Abstract
New (and proposed) advances in packaging, preserving, labeling, and verifying product integrity of individual tablets and capsules may allow for the recycling of certain expensive medicines. Previously sold, but unused, medication, if brought back to special pharmacies for resale or donation, may provide a low-cost source of patent-protected medicines. Benefits of such a program go beyond simply providing affordable medication to the poor. This article suggests that medicine recycling may be a possibility (especially if manufacturers are mandated to blister-package and bar-code individual tablets and capsules). This early discussion of medication recycling identifies relevant issues, such as: need, rationale, existing programs, available supplies, expiration dates, new technology for ensuring safety and potency, environmental impact, public health benefits, program focus, program structure, and liability.
Introduction
Americans crossing over to Mexico and Canada to buy medicine and Internet pharmacies doing a brisk business in the United States (selling both reimported American-made medicines and low-cost, foreign-made products) suggest that medication is seen as high-cost and not very affordable in the United States. Indeed, US spending on prescription drugs has risen 15% or more per year over the past several years and more than 17% in 2001 alone.[1] In 2002, prescription drug spending increased at a slightly lower, but still considerable, rate of 13.2% over its 2001 level.[2] As a proportion of overall national healthcare costs, prescription drugs rose from 5.8% in 1990 to 9.9% in 2001.[3] A recent report[4] from Families USA, a nonpartisan, nonprofit healthcare advocacy group, found that the 50 drugs seniors used most commonly had, on average, a 6% price rise while inflation, excluding energy, rose 1.8%. Not only do drugs rise in price, but direct-to-consumer (DTC) advertising and drug company marketing practices to physicians (eg, provision of samples of expensive, brand-name medications only) attempt to shift consumers to higher-cost but not necessarily better drugs.[5]
Need for Medicine Recycling
The high cost of medicines (both to consumers and third parties) is a problem that seems to be getting worse rather than better. The new Medicare prescription benefit program does not address the problem of acquisition price, since it prohibits the federal government from directly negotiating with the pharmaceutical manufacturers. In addition, as J. D. Kleinke, a medical economist and author, pointed out: “Every time Medicare expands a benefit, patients come out of the woodwork.”[6] Thus, with little or no pressure on the purchase price and more affordability (at least for seniors), the overall national expenditure devoted to medication will continue to rise. Furthermore most of the population is not covered by Medicare.
Many patients, as illustrated by a study[7] of 1.3 million adults with disabilities, do not take their medications as prescribed because of cost; as a result, more than half reported subsequent health problems. Severe disability, poor health, low income, lack of insurance, and a high number of prescriptions increase the odds of cost-related noncompliance. No doubt, the above is but the tip of an iceberg; many Americans are not able to afford medication vital to their health and well-being. They either completely do without, skip doses, or fail to refill medication prescribed for chronic medical conditions — all because of the perceived high cost of medicines.
Rationale for Medicine Recycling
Although other countries have opted for pharmaceutical price controls and/or curtailing patent protection, such actions run counter to American free-market ideology and political realities. Pharmaceutical manufacturers point out that their industry spent more than $30 billion on drug research and development in 2001, as compared with the total National Institutes of Health operating budget of $20 billion.[8] There is also evidence of a competitive marketplace; in the first year that a medicine goes off patent, its generic equivalent sells for about half the price of the brand-name drug.[9] These and other arguments are sure to be heard by politicians, since pharmaceutical industry political contributions have escalated dramatically and doubled between 1998 and 2002.[9] During the 2002 election campaign, the drug industry contributed $21 million to federal political campaigns for parties and candidates. According to the Center for Responsive Politics, that makes the group the largest contributor.[10]
Drug benefit managers and preferred drug lists or formulary restrictions provide some pressure to keep prices down, but that strategy fails for unique, brand name compounds without any available equivalent. The marketplace seems to be missing a way of enhancing competition for medicines still under patent. One possibility is to allow competition from exactly the same molecule made by the same manufacturer while still under patent protection. Reimporting medicine made in the United States from Canada or Mexico is an example of such a gambit. Unfortunately, the drug makers are already undercutting the effectiveness of this tool. For example, GlaxoSmithKline (GSK) announced in January 2003 that it would no longer sell products to Canadian pharmacies and wholesalers that market GSK drugs over the Internet to other countries.[11] Pfizer, the world's biggest drug maker, following along after GSK (as well as AstraZeneca and Wyeth), is carefully monitoring the orders of Canadian pharmacies it believes are exporting to the United States and now limiting orders to those pharmacies.[12] The manufacturers have the capacity to know who is exporting, since data-tracking companies and drug benefit managers monitor individual doctors' prescriptions. When pharmacy orders spike at a particular pharmacy in the absence of a similar jump in nearby doctors' prescriptions, manufacturers are alerted.
