All Hands On Deck: Pharma Meets Packaging Challenges Head-On

Serialization looms large as new technologies prove to be worth their salt

By Doug Bartholomew, Contributing Editor

Once viewed as a mundane part of the business — or in the case of child-resistant closures, a necessary fix — primary packaging of pharmaceuticals suddenly has morphed into a hotbed of creativity. From measured doses of biologic drugs self-administered by syringe, to electronic wearable injectors, to calendarized, unit-dosed blister packs containing multiple pages of patient instructions inside the label, the once-staid business of packaging drugs is evolving into a platform for innovation.

This vastly expanded variety of drug delivery formats has come about largely as the industry has sought to navigate its way through a veritable Scylla and Charybdis of regulatory requirements on the one hand, and security challenges on the other.

Admittedly, some of the latest pharmaceutical packaging trends can be traced to new kinds of drugs — biologics and the new class of biosimilars, for example — that require fresh approaches to the way drugs are administered to the patient, and new technologies that enable them. No one expects the basic plastic pill bottle to go the way the pair of pliers did in dentistry anytime soon, but chances are that most people have already encountered some of these new packaging methods when filling a recent prescription or purchasing an over-the-counter medicine.

This article will examine some of the key challenges having an impact on primary packaging, and how pharmaceutical manufacturers, contract firms and packaging vendors are responding.

SERIALIZATION
Perhaps the biggest single challenge confronting the pharmaceutical industry from a packaging standpoint continues to be the need to combat the onslaught of counterfeiting that has swamped global pharmaceutical markets. The call for serialization has come about largely in response to this problem.

“The main challenge facing the industry in the United States as well as the EU will be the implementation of the requirement for serialization of all pharmaceutical product down to the smallest unit of sale,” points out Rick Seibert, senior vice president for Global Innovation and Technology Services at Sharp Packaging Solutions. “This regulatory-driven change will fundamentally change the way product is packaged, and possibly more importantly, labeled and safeguarded in the future.”

Jerry Martin, Pharmaceutical and Life Sciences consultant for the Association for Packaging and Processing Technologies (PMMI), recalls how several years ago he was contacted by a company that had developed a unique 2D barcode system designed to help eliminate drug counterfeiting. But when he approached some pharmaceutical companies with the idea, they weren’t interested. “We ran up against a complete denial that there was any problem,” he says. “And the FDA said it was not capable of policing the markets for counterfeiting of drugs.”

Finally, the problem got so bad that regulators in Europe and the FDA in the United States issued regulations requiring the serialization of packaging for tamper-proof medications, as well as the establishment of a track and trace system. In the U.S., these regulations go into effect over the next couple of years.

But having the technology to achieve track and trace and manufacture tamper-proof packaging is one thing, and ensuring that the entire global industry adopts the same technologies is another. “Companies are working together to come up with a compatible system for drugs moving through the supply chain,” Martin says. “The challenge is to come up with an internationally harmonized system — not unlike the UPC system for consumer products that we have now.”

In effect, that means everyone will have to use the same hardware and software to connect seamlessly across the various global supply networks throughout the industry — a tall order, to say the least. But Martin, for one, believes it can be done. “Serialization will eliminate the ability of counterfeiters to put product on the market,” he says. “This way, labeling will enable the distribution system to detect counterfeiting before products even get to a pharmacy.”

“Serialization will come to different parts of the world at different times,” says Carlo Domeneghetti, corporate procurement packaging COE Lead at Patheon in Monza, Italy. “But once in place, serialization, combined with tamper-evident packaging, will be the best way to guard against counterfeiting.”

Packagers are likely to take a layered approach to guarantee security and product integrity. “Ideally, there will be additional security features — some covert, some overt — deployed by brand owners as well, offering a tiered/layered program to assure security and product integrity,” says Seibert of Sharp.

One packager taking the lead in the march toward serialization is Wheaton Industries. The company’s crimp-top vials, which have a plastic coating around the glass the company calls DualFusion, come with a 2D barcode laser-etched on the vial bottom that can be read by a barcode scanner. “Using the scanner, the medical professional can verify that they are giving the right drug to the right patient, because the barcode identifies that drug with that hospital and that patient,” explains Wayne Brinster, CEO.

PLASTIC VS. GLASS
The plastic vs. glass debate continues to roil the packaging waters, with the glass camp pointing out their material’s benefits and the plastic adherents doing the same for their material.

At the heart of the dispute is the all-important issue of drug quality — i.e., ensuring that all pharmaceutical substances, especially the expensive biologics, are not reacting with their primary container’s material. Glass contains silicon, which can chemically interact with some substances contained in various drugs.

Glass adherents counter with the claim that plastics can react as well. “Plastic water bottles can leach out chemicals, but Type 1 pharmaceutical glass is not going to change a drug,” adds David Machak, a consultant at American Glass Research in Butler, Pa.

Even so, the trend is toward plastic, especially for biological drugs. “Due to the potential defects of glass, the market is slowly moving to plastic solutions,” says Patheon’s Domeneghetti. “Even in syringes, there is a slow trend to move to plastic.”

