Chain of Custody Dilemma: Recovering Stolen Pharma Products

By: Alan Clock, Senior Vice President, XStream Systems

What happens to pharmaceutical products that are recovered intact, meaning in their original packaging or shipping containers, following a theft or high jacking?

According to most experts, the policy of Pharma companies is to destroy these recovered products because they have broken the chain of custody or transaction. The logic is that no one wants to assume the liability of the efficacy of the products because they are uncertain if the products were affected or somehow altered during their time spent outside of legitimate charge.

This is an obviously an expensive and wasteful expense especially if there is a technology available that would allow the supply chain to test these products, within their sealed, unit-of-sale container. A technology that will verify that the material inside is safe and has not been altered, tampered or somehow counterfeited without destroying or degrading the drug.

Recent statistics are showing a significant surge in criminal organizations targeting Pharma products within the pharmaceutical supply chain (manufacturer, distributor, dispenser and consumer). These groups are stealing large shipments; in transit to sell within gray or black markets for significant profits. Fortunately as the problem escalates, law enforcement and security often are recovering or interdicting these criminal acts quickly.

The following are some recent examples:

- Polish police have recovered eleven tons of human blood plasma that had been stolen at a truck rest stop in Germany while in transit to Austria. The owner of the plasma, BioLife Plasma Services, a subsidiary of Baxter International, valued the shipment at around $1.4m. All of the product had been recovered in its original boxes and packaging.

- Police recovered intact a shipment of Alcon Labs and Teva Pharmaceutical products, stolen on February 22. The value of the shipment has not been disclosed but included 70 pallets of assorted prescription, over-the-counter and personal healthcare products.

- A pharmaceutical shipment including products valued at over $500,000 belonging to Sanofi-Aventis was hijacked in Puerto Rico on January 29. A wide range of prescription medicines and vaccines was taken in the incident.

- AstraZeneca lost in transit, a FedEx shipment in late December/early January. The total value of the shipment, which included Casodex, Seroquel, Nexium, Toprol XL and Crestor and Zomig was in excess of $500,000.

As it stands today, even with the product recovered intact and within its original containers the product will be slated for destruction because of the lost chain of custody. However there is a readily available technology solution.

The most effective way to effectively know that the lost chain of custody has not impacted the quality, efficacy or somehow adulterated the stolen medications is to look inside the sealed container to screen, verify and authenticate the product inside the package.

An ideal solution, it allows packaged drugs to remain intact and is readily available to test products once they are retrieved. This technology provides a level of confidence that the temporary loss of chain of custody has not altered the product and that public safety is ensured.

XStream System’s technology solution is the ideal solution for the pharmaceutical industry's chain of custody challenge by using Energy Dispersive X-Ray Diffraction (EDXRD). This innovative technology allows the user to molecularly screen the product inside its original container without destroying or degrading the product.

This solution transforms the process from looking at the chain of custody and/or transaction to looking inside the packaging with Molecular Screening. Ultimately, this truly provides all of the members of the supply chain, from manufacturer to consumer, the confidence to know that the medications in their inventories or supply chain are safe and efficacious.

EDXRD solutions function by matching the diffraction pattern obtained by the instrument with a library of patterns previously obtained for comparison. The EDXRD diffracted spectral patterns of crystalline substances are markedly different, even to an untrained eye. Much like a human fingerprint, although there may be a few features that are common to both patterns, they are nonetheless very different. In current iterations of the technology, which is fitted with a computer-based detection device, the system relies on a sophisticated mathematical algorithm to extract a unique feature set from the pattern and use them to identify the material giving rise to that pattern.

In general, the EDXRD methods are highly material specific, since the diffraction patterns of crystalline materials are unique. As it relates to pharmaceuticals, the signature of diffracted aspirin is very different from ibuprofen, acetaminophen, codeine, etc. Equally important is the fact that the diffracted patterns of the excipients specific to the unique recipe of the formulation are unique and one can determine differences in manufacturer, packaging, dosage, etc. For example, acetaminophen, 325mg from one vendor, will differ from acetaminophen 325mg from another vendor unless they follow the exact same recipe, density, pill configuration and utilize the exact same packaging.

