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Insight 2019

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Innovatix | 2019

Navigating the Requirements for USP <800> Compliance: Are You Prepared for the December 1st Deadline? HD CAUTION: HAZARDOUS DRUG

HD CAUTION: HAZARDOUS DRUG

HD CAUTION: HAZARDOUS DRUG

HD CAUTION: HAZARDOUS DRUG

PLUS

Pharmacists, Technicians & Nurses: Earn CE credits by completing the program in this issue. Innovatix | innovatix.com

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Table of Contents Insight | 2019

An Innovatix Publication Series

EDITORIAL STAFF EDITOR IN CHIEF

Gary Feit, MS Vice President, Corporate Communications

CLINICAL EDITOR

Liya Davydov, PharmD, BCPS, BCGP Vice President, Clinical Pharmacy Services

1 2 7 10 12 15 18 21 24 31 40 2

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Welcome Letter USP <800>: Navigating the New Requirements for Handling Hazardous Drugs in the Non-Acute Healthcare Setting Trending Online: Eight Ways E-commerce is Changing Healthcare Purchasing Confronting the IVIG Shortage: Q&A with Patrick M. Schmidt Member Success Story: How Northern Light Pharmacy Won Accreditation with the Help of Innovatix Accreditation Advisory Services Food Service Management 101 When Medicare Audits and Pharmacies Collide: What to Expect and How to Handle the Process Three Benefits of the Oncology Care Model and Four Recommendations to Advance It Snapshot of the 2019 U.S. Biosimilar Market Continuing Education: Prevention and Management of Clostridioides Difficile Infection (CDI) in Adults Category Spotlight: Room Refresh Portfolio

MANAGING EDITOR

Eric Rodriguez Director, Corporate Communications

DESIGNER

Jaclyn Alvarado Creative Director, J2 Design NYC

COPY EDITOR Tina Harlan

PROOFREADER Laura F. Yandell

CONTRIBUTORS

Annekka Chao Leigh Davitian, JD Liya Davydov, PharmD, BCPS, BCGP Gary Feit, MS Renee Hofman, MS, RPh Ashlee Perez T. May Pini, MD, MPH Aisha Pittman, MPH Eric Rodriguez Wendy Rossi Jennifer Valentine, CPhT, CPCO

555 West 57th St., 12th Floor New York, NY 10019 phone 888.258.3273 fax 646.638.2641 innovatix.com Insight magazine is published semiannually by Innovatix and is complimentary for Innovatix members. For membership information, please call 888.258.3273. To submit ideas for editorial consideration, please contact Eric Rodriguez at 212.901.1242 or eric_rodriguez@innovatix.com. This publication is intended to provide general information on issues of interest to the members of Innovatix, LLC (â&#x20AC;&#x153;Innovatixâ&#x20AC;?) and the general public. It does not constitute nor should it be used as a substitute for any business, legal, or regulatory advice. Innovatix hereby disclaims all warranties, express or implied, as to the accuracy of any of the information contained herein, whether such information is up-to-date, or its fitness for any particular use or purpose. Nothing contained in it is intended as a treatment recommendation for any particular patient or group of patients. Treating institutions and/ or physicians must make all clinical decisions regarding the use of pharmaceuticals and other products on a case-by-case basis. You should always refer to federal, state, and local laws, rules, and regulations governing the operation of your organization and should consult your own legal counsel. The opinions expressed by the authors of articles included in this issue do not necessarily reflect those of Innovatix, its affiliates, or its representatives. Furthermore, some of the content contained herein may have been originally prepared by or funded by organizations with financial interests in products or services related to the topics discussed in such article. While every effort was made to ensure the accuracy of information conveyed in this magazine, Innovatix, its affiliates, and its representatives do not accept responsibility and cannot be held liable for any errors that may exist within the publication. Innovatix is not responsible for the contents of any Web pages that are referenced by this communication. Links from this communication to other sites do not constitute an endorsement by Innovatix. These links are for convenience only. It is the responsibility of the user to evaluate the content and usefulness of information obtained from other sites. Innovatix has no control over and is not responsible for the information, practices, or content of these or any other sites. The contents of this publication are protected by copyright and are the property of Innovatix. They may not be reproduced or transmitted in any form without the express written permission of Innovatix.


