Statement of Joshua M. Sharfstein, M.D., Principal Deputy Commissioner, Food and Drug Administration, Department of Health and Human Services

Before the Committee on Energy and Commerce Subcommittee on Health, U.S. House of Representatives, March 10, 2010

INTRODUCTION

Mr. Chairman and Members of the Subcommittee, I am Dr. Joshua M. Sharfstein, Principal Deputy Commissioner at the Food and Drug Administration (FDA or the Agency) in the Department of Health and Human Services (HHS). Thank you for the opportunity to discuss the safety of the American drug supply.

Protecting Americans from unsafe or contaminated drugs is not just an important responsibility of FDA-it is our core charge. Drug safety was the primary reason for the passage of our guiding statute. In 1937, more than 100 people, including many children, died from ingesting Elixir Sulfanilamide, which contained the deadly poison diethylene glycol. Congress then passed, and President Franklin D. Roosevelt signed, the Federal Food, Drug, and Cosmetic Act (FD&C Act) to prevent future catastrophes.

And yet, as you know, the threat remains.

I would like to thank the Subcommittee for its leadership on this issue. Numerous hearings in this chamber have helped the public understand the challenge of regulating a global marketplace. Members of this Subcommittee, along with the Chairman of the full Committee and the Chairman Emeritus, were key architects of the Food and Drug Administration Amendments Act of 2007 (FDAAA), which gave the Agency significant new authorities and resources to address postmarket safety. In this testimony, I will address two important issues: import safety and the implementation of the drug safety authorities in FDAAA.

IMPORTS

As the Subcommittee’s work has documented, globalization has created new risks and challenges for the safety of the drug supply. Where Americans once used drugs that were mostly manufactured domestically, now up to 40 percent of the drugs we take are imported, and up to 80 percent of the active pharmaceutical ingredients in the drugs we use are from foreign sources. In addition to the growth in the sheer volume of imports and foreign facilities, there has been an increase in the variety and complexity of imported products, and a large expansion in the number of countries involved in producing these products-including many with less sophisticated regulatory systems than our own. Simultaneously, the supply chain from raw material to consumer has become more and more complex, involving a web of repackagers and redistributors in a variety of locations. This makes oversight significantly more difficult and leaves weaknesses through which counterfeit, adulterated, and misbranded products might infiltrate the legitimate supply chain.

A few examples:

* In 2007 and 2008, contaminated heparin (a blood-thinning drug) came from China and was linked to deaths and a number of serious allergic-type reactions here at home.

* Counterfeit Tamiflu (oseltamivir phosphate) was discovered during the novel H1N1 outbreak.

* In 2007, Xenical (orlistat) capsules ordered over the Internet were found to be composed only of talc and starch.

* In January 2010, counterfeit Alli (orlistat) was discovered, which did not contain the active ingredient but instead contained varying amounts of the stimulant sibutramine, which can lead to serious toxicity if used by people with certain cardiac diseases.

These are global problems. Contamination and counterfeit drugs represent a much greater threat in the developing world, where the systems of laws and regulatory oversight do not afford much protection. And these problems can pose a risk to us at home, when, for example, patients do not get fully treated for infection abroad because of ineffective drugs and as a result, drug resistance intensifies.

Photo above: Fake drugs are made on equipment like this in filthy conditions.

Photo below: Fake drugs are re-labeled and re-packaged so they look “genuine”. This puts you at risk. This could kill you.

When the modern FDA was created in 1938, imports were a tiny part of the products used in our country. Our focus was on stopping harmful products at the border through inspections of imported goods. This approach is adequate to the challenge when the volume is small. But it fails when an estimated 20 million shipments of FDA-regulated imports come into the country each year. To fulfill our public health mission in a global age, FDA must adopt a new approach-one that addresses product safety by preventing problems at every point along the global supply chain, from the raw ingredient through production and distribution, all the way to U.S. consumers.

We are moving from an approach based on reacting to problems to one that proactively prevents such problems from ever occurring. In the food arena, this approach to prevention is embodied in legislation passed by this Committee and the full House of Representatives, and which is now awaiting action in the Senate. This bill would for the first time allow FDA to establish basic preventive controls throughout the food production process and give the Agency strong enforcement authorities and resources to meet these obligations.

In the arena of drugs and other medical products we are taking a number of steps to begin making this shift within our current authorities.

First, we are seeking better controls at the point of production, wherever that may be.

We now have permanent FDA offices in Beijing, Shanghai, and Guangzhou, China, in New Delhi and Mumbai, India, in San Jose, Costa Rica, Mexico City, Santiago, Chile, and soon, Amman, Jordan. These offices enable us to have a regional presence around the world, a home base from which to undertake a range of important activities, including building regulatory capacity. We now have more than 30 agreements with foreign counterparts to share inspection reports and other nonpublic information that can help us make better decisions about the safety of foreign products. So if a shipment of contaminated drugs shows up in a port in Italy, we will hear about it swiftly and be on the lookout for products from the same shipper.