Another possible supply for expensive medication still under patent exists. It is the unused supply that patients are left with when they stop or change medicines. Could we somehow get those unused tablets and capsules to those in need at a reasonable price? Why not recycle widely used expensive medications like atypical antipsychotics, where each tablet may cost $7–$14 each,[13] or Zofran (an antinausea medication often used for cancer patients undergoing chemotherapy), which costs close to $30 per tablet? How about an effort to recycle Gleevec capsules, which cost approximately $27,000 per year for the treatment of a single patient with chronic myelogenous leukemia, a price based in part on the price of interferon, the next best available drug treatment for that disease.[14]
Recycling may also offer a free-market solution to the problem of artificially stimulated demand for a product often paid for by others. The current emphasis on marketing is illustrated by a Families USA analysis[15] of the pharmaceutical industry's brand-name leading companies' 2001 annual financial statements. Brand-name drug makers in the United States employ 81% more people in marketing than in research. Whereas marketing staffs increased by 59% between 1995 and 2000, research staffs declined by 2%. On average, the 9 leading companies spent 11% of revenue on research and development compared with 27% of revenue on marketing, advertising, and administration in 2001.
However, with a recycling program in place, overmarketing expensive, brand-name medicines might backfire on the manufacturer. High initial sales based on unrealistic patient expectations would result in a large supply of abandoned medication available to re-enter the market place at a low price, thereby undercutting sales of newly manufactured tablets. For example, the current blitz of advertising for a variety of brand medications to treat male erectile dysfunction will likely end up with many unused tablets in patients' bathroom cabinets as the medicines do not always work for everyone, nor do they automatically result in happy marriages. Currently, the huge collection of oversold, unused tablets does not adversely affect future sales to other users. However, with medication recycling in place, those unused tablets for erectile dysfunction will come back into the marketplace, offering a cheap alternative to newly produced tablets.
Existing Programs
Leftover drugs prescribed for American patients with HIV are already being recycled for use overseas.[16] Aid for AIDS in Manhattan — a nonprofit group with branches in Italy, Spain and Switzerland — collects drugs after US patients with HIV switch prescriptions, stop medications, or die. The group passes these very expensive retroviral medicines along to more than 500 people with HIV throughout Africa, the Caribbean, and Latin America. In a less formal program, Dr. Mary Annel, a nun working in El Salvador, treats AIDS patients with leftover medicines, prescribed for American patients, that have been collected and shipped by their doctors (who Dr. Annel has enlisted).[16] Both of these efforts are quite legal; current American law makes it illegal to redistribute medications in the United States, but says nothing about exporting them.
There is also a small, domestic medicine recycling program working on a trial basis in Tulsa County, Oklahoma.[17] It operates under a special state statute and involves unused medications from 50 nursing homes. When a resident dies or changes medicines, the remaining medication is transferred to the county pharmacy for the use of indigent citizens. Only about 25 medications are eligible for the program, and each tablet or capsule has to be in its original individual unit (blister wrapped). After weekly pick up by a small corps of retired physician volunteer drivers, the county pharmacist examines the donations for signs of tampering before releasing the medicine for reuse.
The Texas State Board of Pharmacy also just passed a law (HB 2292) that allows all kinds of healthcare institutions to return prescription drugs to pharmacies. These returns must be certified by the facility consultant pharmacist as sealed in the manufacturer's original unopened tamper-evident packaging and either individually packaged or packaged in unit-dose packaging. The pharmacist in the receiving pharmacy also must examine and ensure the integrity of the product. Liability protection for all participants in proper medication recycling is stipulated within the law.