Dear Valued Members, In today’s competitive market, you need to consider every aspect of your operation and its impact on your bottom line. At Premier Alternate Site Programs, we know that you are more than just a healthcare provider — you are also a business. To best serve you, we have developed the most competitive portfolio of products and services — from basic needs such as office supplies, electronics, and facility maintenance — to more advanced ones such as emergency preparedness and room refresh planning. We also want to help you work smarter. In this issue of Insight, we have included valuable information about the ways in which e-commerce is changing healthcare purchasing. The article, which begins on page 7, also provides details on stockd.™, Premier’s new online marketplace. I encourage you to review the article, visit the site, and register for a free business membership at www.stockd.com. One of the most pressing topics in our industry right now is USP <800>, the United States Pharmacopeial Convention’s new standard for handling hazardous drugs. Most organizations have been preparing to comply with USP <800> for years, and many have made considerable progress. But to help those just getting started, this issue’s cover story offers suggestions that may help make the process more manageable. It’s important to remember that no one is exempt from USP <800>. In fact, failure to comply can impact your status with accrediting bodies like the Joint Commission. Speaking of accreditation, this issue of Insight contains a great member success story on page 12. It features Northern Light Pharmacy and details how they achieved accreditation with the help of Innovatix Accreditation Advisory Services. This a must-read for our pharmacy members. As always, Insight offers complimentary continuing education. This issue’s CE provides prevention and treatment strategies for Clostridioides difficile infection in adults. We have also included a thorough snapshot of the U.S. Biosimilar Market on page 24, as well as an in-depth Q&A with FFF’s CEO, Patrick M. Schmidt, about the nationwide IVIG shortage on page 10. Let me close with my personal thanks for your commitment to Innovatix. This is an exciting time for us, as we host our final National Meeting & Expo in Atlanta. If this is news to you, don’t worry — we’re not going away, we’re only getting bigger and better. I cordially invite you to attend our inaugural Premier Alternate Site Programs Meeting and Expo next October 11-15, 2020, at the beautiful Arizona Biltmore in Phoenix. If you’re interested in attending, please contact your Innovatix representative for more details. Sincerely,

John P. Sganga Senior Vice President, Alternate Site Programs, Premier

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USP <800>: Navigating the New Requirements for Handling Hazardous Drugs in the Non-Acute Healthcare Setting Eric Rodriguez, Director, Corporate Communications, Premier Alternate Site Programs Jennifer Valentine, Program Director, Pharmacy Management Solutions, Premier Alternate Site Programs

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harmaceutical compounding â&#x20AC;&#x201D; the science of preparing tailored medications for patients â&#x20AC;&#x201D; is as old as pharmacy itself. Despite the advent and wide use of commercially manufactured medications, compounding remains an indispensable part of pharmaceutical care.

USP <800>

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Several years ago, this vital and longstanding practice returned to the healthcare spotlight when it unfortunately gained notoriety for all the wrong reasons. In 2012, 753 patients in 20 states were diagnosed with a fungal meningitis infection after receiving steroid injections prepared by a standalone compounding pharmacy.1 Of those 753 patients, 64 died, and hundreds more sustained severe, permanent injuries.1 The outbreak was the largest recorded public health crisis caused by a pharmaceutical product, and it immediately sparked calls for increased regulation and oversight.1

HD exposure and the creation of USP <800>

This ushered in a wave of new industry standards and regulations. One of them is USP <800>, the United States Pharmacopeial (USP) Convention’s new standard for handling hazardous drugs (HDs). This chapter outlines practice and quality standards for handling HDs and helps promote patient/occupational safety and environmental protection.2

• Genotoxicity; and/or

USP <800> will affect non-acute healthcare providers across the nation, regardless of their size, provider type, or the volume of HDs compounded on-site.3 With enforcement of USP <800> scheduled to begin on December 1, 2019,3 non-acute healthcare providers must decide how they will navigate the daunting task of attaining compliance before the deadline. USP <800> builds on past USP standards, which historically have not always applied to non-acute healthcare providers because of the individual and short-term duration of their drug compounding.4 Many of these providers now find themselves in new and unfamiliar territory, necessitating a rapid learning curve to meet compliance standards. Those that are not compliant by the deadline could face a loss of market share, damaging publicity, and/or enforcement expenses and other obligations. For these reasons, it’s critical that non-acute healthcare providers fully understand: • Why USP <800> was created; • What the new guidelines are and what they change; and • How to prepare for them.

