An unused drug is an ineffective drug, no matter how much it cost to develop, manufacture and administer. The late U.S. Surgeon General C. Everett Koop offered a simpler observation: “Drugs don’t work in patients who don’t take them.”

Amgen’s Sheldon Moberg, Vice President of Device Technologies, reminded attendees at the 2014 PDA Universe of Prefilled Syringes and Injection Devices meeting of Dr. Coop’s wise words during his talk, “Essential Parts of Innovation in Combination Products: Improving Patient Outcomes.”

Moberg identified a variety of barriers that prevent patients from improving their overall health and healthcare outcomes. Among them were “patients unwilling to initiate treatment” and “lack of compliance/adherence.”

Citing data from several sources, he showed that there is a disturbing lack of follow through on compliance/adherence to simple drug regimens following myocardial infarction. After 120 days, 17% of heart medication scripts and 65% of comorbidity scripts go unfulfilled. And these are relatively easy-to-take oral solids.

Moberg did not have any data on patient compliance with injectable drug products, but one can see where his line of reasoning was going. Oral solids are easy because they are painlessly swallowed, room-temperature stable, portable, discreet, simple (no special preparation) and lack disposal issues. Injections are painful, usually temperature-sensitive (necessitating refrigeration), sometimes complex and require special disposal.

Historically, however, injectable drug products were limited in therapeutic areas. But as PDA’s prefilled syringe-oriented conference has shown over the years (and if you missed last year’s, you can attend this year’s meeting in Vienna; visit https://europe.pda.org/ups2015 for more information), injectable drugs are treating a wider range of therapeutic areas, both primary and specialty care, for an increasing number of less severe diseases with broad patient populations.

Injectable drug developers/manufacturers cannot prepare today’s product users like they did in the old days when patients commonly had to visit their doctor for injections. Back then, it didn’t matter if the patient knew how to use the product because typically the nurse performed the injection. Today, not only must patients be able to use autoinjectors and pen injectors, drug companies must make sure they want to use the products they are selling. In some respects, with the barrier between injectable administration and the patient dissolving, developers of such products now must consider the patient’s motives as much as their medical needs. Drug companies, in a way, are now entering the realm of smartphone manufacturers.

Showing that patients can use a product through a variety of human factors testing and usability studies is the price of entry into the marketplace. Regulators will let companies sell a drug with such data. Yet today’s prefilled syringe developers have to make sure the patient wants to use their product.

Moberg offered three considerations for manufacturers:

• Is the product minimally disruptive to lifestyle?
• What are the patient’s perceptions of pain, discomfort, intimidation and anxiety?
• Can you assess the “total user experience?”

He showed a graph of sales for two insulin products administered in pen injectors. One entered the market nearly a decade prior to the other, yet by 2012 the second product had eclipsed the first in total sales. He stated that differences in the pen injector (the second product’s pen had 30% less force and better dosing accuracy than the other product) was one of the reasons for this discrepancy.

“We are delving into human psychology,” said Moburg, and “all bets are off!”

Thus, gone are the days when manufacturers introduce any old autoinjector to the market. Consumers—many of whom demand the latest in technology and innovation when it comes to personal electronics such as smartphones and tablets—expect an injector that is highly innovative and meets their personal needs and preferences. The Universe of Prefilled Syringes and Injection Devices meeting is always replete with innovative technology that should appeal to increasingly tech-savvy consumers. The conference featured talks on a number of these products.

Consumer-friendly Drug Tech Growing

Jarne Elleholm, Business Development, INJECTOR, presented their “next gen” all-in-one dual chamber autoinjector. Kevin Constable, Director, Technology Development, Terumo Medical Corporation, discussed his company’s “innovative” tapered needle technology.

Drug companies considering partnerships with vendors like INJECTOR and Terumo Medical need to employ a solid risk-based approach to vendor evaluation, according to Ivy Lin, Device Development, Genentech/Roche. She noted that quality issues arising from the use of prefilled syringes/injection devices result from the drug manufacturer’s “poor understanding of primary container interaction with the drug.”

Lin outlined her company’s supplier selection process, which includes multiple criteria with distinct workstreams. A figure accompanying this discussion outlined the various criteria and demonstrated how the workstreams overlap and the amount of time needed to prepare and actively engage suppliers (Figure 1).

One innovative approach adopted by Genentech as part of their supplier selection process was changing their “process and mindset on acceptable quality.” The common method for controlling a process is to set an AQL and a sample size based on ISO 2859-1, she said. This method not only reduces the chances of finding defects, it “favors the supplier by reducing ‘producer risk’” which is the risk of rejecting batches, lots and shipments in this case.

Genentech instead took the approach of understanding the suppliers process capabilities and defining the quality level by defective parts per million (DPPM) or parts per million (PPM). This requires an estimation of the percentage of nonconforming parts based on population mean and standard deviation. To make such estimates, test methods must be developed to generate variable data for statistical analysis.

The benefits, according to Lin, include:

• Aligned understanding of expected quality of product between supplier and customer
• Greater process knowledge
• Estimation of nonconformance possible with few or no defective observations
• Smaller sample sizes

She cautioned that the approach “does require some change in practice and understanding of statistics,” and, as such, introduces “complexities” when implementing the approach at the supplier and internally in QC.

Figure 1 Supplier Selection Process*

* From Ivy Lin’s presentation “Applying a Risk-Based Approach for Prefilled Syringe Vendor Evaluation,” 2014 PDA Universe of Pre-filled Syringes and Injection Devices: Improving Patient Outcomes through Innovation

Marketplace Growing for Inject Tech

The 2014 conference proved once again that prefilled syringes and other types of innovative injection devices are already an important segment of the overall injectable drug marketplace, and probably will become even more significant in a few short years.

Dena Flamm, Product Manager, Robert Bosch Packaging, noted the trend away from the traditional vial/syringe and towards pens and autoinjectors for new therapies and generic injectables. Therapeutic areas where these devices are already used are: anaphylaxis, cancer, hormone (including insulin), hepatitis, infertility, multiple sclerosis, Parkinson’s disease, rheumatic diseases, etc. Citing 2012 data, she noted that there were over 30 million users of disposable (most) and reusable pens. Trends in the healthcare marketplace will drive the numbers ever higher. These include the shift to do-it-yourself healthcare, patient empowerment, and, sadly, the growth of insulin diabetics in the United States (the largest market for these devices already).

Manoj Pananchukunnath, Mylan, also spoke to the growing marketplace for prefilled syringes and injection devices. Currently, of the $243 billion (USD, 2013) marketplace for injectable drugs, prefilled syringes, pens, autoinjectors and implants accounted for just 7%. Still, the market for these products can only continue to grow.

With innovative devices, increasing demand, and the need to deliver drugs in devices that technology-minded patients “want to use,” it is clear that the universe of prefilled syringes, autoinjectors and pens will continue to expand for years to come.

[Editor’s Note: This is the second report from the 2014 PDA Prefilled Syringes and Injection Devices conference. “Exciting Technological and Scientific Advances Drive Prefilled Syringe Market” appeared in the November/December 2014 issue.]