Second, we are working with industry to help them strengthen the safety of their supply chains. In this day and age, companies should be able to effectively demonstrate that safety, quality, and compliance with international and U.S. standards are built into every component of every product and every step of the production process. Some companies already do a terrific job at this, tracking where and how their products and their components are made and the path taken to reach our shores. In fact, I have met with some companies that react with incredible swiftness to questions about the integrity of their supply chain. Obviously they have a vital interest in ensuring confidence in the safety and quality of their products and their brand. These best practices need to become standard practice throughout industry.

There is much more to be done. As Secretary of Health and Human Services Kathleen Sebelius noted when she appeared before this Committee on February 4, 2010, FDA needs additional tools to move our oversight capabilities into the 21st century. FDA needs to access regulatory information quickly, hold all parties responsible for the quality of products in the supply chain, and have reasonable and reliable options for enforcement.

DRUG SAFETY AUTHORITIES IN FDAAA

I will now turn to the drug safety authorities in FDAAA, a milestone legislative achievement that has helped the Agency protect the public health in many different ways.

Because no amount of premarket study can provide the full information about what the benefits and risks of a new drug will be when it is used by the general population, FDAAA provided important new authorities to enhance our ability to monitor approved drugs after they are marketed and to take definitive action when needed. Under FDAAA, FDA can require drug sponsors to conduct postmarketing studies and clinical trials, make certain safety-related labeling changes, and develop and put into place risk evaluation and mitigation strategies (REMS)-all with the goal of better identifying and managing the risks of drugs on the U.S. market.

Here are some details.

With respect to label changes, as of February 28, 2009, FDA had used its new authorities to require safety label changes in individual or classes of drugs 32 times since March 25, 2008. For example, FDA required safety label changes to add the risk of a life-threatening neurological disorder to the prescribing information for certain antidepressants, and changes to the prescribing information of a class of antibiotics to warn about the risk of tendon rupture.

With respect to risk management, if FDA determines that a REMS is necessary to ensure that the benefits of a drug outweigh the risks of the drug, FDA can require manufacturers to have a REMS in place when a drug comes on the market, or implement one later if FDA becomes aware of new safety data . The authority to require REMS provides FDA a very useful set of tools that can be used to reduce the risks of marketed products, while allowing patients to benefit from lifesaving and other beneficial treatments that could not be safely marketed without a risk management program.

In the design of REMS with elements to ensure safe use (the most comprehensive REMS programs), FDA is mindful of the provisions in FDAAA stating that the elements to ensure safe use must be, among other things, commensurate with the specific serious risk listed in the FDA-approved labeling of the drug, not be unduly burdensome on patient access to the drug, and be designed to be compatible with established distribution, procurement, and dispensing systems for drugs.

Most of the REMS with elements to ensure safe use include educating prescribers about the risks and appropriate use of the drug as a condition of certification or enrollment in the REMS program. Other programs require enrollment by pharmacists and sometimes patients as well. Some programs require the prescriber to monitor the patient immediately following drug administration and for a period of time afterwards. Each of these programs is designed to provide critical information to clinicians without unduly restricting access to the drugs.

We have learned that designing and implementing the most comprehensive REMS requires a careful balancing of the need to adequately manage risks and also to maintain patient access to important medications. Since using this authority is a work in progress, FDA is committed to addressing the concerns we have heard from prescribers, pharmacists, distributors, and payers about their roles in implementing REMs and from patient groups about the effects of REMS on access to needed products, and are planning to hold a public meeting to hear from these and other stakeholders. Additional implementation challenges include ensuring consistency in the handling of safety problems with all products, including over-the-counter (OTC) products and generic drugs; the lack of clarity in certain provisions of the law with respect to REMS; and burdens imposed on application holders and FDA that do not contribute significantly to drug safety. We would be very happy to discuss the lessons we have learned over the last two years with Congress and work together to fine tune the program so that it can be even more effective in improving public health.

Sentinel Initiative

FDAAA requires the HHS Secretary to develop methods to obtain access to disparate data sources and to establish a postmarket risk identification and analysis system to link and analyze health care data from multiple sources. On May 22, 2008, FDA launched the Sentinel Initiative with the ultimate goal of creating and implementing the Sentinel System-a national, integrated, electronic system for monitoring medical product safety. The Sentinel System, once up and running, will enable FDA to actively gather information about the postmarket safety and performance of its regulated products-a significant step forward from our current, primarily passive safety surveillance systems. The law sets a goal of access to data from 25 million patients by July 1, 2010, and 100 million patients by July 1, 2012. FDA has gathered public input on issues related to the creation and development of Sentinel, held numerous meetings and a public workshop, and established a working group consisting of representatives of numerous federal agencies to share information and discuss issues related to ongoing efforts that are complementary to Sentinel. FDA has awarded key contracts for a pilot project to gather information that will be essential to fully implementing the Sentinel System.

Track and Trace

FDAAA also required the development of standards for the identification, validation, authentication, and tracking and tracing of prescription drugs as a step towards further securing our nation’s drug supply. Very shortly, FDA will issue a guidance establishing a standard for unique identification for prescription drug packages, which ultimately will help in identifying the whereabouts and authenticity of drug packages and distinguish them from counterfeits.

