Product Safety In The U.S. Pharmaceutical Supply Chain: 3 Strikes And Yer Out!

By Walter Berghahn, executive director, Healthcare Compliance Packaging Council (HCPC)

Current legislation and pharmaceutical packaging fall short of protecting the product and the patient.

Three strikes? Yup, three strikes. The industry, which provides $310 billion of pharmaceuticals to hundreds of millions of Americans, misses on supply chain safety, patient safety, and product safety. How can this be?

The first strike on supply chain safety is attributed to ineffective DQSA legislation that will not guarantee a safe drug supply for U.S. patients. Not only does the law fail to secure the supply chain, but also it will take 10 years to take full effect (or be “in-effective,” if you will). We could be generous and qualify this one as a foul tip, since the industry had “help” from the federal government, but when the industry had the chance to push for stronger, more effective requirements during the legislation’s development, it chose not to, so not much credit on that one.

Strike number two is patients’ safety. Consider the following statement.

Health care costs continue to hit all-time highs with patient noncompliance a significant contributing factor .... Poor adherence to medications causes an estimated 125,000 deaths annually and accounts for 10 to 25 percent of hospital and nursing home admissions .... This makes noncompliance one of the largest concerns facing the healthcare system and managed care (www.amcp.org/).

These figures are supported by numerous sources. At the heart of the problem is a lack of communication with the patient. Specifically, communication about:

• The condition being treated
• What the medication is doing
• What patients might feel while the medication is working
• The importance of adherence to the regimen.

Current prescription packaging does little to accomplish these goals. Some of these important points are addressed in the fine print of patient inserts that are rarely read. Critical information, as well as dosing reminders and a record of doses taken, should be readily visible to patients and caregivers alike. Compliance prompting packaging could be an important tool in the fight to improve adherence, influence health outcomes, and save lives.

And strike number three — product safety. A recent study completed and soon to be available from the Healthcare Compliance Packaging Council (HCPC) provides evidence that solid dose pharmaceuticals are not getting adequate protection from the environment during normal use cycles in standard pharmacy prescription containers.

The HCPC, assisted by member companies Bilcare Research, Legacy Pharmaceutical Packaging, Constantia Flexibles, and Klöckner Pentaplast of America, developed the study to investigate the degradation possibilities of three commonly used chronic condition drugs during standard patient usage periods of 30, 60, and 90 days. The three drugs were packed in five different commonly available packaging formats and exposed to environments similar to those found in the home. The study’s resulting data is supported by numerous past studies that point to drug storage conditions in the average household as having the potential to impact drug quality and efficacy.

Numerous articles going back more than 10 years have alluded to the conditions encountered in mail order (high temps) as being hazardous to drugs and their potential efficacy. Conditions in the home are by no means as severe, but repeated exposure to moisture and oxygen during normal use will degrade a product’s physical characteristics, as the study demonstrates.

The pharmaceutical industry in the U.S. generates $310 billion a year in income, which represents 10 percent of our annual healthcare spending. Due to “strike two” alone, misapplication of pharmaceuticals costs us approximately $290 billion additional per year in costs related to poor medication adherence and outcomes. Even this ignores the potential damage caused by poor safety in the supply chain and possible losses created by substandard drugs due to inadequate protection during normal use. Think about that fact: Our existing system has an error cost ($290 billion) almost equal to the gross income from product sales ($310 billion) due to poor adherence — a total cost of $600 billion to the U.S. healthcare system! It is time to shift the paradigm of our antiquated delivery and dispensing system that is at the core of poor outcomes and higher costs.

The industry (from manufacturer through pharmacy) seems to have forgotten that making a great drug and dispensing it are not enough. It needs to travel safely to the patient, maintain its full potency during normal patient use, and be properly taken by the patient to receive the designed clinical benefit. Anything short of this is a failure.

So, Where To Begin?
Let’s start with DQSA, strike #1. The premise of this legislation is that serialization of primary containers and basic tracking of IDs at points in the supply chain (exchanges of ownership for the most part) will reduce the opportunity to introduce counterfeit, stolen, or diverted products, since the serial ID will show that a product is out of place or has been flagged for one problem or another.

In FDA terms:

• Enable verification of the legitimacy of the drug product identifier down to the package level.
• Enhance detection and notification of illegitimate products in the drug supply chain.
• Facilitate more efficient recalls of drug products.

Sounds plausible. It could work well until we enter pharmacy (retail, central fill, or mail order) and the container is cracked open for repacking into a patientready format. Now all bets are off. We’ve just opened the door for unscrupulous pharmacists (and sadly, they do exist) to introduce any of the following:

• Counterfeit or diverted drugs
• Outdated drugs
• Recycled drugs (returns from patients or institutions)
• Recalled drugs
• Stolen drugs
• Unlicensed drugs
• Misbranded drugs
• Illegally imported drugs (bought from Internet or outside the country).

You might think, “Is he making this up?” Sadly, no. These are all well-documented events in U.S. pharmacies, and no one truly knows the scale of the problem. Some estimate that one percent of the U.S. supply chain may be counterfeit. In reality, we only know what is captured during inspections by state boards of pharmacy, pharma manufacturers’ investigators (they have their own), and law enforcement agencies (DEA, FBI). One would have to imagine that more inspections would likely uncover more problems; i.e., we don’t know what we don’t know. We do know that research on Internet-sourced medications shows as many as 98 percent of those pharmacies are not legitimate. Now, some may say that one percent is not that bad considering some countries, specifically some in Africa, have counterfeit rates higher than 50 to 60 percent. However, consider that in the U.S. with more than 4 billion prescriptions dispensed annually — one percent means more than 40 million prescriptions could be counterfeit. That’s not acceptable.

