Clinical Trials

Compliance

Drug Delivery

Non-adherence

Q2 2016

Single-dose Packaging

<h3>Contract manufacturers, the pharma industry they support and the healthcare community are working hard to address medication non-adherence and improve patient outcomes; but more can be done to ensure innovative medicines achieve their full potential.</h3>
<p>It’s well established that children, seniors and even cogent, non-impaired adults are prone to use their prescribed medications incorrectly. Medication non-adherence is a significant and ongoing risk to patient safety — its consequences create significant waste in health care, and cost even more in terms of poor patient outcomes. The healthcare industry has been studying this problem for decades, yet in spite of all the papers, studies and data, the challenge continues, with non-adherence rates and associated costs still on the rise.<sup>1</sup></p>
<h4>Stakes Are High, Risks Even Higher</h4>
<p>Among the more exciting trends in pharma is how increasingly important the biopharmaceutical sector has become to the future of the industry. Over the past decade, some 300 new prescription medicines have been approved for use by the FDA, and in recent times the agency has accelerated its approval process, completing more approvals in 2014 than any other year in its history.</p>
<p>According to PhRMA, a high percentage of New Molecular Entity-focused development activities are potentially first-in-class (those described by a unique pharmacological class distinct from those of any other marketed products): 78% of projects in phase I, 69% in phase II and 45% in phase III were potentially first-in-class. This means that if all goes well, the best ones are approved and, being first-in-class, have the potential to become blockbuster medicines, improving outcomes for many patients.<sup>2</sup></p>
<h4>Potential Gains In Jeopardy</h4>
<p>The pace of investment and corresponding drug development have contributed to a range of new treatments, resulting in improvements in the length and quality of life and reduced disease burden for individuals and society. But the extent of these dramatic gains may be in jeopardy as actual patient outcomes fail to match clinical results — the same ones that set expectations and measure the net societal health benefits of a given medication. Surprisingly, the results observed in clinical trials for these new and novel therapies do not always translate into what is being experienced by consumers in the marketplace. While there are a variety of causes, one key is that medications in the “real world” are not taken in a controlled manner like in clinical trials. When patients don’t take medicine as prescribed, they don’t get the desired results; the question is why would any pharma innovator invest a billion dollars or more on a new drug only to jeopardize future returns because of an inferior dosage form?</p>
<h4><img src="http://thatsnice-testing3.com/legacy/Q2_%202016/Sidebar%20Images/16Q2_Unither_Sidebar1.jpg" alt="16Q2_Unither_Sidebar1.jpg"></h4>
<h4>Roots Of Non-Adherence</h4>
<p>The causes of poor adherence, according to a WHO report, are often complex. Recently, the WHO analyzed contributing factors related to the specific condition being treated, health systems, social and economic conditions, the therapy itself, as well as the contribution of the patient. The report indicated that the simplicity of the dosage regimen and side effects were the greatest therapy-induced factors related to adherence.<sup>3</sup> The organization noted that the complexity of self-administration increases rapidly with the use of multiple therapies for the same condition or those with multiple conditions in the same patient.</p>
<p>Last July, the Centers for Disease Control and Prevention called adherence rates in the U.S. “unacceptably low,” citing a report that showed only 38% of teen girls and 14% of teen boys finished the three-dose Anti-HPV vaccine series. Comparatively, the adherence rate for two doses was 57% for girls and 35% for boys. CDC’s report reveals that even patients with access to care givers and medical guidance have trouble adhering. In response, the required three-dose course was trimmed by dose, a change to improve adherence.</p>
<p>Awareness is helping, and while physicians, pharmacists and others providing care to patients are playing their part to fight non-adherence, the industry must remain proactive, pursuing new opportunities and innovating consumer-friendly dosage forms to mitigate this chronic healthcare issue.</p>
<h4>Multi-Faceted Approach Best</h4>
<p>Education of patients about their diseases, the action of the medications, the expected response time and the consequences of failing to adhere to prescriptions are crucial for increasing adherence. Physicians must consider their patients carefully and learn how best to communicate with each individual, taking into account his/her risk factors for nonadherence. Similarly, modern technology allows pharmacists to more actively monitor adherence for customers who regularly purchase medications from them.</p>
<p>Simplifying medication regimens and increasing the convenience and access to medications are two popular strategies for improving patient adherence. For example, the number of medications can be reduced by using combination therapies and finding alternative drugs that can treat multiple diseases. Similarly, formulation and dosage strategies to lessen daily dose frequency are proving effective (as the CDC report showed). For example, switching to extended-release versions of current medications can reduce the dose frequency. Prescribing a convenient and easy-to-use dosage form in pharmaceutical packaging designed to encourage adherence has become a cost-efficient and effective tactic by drug makers. Better adherence leads to higher volumes and efficiencies, which improve drug affordability—an important factor that supports everyone’s access to health care.</p>
<h4>Better Compliance By Design</h4>
<p>Simple things like deploying easy-to-open, easy-access containers can have a significant and positive impact on geriatric patient adherence. Similarly, better-tasting formulas or easier-to-swallow forms can result in improved compliance. The pharmaceutical manufacturing industry needs to follow the lead of other consumer-focused industries, such as personal electronics, by designing better packaging and administration devices, then using advanced manufacturing technologies to manufacture affordable, convenient and easy-to-use drug forms.</p>
