Drug-Device Co-Packing Solutions to Enhance Differentiation and Improve Experience

DRUG-DEVICE CO-PACKING SOLUTIONS TO ENHANCE DIFFERENTIATION AND IMPROVE EXPERIENCE

In this article, Janice Adkins, Associate Director, Global Marketing, BD, discusses the benefits that co-packing, the practice of providing drug preparation and delivery systems along with a medication, can bring to pharmaceutical manufacturers, clinicians and patients.

A WELL-ESTABLISHED SOLUTION TO AID IN MEDICATION ADHERENCE “Providing a vetted,

With medication nonadherence estimated co-packaged device at 50%,1 packaging solutions have emerged alongside a drug product as useful tools to help patients manage their can put manufacturers at therapies. Several studies have suggested an adherence benefit as a result of packaging ease that their products interventions, such as calendarised blister are being used as packages.2-6 In addition to adherence intended and help prevent packaging, some manufacturers have employed co-packing strategies to facilitate variability that may lead improved adherence to medications that are to product complaints.” co-administered. Examples include:

• Kisqali® (ribociclib) and Femara® complex dosing regimens and/or (letrozole) Co-Pack for breast cancer by reconstitution requirements has spurred Novartis (Basel, Switzerland) innovation in packaging solutions as • Viekira Pak-RBV® (ombitasvir/ well. However, rather than drug-drug paritaprevir/ritonavir, dasabuvir and co-packing, as is the case with ribavirin) for hepatitis C from AbbVie co-administered oral medications, (Chicago, IL, US) parenteral medications often require • Orkambi® (lumacaftor/ivacaftor) for packaging solutions where drugs are cystic fibrosis from Vertex (Boston, provided alongside delivery devices or MA, US). other supplies to enable their preparation Janice Adkins or administration. This is most apparent Associate Director, Global Marketing Not all of these packaging configurations in areas where patients or caregivers are T: +1 201 847 4176 E: [email protected] are complex, with some involving a simple required to manipulate drug components, “box within a box” design. for example reconstitute a lyophilised product. In some of these cases, simple BD Medical Delivery Solutions Co-Packing Medications With Devices supplies, such as vial adapters, blunt fill 1 Becton Drive Franklin Lakes, NJ 07417 The growing number of self-administered, needles or intravenous infusion sets, are United States parenteral medications entering the market co-packed with medications, while others with large volumes, high viscosities, involve specifically-designed devices to www.bd.com

High Viscosity New Use Environments “As drug preparation and administration demands continue to increase, pharmaceutical Chemical Sensitivity Complex Dosing manufacturers will require an even higher degree of quality control for Hazardous Properties High Potency device specifications and performance data.” Figure 1: Complicating factors. Figure 1: Complicating Factors aid in performing particular use steps.7-15 application. Moreover, BD’s extensive One approach is a fully-integrated solution Examples include: experience in drug delivery and its global where the pharmaceutical manufacturer presence make it able to help customers provides the appropriate device(s) within • Genotropin Mixer® from Pfizer (New understand market needs and make data- the same unitary package, directly York, NY, US) driven device decisions. BD has successfully alongside the drug product (Figure 2). • saizenpro® from EMD Serono (Rockland, partnered with manufacturers to accomplish This configuration ensures that patients MA, US). this in several therapeutic areas, including uniformly have every component they rheumatoid arthritis, multiple sclerosis, need when they receive the drug product, Increasing molecule complexity has also haemophilia, short bowel syndrome, and minimises complexity for other demanded a higher degree of rigour and oncology and radiology. healthcare providers and prescribers. In consideration from drug manufacturers Pharmaceutical manufacturers have a second configuration, pharmaceutical to ensure drug and clinical compatibility integrated BD’s drug delivery devices in manufacturers supply the desired devices with their chosen drug delivery device their co-packing designs in various forms. separately from the drug product as a (Figure 1). This is particularly true in areas where new devices are adopted and used in clinical practice without pharmaceutical manufacturers having a clear idea of exactly which devices are being used for what purpose. A recent study published in the PDA Journal of Pharmaceutical Science and Technology evaluated several Co-Packed Supplies chemotherapy vial spikes for their propensity to cause stopper push-in at the device-to-vial interface, and concluded that variability in device size, design and lubricity may contribute to primary container complications.16 Providing a vetted, co-packaged device alongside a drug product can put manufacturers at ease that their products are being used as intended and help prevent variability that may lead to product complaints.

