimated that over 80 percent of the active pharmaceutical ingredients (APIs) found in approved drugs are made in manufacturing plants found mainly in China, India and Latin America. Because of funding and “manpower” shortages, most of these API manufacturing facilities are rarely inspected for regulatory compliance. According to the report, many kinds of antibiotics, oncology drug and other medications are no longer produced in the US or in many cases anywhere in the Western world. Finally, roughly 50 percent of all approved medical devices sold in the US are made in foreign production facilities.

In 2008, government officials determined that the agency would need approximately 13 years to inspect all foreign drug manufacturing plants, 27 years to check every foreign medical device production facility and a whopping 1,900 years to check every foreign food production plant! This is because FDA has only several hundred inspectors who are empowered to perform these inspections. Consequently, only a fraction of the food and APIs imported to the US are inspected. For example, less than one pound in a million of imported seafood gets as much as a “visual inspection” to determine whether or not it is fit for American consumption. This led the report’s authors to contend that “the safety of America’s food and medical products remain under serious threat.”

Yet, despite this ongoing threat, Republican lawmakers last week voted to cut the agency’s budget rather than increase it to perform the necessary number of food and drug inspections. Further, the same lawmakers oppose any corporate or consumer fees, whether voluntary or forced, to help to underwrite the inspections calling them an unacceptable tax. This has forced the agency to enlist the help of regulators in other nations to create a global coalition or network to perform the required inspections to insure the regulatory compliance and safety of foods, drugs and devices imported into the US. While the FDA has limited cooperation agreements with regulators in Europe and other Western countries, it just recently stationed its own inspectors in emerging markets like China, India and Central America. In theory this should work. However, in the past, some of the governments of these countries have refused to fully cooperation with FDA. Further, and perhaps more problematic, is that regulatory agencies in some other countries are largely corrupt or nonexistent. Finally, some outspoken former FDA employees and critics contend that improvements in the communication between FDA in Washington and its field offices in US states may be necessary before the agency can effectively enlist the cooperation of foreign regulators.

There is no doubt that contaminated foods, counterfeit medical devices and tainted drugs are increasingly finding their way into the US. It is FDA’s legislated responsibility to insure that all foods and drugs sold in the US are safe and effective for all Americans. Republican lawmaker’s refusal to increase FDA’s budget to allow the agency to fulfill its mandate is unconscionable and indefensible. The safety and health of all Americans is critically important for the well being of the nation and ought to take precedent over budget shortfalls and a looming US trade deficit.

Until next time…

Good Luck and Good Job Hunting!!!!!!


FDA Inspections: Insights into Responding to FDA Inspectional Observations

Posted in BioBusiness

US Food and Drug Administration (FDA) inspections of drug and devices manufacturing facilities are typically anxiety ridden exercises that can strike fear into even the most seasoned quality and regulatory affairs professionals. And, most manufacturing facilities do not escape these inspections unscathed and are routinely cited, in many cases, for minor infractions.

For those of you who may not be familiar with FDA inspections, manufacturing facilities that produce approved drugs and devices must be inspected every two years for insure regulatory compliance with Current Good Manufacturing Practices (CGMPs). During the inspection, FDA inspectors document “significant objectionable conditions, relating to products and/or processes or other violations of the Food Drug and Cosmetic Act” that they observe. These are known in the industry as Form FDA 483 Inspectional Observations or simply 483. Companies that receive 483s must correct the so-called objections conditions to remain CGMP compliant.

While receiving 483s during an inspection may be routine, it can be overwhelming to inexperienced companies and their representatives. With this in mind, I found a great blog post by Bruce McDuffee, Global Marketing Manager, Veriteq that provides insights on interacting with the agency to manage 483s. He offers the following advice:

“One thing that you should be clear about is that this is not a ‘warning letter’; it is an offer to help you resolve issues and improve your quality system. The FDA may or may not issue a warning letter next if you have not addressed the conditions of the 483 to its satisfaction. Receiving a 483 does not necessarily mean you are out of compliance.

In responding to a 483, your objectives should include these three things; establish credibility, demonstrate acknowledgement and understanding of the observations and the associated requirements and show commitment to corrective actions."