<p>Unither Pharmaceuticals, for example, specializes in the development and contract manufacturing of unit-dose pharmaceutical products. The company also offers a range of dosage forms and delivery systems that are convenient, affordable and easy to use.</p>
<p>Unit-dose delivery of medication is widely used in healthcare facilities in the U.S. and Europe to prevent medication errors. It’s clear the benefits of single-dose packaging are an advantage for many patient populations, such as helping the elderly to live more independently. Single-dose delivery systems are accurately filled to hold only the quantity of drug intended for a prescribed single dose and are meant to be opened only once. Many dosage forms — oral, topical and injectable — can be packaged as unit doses: blister or pouch packages for oral solid formulations, plastic syringes with rubber tips and squeeze tubes for oral liquid medications, sterile blow-fill-seal forms for ophthalmic and inhalation therapies, pre-filled syringes and cartridges for injectables, and stick-packs for liquids, suspensions and gels for oral and topical administration.</p>
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<h4 class="callout-title">Unit-dose delivery of medication is widely used in healthcare facilities in the U.S. and Europe to prevent medication errors.</h4>
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<p>Study after study shows single-dose packaging helps reduce medication errors.<sup>3,4</sup> Medications, especially tablets delivered by the hundreds in bottles, can be problematic for many, and even the simple act of sorting for one or two pills can expose medicine to loss, contamination and plain old gravity if the bottle is dropped. Single unit-dose medications can be clearly labeled and also include information on the dosing regimen, including calendars and other prompts such as color coding to guide consumption. For active patients away from home, single-dose packaging provides great convenience and portability. There is also reduced concern over contamination when traveling because each dose is surrounded by protective packaging. In many cases, the use of unit-dose technology allows for the removal of artificial preservatives and longer shelf life. The most effective pharmaceutical packaging designs also serve as deterrents to counterfeiting and incorporate child-resistant features, while still allowing easy access for elderly patients. Another type of single-dose package that is portable, easy to open and administer are stick-packs. The premeasured sticks can be filled with powders or liquids. Liquid stick-packs reduce the likelihood of spilling a spoonful of medication while trying to gain a resisting child’s compliance or when administering liquids to geriatric patients with tremors. The Healthcare Compliance Packaging Council (HCPC), established in 1990 to promote the many benefits of unit-dose packaging, highlights several case studies demonstrating increased patient adherence for various types of medications (e.g., birth control pills, certain antibiotics, hormone replacement therapies, steroids, etc.) through the use of modern packaging solutions, and particularly compliance-prompting packaging that reminds people whether they have taken their medications.<sup>4</sup></p>
<p>Pharma is becoming increasingly aware of the need to develop consumer friendly dosage forms. The market success of Humira is a good example. Cited by Drug Development &amp; Delivery’s 2015 “Global formulation Report,” analysts noted that while the formulation for Humira has remained largely constant since its launch, AbbVie has consistently developed improvements in the drug/device configuration to better match outpatient needs and be easier to administer.<sup>5</sup> Launched in early 2003 with a vial presentation, the study notes a switch was made in mid-year 2004 to prefilled syringes. In 2006, according to the report, the company launched a single-use disposable pen presentation. Even with twice-monthly maintenance dosing, the study said the requirement for patient self-injection has not limited the uptake of Humira and its climb to the number one sales position (total sales since launch $65 billion).</p>
<p>AbbVie’s experience with Humira highlights how an effective dose delivery strategy can sustain increasing sales and improve patient outcomes. This best practice is being led by contract manufacturing and packaging service providers who are at the forefront of this trend, engaging patent holders and drug owners to consider this vital aspect of their therapy at the earliest stages. Unither, for example, invests a great deal to pursue dose form and packaging-related compliance strategies for its customers, including sterile single-dose vials using blow-fill-seal (BFS) technology and liquid stick-packs, two forms that have the potential to promote dose adherence and improved patient outcomes.</p>
<p>Although the pharmaceutical industry has been widely successful in innovating new drugs to treat disease, it must now focus on the user experience before non-adherence has a chance to slow the dramatic health care gains biopharmaceuticals and other new medications can have on future generations of patients.</p>
<h4>References</h4>
<ol>
<li>IMS Institute for Healthcare Informatics, IMS Health Study Identifies $200+ Billion Annual Opportunity from Using Medicines More Responsibly, Press Release. Jun 2013.<a href="http://www.imshealth.com/portal/site/imshealth/menuitem.%20c76283e8bf81e98f53c753c71ad8c22a/?vgnextoid=12531cf4cc%2075f310VgnVCM10000076192ca2RCRD.">http://www.imshealth.com/portal/site/imshealth/menuitem. c76283e8bf81e98f53c753c71ad8c22a/?vgnextoid=12531cf4cc 75f310VgnVCM10000076192ca2RCRD.</a></li>
<li>PhRMA “2015 Profile Biopharmaceutical Research Industry,” {Pharmaceutical Research and Manufacturers of America}.</li>
<li>Connor, J., Rafter, N., and Rodger, A., “Do Fixed-Dose combination pills or unit-of-use packaging improve adherence?” A systematic review. Bulletin of the World Health Organization. Dec 2004.</li>
<li>Healthcare Compliance Packaging Council, Improving Medication Adherence Through Packaging. http://www. hcpconline.org/member-news-document/HCPC-White-PaperImproving-Medication-Adherence-with-Packaging.pdf.</li>
<li>Drug Development &amp; Delivery; Vol.15 No. 6, “Global Formulation Report.” Jul/Aug 2015.<a href="http://www.pharmacircle.com/rc/files/userfiles/Global%20Formulation%20Report_Low.pdf">http://www.pharmacircle.com/rc/files/userfiles/Global%20Formulation%20Report_Low.pdf</a>.
</li>
</ol>

Dose and Form Matter: Future of Care Demands Optimal Drug Delivery