This material sensitivity of EDXRD has two important ramifications - high detection/verification rates and low false alarm rates. Under ideal conditions (i.e. - low absorption and high test mass), the detection rate is close to 100% and the false alarm rate is 0.1% or lower. In addition because it uses X-Ray, EDXRD technology can penetrate through nearly all plastics, cardboard, wood and metals in order to screen the material.

XStream Systems has succeeded in establishing EDXRD as a robust Molecular Screening tool that can be used within the supply chain. XStream has conceptualized and architected the world’s first countertop EDXRD machine, the XT250 Material Identification System.

The XT250 has turned a complex technology into an easy to operate solution for the average end user. The XT250 system is now fully deployed in drug wholesalers, pharmaceutical manufacturers and pharmaceutical reverse logistics companies. The system is designed to be used either in a standalone or integrated capacity anywhere along the supply chain; the deployment can be in a warehouse setting and operated by a non-technical warehouse worker.

With the XT250, there no longer needs to be the very expensive and wasteful dilemma of product destruction because the product has lost its chain of custody. Because the XT250 can authenticate products non-destructively, will no longer be incumbent on the supply chain to absorb multi-million dollar losses as the threat of cargo theft proliferates.

To learn more about XStream Systems, material identification solutions, visit: http://www.xstreamsystems.net/.

Drug Resistant Diseases Fueled by Counterfeit Medications Impact Developed Nations

As has been repeatedly discussed on this blog, drug resistant strains of diseases have evolved in underdeveloped countries by counterfeit medications that contain just enough of the active ingredient of the drug used to treat the disease to fool rudimentary analytical testing used to verify the drugs authenticity. Unfortunately these fake medications, with minor amounts of the real drug add injury to insult by not only not treating the disease but in creating drug resistant strains of the disease itself.

Until lately this issue has largely impact underdeveloped nations in Africa and Asia but as you can see by recent media reports and this article which appears in the Minneapolis Star Tribune, this phenomenon is now hitting US shores with drug resistant strains of Tuberculosis.

This problem of drug resistant strains in Africa kills thousands every day.
Developed and underdeveloped nations need to take action and utilize a variety of solutions to put an end to this issue which makes deadly diseases more sophisticated and deadlier.

Solutions such as XStream System’s, XT250 are able to do on-site, molecular screening of pharmaceuticals that can verify active ingredients, excipients and packaging to authenticate and verify medications inside their sealed, unit-of-sale container would drastically curtail the ability of counterfeiters to sell and distribute substandard medications in developed and underdeveloped nations.

To read the Star Tribune story visit: http://www.startribune.com/lifestyle/health/80160622.html?elr=KArks7PYDiaK7DUvDE7aL_V_BD77:DiiUiacyKUnciaec8O7EyUr.

To learn more about XStream Systems and its XT250, visit: http://www.xstreamsystems.net/.

Are Counterfeit Products Contributing to Drug Resistant Strains of H1N1?

As reported in many media outlets, European physicians and the World Health Organization (WHO) are investigating drug resistant strains of the H1N1 virus.

To date, H1N1 has been effectively treated by anti-viral medication Tamiflu and Relenza.

As also reported in many media outlets and in SecurePharmChainBlog.com there is an emerging proliferation of organized crime organizations making hundreds of millions of dollars by counterfeiting and selling via the Internet the anti-viral drugs used to treat the H1N1 virus.

With the malaria and tuberculosis healthcare epidemics in Africa and Asia, counterfeit medications have been a significant contributor to the increase of drug resistant strains and are a considerable factor in the deaths of hundreds of thousands across the globe. In these incidents, unscrupulous counterfeiters manufacturer medications with just enough of the active ingredient to fool rudimentary testing devices. These counterfeit medications are more than just worthless, they actually facilitate drug resistant strains of the illness.

This begs the question of the correlation and impact on counterfeit drugs to the emergence of drug resistant strains of the H1N1 virus.

Are counterfeit medications contributing to drug resistant strains of the H1N1 virus?