Bruce recommends that you take the following actions when dealing with 483s:

  1. Get your response in on time or even early if possible. The FDA wants to see the response within 15 days, so plan your review and internal processes accordingly.
  2. In the first paragraph, demonstrate your understanding of and desire to comply with FDA regulations.
  3. Respond individually to each item addressed on the form. Give a corrective action and time-frame for implementing.
  4. Prioritize by first addressing the conditions that will most likely affect product quality.
  5. Outline how and when each deficiency will be corrected.
  6. Avoid talking about whose fault the issue is or how it came to be. For example, keep a positive tone and indicate how the quality system will be improved.
  7. Include any reference documents, such as purchase agreements for a new monitoring system or employment agreement for a new quality manager.
  8. Keep in mind that there is a formal process available for you to dispute the findings.
  9. Be proactive in addressing the conditions. For example, address why the deficiencies were not detected internally and what will be done to correct this condition.
  10. Seek clarification with the inspector when you receive the 483 on the spot. Be sure you understand each objectionable condition before the inspector leaves the site. It may behoove you and your firm to seek out an industry expert if the matters seem complex or if the issues are not able to be resolved by your own personnel.”

While CGMP and regulatory compliance may seem like arcane concepts, they are vitally important and must be clearly understood by companies that are manufacturing FDA-approved drugs and devices. Failure to comply can result in penalties, monetary fines and revocation of a license to manufacture a drug or device.

Until next time….

Good Luck and Good Job Hunting (try regulatory affairs or quality assurance and control)


What's Up With FDA Inspections Anyway?

Posted in BioBusiness

BioJobBlog readers who understand Current Good Manufacturing Practices (CGMP) for pharmaceuticals and biologics know that the US Food and Drug administration is mandated to review approved drug manufacturing facilities once every two years. While this is the mandated inspection schedule, most industry insiders know that manufacturing plant inspections now take place once every three or more years. This has resulted because of an increased reliance by US drug makers on foreign manufacturing facilities to produce licensed pharmaceuticals and biologics, a lack of regulatory oversight by the agency during the Bush administrations and funding shortfalls that have resulted in a shortage of FDA inspectors.

Congress recently took the agency to task about a lack of oversight for food and drugs manufactured in foreign countries. In September, the Government Accountability offices reported that FDA inspects foreign drug facilities on average once every nine years as compared with every 30 months or more with US plants. To correct this, FDA announced that it aims to increase reliance on third party inspectors in other countries to maintain better oversight of ex-US manufacturing plants. In other words, it is less costly to train and work with inspectors already in foreign countries rather than send US inspectors overseas.

In a post last week on the Pharmalot Blog, Ed Silverman reported that Bloomberg News reviews almost 10,000 inspections at US manufacturing plants from 2000 until September 30, 2010. While the Bloomberg report did not provide details on the frequency and nature of violations uncovered at the inspections, the results of the reports were eye-opening. According to Ed:

“The FDA makes 0.9 visits, on average, to each facility each year, compared with 0.6 visits annually when George W. Bush was in the White House. Looked at another way, the agency NOW visits each of the 2,567 plants registered in the US almost once a year.”

Further he noted:

“Some of the biggest drugmakers do not have a good track record when it comes time for FDA inspectors to visit their plants. Overall, the FDA found violations at 54 percent of plants inspected last year, up 20 percent from a decade low in 2007, according to data obtained from the agency by Bloomberg News. And 80 drugmakers failed more than half of their inspections.”

So, which companies had the poorest inspection track records? Ed noted

“Abbott Labs failed 59 percent of 111 inspections; Pfizer flunked 57 percent of 202 inspections; Merck bombed out on 52 percent of 134 visits and Johnson & Johnson failed 48 percent of 161 inspections. By contrast, [generic drug manufacturer] Mylan passed 79 percent of 56 inspections!”

Republicans are threatening to slash FDA funding for US inspections mainly because the agency is focusing more on overseas manufacturers and suppliers. In response to the funding cut threats, the Obama Administration proposed that drug manufacturers whose production plants fail inspections would be required to pay fines of roughly $49,000. At present, there are no mandatory fines levied against drug makers that fail FDA inspection (the agency can and does impose fines if companies that fail inspections refuse or are reluctant to fix the problems that were uncovered).