SAFE USE INITIATIVE

Before I close, I would like to briefly mention a new drug safety initiative at FDA called the Safe Use Initiative. Every approved drug has both benefits and risks. Underlying FDAAA is the principle that Congress wants to see the benefits maximized for patients and the risks minimized. We all want patients to get better on medication and avoid unnecessary injuries, even death, as a result of preventable medication errors or misuse. In November 2009, we announced the launch of FDA’s Safe Use Initiative. Through this initiative, FDA will identify, using a transparent and collaborative process, specific candidate cases (e.g., drugs, drug classes, and/or therapeutic situations) that are associated with significant amounts of preventable harm. FDA will then work with hospitals, doctors, nurses, patient groups and others to recognize and mitigate these risks. In a voluntary complement to the REMS program, we will use our understanding of drug risk as a tool to gather partners together and develop and implement strategies for progress.

CONCLUSION

Over the last seven decades, so much has changed in pharmaceutical science and drug regulation. Yet in 2007, when scores of patients died of contamination in Bangladesh, and in 2006 when children died in Panama, the culprit was familiar. It was diethylene glycol, or DEG-the very same poison that had led to the passage of the FD&C Act in 1938.

FDA’s work is far from done. The scientists, doctors, nurses, inspectors, and other public health professionals who make up FDA thank you for your support and confidence in our mission.

Thank you very much for the opportunity to testify today. I welcome your ideas and your questions.

Joshua M. Sharfstein, M.D.

FDA Warns Consumers about Counterfeit Drugs from Multiple Internet Sellers

If you purchase medications from sources that you do not know, and the product you take is purchased on the sole basis of “price”, then I believe you are playing a dangerous game of “you bet your life”.

The Food and Drug Administration (FDA) is cautioning U.S. consumers about dangers associated with buying prescription drugs over the Internet. This alert is being issued based on information the agency received showing that 24 apparently related Web sites may be involved in the distribution of counterfeit prescription drugs.
On three occasions during recent months, FDA received information that counterfeit versions of Xenical 120 mg capsules, a drug manufactured by Hoffmann-La Roche Inc. (Roche), were obtained by three consumers from two different Web sites. Xenical is an FDA-approved drug used to help obese individuals who meet certain weight and height requirements lose weight and maintain weight loss.

Above photos: Counterfeit Xenical, complete with instruction sheet, blister pack with exp. date, and lot serial numbers. What’s missing? ATL’s security labeling/ packaging: This is an invisible (non-degradable) digital forensic code that cannot be duplicated by the counterfeiters.

Photos below: If your prescription medications are not authenticated as genuine, how do you know that (your prescription medications) were not produced (by counterfeiters) on equipment such as this?

None of the capsules ordered off the Web sites contained orlistat, the active ingredient in authentic Xenical. In fact, laboratory analysis conducted by Roche and submitted to the FDA confirmed that one capsule contained sibutramine, which is the active ingredient in Meridia, an FDA-approved prescription drug manufactured by Abbott Laboratories.
While this product is also used to help people lose weight and maintain that loss, it should not be used in certain patient populations and therefore is not a substitute for other weight loss products. In addition the drug interactions profile is different between Xenical and sibutramine, as is the dosing frequency; sibutramine is administered once daily while Xenical is dosed three times a day.

Other samples of drug product obtained from two of the Internet orders were composed of only talc and starch. According to Roche, these two samples displayed a valid Roche lot number of B2306.
Roche identified the two Web sites involved in this incident as brandpills.com and pillspharm.com. Further investigation by FDA disclosed that these Web sites are two of 24 Web sites that appear on the pharmacycall365.com home page under the “Our Websites” heading. Four of these Web sites previously have been identified by FDA’s Office of Criminal Investigations as being associated with the distribution of counterfeit Tamiflu and counterfeit Cialis.

At this point, it appears that these Web sites are operated from outside of the United States. Consumers should be wary, if there is no way to contact the Web site pharmacy by phone, if prices are dramatically lower than the competition, or if no prescription from your doctor is required. As a result, FDA strongly cautions consumers about purchasing drugs from any of these Web sites which may be involved in the distribution of counterfeit drugs and reiterates previous public warnings about buying prescription drugs online. Consumers are urged to review the FDA Web page at www.fda.gov/buyonline/ for additional information prior to making purchases of prescription drugs over the Internet.
The 24 Web sites appear on pharmacycall365.com.
AllPills.net
Pharmacy-4U.net
DirectMedsMall.com
Brandpills.comEmediline.com
RX-ed.com
RXePharm.com
Pharmacea.org
PillsPharm.com
MensHealthDrugs.net
BigXplus.net
MediClub.md
InterTab.de
Pillenpharm.com
Bigger-X.com
PillsLand.com
EZMEDZ.com
UnitedMedicals.com
Best-Medz.com
USAPillsrx.net
USAMedz.com
BluePills-Rx.com
Genericpharmacy.us
I-Kusuri.jp

If you are a brand owner, ATL can show you how to authenticate your products in the field. If you are a consumer, we suggest that you purchase only authenticated prescription drugs from reliable sources.

We thank the FDA for materials used in this article.