Without fanfare, hospitals, too, all across the country have long internally recycled unused medications returned from patient floors, whenever the original unit dose packaging is intact.
Supply Sources for a Medicine Recycling Program
Nursing homes and other healthcare facilities are not the only possible sources of recyclable medicines. A more important source may be medication in consumers' homes that is unused. Many prescriptions are frequently switched or simply stopped in midstream by prescribers. Leslie and Rosenheck[18] documented the switching phenomenon in a recent article tracking the prescription of antipsychotic medications within the Department of Veterans Affairs. Of the 21,873 patients with schizophrenia who were on stable 3-month prescriptions of any antipsychotic medication, 25% had their medications switched during the next year.
Patients are also likely to stop medication on their own. Not more than 50% of patients adhere to a chronically prescribed antipsychotic medication, typical or atypical in type, for one year.[19] Antidepressants, another costly and widely used medication class, are discontinued even more frequently.[20] As we move away from the mental health arena, adherence is still a major problem. The cholesterol-lowering statins, which, like atypical antipsychotic medications and antidepressants, are prescribed most often for chronic use, show a similar pattern of premature discontinuation, leaving much unused, expensive medicine in consumer hands.[21] Adherence rates for all medications prescribed for asthma range from 30% to 70%.[22] Mail order prescriptions for 90 days (rather than the 30-day supplies usually available from local pharmacies) have further increased the amount of unused medication in consumers' hands.
Expiration Dates
“Expired medication” also represents a potentially large source of supply of medicine for a recycling program. As things stand now, expiration dates get a lot of emphasis. For instance, there is a campaign, cosponsored by some drug retailers, that urges people to discard tablets or capsules when they reach the date on the label.[23] It turns out that the date on the label, however, is often much earlier than the official expiration date. Pharmacists are required to put a “beyond-use” date on prescriptions, which is either the manufacturer's expiration date or 1 year from the date the drug is dispensed, whichever is earlier. The rationale is that containers into which dosage forms are repackaged may not have the integrity of the original package.[24]
However, not only the beyond-use date, but the official drug expiration date itself is usually determined conservatively, and very expensive medication is being wasted. Data from the Department of Defense/US Food and Drug Administration (FDA) Shelf Life Extension Program, which tests the stability of drug products past their expiration date, showed 84% of 1122 lots of 96 different drug products stored in military facilities in their unopened original container would be expected to remain stable for an average of 57 months after their original expiration date.[25] Some US Army studies on Valium, for example, show that the drug is very stable and completely safe and effective for up to 8 years after manufacture. Tablets of ciprofloxacin, an expensive antibiotic, were found completely safe and effective when tested 9.5 years after the expiration date. A recent issue of The Medical Letter[26] quoted not only the above study but others showing expensive medications like amantadine (Symmetrel) and rimantadine (Flumadine) remained stable after storage for 25 years under ambient conditions and retained full antiviral activity after boiling and holding at 65–85° C for several days. Theophylline, in tablet form, shows 90% stability even after 30 years beyond the expiration date.[27] Such stability is not reflected in the manufacturer or pharmacy dating about when tablets or capsules must be discarded. In general, although published data are not available for all medicines, The Medical Letter consultants believe that most drugs stored under reasonable conditions retain at least 70% to 80% of their potency for at least 1 to 2 years after the expiration date, even after the container has been opened (nb: current US Pharmacopoeia [USP] standard is generally 90% potency).[28] With new individual pill packaging techniques, it is highly likely that USP acceptable potency would be the norm over that same time period.
The only report of human toxicity that may have been caused by chemical or physical degradation of a pharmaceutical product is a disputed article (published in 1963) alleging renal tubular damage associated with use of degraded tetracycline.[29,30] The lack of other reports of toxicity from expired medication is reassuring, but the topic of out-of-date medication toxicity is not a well-researched issue.