XStream Systems encourages all drug regulatory agencies to utilize robust screening methods in the testing of all medications within the pharmaceutical supply chain. XStream's XT250 allows the end users to deploy as system within the supply chain and materially screen products for active ingredients, excepients and packaging, non-destructively, within its sealed unit-of-sale container.

To learn more about the XT250, visit XStream at: http://www.xstreamsystems.net/.

New England Journal Medicine: Multinational Medicines — Ensuring Drug Quality In an Era of Global Manufacturing

In the August 20, 2009 issue of the New England Journal of Medicine, Susan Okie, MD writes about the emerging health care issue regarding the quality of branded and generic drugs in the new era of a globalized pharmaceutical supply chain.

In this new global economic age, Dr. Okie describes the problem and proliferation of a major global health care epidemic due to quality control and fraudulent prescription medications that are manufactured overseas in countries with a poor record of quality processes. In the article Dr. Okie also writes about the challenge of regulation and oversight as many pharmaceutical manufacturers and providers move their supply chain overseas to make and procure medications.

One of the more disturbing examples of the potential danger of lack of quality oversight regards the super potency of Digitek in 2008:

"…FDA’s Adverse Event Reporting System (AERS) contains data on adverse reactions to medications in a self selected subgroup of an exposed population of unknown size. In April 2008, the FDA and Actavis Totowa, the manufacturer of Digitek, a widely prescribed generic digoxin, announced a nationwide recall of 800 million tablets, triggered by concern that double-thickness tablets containing twice the approved dose might have been released commercially. Between April and September 2008, AERS received reports of 2,912 serious injuries and 1,094 deaths associated with digoxin, about 80% of them linked to the recalled product. Thomas Moore and colleagues at the nonprofit Institute for Safe Medication Practices have called for systematic testing of the recalled tablets, commenting that “if many of these cases prove to be linked to manufacturing problems, then the nation has experienced a little noted drug disaster of major proportions.”

As have been reported in this blog for sometime the incidents of recalls related to lack of quality control and oversight connected to product production has spiked in the past several years and according to Dr. Okie may continue to increase due to the FDA’s lack of resources.

XStream Systems endorses the concept that both private industry and government regulatory agencies use technology such as XStream’s XT250 to screen, authenticate and verify the contents of products within the supply chain from point of production to the consumer. By using a material screening process, which verifies the material inside its unit-of-sale container, the entire supply chain mitigates its liability and ensures the consumer that the product is safe and efficacious. The current costs of the issue of poor quality medications within both the supply chain and the health care of the consumers, seems nearly impossible to effectively gauge or predict but it seems reasonable that whatever the price, the costs in both dollars and human suffering are far too high. Through proper verification within the supply chain, XStream feels that many of these incidents can be averted and the health care of the consumer protected.

To view Dr. Okie’s article in the August 20, 2009 issue of the New England Journal of Medicine, visit their website at: http://www.nejm.org/.

To learn more about XStream Systems verification technology, visit: http://www.xstreamsystems.net/.

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)

Track and Trace versus Inspection and Authentication Technologies?

In a comparison of Track and Trace versus Inspection and Authentication technologies it is apparent that Track and Trace solutions such as RFID, bar coding, holograms, tracing and pedigree products are not a one-size-fits-all solution to protecting the domestic and global pharmaceutical supply chain.

Track and Trace products might be sufficient, when employed throughout the Supply Chain to protect it from Drug Diversion which is one source of counterfeit activity, but these Track and Trace technologies cannot provide full protection for the product within the package. For example, how can anyone expect a Track and Trace product to determine if, either in the manufacturing or distribution process, the wrong ingredient was purposely or accidentally added into the product? Pedigree or Serialization may help, after a threat has propagated to the general public and was detected by other means, to help backtrack to the source of the problem. But by then it may be too late and the consumer will have already suffered.…

Only through the use of Inspection and Authentication technology such as XStream Systems’ XT250 Pharmaceutical Authentication System can those within the drug supply chain immediately inspect and authenticate the product within the container. Don’t let problems reach the general public. Stop the issues in their tracks.

For more information on XStream Systems and the XT250™ Pharmaceutical Authentication System, visit their website at www.xstreamsystems.net.