You Bet Your Life: The Fakes. A Lesson For You In Loss Prevention.
A counterfeit drug or a counterfeit medicine is a medication or pharmaceutical product which is produced and sold with the intent to deceptively represent its origin, authenticity or effectiveness. For legal drugs, a counterfeit drug may be one which does not contain active ingredients, contains an insufficient quantity of active ingredients, or contains entirely incorrect active ingredients (which may or may not be harmful), and which is typically sold with inaccurate, incorrect, or fake packaging. Fake medicines and generic drugs which are deliberately mislabeled in order to deceive consumers are therefore counterfeit, while a drug which has not received regulatory approval is not necessarily so. Counterfeit drugs are also related to Pharma Fraud.

Most illegal drugs are produced and sold with the intent to deceptively represent its origin, authenticity or effectiveness, at least to some degree. The counterfeiting ranges from drugs which do not contain any active ingredients (e.g., when a bag of lactose is sold as cocaine), to cases where the active ingredients are “cut” with a dilutant or “spiked” with a chemical “enhancer”, to cases where the actual active ingredients differ from the purported active ingredients (e.g., when methamphetamine is sold as cocaine).

You Bet Your Life: Brand Piracy. Prescription and over-the-counter drugs.

Counterfeit legal drugs include falsely-labeled drugs that were previously expired, drugs where the active ingredient is fraudulently diluted, adulterated, substituted, completely misrepresented, or sold with a false brand name. An individual who uses a low quality counterfeit medication may experience a number of dangerous consequences to their health, such as unexpected side effects, allergic reactions, or a worsening of their medical condition. A number of counterfeits do not contain any active ingredients, and instead contain inert substances, which do not provide the patient any treatment benefits. Counterfeit medications may also contain incorrect ingredients, improper dosages of the correct ingredients, or they may contain hazardous ingredients.

The extent of the problem of counterfeit drugs is unknown. Counterfeiting is difficult to detect, investigate, and quantify. What is known is that they occur worldwide and are said to be more prevalent in some developing countries with weak regulatory regimes. It is sometimes estimated that upwards of 10% of drugs worldwide are counterfeit, and in some countries more than 50% of the drug supply is made up of counterfeit drugs. In 2003, the World Health Organization cited estimates that the annual earnings of counterfeit drugs were over $32 billion (US).

The high prices of patented medicines and the great divergence between manufacturing costs and prices are seen as important incentives for counterfeiting, including cases of high quality counterfeiting which can be difficult to detect. Fake antibiotics with a low concentration of the active ingredients can do damage world wide. Courses of antibiotics that are not seen through to completion allow bacteria to regroup and develop resistance.

Above Photo: Which are real and which are fake? Without traceability and authentication, how do you know? Would “You Bet Your Life” on not knowing?

You Bet Your Life: Some Solutions (RFID & Mass Serialization).

There are several technologies that may prove helpful in combating this problem, such as radio frequency identification (RFID). These are electronic devices to track and identify items, such as pharmaceutical products, by assigning individual serial numbers to the containers holding each product. The FDA is working towards an Electronic pedigree (ePedigree) system to track drugs from factory to pharmacy. This technology may prevent the diversion or counterfeiting of drugs by allowing wholesalers and pharmacists to determine the identity and dosage of individual products. Some techniques, such as spectroscopy and Energy Dispersive X-Ray Diffraction (EDXRD) can be used to discover counterfeit drugs while still inside their packaging.Some of the proposed anti-counterfeiting measures present concerns regarding privacy, or the possibility that drug manufactures will seek to use anti-counterfeiting technologies to undermine legitimate parallel trade in medicines. The term “counterfeit” should not be applied to generic drugs that are legally manufactured and sold, and which do not have deceptive labeling concerning the product. According to BBC reports, many of the fake drugs came from the same countries that make normal drugs, especially China and India. In the case of India, while it is against the law to sell fake drugs for domestic use, there is no regulatory regime that applies to the export market.

Graph Above: The top 5 anti-counterfeiting techniques are date codes, various printing, tamper evident, UPC codes, and mass serialization.

China
Many counterfeit drugs sold in the Third World or on the Internet originate in China. The State Food and Drug Administration is not responsible for regulating pharmaceutical ingredients manufactured and exported by chemical companies. This regulatory hole, which has resulted in considerable international news coverage unfavorable to China, has been known for a decade, but failure of Chinese regulatory agencies to cooperate has prevented effective regulation.
The Chinese press agency Xinhua reported that the World Health Organization had established Rapid Alert System (RAS), the world’s first web-based system for tracking the activities of drug counterfeiters, in light of the increasing severity of the problem of counterfeit drugs.

Russia
A few years ago, the Coalition for Intellectual Property Rights, an independent Russian group, conducted a survey that found that 12 percent of the prescription drugs distributed in Russia were counterfeit.

India
According to a report released by the Organization for Economic Co-operation and Development (OECD), 75 per cent of fake drugs supplied world over have some origins in India, followed by 7 per cent from Egypt and 6 per cent from China. It must be noted that India also is a leading source of high quality drugs sold by legitimate drug manufacturers, including most leading brand name drug makers operating in the US and Europe.

United States
The United States has had a growing problem with counterfeit drugs, and to help address it, the U.S. Food and Drug Administration (FDA) holds regular hearings to review trends and problems. The U.S. is an especially attractive market for counterfeiters because 40 percent of worldwide annual prescription drug sales were sold in the United States in 2007.