New Technology for Assuring Safety and Potency of Recycled Medicine
If we have already learned how to recycle everything from newspapers to soda cans and rubber tires, eyeglasses and human organs such as corneas and kidneys, then why not medicines? Medicines would not even have to be remanufactured, just verified. Many tablets or capsules already are packaged individually in tamper-proof wrappings with the name and date of expiration stamped on each one. Such blister packaging is already routine for many over-the-counter medicines and physician samples.
Bar coding of identifying information on the individual pill or capsule wrapper would also be helpful, and we may be closing in on that possibility. The FDA just passed a final rule requiring bar coding on all medication labels (ie, immediate container label and the outside container or wrapper) for all products that might be dispensed in a hospital or other institutional setting.[31] The labels would have to be imprinted with a bar code containing the National Drug Code number that identifies each drug and its dosage form and strength. The requirement would not preclude the inclusion of other information, such as the drug's lot number and expiration date. Bar codes on the medication label would allow for computer scanning at the bedside in hospitals and nursing homes to verify that drug and dosage matched the patient bar code imprinted on patient-specific bracelets — thereby guarding against medication errors.
Unfortunately, since the FDA did not mandate unit dose packaging along with the bar coding, there is still a possibility of bedside errors. Even more ominously, the additional cost of requiring bar codes may cause a decline in the use of unit dose packaging. So, what looks like a very good safety measure may not be such a clear winner. As far as our discussion of the feasibility of recycling, it is clear that bar coding of each unit dose of medicine would be what would be required.
The FDA is also assessing the extent to which new technologies in development, such as color-shifting inks and images (seen only when the package is turned in a certain way) could defeat unlawful copying and counterfeiting. Micro-bar-code tags, special perfumes, embedded threads, and/or implanted radio frequency chips within an individual tablet or capsule blister package might be utilized to establish authenticity and integrity of medicines.[32] While most of these new approaches have not yet been fully developed, implemented, and tested, they hold the promise of a more secure drug distribution system in the years ahead.[33] Not only do these technologies have the potential to make recycling more feasible than previously thought, they will come about anyhow to counter the growing problem of counterfeit drugs.
Additional new developments in packaging address the many compounds that are moisture sensitive, for which exposure to sustained high temperatures and humidity results in significant degradation. However, when a very moisture sensitive compound (eg, PGE-7762928) is packaged in cold-form aluminum blisters, even harsh conditions — 6 months at 40° Centigrade and 75% humidity — results in 100% preservation of physical and chemical stability.[34] Not all blister packaging works as well. In the same study, with a baseline of 82% sustained activity of the compound when unpackaged, there was 84% stability when stored in polyvinyl chloride blisters, 91% in cyclic olefin blisters, 97% in aclar blisters, and 99% in a high-density polyethylene bottle with a foil induction seal. Other studies show that mathematical models can predict moisture uptake by packaged pharmaceutical products during storage under different conditions.[35]
Oxidation is another common way for medicines to lose potency, and there are great complexities in how that may happen, depending up on the compound involved. Still, modern individual dose packaging, either by the manufacturer or wholesaler, can help enormously. Blister packaging, especially in opaque foil blisters, works extremely well. It is even feasible to blister package under nitrogen or argon to reduce the oxygen in the package to begin with.[36] Alternatively, blister packaging with oxygen absorption capacity (eg, self-activated, iron-based oxygen scavengers) could be utilized such that single doses can be maintained under anaerobic conditions.[37] Plastics containing oxygen scavengers have also become available and result in what some have termed “active packaging.”[38] Another new tool, high-pressure processing,[39] already useful in protecting food and extending its shelf life, might be used for the stabilization of heat-labile, fragile pharmaceuticals.
As medicines have risen in price, the differential cost for more expensive protective blister packaging becomes a relatively trivial expense. When one is talking about tens of dollars or more for each pill or capsule, a few cents investment is clearly worthwhile to maintain the integrity of a product long enough (even under adverse storage conditions) to be able to reach a needy patient. Either the FDA or Congress might mandate the use of individual tablet/capsule packaging and identification, or wholesalers or large pharmacy chains might do it for all new prescriptions, expensive items, and any items deemed eligible for return credit and recycling.
