In these post-9/11 days, threats of both terrorism and counterfeiting represent complex threats to all elements of the drug manufacturing, transport and sale environments. Drug-product packaging makers, converters, and drug packagers know they face a new world of security issues, but few fully understand how these new issues are changing the legal landscape as well.

Undoubtedly, many strategies that have long been used to enhance quality and control of processes, also now serve to prevent terror or help limit its effects. For example, Good Manufacturing Practices such as quarantining incoming components before use, and undertaking in-process controls of various kinds, are the type of steps that thwart counterfeiting and terror that are already part of many company standard operating procedures.

Steps like these have long been a routine part of drug processing in order to assure the strength, quality and purity of drug products for legal compliance purposes, not security, yet they now have an additional benefit.

Similarly, steps like instituting use of tamper-evident packaging structures; having a recall strategy in place in advance of trouble; lot and batch numbering; integration of the numbering into the distribution system; and even routine security measures at the plant facility, all have been utilized as steps to enhance and assure product quality or control costs, but now also can help serve to prevent terror and counterfeiting.

Therefore, because so many of the steps you are already taking can now serve double-duty as anti-terror and anti-counterfeiting measures, the question is not what should be done, but what else should be done.

When analyzing these questions from a legal perspective, it's interesting to examine the legal definition of a drug product that is "adulterated." The legal definition of adulterated drugs in Section 501 of the Federal Food, Drug and Cosmetic Act and its many subparts, is intended to convey the idea that if anything is wrong with a drug product, that is, anything is not as it is intended to be by a manufacturer, then the drug is adulterated and in violation of the law.

So, for example, the statutory definition says the product is adulterated if it contains any "filthy, putrid or decomposed substance," that a drug is adulterated if it has been packed or held under conditions where it may have become contaminated with filth; or if the product was made in a facility that was not operating in compliance with Good Manufacturing Practices. Even a drug's container, if it is "composed, in whole or in part, of any poisonous or deleterious substance which may render the contents injurious to health," can render the drug product adulterated. Also, if the product purports to be a product recognized in an official compendium, such as the National Formulary, but it differs from that official product in some respect, it is adulterated.

It could be said that this broad-based definition of adulteration evokes, or fits well with, the strategy for preventing terrorism or counterfeiting. Both are broad-based, encompassing every aspect and element of the drug manufacturing and distribution operation, from raw materials through retail shelf.

By contrast, the statutory definition of "counterfeit drug" is rather restrictive. As we know, nowadays a product referred to as "counterfeit" can have one or more of a wide variety of defects or problems. A counterfeit product might simply have the wrong ingredients in it; might have the right ingredients, but the wrong amounts of those ingredients; might have the right ingredients, but the wrong purity specification of them; might be the correct product, but with a false label attached; might be the correct product but distributed in an unauthorized fashion; might be a validly made and authentic product, but be out of date at the time sold; might be a product that has been diverted from the proper distribution scheme; and, although typically thought of as a terror-related concept, might be a poisoned or tampered-with product.

Though each of these types of product defects have been recognized as potential concerns under the broad heading of "counterfeit product," the Federal Food, Drug and Cosmetic Act defines "counterfeit drug" as "a drug which, or the container or labeling of which, without authorization, bears the trademark, trade name, or other identifying mark...of a drug manufacturer...other than the person or persons who in fact manufactured...such drug which thereby falsely purports or is represented to be the product of...such other drug manufacturer."

It is interesting to note the limited sense of the definition of counterfeiting. Happily, this limited definition has not prevented the Food and Drug Administration or other interested parties from attacking drug counterfeiting. FDA has other weapons to rely on, not the least of which is the broad definition of adulteration examined above.

It is becoming increasingly clear that packaging structures and packaging-related strategies can help thwart terror and counterfeiting in a variety of senses. Most obviously, tamper-evident structures and labeling, which have been present for decades, can alert consumers to a product that may not be in its intended form.

If the concern is not with an isolated retail container or package, however, a variety of packaging techniques might be used to authenticate the nature of the product, and confirm its identity. Specialized inks and coatings, and latent codings of wholesale and retail-level packages are examples of such approaches, as are the kinds of track-and-trace techniques that can allow confirmation that a product is what it is supposed to be, and is where it is supposed to be.

Measures aimed at improving security within a manufacturing plant and the chain of distribution are best seen as part of an overall system including these other techniques, and also will work together with packaging, labeling and information systems. Newer forms of bar-coding and radio-frequency identification (RFID) labels are powerful emerging weapons in this connection.

Because the element of consumer education is so crucial to the proper operation of tamper-evident packaging, alerting consumers to be aware of the proper appearance and configuration of a specific product can be crucial. If a consumer is educated to be aware of the color of a package, or a logo, or even the structure and design of the product itself, he or she can look for it to confirm the authenticity of the product. Awareness and education of consumers is and will always be an important element in any security program. Even as it is true that many techniques are designed to be latent, others intended to be seen will often require the conscious participation of the individual consumer. Unfortunately, even if consumers are attuned to spotting differences, counterfeiters are increasingly sophisticated, and can quickly create convincing duplicates of even many sophisticated package designs and products.

We are now more than two years beyond the 9/11 attacks, and a variety of response strategies have been put in place by the US government that affect the way drugmakers do business. Even before 9/11, the FDA had been taking aim at the complex and growing world of counterfeit drugs. It recently reaffirmed its dedication to eradicating this problem by acting to identify risks and threats, establishing coalitions to attack the problems, improving coordination among the various government agencies involved, and developing new tools to prevent counterfeiting and defend against it.

Also important in terms of response to the terror threat was the so-called Bioterror Law, formally known as the Public Health Security and Bioterrorism Preparedness and Response Act of 2002. Among its provisions are requirements for foreign establishment registration, and notice prior to import of products. The law also provided for speeded development of drugs that would be of particular help against bioterror attacks.

In terms of advice for enhancing security, drug packagers in particular might find assistance by examining the "considerations" FDA generated for the food industry. Those included a number of considerations specifically aimed at packaging operations, along with considerations for management of food security, the physical facility, employees, computer systems, raw materials, operations, and finished products.

Among the packaging-related considerations for those in the food industries—again, quite useful for review by the drug industry as well, although often already incorporated into GMPs—are to use only known, appropriately licensed or permitted sources for packaging.

Although the focus thus far has been on regulatory issues and the interaction between these new threats and the traditional statutory provisions, civil product liability will always be a concern if a company is the victim of product tampering or counterfeiting. Because failure to protect against a "foreseeable hazard" is an important concept to a negligence cause of action, one of the important questions—and one that cannot now be answered definitively—is whether a bioterrorism incident, such as a tampering or poisoning of a drug, is a foreseeable hazard right now. Similarly, is a counterfeiting of one's drug product a foreseeable hazard?

It is impossible right now to properly answer the question, nevertheless, the questions should be raised and analyzed. "What is foreseeable?", in the current circumstance, where there is widespread fear and concern about tampering and counterfeiting, but, at least in the case of tampering by terrorists, very limited experience.

Of the many strategies and steps that can be taken to enhance drug-product safety and avoid liability, packaging structures and label structures will always be an integral part. They are best viewed as a central set of considerations that can provide a great deal of assistance in addressing the distinct threats of terror-inspired tampering and product counterfeiting. n