Compounding pharmaceuticals often involves dealing with ingredients deemed hazardous by the National Institute for Occupational Safety and Health (NIOSH). According to NIOSH, a hazardous drug is a substance that exhibits one or more of the following six characteristics:5 • Carcinogenicity; • Teratogenicity or other developmental toxicity; • Reproductive toxicity; • Organ toxicity at low doses; • Structure and toxicity profiles of new drugs that mimic existing drugs determined hazardous by the above criteria. USP <800> was created to protect the more than eight million U.S. healthcare workers exposed to HDs annually.6 Concerns about worker safety began appearing in medical literature as early as the 1960s.7 Studies show a variety of health risks for HD-exposed workers including headaches, eye issues, rashes, hair loss, reproductive problems, and increased risks of cancer.7 Prior to USP <800>, the main guidance for handling HDs was 2008’s USP <797>.8 This regulation described guidelines for sterile compounding of both HD and non-HD drugs, with the goal of preventing harm to patients that could result from contamination of sterile products.8 In contrast, USP <800> targets healthcare workers in addition to patients and the general public, who have access to facilities where HDs are prepared.2 It addresses the entire drug handling process, from receipt to proper disposal, and applies to all who handle HDs — even those who receive the shipments at loading docks or work in cleanrooms where the drugs are prepared.2

What are the key requirement changes? USP <800> will bring about big changes to non-acute care providers’ practices,

Did You Know? The Innovatix/Premier group purchasing portfolio includes contracts with the nation’s leading suppliers of USP <795>, <797>, and <800> solutions. Our contracts cover the following product and service categories: • Air quality testing and certification; • Cleaning supplies and equipment; • Cleanroom planning and design; • IV Hoods; • Personal protective equipment (PPE); • Pharmacy refrigerators; and • Wireless temperature monitoring.

budgets, and physical environments. That’s why it’s important for organizations to become familiar with the changes. (See Figure 1 for a detailed list.) As Jennifer Valentine, Program Director, Pharmacy Management Solutions, Premier Alternate Site Programs, stresses, “Comprehension and compliance with the guidelines set forth in Chapter <800> is paramount to ensure compounding is done safely and that staff involved throughout the entire HD handling process are protected from potentially harmful exposure.” Valentine notes that, due to the potential impact of these changes, “The chapter heavily emphasizes education and training for all staff members who may be involved with HDs, with a strong focus on nursing and pharmacy personnel.” As an example, Valentine points to the fact that USP <800> “frequently mentions the importance of closed system transfer devices (CSTDs).” First introduced in 1999, CSTDs are designed to contain HD drips, sprays, and vapors.9 Due to their ability to safeguard both staff and the environment, USP <800> recommends using CSTDs during HD compounding and requires their use during HD administration.10 “For nurses not already using a CSTD, incorporating them into administration requires a significant change in practice, since there are a number of possible configurations depending on the specific device and tubing arrangement,” notes Valentine. Innovatix | innovatix.com

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“The changes are potentially significant for many organizations,” she says. “But the two most important elements of success are ensuring all staff who come into contact with HDs are completely familiar with what the new guidelines change and creating a workplace culture that places the safety of staff at the forefront.”

How to prepare Most organizations have been preparing to comply with USP <800> for years, and many have made considerable progress. But for those just getting started, these steps can make the process more manageable:

Create a USP <800> strategy team Meeting the demands of USP <800> requires the development of a collaborative, cross-functional team that includes leaders from both pharmacy and nursing departments, as well as representatives from any other area that will be impacted. According to Valentine, “This team should meet frequently, until a USP <800> strategy is established, and quarterly thereafter.” Developing an HD strategy, gaining buy-in, and soliciting support from nursing and other clinical service staff are crucial steps. After that, as Valentine notes, “The strategy team will drive the initiative to make the needed changes, but it is the staff pharmacists, nurses, and pharmacy technicians handling HDs who will be instrumental in identifying areas requiring compliance assistance.”

Develop procedures and assign a project lead The creation and maintenance of a standard operating procedure (SOP) manual is essential in creating a culture of compliance and workplace safety. According to Valentine, “Every organization will need to designate someone to oversee their HD compliance program to ensure all areas comply with USP <800>, that environmental controls are suitable and in good working condition, and that personnel are properly trained in handling HDs.”