Environmental Impact
Although a clean environment is widely championed, we hardly ever talk about pharmaceutical pollution. Recently, pharmaceuticals have been detected in surface water, ground water, and drinking water. Furthermore, resistant bacteria may be selected in the aeration tanks of sewage treatment plants by the antibiotic substances present.[40] Efforts to make sure terrorists do not contaminate our drinking water are in force, herbicide and pesticide levels are examined, but pharmaceuticals abound, and while they are likely safe for humans directly, this may not be so when they are unleashed to work indiscriminately and over time in our environment. One advantage of a pharmaceutical recycling program would be the safe disposal of whatever is unneeded or truly out of date. A 1996 report[41] of how expired medications are being disposed of found that 1.4% of respondents returned medications to a pharmacy, 54% disposed of medications in the garbage, 35.4% flushed medications down the toilet or sink, 7.2% did not dispose of medications, and 2% related they used all medications before expiration.
Another source of environmental pollution, pharmaceutical contamination by way of intact molecules (or active metabolites) passing through urine and feces, may actually be a larger problem, but it is one far removed from the issue of medication recycling.
Public Health Benefits of Recycling Medicines
Unfortunately, when consumers do not properly dispose of medicines, there is also the problem of accidental or, more likely, purposeful overdosage. Suicide is a major public health problem, and the most likely form suicide attempts take is with overdosages of medicine. Whereas many physicians treating suicide-prone patients limit prescription quantities of potentially lethal medicines, that does nothing for the stored bottles of medicines that reside in consumers' homes. Lethal quantities of residual pills in medicine cabinets invite impulsive suicidal action, as well as accidental ingestion by children.
Another benefit from a recycling program would be information about why patients prematurely stop their medication. Information compiled about which medicines seemed to get turned in most frequently is sorely needed to learn about real-world medication effectiveness, side-effects, and adherence. Such data would highlight problems with specific medicines quickly and would certainly be of interest both to pharmaceutical manufacturers and the FDA. Recycling pharmacists might also notify prescribers about the early return of vital medication and/or directly educate patients about the need for continuing medication for chronic indications such as diabetes, hypertension, dyslipidemia, major depression, schizophrenia, AIDS, etc.
Program Focus
A drug-recycling program might begin with a few high-cost products, what the industry calls “blockbusters.” Blockbuster drugs like Lipitor, Viagra, Nexium, Zyrtec, Celebrex, Vioxx, Depakote, Neurontin, Paxil, Zoloft, Risperdal, Zyprexa, and others with sales of $500 million per year or more account for more than 50% of total drug sales in the United States, up from 28% for the year ending July 1997, according to IMS Health.[42] At its peak, $4-per-pill Prilosec pulled in more than $4 billion in the United States alone. These blockbusters are highly advertised and characterized by extremely high mark-ups for manufacturers. Moreover, direct-to-consumer advertising[43] is also highly concentrated on this subgroup of products. Not only the high cost, but widespread use would make blockbusters relatively easy to recycle. For many of the other medicines, there is less demand and better affordability (especially if they are generics). These cheaper and less widely used medicines might or might not be recycled, but even if not resold, would at least be out of the household medicine chest and properly disposed of — at no cost to the person bringing in the unused medicine.
Program Structure
Obviously, much discussion and planning is needed before medicine recycling could become a reality — new laws, regulations about what might be recycled, individual pill packaging for the selected items, rules about who might be eligible to return medication, who might be able to purchase it, rules for exchanging the old pills for a new prescription, how to pay for the infrastructure support, etc.
It might be wise to concentrate at first on recycling from nursing homes and other facilities where there is an unbroken chain of accountability for the medicine. Such medication has never been out of the hands of accountable healthcare workers, and there is a clear trail of when it was purchased for whom and why it was not used. Recycled medicine would have to be individually packaged or still in its sealed original container.