The Challenges of Product Safety in a Global Market Place

Andrew C. von Eschenbach, M.D., Commissioner of Food and Drugs Administration recently spoke at the Import Safety Summit and posted his view of import safety in his newsletter Andy’s Take:

“You are aware that an increasing number of products – especially those affecting your health, like food and medical products – are being imported from beyond our borders. This has raised great concern recently about FDA’s ability to ensure the safety of those products. This week, I attended a summit with hundreds of industry leaders to collectively address the challenges of product safety in a global market place.

My take is that the challenge of imported product safety will increase because as American consumers, we have come to expect - and even demand – year round variety in the food we eat. And because the production of many of the drugs and medical devices we use is now a global enterprise. So if we are going to want safety in all these products, it will require a collective effort, through collaboration with industry and international regulatory counterparts. This is to build safety in to the production of food and medical products as well as to create systems that assure their safety through distribution and consumption.

That’s why the FDA is accelerating initiatives like our participation in a groundbreaking program with partners in the European Union and Australia. Through a new pilot program we will jointly plan, allocate, and conduct certain inspections of facilities in developing countries that manufacture the starting materials for many of the drugs you take. If this program is successful, it could be expanded to include other types of drug manufacturing facilities. By leveraging the resources of each agency and sharing vital information, the number of foreign facilities in our inspection data base expands while allowing FDA to target its resources on products that we believe present the highest risk to US consumers.”

We at XStream System agree with Commissioner vonEschenbach on the importance of safety throughout the distribution chain and believe that the molecular pharmaceutical authentication possible with the XT250™ Material Identification System will further the industry’s ability to ensure safety to the consumer.

What the True Pharmaceutical Security Focus Should Be: Authentication

As many of those who have spent many years within the Pharmaceutical Supply Chain, I watch the major players within the pharmaceutical industry jockey and debate the current initiatives that are intended to secure the safety and efficacy of the medications that we in the United States take daily.

In this era of globalization we in the United States find ourselves increasingly consuming medications that use foreign produced raw materials, outsourced manufacturing and are packaged overseas. Although most of these efforts are managed and regulated according to tight corporate and FDA scrutiny, serious issues have arisen recently which demonstrate nefarious intent to circumvent the safety and security of these globally produced products.

Additionally we find international and domestic criminal organizations, realizing the potential of high profits and low risk, using sophisticated operations to adulteration, dilute or counterfeit medications that make their way into our drug stores and healthcare providers.

The threats to our safety as a nation are real. The danger that contaminated, adulterated, diluted or counterfeit medications that our population currently faces is increasing every day.

Unfortunately we find that there are few deterrents or regulatory processes in place to adequately protect our population from these sophisticated threats to our collective health.

Currently the Congress, Federal and State regulatory agencies are grappling with the most effective way to deal with this clear and present danger. To date most if not all of their efforts have been focused on track and trace technologies and protocols. Track and trace encompass RFID, advance bar codes; hologram labels technology and pedigree protocols.

Although these efforts are part of the solution, they fall short of truly and efficiently solving the problem. The obstacles to quickly adapting them as an effective solution are many. They are costly, time consuming to adopt, have numerous technical challenges, are not standardized and most importantly require each member of the supply chain to be synchronized and monitored for them to be an effective deterrent.

However the biggest drawback is that the only thing that track and trace technologies and protocols adequately track and trace is the packaging that the medication is packaged. Despite all of the cost, technical challenges and time consuming efforts that they entail, these efforts do not authenticate or verify the actual contents which may have been adulterated, counterfeited, diluted or contaminated at one of various points within the supply chain.

Currently XStream Systems, XT250 technology has the ability to quickly, efficiently and effectively authenticate and verify the contents of the medication within the sealed container. This process can happen in a very cost effective manner anywhere within the Pharmaceutical Supply Chain with little or no change in processes or protocols. It can complement existing Track and Trace initiatives by actually providing authentication documentation or operate as a standalone system.

The cost of implementing and operating authentication technology such as the XT250 is a fraction of the initial start up costs of an RFID system and it could be operational in a fraction of the time that it would take for one segment of the Pharmaceutical Supply Chain to implement universally.