As an example of this shift, West Pharmaceutical Services is using its Daikyo Crystal Zenith vials with its FluroTec stoppers to contain Amgen’s FDA-approved oncolytic virus therapy, Imlygic. Manufactured from a cyclic olefin polymer, the CZ vials offer a break-resistant alternative to glass for complex drugs.

Some packagers have solved the problem by marrying glass and plastic. In the case of Wheaton Industries’ DualFusion plastic-coated vials, because both the glass and the plastic layer are fused together, the finished vial can withstand breakage when dropped on a hard surface such as a terrazzo or concrete floor. “The inner layer of organosilicate eliminates exposure to metals or problems with delamination,” Brinster says.

SELF-ADMINISTRATION
As more biological drugs including biosimilars are being self-administered by patients at home, the dual issues of ease of use and convenience take on greater emphasis than in the past, when such drugs typically would be given in a clinical setting by healthcare professionals. For instance, having primary packaging designed to deliver a consistent injection rate can help ensure that patients taking drugs at home receive the accurate dose for their treatment regimen.

Packaging industry experts caution that self-administration of drugs must by necessity place the emphasis on clear instructions to the patient. “There is a need to provide patient education and training on the devices and delivery systems in addition to the traditional dosing information,” says Seibert. “Coupling these types of programs with the physical package is a solid value proposition we discuss with all clients in the design phase of our project development process.”

INNOVATION
One of the challenges posed by this brave new world of pharma packaging is the need to innovate to avoid falling behind the competition. Among those taking the lead in this area is West Pharmaceutical Services, asserts Martin of PMMI. In July, Amgen received FDA approval for a single, monthly 420 mg dose delivery option for the Repatha cholesterol-lowering drug using West’s hands-free device called the SmartDose electronic wearable injector. The device adheres to the patient’s body, usually on the abdomen, allowing the patient to be hands-free while taking the drug.

“This is clearly an example of differentiation and innovation in pharmaceutical packaging,” Martin says. “The auto-injector makes it easy for patients to take the drug called without having to see the needle. The patient uses a self-contained syringe mechanism with a pushbutton, so everything in the self-administration process is automatic.”

In another example of innovation, Pharma Tech Industries, a contract manufacturer, received approval last January for a novel approach, a drug-device combination consisting of a nosepiece device containing two doses of a common migraine medicine for patients to take the drug in a nasally inhaled form. “The drug is sent to us from the drug manufacturer Avenir Pharma, and we make the product for a distributor,” says Lori Hall, director of quality engineering at Pharma Tech in Athens, Ga.

PATIENT COMPLIANCE
Exacerbated by an aging patient base as waves of baby boomers reach the age of seniority, the challenge of ensuring that patients take their prescription medicines in the proper doses and at the proper times looms larger than ever. The global revenue loss to the pharmaceutical industry as a result of the failure of patients to take their medication for chronic conditions alone is estimated to be $564 billion, according to research by CapGemini Consulting.

“A key challenge for the packaging industry is the aging patient base and compliance,” Martin says. “Pharmaceutical containers have to be tamper-proof, but they also have to be easy for elderly people to open. I’ve seen some blister packs that are more difficult for people who don’t have the dexterity with their hands that’s required to open them. As the baby boom ages, drug containers have to be designed so it’s easier for people to take their medicine.”

By contrast, he says, the use of auto injectors for biological drugs are an example of easy-to-use packaging. “I envision greater use of devices to ensure compliance,” Martin adds. “Already we are seeing more pre-filled syringes. Companies are coming out with packaging systems that make it easier for people to self-administer drugs.”

Pharmaceutical benefit managers today are requiring results in the form of improved health outcomes, but the simple fact is that “drugs only work for people who take them,” says Eric Resnick, vice president and chief technology officer at West Pharmaceutical Services in Exton, Pa. In the last decade, the 90-plus-year-old company has evolved beyond the traditional approaches, developing new packaging designed to provide both containment and drug delivery mechanisms.

“Simply saying that a device or package has to work is no longer acceptable,” he says. “We need to understand why people are not using a specific drug — is the device too complex or too difficult to use?”

West Pharmaceutical Services helps ensure patient compliance through its alliance with HealthPrize Technologies, which integrates a medication adherence and patient-engagement platform with West’s injectable drug delivery systems. The combined approach provides a voluntary, electronically connected drug delivery system that tracks when patients take their medication, with patients receiving reward incentives for taking their medication on a regular basis as prescribed.

Additionally, a number of “smart” technologies are entering the pharmaceutical packaging scene. Silicon Valley startup Proteus Digital Health has developed a “smart pill” embedded with an ingestible sensor that sends a signal to a wearable sensor patch when the pill is digested. Patients and doctors get alerts when pills are swallowed, so that doses are not missed. NYC-based startup AdhereTech offers a smart pill bottle that uses wireless technology to collect and send adherence data in real-time. The pill bottle lights up to remind patients to take pills, as well as sends customizable reminders when a dose is missed.

A COMMON PLATFORM?
Today’s drug packagers are actively pursuing a host of new solutions to the various challenges they face, including those posed by regulatory, security and new drug therapies. But the jury is still out on how quickly the global pharmaceutical industry will be able to pull together a common technology platform that will enable drug packagers to achieve global serialization, thereby reducing or eliminating drug counterfeiting and diversion.