Identify HDs Identifying the HDs handled and developing an inventory list is another critical step in meeting USP <800> guidelines.10 A thorough reading of the 4

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NIOSH’s 2016 list of HDs is necessary to determine which are classified as hazardous. The list is available on the Center for Disease Control’s website at: www.cdc.gov/niosh/docs/2016-161/ pdfs/2016-161.pdf. Organizations should also record dosage forms and keep in mind that HD training often focuses on IV medications, while USP <800> applies to oral preparations as well.10 “Although not all drugs defined as hazardous may pose a definite risk based on their final dosage form, any manipulations of these forms, such as crushing tablets or opening capsules, may involve risk,” says Valentine.

Conduct a walk-through to assess how HDs travel through the facility. Once an organization is comfortable with the new USP <800> requirements, staff should focus on how HDs move through the facility. This will identify trouble spots where compliance is not up to par. Pay particular attention to compounding room design and personal protective equipment (PPE). USP <800> includes minimum requirements that must be met regarding compounding room design and engineering controls.10 As Valentine explains, “This represents the greatest challenge to general compliance, because many organizations do not yet conform to the requirements. If changes are needed, they may require over a year to complete.” Understanding the degree to which staff members embrace PPE will also prove important to developing realistic improvement initiatives. “Once an organization has a good understanding of staff compliance, then it can properly identify improvements and begin drafting policies and procedures,” says Valentine. “Training processes that include competency exams should be put into place, and strategies should be developed to ensure that the proper and consistent use of PPE becomes part of the organization’s culture.”

Conclusion Pharmacy regulations will affect non-acute healthcare providers under the new USP <800> chapter. Some providers that typically have only had to operate under state medical boards will soon experience visits from state pharmacy boards as these entities

monitor compliance beginning December 1, 2019. Depending on the enforcement agency, mixing rooms could be shut down until they are compliant, a move that could bankrupt many organizations or cause them to sell to a larger competitor with a corresponding capital budget to meet compliance expenses. Planning ahead offers the best chance for a non-acute healthcare provider to implement these new regulations. Those that have yet to comply or are waiting to see how enforcement will be rolled out should consider: • The court of public opinion: The USP <800> standards were written to protect staff and patients;2 it would be difficult to argue that they should not be followed in any setting. • Enforceability:3 USP chapters numbered below <1000> are considered enforceable. The USP <800> regulation is national in scope and applies to all healthcare providers regardless of type or size —private or hospital-based, pharmacy, or physician. Although the USP does not have its own enforcement body, enforcement can be carried out by the Food and Drug Administration, OSHA, and individual state pharmacy boards. • Accreditation:11 URAC recently released v4.0 of its Specialty Pharmacy and Mail Service Pharmacy Accreditation Program standards, which now require USP <800> compliance. Organizations that wish to remain accredited must now be compliant with the new guidelines. This is true for specialty, infusion, and community pharmacies. Regulatory compliance is rarely easy. However, non-acute healthcare providers have a responsibility to protect the environment, patients, and staff from HDs. The time to develop a USP <800> compliance strategy is now. Providers shouldn’t hesitate to reach out to government agencies, suppliers, and other resources to help them attain compliance before the deadline. “We’re just a few months away from when USP <800> becomes official,” says Valentine. “If any organization is handling an HD, it needs to take this deadline seriously.”


Figure 1: Valentine’s List of Key USP <800> Requirement Changes Key USP <800> Requirement Changes

Details

Designated HD program oversight

• Oversee HD monitoring for the facility. • Identify options to minimize risk of HD exposure and contamination. • Implement policies and procedures for safe work practices, maintaining compliance and competency relating to HDs. • Manage HD exposure incident reporting and action plans. • Oversee environmental monitoring. • Implement and oversee a hazard communication program.

Official listing of all HDs handled

• Identify hazardous drugs that are currently stocked. • Consider including drugs that mimic HDs, strong acids or bases, or toxic cleaning agents that may pose a risk when handling.

Policies and procedures

• Provide annually reviewed documentation of procedures that address the safe work practices implemented for handling HDs. • Ensure accessibility for all staff who handle HDs.

Risk assessment

• Complete risk assessments for all eligible HDs that do not require the full containment strategies of <800>. • Create safe work practices for HD handling. • Consider HD type, dosage form, packaging, handling/manipulation, administration, and disposal.