BD PROVIDES DRUG DELIVERY SOLUTIONS FOR CO-PACKING

BD brings its long history of device excellence and diverse product portfolio to co-packing engagements. With a wide range of best-in-class syringes, needles, vial adapters, catheters and hazardous drug solutions, pharmaceutical manufacturers Figure 2: Pharmaceutical Manufacturer- partnering with BD have the flexibility to Drug Primary Figure 2: SuppliedA pharmaceutical Unitary manufacturer Package select the optimal product for their specific Container provided unitary package.

drug is prepared and delivered as intended by the manufacturer. This is especially important when patients are presented with unfamiliar use steps or when specific supplies are required. One representative ® Slot for example is Gattex (teduglutide) from Shire Drug Supplies (Lexington, MA, US), a medication that Packaging requires reconstitution with a supplied prefilled diluent syringe, withdrawal of Drug Packaging very small dose volumes, and potential pooling of the contents of more than one drug vial before subcutaneous injection. ccc cc To facilitate these use steps, patients are cc cc c cc

cc c cc cc cc c cc cc c cc c cc cc cc c cc cc c provided a kit that contains BD 22G 1.5”

cc needles for attachment to the diluent syringe

cc c cc and reconstitution and BD disposable 1 mL graduated syringes with attached 26G 5/8” needles for dose withdrawal and injection.20 Along with the product’s instructions for use, co-packing of these Figure 3: Pharmaceutical Manufacturer-two particular supplies (i.e. a fill needle and Figure 3: A pharmaceutical manufacturer Supplied provided Package “combined for Combinationseparate pre-attached needle and syringe) Supplies atpackage Point-of-Use at point of use”. aids in the proper use steps to the user and may help prevent use errors, such discrete package, which is then combined data. When directly collaborating with as accidental injection with the incorrect with the drug packaging at the point pharmaceutical customers, BD can offer needle and syringe. of dispensing (Figure 3). This option visibility on the product capabilities of Moreover, in situations where minimises the burden on manufacturers its industry-leading devices to its direct provided supplies are not standardised, and allows the drug product and devices to partners. This becomes of key importance device variation can have unintended be treated separately in the supply chain. when specifications such as materials implications. This may occur when a device of construction and device performance is not co-packaged by the manufacturer but Pharmaceutical Manufacturers – are critical. rather by another party, such as a specialty Quality Assurance and Consistency Finally, BD’s broad portfolio of drug pharmacy, at the point of dispensing. As a partner in optimising drug preparation preparation and delivery solutions for In these cases, pharmacies may provide and delivery process, BD can be relied upon co-packing can help pharmaceutical supplies that are intended to aid the patient by manufacturers to provide performance partners standardise clinical trial supply in taking their medication but may not be quality assurance and supply assurance. and ensure performance consistency ideal for the particular drug. Common As drug preparation and administration as molecules progress towards examples of this include medications with demands continue to increase, commercialisation. Several organisations complex preparation steps. pharmaceutical manufacturers will require have reported challenges associated with In addition to not necessarily being an even higher degree of quality control managing clinical trial ancillary supplies, intended for use with particular products, for device specifications and performance including difficulty sourcing the right pharmacy-provided supplies pose other supplies for each trial efficiently and challenges. First, because the devices cost-effectively, overlooked the make or are supplied in bulk, storage of such “BD’s broad portfolio manufacturer of supplies, and the need large quantities may be burdensome for for expensive repacking.17-19 A clinical patients. Second, there is likely a lack of of drug preparation trial strategy that utilises co-packing to standardisation of these provided supplies and delivery solutions guarantee the right devices are supplied across pharmacies, or even within the for co-packing can with investigational drugs can mitigate same pharmacy, if purchasing is made these risks, and a partnership with BD solely based on product price. As a help pharmaceutical enables manufactures to study their result, there could be differences in the partners standardise medications with the supplies that particular device and associated training clinical trial supply and patients and clinicians may ultimately use that patients receive, potentially causing upon approval. unnecessary confusion. ensure performance For clinicians, the benefits of a BD consistency as molecules End-Users – Intuitiveness, co-packing strategy are two-fold: progress towards Confidence and Convenience confidence and convenience. Due to BD’s From a patient perspective, a co-packaged industry leadership, clinicians may be commercialisation.” offering utilising BD devices can help to aware of BD products and may be already encourage proper use and ensure that the comfortable using these devices if provided

