KV Pharmaceutical Issues Recalls on Dozens of Products

2008 was a rough year for KV Pharmaceuticals, and 2009 is starting off even worse.

Plagued with recalls in 2008 (a total of five), they now start off 2009 by suspending manufacturing and issuing a voluntary recall of all of their products for two of their subsidiaries, Ethex Corporation and Ther-Rx Corporation.

So what spurred this action that is being touted as one of the largest generic recalls in history? The recalls started with an FDA inspection in December 2008. The recalls are being done because the products manufactured did not sufficiently comply with current Good Manufacturing Practices (cGMPs).

Previous recalls in 2008 were due to oversized tablets delivering higher than labeled doses. At least one of those items has a pending litigation from a patient in Texas. Judy Goodman took Morphine Sulfate ER tablets (manufactured by Ethex) from June 2007 until she died on April 10 from drug toxicity. In June 2008, Frank Goodman received an "Urgent Drug Recall" notice informing the family that "her tablets may be over-sized and to contact her physician." The family has filed suit against Ethex Corporation and KV Pharmaceutical.

Along with lack of oversight during the manufacturing process, it also begs the question as to what kind of process is in place for quality control in general before any manufacturers send their products out into the various pharmaceutical supply chains.

XStream Systems is encouraging all members of the pharmaceutical supply chain to utilize authentication technologies in their business processes including manufacturing, quality control, distribution and dispensing.

XStream’s XT250 system enables all within the pharmaceutical supply chain to authenticate and verify the medication inside its sealed, unit-of-sale container and is nondestructive. These technologies detect counterfeit, adulterated, fraudulent and substandard materials.

By all members of the supply chain utilizing cost effective authentication technologies, these recalls and unfortunate deaths may have been avoided altogether.

For a listing of drugs being recalled please view the FDA notices:

Ethex
For complete recall listing: http://www.fda.gov/oc/po/firmrecalls/ethex01_09.html

Ther-Rx Corporation
For complete recall listing: http://www.fda.gov/oc/po/firmrecalls/therrx01_09.html


Previous Recalls
ETHEX Corporation Initiated Nationwide Voluntary Recall of a Single Lot of Hydromorphone HCl 2 mg Tablets Due to Potential for Oversized Tablet (12/23/08)


ETHEX Corporation Initiated Nationwide Voluntary Recalls of Specific Lots of Five Generic Products Due to the Potential for Oversized Tablets (11/07/08)

ETHEX Corporation Voluntarily Recalls Three Lots of Dextroamphetamine Sulfate 5mg Tablets Due to the Potential for Oversized Tablets (10/15/08)

ETHEX Corporation Voluntarily Recalls Specific Lots of 30 mg. and 60 mg. Morphine Sulfate Extended Release Tablets Due to the Potential for Oversized Tablets NDC #58177-320-04 & 58177-330-04 Lot Numbers listed below (6/13/08)

ETHEX Corporation Voluntarily Recalls a Single Lot of Morphine Sulfate 60 mg Extended Release Tablets Due to the Potential for Oversized Tablets (6/9/08)

GOOD and PLENTY

Charles R. Earl, M.A., ABD
CEO, Communication Connections

No, we’re not discussing the licorice candy that resembles cold treatment capsules. Rather, “good and plenty” could be used to describe the current state of the global and national pharmaceutical industry. Just review an episode of “Dr. Quinn, Medicine Woman” to get a sense of how pharmaceuticals have progressed in the last 150 years. Dr. Quinn was generally limited to coal oil (a kerosene derivative), cod liver oil, mustard plaster and various bi-products of opium for her medicines. Local residents without the benefit of a knowledgeable physician were forced to purchase their pharmaceutical products from traveling medicine wagons (often ineffective, generally risky), or to form their own medicines after foraging the land.

The point of this exercise is that Today’s pharmaceuticals are more plentiful and effective than ever would have been imagined in the past. With success, however, comes temptation. As pharmaceutical remedies have become more prevalent, so have the opportunities for fraud and misuse. Individuals have discerned that they can substitute worthless copies for effective drugs and reap enormous profits from resale either in the legitimate supply chain or from illicit sales “on the street.” Unethical entities have also discovered that they can exchange slight variations in certain compounds that dramatically lower the cost of production and…radically undermine the effectiveness of the product, thus placing the well-being and lives of patients in peril.