I find it interesting that despite the numerous drug recalls and problems with drug safety of approved drugs over the past few years that the Republicans, could in good conscience, threaten to cut FDA funding to increase the frequency of inspections to bring them in line with the mandated once every two years rather than once every 2.5 to 3.0 years that has been the norm for the last decade.

Until next time….

Good Luck and Good Job Hunting!!!!!


A Good Example of Why Politics and Science MUST NEVER Be Mixed

Posted in BioBusiness

Last week, the US House of Representatives voted to cut FDA funding by $220 million. The House vote was not surprising given the prevailing attitude among many pharmaceutical and biotechnology company executives that FDA approval of new drugs and devices has become increasingly difficult. While there is no question that the current approval process for new drugs and devices has become more rigorous as compared with the incredibly lax process (and in some cases, the almost non-existent process) used during the Bush Administration, the FDA is simply fulfilling the mandate for the agency when it was created in 1938. That is: to provide the American public with SAFE and efficacious drugs to treat unmet medical need. 

Until recently, the FDA had been chronically under funded. And, because of this, the American public was forced to suffer through the Vioxx scandal, the heparin scare and the appearance on the market of many unapproved medical devices. These and other events that occurred over the past decade beg the question: “Should the American public’s safety be placed in jeopardy again simply because the Republican-controlled House is looking for ways to cut deficit spending?”

Unfortunately, the activity of anti-FDA lobbyists (funded mainly by US pharmaceutical and biotechnology companies) has been ramped up ever since the Democrats lost control of the House. And, since most Republicans believe that any government regulation whatsoever is too much regulation, it is easy to understand the House would vote to cut FDA funding. Nevertheless, insufficient funding will not allow the agency to hire the number of inspectors required to insure that drug manufacturing is conducted according to FDA-mandated regulatory guidelines. These activities are essential to insure the safety of the prescription drugs and medical devices sold on the US market.

According to FDA Current Good Manufacturing Practice (CGMP) guidelines, drug manufacturing plants for all approved drugs and devices are to be inspected every two years. Inspections are required for all manufacturing plants in the US as well as FDA-approved manufacturing facilities overseas. Because of ongoing shortages of FDA inspectors (and the emergence of numerous overseas manufacturing facilities), these inspections are typically conducted every three to five years rather than every two years! Clearly, this is not in the best safety interests of the American public.

A report published by the General Accounting Organization about the heparin scare of three years ago nicely sums up the issues.

“In its response to the heparin crisis, FDA took several actions related to its responsibility to protect the public health by ensuring the safety and security of the nation’s drug and medical device supplies. FDA increased its activities related to oversight of heparin firms by conducting inspections and investigations and monitoring heparin imports, and worked with drug and device manufacturers to recall contaminated products while ensuring that an adequate supply of uncontaminated heparin was available. With the help of external entities, FDA identified the unknown contaminant and developed tests to screen all heparin products. Additionally, the agency reached out to its international regulatory partners during the crisis. However, FDA faced some limitations in its efforts to inspect heparin firms in China and collaborate internationally, and the agency was unable to determine the original source of contamination.”

Interestingly, as today reported by the EyeonFDA blog, the U.S. House of Representatives Energy and Commerce Committee announced today that it was re-opening examination of the heparin contamination issue.  A letter was sent by the Chair of the Committee, Rep. Fred Upton (R-MI) as well as other members to FDA Commissioner Margaret Hamburg requesting that the agency supply all documents in connection with the heparin investigation from January 1, 2008 until present.  In its announcement, the Committee stated:

“It has been almost three years since the FDA linked deaths and serious allergic-type reactions of patients in the United States to supplies of heparin that came from the People’s Republic of China which was adulterated with overly sulfated chondroitin sulfate (OSCS). FDA officials believe this was an instance of economically motivated adulteration,” the members wrote. “However, neither the Chinese government nor the FDA has identified those responsible for the contamination or described how the heparin actually came to be contaminated.”

Mark Senak, author of  EyeonFDA blog aptly noted:

"It is certainly important in that any public health crisis involving the contamination of food or drugs be thoroughly investigated. But the investigating body can’t have it both ways. You can’t criticize an agency for not conducting inspections that are not funded by the same members of the same investigative body."

Is this any way to run a country?

Until next time…

Good Luck and Good Job Hunting!!!!!!!