HD handling risk identification

• Consider all activities where there is a potential for HD exposure. • Review operational processes, including receipt, storage, handling or manipulation, labeling, packaging, transport, administration, and spill/waste management.

Facility/engineering controls and designated HD areas

• Designate areas for HD receipt, handling, and storage. • Ensure facility is equipped with appropriate protections to limit personnel and patient exposure as well as prevent contamination of non-HD areas. • Restrict access to areas where HDs are handled to authorized personnel only. • Assess compliance of existing compounding equipment and cleanroom design. • Ensure appropriate equipment and conditions for storage and both sterile and non-sterile compounding. • Ensure spill kits and eye wash stations are easily accessible.

Use of closed system transfer devices (CSTDs)

• If dosage form allows, use CSTDs when compounding HDs and when administering antineoplastic HDs. • Do not use CSTDs as a substitute for a C-PEC or instead of a negative pressure system.

Personnel training and competency

• Train all personnel before they handle HDs. • Have staff acknowledge risk associated with exposure to HDs. • Relate training to job function and include appropriate use of personal protective equipment (PPE) and spill kits. • Review and assess training and competency on an annual basis.

Personal protective equipment (PPE)

• • • •

HD handling activities

• Receipt - Accept HDs from the supplier in impervious plastic segregated from other drugs. - Implement procedures for handling damaged or non-plastic enclosed HD containers. - Develop processes for decontaminating containers to lessen the risk of contamination.

Ensure there are standard procedures for personal protective equipment before HDs are handled. Consider the HD type, the activity performed, and the risk of exposure. Review what PPE is mandatory and what should be implemented as best practices. Be sure PPE includes: - Gloves that are powder-free and meet the American Society for Testing and Materials (ASTM) standard D6978. - Gowns that are impervious to liquids or powders, close in the back, and have long sleeves and closed cuffs, - Eye and face protection (including goggles) that are worn when there is risk of spills or splashes. - Head, hair, shoe, and sleeve covers that provide protection during compounding or deactivation/ cleaning activities. - Respiratory protection that may include fit tested, N-95 respirators, elastomeric half-mask with a multi-gas cartridge and P100-filter, full face respirator (FFR), or powered air-Purifying respirator (PAPR).

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Key USP <800> Requirement Changes

Details

HD handling activities

• Storage - Store HDs in a manner that prevents spillage or breakage. - Review which HDs must be stored under negative pressure conditions, in a refrigerator, in a refrigerator under negative pressure conditions, or in a designated space in the pharmacy area. - Consider HD active pharmaceutical ingredients (APIs), antineoplastics that will be manipulated, antineoplastics in final dosage forms that will not be manipulated, non-antineoplastics reproductive risk only HDs that are in final dosage forms/manufactured products, and those that require refrigeration. - Consider sterile vs. non-sterile, whether the HD type and manipulation are required. - Evaluate use of lidded bins for shelving in the pharmacy area. - Ensure all shelves are labeled as HDs. • Labeling, packaging, transport - Implement procedures to minimize risk of exposure and contamination during these activities. - Review state and federal laws and local regulations as well as guidelines set forth by HD transport carriers used outside of the facility. • Administration - Implement standard procedures and PPE requirements for staff who will be administering HDs. - Consider how and where the HD will be prepared (pharmacy area vs. on the floor or nursing unit). • Deactivating, decontaminating, cleaning, and disinfecting - Implement standard procedures for deactivation/decontamination and cleaning for all areas and equipment exposed to HDs. - Ensure areas and equipment involved in sterile compounding include a disinfection step. - Direct staff to wear appropriate PPE during these activities. • Disposal - Use appropriate HD waste containers to ensure compliance. - Devise procedures to treat contaminated items (containers, tubing, utensils, supplies, PPE, etc.) as “trace” or “bulk” hazardous waste when handling antineoplastics. - Ensure compliance with all current local, state, and federal rules and regulations regarding HD disposal. • Spill management - Ensure qualified personnel trained in spill management are working whenever the facility is operating. - Have spill kits readily available in all areas where HDs are handled, - Develop a procedure for managing spills that are larger than what can be contained by a spill kit.

(Continued)

Medical surveillance

• Include medical surveillance as part of occupational safety program to minimize adverse health effects from HD exposure. • Ensure assessments, description of symptoms, documented incidents of exposure, and any physical or laboratory findings are documented.