You Bet You Life: Anti-Counterfeit Platforms.
In 2007, the world’s first free to access anti-counterfeit platform was established in the West African country of Ghana. The platform relies on existing GSM networks in that country to provide pharmaceutical consumers and patients with the means to verify whether their purchased medicines are from the original source through a free two-way SMS message, provided the manufacturer of the relevant medication has subscribed to a special scheme. Still in trial stages, the implementers of the platform announced recently that they are in partnership with Ghana’s Ministry of Health and the country’s specialized agency responsible for drug safety, the FDB (Food & Drugs Board), to move the platform from pilot to full-deployment stage.

An Epedigree is another important system for the automatic detection of counterfeit drugs.

Photo Above: Hard copy of typical pedigree papers.

Photo Above: Pedigree papers can provide traceability of your prescription medications.

States such as California are increasingly requiring pharmaceutical companies to generate and store ePedigrees for each product they handle. On January 5th, 2007 EPCglobal ratified the Pedigree Standard as an international standard that specifies an XML description of the life history of a product across an arbitrarily complex supply chain.

You Bet Your Life: Illegal Drugs.
Illegal drugs can be counterfeited easily because the illegal drug market is an unregulated underground economy that rarely adheres to quality norms or safety standards. While there are some isolated examples of illegal drugs being sold under “brand names” that indicated that certain standards or dosage levels were being adhered to, this is the exception. The illegal “brands” can also be counterfeited by drug dealers who want to be able to sell their product at a higher price.
The use of dilutants in illegal drugs reduces the quality and potency of the drugs, and makes it hard for users to determine the appropriate dosage level. Dilutants include “foodstuffs (flour and baby milk formula), sugars (glucose, lactose, maltose, and mannitol), and inorganic materials such as powder.” The type of dilutants that are used often depend on the way that the drug purchasers will typically consume the drug in a given part of the illegal market. Dr. Hirsch, the New York Medical Examiner, claimed that buying illegal drugs is “… like playing Russian roulette.”

This is why we say that if you take prescription medications without “drug authentication”, you are playing a dangerous game of “You Bet Your Life“.

End.

Below: Article break. Are prices “sky high”?

By Lisa Richwine Mon Jan 25, 2010

WASHINGTON (Reuters) Fake versions of GlaxoSmithKline’s over-the-counter diet pill were contaminated with dangerously high levels of a prescription weight loss ingredient, U.S. officials warned on Saturday.

Lab tests showed counterfeit versions of Glaxo’s pill Alli contained high levels of sibutramine, Food and Drug Administration officials said.

Sibutramine is the active ingredient in Abbott Laboratories Inc’s prescription diet drug Meridia.

“The amount of sibutramine in the counterfeit Alli poses a serious health risk to some individuals,” Dr. Janet Woodcock, head of the FDA’s drug unit, told reporters on a conference call.

“A person taking the counterfeit Alli as directed would be exposed to twice the maximum prescription dose of sibutramine every day,” she said.

The FDA warned earlier this week that sibutramine should not be used by people with a history of cardiovascular disease because it can raise the risk of heart attacks and strokes.

Regulators in Europe concluded sibutramine was too risky and Abbott agreed to suspend sales there.

Woodcock said even healthy people exposed to the counterfeit Alli pills could experience effects including palpitations, sleepiness, anxiety, nausea and slightly elevated blood pressure.

The fake versions were sold on the Internet, including through online auction sites, FDA officials said. There is no evidence of counterfeit versions in stores, they said.

The fake products were sold as 60-milligram, 120-count refill packages only, Glaxo said. The company said it was working with the FDA to have the counterfeits removed from online auction sites.

The agency urged all consumers taking Alli to check they had bought legitimate versions and discard any fake products immediately.

The fake versions have some differences on the packaging, including a missing lot code on the outer cardboard packaging. The FDA posted links to photographs of Glaxo’s approved versions and the counterfeits here.

Today’s Topics – FDA Q&A. Counterfeit Prescription Drugs.
In the fight against counterfeited prescription medicines, don’t bury your head in the sand. Expect the unexpected. Listen for evil, look for evil, and blow the whistle when you encounter evil.

FDA Questions And Answers. Q. What is the definition of a counterfeit drug? A. U.S. law defines counterfeit drugs as those sold under a product name without proper authorization. Counterfeiting can apply to both brand name and generic products, where the identity of the source is mislabeled in a way that suggests that it is the authentic approved product. Counterfeit products may include products without the active ingredient, with an insufficient or excessive quantity of the active ingredient, with the wrong active ingredient, or with fake packaging.

Donfucius Note: As they dilute or divert legitimate products, counterfeiters also make false and wild claims. In the illustration below, would you rather go camping at a three star campground, five star campground, or fourteen-star campground? There is an old phrase that says: “Let the buyer beware”. In most cases, you will get what you pay for: “The bitter taste of poor quality lingers long after the sweet taste of price has evaporated” (Donfucius).