So, while the availability of effective pharmaceuticals is “good and plenty,” the nefarious schemes by unscrupulous characters can severely affect the value of the products and seriously erode public confidence in the industry. This diminished faith will impact every link in the pharmaceutical supply chain. If patients and end users suspect the reliability of the pharmaceutical industry, then they may become more apt to seek their remedies from the back pages of various supermarket magazines. This type of activity would be the 21st Century version of medicine-show purchasing and foraging. While some “quack” remedies may have a short-term “placebo” effect, the long-term consequences will be unfavorable for patients and the industry.

At every step in the pharmaceutical supply chain, industry representatives must do everything possible to insure that the product has not been substituted or changed. Each and every patient, each and every dispenser, each and every handler of the product must have confidence in its efficacy. One old axiom states that “if you want something done right, do it yourself.” When examining the issue of medical safety, that axiom is warranted.

Pharmaceutical Returns: The Weak Link in the US Rx Supply Chain

By: Alan Clock, Senior Vice President, XStream Systems, Inc.

As many within domestic regulatory agencies and pharmaceutical industry leaders ponder the battles against counterfeit medications and the many solutions available to combat this global scourge, most have over looked probably the most obvious and weakest link in the overall supply chain, returns.

Pharmaceutical returns, although a small percentage of the overall transactions of the supply chain, account for a significant amount of fraud and counterfeit activities. Most major wholesale pharmaceutical distributors average less than 1% of their monthly gross sales revenues in returns however given the size of their transactions and revenues; this is still a multi-billion dollar weak link that cannot be ignored.

In addition, product transfers within a given distributor, entity or dispenser also are part of this weak link. It is not unusual for a single bottle of pills to be transferred a dozen or more times before a product reaches the dispenser.

Returns are also a necessary component of any supply chain; it is unlikely that restricting the process altogether is a reasonable solution given the enormity of the cost and the thin profit margins of most of the members of the pharmaceutical supply chain.

Most current anti-counterfeiting solutions are capturing the transaction (pedigree) or utilize a sensor based technology on the packaging (RFID) and are totally ineffective in tracking the validity of the product once it has left a secure chain of custody and is returned back into a distributors inventory.

In a time of economic tough times it is far too easy and far too profitable for a pharmaceutical provider or dispenser to fraudulently extract good product, replace all or some of it with inexpensive fillers and then re-seal the bottle. At best a pharmacist can double his profitability on a bottle of pharmaceuticals by replacing good product with harmless fillers, minimally he can re-coup margin lost to unprofitable reimbursement by replacing some pills from a bottle to cover his losses.

Although all pharmaceutical wholesalers require some sort of statement from the provider stating that the product they are returning is the original product that was purchased, sophisticated providers realize that the distributor has very little chance in identifying the adulterated products in its returns as most are tracking hundreds of thousands of bottles that flow through their receiving and returns departments daily. These healthcare professionals must rationalize that their fraud will ultimately be realized in a future transaction by a dispensing pharmacist when they go to fill a prescription and realize that the product in the sealed container is filler and not the actual medication. Even though a pharmacist will be dispensing the medication, it seems likely that too high of a percentage of this fraudulent product will make its way to the consumer and will impact their health adversely.

To date, the majority of the counterfeit materials that XStream’s Authentication solution is discovering at our distributor end users are primarily products that have been fraudulently tampered/adulterated and somehow brought back into the pharmaceutical supply chain inventory via a return goods or transfer process.

XStream encourages all within the pharmaceutical supply chain to protect their inventories by validating their inventories and using an authentication solution to identify the product. The only way that the pharmaceutical supply chain can protect itself is for its members to authenticate its inventories especially when it is processing returns.

If you are a member of the pharmaceutical supply chain or an end user consumer it is important that you are aware of and insist that the partners that you trade with as it relates to pharmaceuticals utilize an authentication technology to protect their inventories and fill in the holes that potentially will impact your health.

Are Lawmakers Finally Showing Concern Over Counterfeit Medications and Bioterrorism?

By Alan Clock, Senior Vice President, XStream Systems, Inc.