Introducing Innovatix USP <800> Compliance Services To ensure adequate preparation for USP <800>, many leading non-acute healthcare providers are turning to supply chain experts like Innovatix for help. Innovatix USP <800> Compliance Services works with these providers to identify critical gaps in their USP <800> policies and procedures. The program also offers: • Guidance on requirements; • Completion of a gap analysis; • Creation of HD assessments of risk; • USP <800> basic policy template updates; • Policy and procedure development; and • Simulated on-site reviews. To learn more, visit www.innovatix.com/usp800

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REFERENCES 1. U.S. Department of Justice, Owner of New England Compounding Center Sentenced for Racketeering Leading to Nationwide Fungal Meningitis Outbreak, June 26, 2017, https://www.justice.gov/opa/pr/ owner-new-england-compounding-center-sentenced-racketeering-leading-nationwide-fungal. 2. United States Pharmacopeial Convention, “General Chapter <800> Hazardous Drugs—Handling in Healthcare Settings,” United States Pharmacopeia 39, NF 34 First Supplement (2016). 3. United States Pharmacopeial Convention, “Frequently Asked Questions: <800> Hazardous Drugs— Handling in Healthcare Settings,” https://www.usp.org/frequently-asked-questions/hazardousdrugs-handling-healthcare-settings. 4. Dawn Holcombe, “Preparing for Implications of USP 797 and USP 800,”Oncology Practice Management 5, no. 5 (June 2015), http://oncpracticemanagement.com/issues/2015/june-2015-vol-5no-5/538-preparing-for-implications-of-usp-797-and-usp-800. 5. U. S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, “NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings,” 2016, https://www.cdc.gov/niosh/docs/2016-161/ pdfs/2016-161.pdf. 6. Pharma Logistics, “Preparing your Pharmacy for USP <800>,” Modern Healthcare, May 28, 2019, https://www.modernhealthcare.com/law-regulation/preparing-your-pharmacy-usp. 7. S. Morgan, S. Becker, and L. Jinga, “Hazardous drugs, a safety blind spot,” American Nurse Today 12, no. 11 (November 14, 2017): 24. 8. Marina Reed, “Key Points to Consider From USP <800>,” Pharmacy Times (January 24, 2018), https:// www.pharmacytimes.com/publications/health-system-edition/2018/january2018/key-points-toconsider-from-usp-800. 9. Fred Massoomi, “The Evolution of the CSTD,” Pharmacy Purchasing & Products 12, no. 2 (February 2015): 1. 10. United States Pharmacopeial Convention, “General Chapter <800> Hazardous Drugs—Handling in Healthcare Settings,” United States Pharmacopeia 39, NF 34 First Supplement (2016), https:// www.usp.org/sites/default/files/usp/document/our-work/healthcare-quality-safety/generalchapter-800.pdf. 11. URAC staff, “URAC Enhances Pharmacy Accreditation with Standards Revision,” October 3, 2019, https://www.urac.org/blog/urac-enhances-pharmacy-accreditation-standards-revision.


Trending Online: Eight Ways E-commerce is Changing Healthcare Purchasing Gary Feit, Vice President, Corporate Communications, Premier Alternate Site Programs

T

he Internet continues to change American purchasing habits. According to a recent study by Internet Retailer, e-commerce accounted for more than half of all retail sales growth in 2018 (and more than 14 percent of total retail purchases). How has this trend translated to business purchasing for healthcare providers? Not surprisingly, businesses are seeking the same benefits â&#x20AC;&#x201C; cost, convenience, and the ability to comparison shop â&#x20AC;&#x201C; as online consumers. Innovatix | innovatix.com