Q. What risks are involved with taking counterfeit drugs?
A. An individual who receives a counterfeit drug may be at risk for a number of dangerous health consequences. Patients may experience unexpected side effects, allergic reactions, or a worsening of their medical condition. A number of counterfeit products do not contain any active ingredients, and instead contain inert substances, which do not provide the patient any treatment benefit. Counterfeit drugs may also contain incorrect ingredients, improper dosages of the correct ingredients, or they may contain hazardous ingredients.

Q. What can consumers do to protect themselves from counterfeit drugs?
A. Consumers can protect themselves from the risks associated with counterfeit drugs by purchasing prescription medications from state-licensed pharmacies in the U.S. Consumers must be vigilant when examining their personal medications, paying attention to the presence of altered or unsealed containers or changes in the packaging of the product. Differences in the physical appearance of the product, taste, and unexpected side effects experienced should alert the patient to contact their physician, pharmacist, or other healthcare professional who is providing treatment.

Donfucius Note: Ortho Biotech Products issued a warning to health care professionals about the existence of counterfeit vials of its anti-anemia drug Procrit. The concentration of the active ingredient was 20 times lower than what was listed on the label. The two photos (below) show the boxes of the authentic (top) and counterfeit (bottom) product. The counterfeit boxes could be identified by the text running off of the right side of the box. The average consumer would probably not notice this. ATL Pharma Security Label Systems is cGMP compliant. We operate under the strict regulations of 21 CFR 210 and 211. This means we must hold tight registration for both commercial pharmaceutical labels and clinical trials. It is our suggestion that you always buy your brands from reputable companies with anti-counterfeiting protection.

Q. How does FDA work with domestic and foreign government agencies to combat counterfeits?
A. FDA is currently working with various U.S. government agencies, such as the Department of Homeland Security (Customs and Border Protection) and the Department of Justice, to combat counterfeit drugs. FDA is also very active in WHO’s International Medical Products Anti-counterfeiting Task Force (IMPACT) which is a public/private effort to develop regulatory, legislative, enforcement, communication, and technological tools to combat counterfeit drugs around the world. FDA also works bilaterally and multilaterally with individual countries and regions.

Q. Are there any promising technologies that have the capability of preventing counterfeiting?
A. There are several technologies that may prove helpful, including radio frequency identification (RFID) chips and taggants. For example, radio waves are used to automatically read RFID tags that are contained on items, such as pharmaceutical products. These tags could have individual serial numbers on each product, thus allowing the product to be tracked and traced through the supply chain. Appropriate implementation and use of this technology can help decrease the opportunities for diversion and counterfeiting by allowing wholesale distributors and pharmacies to authenticate that the product was handled by legitimate, licensed entities in the drug supply chain.

The fight against counterfeited drugs. Below are two photographs of counterfeited drugs. The average consumer will have a very difficult time telling apart the real from the fakes.

You (as a brand owner or as a consumer) must be able to rely on the labeling/ packaging integrity to identify (thus stop) counterfeiting. ATL has nine trademarked products that provide a mix and rotate (M&R) approach (during sequential production runs) for anti-counterfeiting protection. These include: SecurLock: Tamper-Evident breakaway closure; SecurDetek: Invisible, Hidden Page Marker; SecurMark: Anti-Counterfeiting holograms; SecurStretch: Tamper-Evident Unit Closure; SecurPly: Booklets for soft squeeze tubes; PharmaVoid: Security Closure/ Destructible Tapes; Triple-Ply: Three-Tier overt and / or covert levels of anti-counterfeiting; D2 WAO: Wrap-Around style (up to 35 panels) that fit most cylinders – (U.S. Patent Applied For). Below is an example of ATL’s SecueDetek. This label features an invisible, non-degradable (to 3,000 degrees centigrade) digital forensic code. With this system you can authenticate (anywhere in the world) in one second.

Thus far, the counterfeiting targets discovered in the United States have been largely the popular and expensive “high-value pharmaceuticals”-cancer drugs, performance-enhancing growth hormones, drugs used to treat AIDS, and Viagra. In other parts of the world, however, anti-malaria drugs, antibiotics, and even common analgesics have become counterfeiting targets.
According to the international police agency Interpol, at least 5% of the world pharmaceutical trade involves counterfeit drugs, and up to 60% of medicines in the developing world may be counterfeit. Not only has this cost the drug industry more than $12 billion annually, but it has also resulted in an untold number of deaths. This vulnerability was illustrated when 109 Nigerian children died after taking counterfeit paracetamol (acetaminophen) syrup.

Although many-if not most-counterfeit drugs are manufactured and distributed in India, China, Brazil, South Africa, and Russia, they are poised to make their way to the U.S. market. That is because they are increasingly turning up at pharmacies in Mexico and other intermediary countries and through difficult-to-trace online pharmacies. As a growing number of Americans attempt to save money by purchasing their medication in Canada, Mexico, and other foreign countries or through the Internet, the number of counterfeit or adulterated drugs making their way into the U.S. market is potentially staggering.

ATL strongly suggests that you protect your brands. In so doing you will be protecting the public. Coach Pat Riley said it best: “There’s no such thing as coulda, shoulda, or woulda. If you shoulda and coulda, you woulda done it.”

We would like to give you a glimpse of the counterfeit drug issues as they exist today. The simple fact is that your life may be at risk, or the life of someone close to you. As you read of the startling facts, please look for the words “ATL Security Note”. At this juncture we will recommend a solution that will inhibit (or eliminate) the counterfeiters ability to provide you (the public) with fake or diluted medicines.