Drug Store News reported that US Lawmakers and Analysts are finally beginning to question the globalization of the pharmaceutical supply chain, namely the disproportionate amount of manufacturing and raw materials that are produced overseas in countries like China and India.

With the rapid rise of counterfeit medications and food products in these countries within their own population it seems likely that the US domestic pharmaceutical supply will also see a significant rise in reported and unreported incidents of counterfeit medications and the rise in likelihood of bioterrorist threats.

Without the use of a variety of anti-counterfeiting methods and solutions, the US consumer will be at greater risk in 2009 than ever before.

XStream continues to work with agencies, regulators and industry thought leaders to introduce its authentication technology as a solution to safeguarding supply chain inventories. Its technology allows the manufacturer, distributor and dispenser the ability to authenticate the product within its sealed, unit-of-sale container.

The full Drug Store News article is available here:

http://www.drugstorenews.com/story.aspx?id=91433

LAWMAKERS CONCERNED INTERNATIONAL DRUG MANUFACTURING PRESENTS RISK OF COUNTERFEITS

By Alaric Dearment

New York (Jan. 20)Concern has arisen about the manufacturing of ingredients for drugs in other countries, especially antibiotics like penicillin, according to published reports.

Drug manufacturing has mostly moved to countries such as India and China, but some lawmakers and analysts have said it increases the risks of counterfeits and bioterrorism.

Already, more than 200 Americans have experienced dangerous drug reactions since November 2007 after taking counterfeit versions of the blood-thinning drug heparin manufactured in China containing a toxic chemical that merely mimics heparin. Last November, the Food and Drug Administration confiscated 11 lots of counterfeit heparin from a company based in Cincinnati.

Counterfeit Drugs – The Silent Killer of Our Time?

Don’t do the Crime unless you can do the Time – At least that is how the saying goes. But what kind of deterrent is a relatively short sentence vs. the potential loss of thousands of lives?

Recently Mr. Kevin Xu, a known counterfeiter from China was sentenced for his role in a massive plan to distribute counterfeit drugs here in the United States.

He sold counterfeit drugs to U.S. citizens via the Internet. The income from the sales in the U.S. in 2007 totaled $232,568.

His next step was to make inroads into the legitimate supply chain. In negotiations with undercover agents he thought were potential buyers, he listed 25 drugs he could manufacture. These medications included Tamiflu, Plavix, Zyprexa, Aricept and Casodex. What’s more, the samples he provided to “the buyers” looked identical to the real pills.

His plan was ultimately foiled by the undercover agents from U.S. Immigration and Customs Enforcement (ICE) and U.S. Food and Drug Administration(FDA).

In their investigation, agents also learned that Xu distributed counterfeit pharmaceuticals in the United Kingdom which had penetrated the legitimate supply chain in London, and prompted a massive recall for Zyprexa, Plavix and Casodex by the Medicines Health and Regulatory Agency in London, England.

Xu received more than $1.5 million from selling counterfeit pharmaceuticals globally in 2007 alone, yet his sentence was only 6 ½ years!

POLITICAL INSIGHT

By Charles R. Earl, CEO Communication Connections

Any industry that contends with government oversight and regulation should be aware of the nature of a democratically structured system. Problems and issues are rarely addressed when first perceived or detected, but when those issues become significant enough for media and public notice, then government “solutions” are often undertaken in a hasty and “knee-jerk” manner. The result is often a myriad of restrictive and seemingly counterproductive rules and regulations. For example, how many of you would routinely use the very top of your stepladder for simple chores yet OSHA requires that ladder manufacturers and distributors inform you (via a strategically placed sticker whose location and wording are tightly regulated) that it is dangerous for you to use the upper platform of your ladder as a standing platform. Thus, because of stickering and compliance issues, stepladders are inherently more expensive than they need to be.

A co-conspirator with over regulation is the threat of litigation. Resourceful trial lawyers have brazenly attempted to hold manufacturers, distributors and retailers responsible for every use and mis-use of their products. Legal and judicial developments have generally supported the business community if due diligence and proper precautionary practices were followed, although the occasional “rogue” jury has defied reasonableness. The judicial system, along with governmental bodies, have been struggling with how to define “due diligence.” When has a manufacturer, distributor or retailer “done enough” to provide a reasonable expection of safety for the end consumer/patient?