Another approach might be to limit an initial recycling program to only new prescriptions, making them returnable at a discounted rate, perhaps within 1 month of original issue. The consumer would have to bring the medicine back to the same place where it was purchased, with the sales receipt, and fill out a form establishing that the medicine was properly stored and checking off the reason(s) for which it was being returned (eg, allergy, didn't work, side effects, condition cleared sooner than expected, medicine changed, etc.).
Credit for returned medicines might be a fixed percentage of the selling price, with credit going back to the original payers. That would allow the recycling programs to sell or exchange medicine at a sizeable discount. Medicine recyclers might use the difference between acquisition cost and sales price to fund expenses, including overhead, and profit. It would be up to the consumer whether to purchase medicine from regular pharmacies or recycling pharmacies. Indeed, since it is likely that the major recyclers would be retail pharmacy chains, the consumer might be offered the alternative of brand new vs recycled medicine at the same point of sale. Such a system is already in place at certain vendors such as Amazon.com, where returned books are offered for sale alongside of brand new books of the same title. In any event, a valid prescription would be required for any medication. Medication insurance coverage might apply to purchases of recycled medication, although copays might be entirely waived for this cheaper source.
Commercial insurers as well as government programs would benefit from the lower prices and might offer consumers incentives for returning or purchasing medicine at recycling pharmacies that were even greater than just decreased or waived copays. Whatever the rules for who could return or purchase recycled medicine, care would be needed to prevent fraudulent schemes. There should be no chance to recycle for personal gain, especially when the original medication was purchased for the patient by some third party, public or private.
Liability Risks
Liability is a particular concern in our litigious society. One can make the argument that pharmaceutical manufacturers, like car manufacturers, should not be held responsible for resold products. Recycled medicine, like used cars, are not brand new, so the original manufacturer carries limited responsibility for what happens after the original sale. Special recycling pharmacies would carry malpractice risk if they mistakenly certified a particular set of pills as still usable when they were not. Like all such professional risks, this one might be insurable and become a routine business expense.
Conclusions
Individual tablet and capsule tamper-resistant packaging, including bar code identification of manufacturer, date of manufacture, expiration date, medication name, and dosage would bring us close to the possibility of recycling appropriately chosen medications. Such a system, combined with appropriate safeguards to assure product authenticity, is worth discussing.
Special recycling pharmacies would have to work with manufacturers, wholesalers, retail pharmacies, health insurers, and the FDA to work out ways to make the whole process of drug manufacturing and distribution compatible with recycling. No doubt Congress would have to pass new laws and insurance companies would have to determine liability risk. That is a lot of work and a lot of change.
Clearly, there would also be the need for the FDA to fully monitor and stop the distribution of recycled medicines that might be adulterated, misbranded, expired, subpotent, contaminated, or counterfeit. That task may not be one that the FDA embraces, unless substantial additional funds for monitoring are made available either by Congress or medication recyclers.
Recycled medication may actually be easier for the FDA to police than the current situation in which imported drugs are already a big problem.[44] Starting out with approved products, with a known date of domestic manufacture and original sale, verified by special pharmacists, may be safer and easier to monitor than Internet arrangements from foreign suppliers. Those risky medication purchases are sure to increase unless there is an affordable alternative source of medication for people pushed to the wall by the current high cost of essential medicines.
Whatever the safeguards, recycled medicine, like imported medicine, may pose an additional risk to consumers, but so does going without needed medication or skipping doses to save money. It comes down to the following: in an ideal world, no one would chose to buy a used car, day old bread, clothes from Goodwill stores, or retreaded tires. Although recycling medication may seem like a risky and bizarre idea, new technologies may make it reasonably safe — or at least safer than no medicine at all for whole groups of people. Throwing away valuable resources when there is apparently not enough to go around is cavalier and unfeeling, not to mention poor public policy. Either medication prices come down, insurance covers medication for all Americans, or we begin a discussion of other options, like recycling.
By no means should we ignore patient safety issues or liability concerns. These are thorny issues, yet new technology offers interesting solutions. We will never know if any plan for medicine recycling can be safely done unless we begin the discussion. Although less preferable than newly manufactured medicine, recycling unused, expensive medicines may be a better alternative than the existing status quo.
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