Nurs, 2013, Vol 28(1), pp 55–63. “Due to BD’s industry leadership, clinicians may be aware 8. Dumas H et al, “Understanding and meeting the needs of those using of BD products and may be already comfortable using growth hormone injection devices”. these devices if provided alongside drug products.” BMC Endocr Disord, 2006, Vol 6(5). 9. Rohrer TR, Horikawa R, Kappelgaard AM, “Growth hormone alongside drug products. Additionally, improving medical discovery, diagnostics delivery devices: current features providing the appropriate devices at the and the delivery of care. The company and potential for enhanced treatment point of use can increase convenience develops innovative technology, services adherence”. Expert Opin Drug for clinicians, especially in acute clinical and solutions that help advance both Deliv, 2016, Vol 14(11), situations or those that require the use clinical therapy for patients and clinical pp 1253–1264. of special supplies, such as filter needles, process for health care providers. BD 10. Cimino E et al, “Patient filtered extension sets, closed-system has 65,000 employees and a presence in preference and ease of use for transfer devices and vented vial adapters. virtually every country around the world different coagulation factor VIII to address some of the most challenging reconstitution device scenarios: MAXIMISING THE VALUE OF global health issues. BD helps customers a cross-sectional survey in five PACKAGING SOLUTIONS enhance outcomes, lower costs, increase European countries”. Patient Prefer efficiencies, improve safety and expand Adherence, 2014, Although a BD co-packing solution offers access to healthcare. Vol 8, pp 1713–1720. a number of benefits, manufacturers can 11. Wickramasuriya BP et al, “Factors refer to the expected use environment REFERENCES Determining Patient Choice of characteristics to inform selection of which Device for GH Therapy”. Horm Res, products would receive the greatest benefit 1. Cutler RL et al, “Economic impact 2006, Vol 65(1), pp 18–22. from co-packing. Co-packing may add the of medication nonadherence by 12. Munn J et al, “Patient and caregiver most value when: disease groups: a systematic review”. perceptions of a pre-filled diluent BMJ Open, 2018, Vol 8(1). syringe (MixPro®)”. J Haem Pract, • Specific supplies are needed to support 2. Schneider PJ, Murphy JE, Pedersen 2016, Vol 3(1), pp 33–38. use steps, such as reconstitution, CA, “Impact of medication 13. Khair K, “Children’s preferences of filtering, complex manipulation or large packaging on adherence and transfer devices for reconstitution of volume transfer. treatment outcomes in older factors VIII and IX for the treatment • Dosing- or clinical practice-related ambulatory patients”. J Am Pharm of haemophilia”. Haemophilia, circumstances require device Assoc, 2008, Vol 48(1), pp 58–63. 2009, Vol 15(1), pp 159–167. standardisation, for example to protect 3. Dupclay L et al, “Real-world 14. Vidovic N et al, “Postmarketing the user from hazardous drug product impact of reminder packaging on surveillance study of KOGENATE and/or minimise device dead space. antihypertensive treatment adherence Bayer with Bio-Set in patients • Use setting is a home or specialised and persistence”. Patient Prefer with haemophilia A: evaluation of clinic, rather than a general hospital Adherence, 2012, Vol 6, pp 499–507. patients’ satisfaction after switch environment, therefore favouring the 4. Valenstein M et al, “Using A to the new reconstitution system”. convenience of co-supplied devices. Pharmacy-Based Intervention To Haemophilia, 2010, Vol 16(1), • Acute or emergency clinical situations Improve Antipsychotic Adherence pp 66–71. demand that the correct devices are Among Patients With Serious Mental 15. Fernández-Arias I, Kim HK, immediately accessible. Illness”. Schizophr Bull, 2011, “Factor VIII delivery devices in • Certain patient populations, for example Vol 37(4), pp 727–736. haemophilia A. Barriers and drivers psychiatric, paediatric or geriatric, 5. Mahtani KR et al, “Reminder for treatment adherence”. Farm mean that special device considerations packaging for improving adherence Hosp, 2016, Vol 40(6), pp 579–603. are necessary. to self-administered long-term 16. Zhao XC et al, “A Case Study to • Required supplies are barriers to medications”. Cochrane Database Address a Gap in the Device-to-Vial adoption into clinical practice. Syst Rev, 2011. Interface Stopper Push-in by Chemo 6. Zedler BK et al, “A Spikes - An Overlooked Oncology BD is excited to work with the Pharmacoepidemiologic Analysis of Safety Risk”. PDA J Pharm Sci industry to navigate these factors and the Impact of Calendar Packaging Technol, 2018. bring the highest-impact packaging on Adherence to Self-Administered 17. Cullen H, Rake D, Polkowski D, solutions to market. Medications for Long-Term Use”. Clin “Ancillary Supplies for Clinical Ther, 2011, Vol 33(5), pp 581–597. Trials”. Imperial CRS, 2017. ABOUT THE COMPANY 7. Kremidas D et al, “Administration 18. “Optimizing the Clinical Trial Burden Associated With Supply Chain”. Parexel, 2015. BD is one of the largest global medical Recombinant Human Growth 19. “Managing Your Clinical Trial technology companies in the world and Hormone Treatment: Perspectives of Ancillaries Supply”. MESM, 2018. is advancing the world of health by Patients and Caregivers”. J Pediatr 20. GATTEX® package insert, 2016.

92 www.ondrugdelivery.com Copyright © 2019 Frederick Furness Publishing Ltd WITH ONE TRUSTED PARTNER FOR YOUR DRUG PREPARATION AND DELIVERY SOLUTIONS. BD has a unique perspective on the needs of pharmaceutical companies. In developing the industry’s most comprehensive portfolio of drug preparation and delivery solutions, we’ve learned what it takes to partner closely with leading companies worldwide. It’s why you can rely on us to understand the demands of your business, the regulatory environments and your unique technical requirements at every stage—from the lab, through clinical trials, all the way to market. And why no other company combines the collaborative experience with the breadth and depth of safe and innovative delivery systems that BD brings to you. Discover the difference of one trusted partner. Discover the new BD.

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