The real concern is that none of the abovementioned problems will be stopped under DQSA because quite simply, the law doesn’t cover the backdoor of the pharmacy. Some pharmacy lobbyist groups worked with Congress to be sure that wouldn’t happen. I understand protecting your turf, but at what cost?

The Impact Of Poor Medication Adherence
Current containers that are distributed by pharmacies do little to help patients understand the drug and the disease being treated, remind them of dosing times, or say why adherence is important. They lack critical bits of information that help create compliant patients, so they can receive the designed clinical benefit of a medication. At the core of this problem lies the amber vial, a container by the way that was introduced in 1955! Well, why is this a problem?

The amber vial (or white HDPE bottle found in mail order and central-fill pharmacies) has been a container of convenience for pharmacies. It is not designed to facilitate proper use or educate the patient about the condition being treated or the importance of adhering to regimen. Going back 25 years, the HCPC has been working to promote broader adoption of compliance prompting packaging, which, in many cases, is unit dose format with a calendar feature providing a visual reminder to patients of doses taken (think the birth control compact), as well as providing space for critical messaging from the manufacturer. Examples of studies supporting this approach can be found in a whitepaper on the group’s website.

We live in the information age surrounded by all manner of devices spouting information to aid us in navigation, communication, shopping, exercising, and on and on, yet our prescription container that holds life-saving medications is mute. It’s truly in this day and age, inexcusable. At the very least, a complianceprompting package will provide visual reminders to patients of doses taken, provide visual evidence of dosing for caregivers who come into the home, and provide visual reminders for refill timing. The ability to link with email, texting, or other social media features only enhances the package, reenforcing the visual reminders in place.

To give some perspective to the scale of the problem, consider this — 125,000 deaths per year from poor medication adherence-related problems, the statistic noted earlier from the Academy of Managed Care Pharmacy, is the equivalent of a jumbo jet crashing and killing all on board every single day of the year. Think about that. If jets were dropping from the sky daily, it would get our attention. You might also be afraid to step outside. If that were happening, do you think we’d take action? I like to think so. So why has this poor performance of pharmaceuticals been off the radar for so long?

On to strike three and the referenced stability study. In short, the study from HCPC shows that the physical characteristics of three common medications (Lisinopril, Metformin, and Simvastatin) are significantly impacted by repeated exposure to anticipated environmental conditions that are encountered during normal prescription use cycles. The drugs’ hardness and disintegration times were altered by as much as 60 percent in as little as 30 days.

For example, in a 30-day supply of Lisinopril, there are significant changes in hardness, as much as 60 percent, in 30 days. This directly impacts the disintegration time of the drug, which can affect product absorption into the body. The study did not look at impact on active ingredients and cannot make any claims regarding true impact on efficacy, but the mere fact that such a dramatic physical change takes place in a relatively short time demonstrates that current packaging methods lack protection. Faster disintegration alters the product’s absorption rate, which, for some drugs, will alter performance and could even be dangerous.

The complete study can be found at www.hcpconline.org.

What Do The Three Strikes Have In Common?
Well, most notably, better packaging of the prescription could help alleviate them — all of them. The concept of unit dose packaging is not new. The first and probably most famous of these packs was the birth control blister or compact, which was developed in 1960 to accommodate a drug that required a specific dosing regimen be maintained for product efficacy. But isn’t that the case for most medications? Isn’t a consistent dosing regimen the goal? So this package, in addition to being unit of dispense (maintain supply chain security, no repacking in pharmacy), also represents the first complianceprompting package and, to date, compliance with birth control pills is among the highest of any drug category, more than 95 percent by most accounts.

The immediate reaction to this statistic is always, “Of course women are compliant with birth control pills; they understand the risks of noncompliance!”

So, by that logic, we have trouble explaining the following adherence rates.

• Organ rejection drugs — 82 percent compliance where the risk is death (now, pregnancy may be bad, but death is worse)
• Beta blockers following a heart attack — 45 percent
• Various medications for diabetes or congestive heart failure — 42 percent compliance
• Glaucoma patients having been told their sight is in jeopardy — 42 percent; goes to 58 percent once they have actually lost sight in one eye (NCPIE).

So, the argument of understanding risk and medication adherence falls away. Where does that leave us? Three strikes addressed: Original manufacturers’ packaging passing through the pharmacy for security, aiding patients in adhering to regimen, and protecting the product through the normal use cycle. Sounds like a plan.

Primary packaging, whether manufacturer- or pharmacy- based, is the only component other than the drug itself that reaches every patient. Unlike cartons and leaflets, which may not survive the pharmacy, and well-intended advice, which travels in one ear and out the other, primary packaging will reach the patient and is capable of communicating critical information about the drug, the regimen, and the condition being treated. Why shouldn’t we demand more of this component which transports, protects, and delivers life-saving medications? Pharmaceutical packaging has an important job to do, and we have the capability to enable it to perform — we simply need to decide to do it.

Patients need to take effective medications in the prescribed manner to gain the designed benefit of the drug. That is the goal. Nothing else matters. Anything less is failure.

Prior to his current role as the Executive Director of the Healthcare Compliance Packaging Council (HCPC), Walter Berghahn worked as the VP of Packaging Technology for AmerisourceBergen Packaging Group, participating in numerous supply chain security projects, including Drug Security Network, GS1 Healthcare Users Group evaluating serialization, RFID, and anti-counterfeiting solutions.