Maybe it is just too obvious but I hope that those in a position to make a difference take time to look at filling in the gaps in the current mindset and direction of protecting our Pharmaceutical Supply Chain. Hopefully they discover that the ultimate solution is to authenticate and verify what is in the bottle.

Alan Clock, Senior Vice President, Sales and Marketing, XStream Systems, Inc.

Human Error Eliminated?

Pharmaceutical authentication is ever evolving to meet users’ needs and at the top of their wish list is the desire to eliminate as much human entry errors as possible. This is why the new scanning feature on the XT250 System is so exciting.

Using the product barcode already on the pharmaceutical in question, an operator scans the container; thereby, automatically selecting the drug name, manufacturer, NDC code, dosage, and quantity. The XT250 will use this information to locate the medicine’s signature standard and compare along side the sample. The results will display as “passed” or “failed”.

Simple authentication with this new feature enables the entire process to run smoother, quicker and more efficiently by eliminating entry error.

Where, Oh Where Did My Medicine Come From?

You may think you know where your medicine originated. It came from Pfizer, or Merck, or Bayer, or some other big name pharmaceutical manufacturer. The question is where did they get it?

Many of our modern day medications are complex. They might be synthesized from chemicals or use biological agents and all have some kind of filler, bulking agent, or suspension liquid. So where do all those ingredients come from and why can’t you tell where your medication was made?

Almost 80% of the active ingredients come from overseas and many of the companies that supply the fillers or chemicals are not inspected by the FDA because the product is not considered pharmaceutical. Even to inspect only the active ingredients, the FDA has stated it would take them over 13 years to inspect each plant.

What’s more – pharmaceutical companies are only required to list active ingredients not the raw material or fillers that make up the medicine.

It’s like a giant puzzle; but what if you could zoom out and see the whole picture, match it against the picture on the box and know if something didn’t fit? That might be just around the corner with EDXRD technology. A new product, the XT250 System, uses this technology to build an industry standard of a compound and then use it when comparing a sample. The software will even do the thinking for you to determine if it is or is not a match – no scientific knowledge required. It’s like a pharmaceutical lie detector to stand guard at our gates.

It would give consumers the peace of mind to know “what they see is what they get” because after all, isn’t that what really counts?

Completion of FSP training

A five day training seminar for new Field Service Providers (FSPs) was held the week of 3/03/08 at the XStream Systems Sebastian plant. Attendees included x-ray service technicians from Remetronix, Eastern Applied Research and Compass Engineering.

The class time was split between classroom theory and hands-on sessions from unpacking the unit at a customer site, to assembling components and performing an initial test, to readying the system for the Alignment, Calibration and Tool matching Process (ACT Process).

All participants will receive a factory certification authorizing them to install the XT250 System.

Although the ACT Process had been explained during classroom theory, this certification will be issued by an XStream Systems scientist during a field installation. XStream will now have service coverage throughout the US, Canada and the UK.

Part 4: Who is liable when a counterfeit or adulterated medication gets to the consumer?

Liability Opinion Series (4 of 4)
by Alan Clock, Senior Vice President, Sales and Marketing
XStream Systems, Inc.

Now, with the release of the XT250 System and its use of EDXRD technology, everyone within the pharmaceutical supply chain has a tool that allows them to authenticate, verify and document the actual contents of a sealed container down to its molecular structure.

Additionally XStream Systems has built in a robust networking capability within the XT250 System which allows the user to interface the results of its analysis into the production, inventory, pedigree and a variety of other industry software so that the tested product can be tracked throughout the process. This networking capability will allow the Production or Corporate Security Manager to track and trace the analysis, QA/QC, receiving, returns or pedigree process globally, within a distribution network or within a warehouse.

Maybe now that there is finally a solution to an ever increasing problem of counterfeit and adulterated medications, the manufacturers, distributors and dispensers won’t feel the need to pass on the responsibility, especially since they are ultimately liable and will be able to engage XStream Systems in a proactive solution.

About the author: Alan Clock is an industry veteran and a pharmaceutical supply chain expert with over 20 years experience in senior roles at AmerisourceBergen, McKesson and Cardinal Health.