Retailers, distributors and manufacturers have an ethical and legal responsibility to assure that their products are what they say they are, and will do what they claim. One can remember how the Tylenol scare revolutionized OTC packaging. Now, counterfeiting and alterations have surfaced to create a hazard to the integrity of the chain of custody model. Due diligence seems to require that product be examined at every stop along the chain.

Fake Drugs More Deadly than Terrorism?

Since 911, we are well familiar with the deadly effects of terrorism, but are you aware there is another danger lurking that has silently killed hundreds of thousands of individuals worldwide?

I am speaking of counterfeit medications, which have been a growing problem in underdeveloped countries for years and are now showing a steep increase in developed countries as well.

According to The Observer, British intelligence has found that criminal gangs (mostly out of China) have shifted away from selling “lifestyle” drugs like Viagra and have switch to “life-saving” medications. These drugs have infiltrated the regular supply chain in Britain and are threatening the health of millions of their citizens.

In fact more the ₤3M of these fake “life-saving” medications for ailments such as heart disease and cancer were seized in the first 10 months of 2008. Some of these medications were found within the official healthcare supply chain. These included Zyprexa, 40,000 doses of Casodex, a hormone treatment for men with advanced prostate cancer, and Plavix, a blood thinner.

Graham Satchwell, the former head of Scotland Yard’s organized crime group believes a significant number of patients may have died already, but it has not been attributed to counterfeit drugs. “They may have less of the active ingredient, meaning people could die because they are not receiving their life-saving treatment. Even now, though, healthcare professionals never assume it is the drug. No one asks whether deaths are attributable to fake medicines,” said Satchwell.

Interpol recently revealed it is investigating reports that profits received from counterfeiting activities are being used to fund terrorist groups such as al-Qaida. And these profits can be huge – as much as ₤1M for the shipment that successfully penetrates into the normal supply chain.


These criminals prey on the most vulnerable: “The counterfeiters target the weakest members of our societies – the young, the sick, the economically disadvantaged, and it is our obligation to take action,” said Ronald Noble, Interpol’s secretary-general.

While the European commission is considering several anti-counterfeiting methods, most are tied to the packaging rather than the drug itself. History has shown that such deterrents such as holograms are only temporary solutions as they themselves are usually copied within a few months. What is needed is verification of the drug itself – such authentication would act as a firewall to make the legitimate supply chain immune from threats.

Counterfeit Drug Definition Absent from Agenda of WHO Executive Board Meeting

Currently the World Health Organization definition of a counterfeit medication definition reads as:

"A counterfeit medicine is one which is deliberately and fraudulently mislabeled with respect to identity and/or source. Counterfeiting can apply to both branded and generic products and counterfeit products may include products with the correct ingredients or with the wrong ingredients, without active ingredients, with insufficient (inadequate quantities of) active ingredient(s) or with fake packaging."

Once again, bowing to pressure from some member countries, the WHO's Executive Board has left the important issue of counterfeit medication definition off the agenda for its meeting in January 2010 because of controversy surrounding the definition of counterfeit medication.
The WHO contends that a strong, consistent definition of counterfeit is necessary in order to develop global strategies to combat the problem and has been engaged for some time in developing a standard definition that all member countries can agree on.

At the heart of the definition’s continued delay is the objection from countries like India and Brazil over the use of the term "counterfeit" and the contention that it will cause some legitimate generics manufactured in these countries to come under the WHO definition. Essentially these countries believe that drug manufacturers that own international intellectual property rights for medications will use the WHO definition as a legal tool against drug manufacturers in their countries which produce generic medications that may infringe on the intellectual property of companies globally.

These countries are delaying the issue within the Executive Board and continue to ask for a revised definition which would be more specific to falsified or substandard medicines.

The WHO is now hoping that this issue will be discussed at the 2010 World Health Assembly in May.

Although a definition seems trivial and simple to some, this is an important step forward in combating an important healthcare issue that impacts everyone globally. Without this definition, it is difficult for regulatory and law enforcement agencies to collaboratively and comprehensively work together on attacking counterfeit medications at their source. Basic agreement on what is or is not a counterfeit allows unscrupulous organizations and individuals the ability to usurp legal loopholes and to operate, hide and spread their dangerous wares throughout the globe.