Photo Above: Illicit drugs that were gathered during a law enforcement raid.

Counterfeit Medications – History

First documented cases of counterfeit medicines date back to 4th century BC. For more than 2,000 years, issue of fraudulent production of medicines has mostly been ignored.
Today it is multi-billion-dollar worldwide trade. Fake drugs are estimated to lead directly to the deaths of more than 500,000 people a year across the globe.

WHO (World Health Organization)

Definition of a Counterfeit Medicine

“A counterfeit medicine is one which is deliberately and fraudulently mislabelled with respect to identity and/or source. Counterfeiting can apply to both branded and generic products and counterfeit products may include products with correct ingredients, wrong ingredients, without active ingredients, with insufficient quantity of active ingredient or with fake packaging.”

Counterfeit Medications

The illicit business is worth $18 billion. It is estimated that it will double in the next two years. It represents about 10% of all pharmaceutical sales worldwide.
30% of medicines in Russia and some countries in Africa, Asia and Latin America are counterfeit. In wealthy nations this figure is approximately three percent.
In the United States this equates to eight million packs of medicines worth approximately $975 million a year.
Approximately 25% of all emails – 15 billion messages a day – are spam advertising drugs. 50% of medicines offered by websites that conceal their physical addresses are fakes. Counterfeited, diverted, and diluted medications make more illicit money than cocaine and heroin.
In 2005, more than 500,000 single doses of fake medicines were discovered across Europe. In 2006 this number had shot up to 2.5 million. Only because fake drugs have spread from local markets to more global outlets, aided by the rise of the internet, has the world recognized the magnitude of the problem.

Photo Above: This machine is manufacturing fake drugs.

WHO & IMPACT

In February 2006, WHO created first global partnership known as International Medicinal Products Anti-Counterfeiting Taskforce (IMPACT). It is made up of all 193 WHO Member States on voluntary basis. The goal is to improve coordination and harmonization across and between countries so eventually production, trading and selling of fake medicines will cease.

IMPACT focuses on following key areas:
Looks at existing laws in countries.
Provides effective models countries can use.
Develops set of principles for establishment of appropriate legislation and penal sanctions.
Coordinates action at local levels between health authorities, police, customs, and judiciary institutions to ensure proper regulation, control, investigation and prosecution.
Helps countries with weak regulatory systems to strengthen them.
Comprised of five working groups to combat the spread of counterfeits:
- legislative and regulatory infrastructure
- regulatory implementation
- enforcement
- technology
- communication

The United States and Fake Medicines

The US is a lucrative market for counterfeiters of medicines and medical devices. This is because of high prices, a large market, widespread internet connectivity, and complex supply chain. Counterfeits are not normally manufactured in US. They are distributed through online pharmacies, most of which are outside the United States.

50% of medicines sourced from websites that conceal their physical address are counterfeit. These websites advertise and supply medicines illegally, with no prescriptions.
The fake drugs are discovered in the regulated supply chain, through licensed wholesalers, parallel traders, and pharmacies.

Thus, counterfeit medicines reach patients necessitating batch recalls. Fake medicines found in US regulated supply chain are designed to deceive pharmacists and patients into believing that they are genuine. Often only laboratory analysis reveals counterfeit product.

ATL Security Note: the need for lab analysis can be reduced by the use of a mixed and rotated “layered” security approach in labels and packaging. Invisible forensic digital markers can authenticate the product as genuine from virtually anywhere in the world.

Counterfeit medicines discovered in US typically contain reduced amount of active
pharmaceutical ingredient, or wrong ingredient, or no ingredient.

All counterfeit medicines are dangerous.

There are also reports of counterfeit medical devices discovered in US, or seized on their way to US.
Drug counterfeiting occurs less frequently in the US due to strict regulatory framework that governs production of drug products and distribution chain, and enforcement against violators.
The FDA works to ensure overall quality of drug products that consumers purchase from US pharmacies remains high.
The FDA advises pharmacists, physicians, and other healthcare professionals on drugs most likely to be counterfeited and how to identify them.

A suspect patient may have received counterfeit drug if:
He has unexplained worsening of medical condition or unexpected side effect.
He reports drug tastes or looks different, tablets chipped or cracked.
He experiences unusual burning at injection site.

Photo Above: Are you willing to keep taking drugs that are not authenticated as genuine? Will you do this until “death do you part?”

The Internet

Online pharmacies offer benefits of convenience, privacy, and (often) cheaper prices.
Many online pharmacies appear reputable and similar to legitimate retail pharmacy websites BUT sell fake pills that:
- do not contain medicine approved by regulators.
- have doses that are too strong or too weak.
- contain dangerous ingredients.
- aren’t manufactured using safe standards.
- aren’t labelled, packaged or shipped properly.
- are out of date.

Online pharmacies flourish because the public cannot get many new medicines for cancer, dementia, or influenza from publicly funded services. Many sites connected to other sites and have multiple links making investigation difficult. There are jurisdictional challenges as regulatory and enforcement issues cross international lines. The system is difficult to regulate – but governments can do more to warn public of the dangers.

India

India accounts for approximately one-third of counterfeit (fake, diverted, or diluted) drugs.
The EC claims India largest source of 2.7 million counterfeit drugs was seized by its customs in 2006.
India is the number one source of counterfeit medicines, followed by UAE and China.
India’s existing regulations pose little deterrence to unscrupulous drug vendors.

India is to introduce the death penalty for sale and manufacture of fake and counterfeit medicines that cause grievous harm. The minimum prison sentence is to be increased from five to ten years. There will be higher fines for those convicted for trading in fake drugs.

Drug regulatory officials are often in collusion with manufacturers of fake medicines.
It is against the law to sell fake drugs for domestic use, but no regulatory requirements apply to India’s export market.
Common fake drugs are antibiotics, drugs for tuberculosis, malaria, and cough syrups, as well as ingredients for lifestyle drugs.
Exportation of Active Pharmaceutical Ingredient (API) plays integral role in the manufacture of counterfeit medicines.

ATL Security Note: the use of a mixed and rotated “layered” security approach in labels and packaging works just the same when protecting the public for the purity of API (Active Pharmaceutical Ingredients). Invisible forensic digital markers, color-shifting inks, and other covert features can protect the public by ensuring the API are genuine. This is commonly known as maintaining the “pedigree”.

During first six months in 2005, more than 250kg of sildenafil citrate, Viagra’s active ingredient, were exported from India to Europe. Out of one kilogram sildenafil citrate, approximately 14,000 tablets of counterfeit Viagra-pills can be produced. If sold at normal market price of genuine Viagra a profit of up to 2,000% could result.

Photo Above: Real and fake drugs, side by side. Which would you take?

China

In China, between 200,000 and 300,000 people are estimated to die each year because of counterfeit or substandard medicines. The current baby formula incidents are a sad reminder of the human pain and suffering.

China has 80,000 chemical companies, and the FDA does not know how many sell ingredients used in drugs consumed by Americans. China exports “drug ingredients” to customers in 150 countries.

China’s State Food and Drug Administration is not responsible for regulating pharmaceutical ingredients manufactured and exported by chemical companies.
Corruption and lack of protection for whistleblowers undermines China’s attempt to establish a more rigorous drug regulatory system.

In 2007, a series of scandals involving counterfeit pharmaceutical exports led to intense international pressure on the Chinese government. This resulted in conviction and subsequent sentencing to death of the country’s two top drug regulators for accepting bribes.
Some counterfeiters have the same equipment used by pharmaceutical companies.
Cases have occurred of pharmaceutical laboratories that manufacture genuine drugs during business hours and produce counterfeits at night.
Counterfeiters have set up companies that provide service of disposing of expired medicines, thus they obtain real expired medicines that they repack and re-label.

ATL Security Note. Repackaging and relabeling (as described above) could be detected if an invisible forensic code was used in security packaging for the pharmaceuticals. If this covert technique was used, the break in the pedigree could be discovered before the consumer is harmed.

Photo Above: Fake hologram (left), and genuine hologram (right).

ATL Security Note. The following is a portion of the FDA’s conclusions from 2006: “The FDA’s vision of a safe and secure prescription drug supply chain is based on transparency and accountability by all persons who handle the prescription drug throughout the supply chain. With the implementation of the pedigree regulations in December 2006, the FDA expects that supply chain stakeholders will move quickly to adopt electronic track and trace technology, implementing RFID or an alternative track and trace technology in a phased-in approach. Although there are important issues that still need resolution, these issues should not hinder the forward progress and momentum toward widespread adoption. In the meantime, the FDA believes that public health would be better protected if all stakeholders work cooperatively to enable all distributors to pass pedigrees.”

The 2006 Report also considered several technical issues related to adoption of electronic track and trace technology that were perceived as obstacles to implementation and are in need of resolution. These include:
Mass serialization and unique identification of each drug package; and Universal pedigree with national uniform information.

As a brand owner ATL believes that you can protect the public by maintaining a record containing information regarding each transaction that results in a change of ownership of a given drug or pharmaceutical ingredient. This includes its sale by the manufacturer, through the wholesalers, distributors, and pharmacies.
As a brand owner, ATL can work with you to develop:

Lot or batch codes;
Integrated Mass Serialization;
2D DataMatrix Codes;
Forensic (invisible, non-degradable, nano-molecular markers);
Many other covert techniques.

In the 1950’s, when W. Edwards Deming tried to teach U.S. Manufactures about statistical quality control, he was not listened to. At the time, the stigmas of the past (as well as arrogance and ignorance) lived within the powerful decision makers in this country. Dr. Deming went on to huge success in Japan. He believed in quality before it was a buzzword.

“We are here to make another world.” W. Edwards Deming

Photo Above: W. Edwards Deming.

I believe that U.S. pharmaceutical manufacturers (and other brand owners) must protect the public from harm by providing safety and security for the genuine purity of their products. The citizens of the world must demand this.

“We must not inhibit our forward thinking by the comfort levels of the past. If something is not working, you must fix it, repair it, or invent a new paradigm. If you don’t, how many people are you willing to harm for the sake of a few dollars?” Donald J. Dobert, President, ATL.