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However, there are even more important questions to ask, including: • To what extent has e-commerce disrupted traditional business purchasing; and • What capacity does it have for future disruption? To better understand the impact of e-commerce on purchasing for non-acute healthcare providers, Premier, an industry leading healthcare improvement company, conducted a series of member surveys over the past year. The responses from our healthcare provider members offer insight into how and why businesses are supplementing traditional purchasing through e-commerce channels. We’ve summarized the following eight important takeaways about e-commerce and business purchasing from our members. 1) Providers are purchasing through traditional and non-traditional channels. The majority of healthcare providers are purchasing through suppliers or distributors, but they also supplement their purchasing through e-commerce sites and in retail stores. More than 75 percent have made purchases in the past year from an online retailer or e-commerce site not affiliated with a supplier or distributor, and 54 percent purchased from a retail store. 2) Both cost and convenience drive online purchasing. Cost is a primary driver of online business purchasing, but a secure, timesaving platform built by a trusted partner is nearly as important. According to our survey, the top three factors that influence online business purchasing are cost of products, convenience, and trust in the company providing the online platform. 3) Most business purchases are made via computer. The overwhelming majority of business purchasing occurs online using a laptop or desktop computer. More than 75 percent of respondents report making at least half of their business purchases using a computer, with significantly fewer using other methods. Mobile devices have not yet surpassed paper forms or in-store sales as a significant platform for business purchases. 4) Online purchasing occurs across categories. Top categories in which more than half of respondents indicate they’ve made an online purchase in the past year include office supplies (69 percent), facilities and maintenance (62 percent), and IT hardware (58 percent). 8

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Slightly less than half report purchasing electronics, medical/surgical supplies, and foodservice products; online purchasing for these contract categories has the most room for growth. 5) Influential purchasing advice comes from experts as well as from peers. When it comes to researching which products to buy, healthcare providers value input from both subject matter experts (SMEs) and their own peers. On the SME side, nearly two-thirds of respondents use supplier or distributor sales representatives for purchasing research, and 43 percent use group purchasing organizations (GPOs.) At the same time, more than half of respondents incorporate online reviews into purchasing decisions, while slightly less than half consider professional associations as well as word of mouth from colleagues. 6) Businesses are constantly making purchases. Purchasing is an ongoing task for most healthcare providers, with nearly 40 percent making daily purchases and just over 30 percent purchasing between twice and four times a week. Just 14 percent of respondents make business purchases less often than weekly. 7) Purchasing occurs on multiple platforms. Most providers rely on a handful of online platforms for their purchasing, with 57 percent buying from between one and five websites a month. Still, a substantial number (39 percent) purchase from more than six websites each month, including a few who purchase from more than 20 sites. 8) Online purchasing is trending up. When asked about the role of online purchasing in their buying process over the next three years, respondents were nearly evenly split. A third said they would be more likely to purchase online; a third indicated online purchasing would remain at current levels; and a third were unsure. Only 3 percent thought they’d be less likely to purchase online. Based on this input, healthcare providers still rely heavily on the value and cost savings of traditional purchasing channels. At the same time, they’ve shifted to e-commerce to supplement traditional business purchasing. As new platforms offer more convenience, transparency, and products tailored to their needs, more healthcare provider purchasing may shift online.

LAUNCHING NOW ™

As businesses increasingly supplement their traditional purchasing channels through e-commerce, the need for a platform that offers solutions for healthcare providers is apparent. To that end, Premier has invested in stockd.™, a newly launched digital marketplace. At its core, stockd. connects healthcare providers and businesses to the right suppliers and products. It provides an exceptional digital purchasing experience complete with tools and insights to help providers and other businesses thrive in an online environment.

Key features of stockd. include: • Transparent pricing listed directly on the site; • Pricing that is not dependent on purchase volume or supplier-imposed tiers; • The ability to easily compare products and pricing from multiple suppliers, allowing businesses using the platform to find the right product at a competitive price; • A single purchasing platform, leading to reduced operating costs and significant time savings; • Products from reputable manufacturers and distributors that healthcare providers and businesses can trust; and • The ability to leverage Premier’s healthcare purchasing expertise and the stockd. community to help inform purchasing decisions. Want to learn more? Visit www.stockd.com and register for a free business membership!


PROVIDERS ARE PURCHASING

through multiple channels:

Top 5

Directly from supplier: 85%

FACTORS

Through distributor: 82%

1) Cost of products 2) Convenience / efficiency of site 3) Trust in company offering platform 4) Product selection 5) Ease of site use

Online retailer / e-commerce site: 75% Retail store: 54%

2

/3

of providers use computers for more than 75% of their business purchases.

Go-to sources for PURCHASING ADVICE: Distributor / supplier sales reps

$

Group Purchasing Organizations

Top five

ONLINE PURCHASE CATEGORIES FOR PROVIDERS:

Office supplies & furnishings

Frequency of business purchases FOR HEALTHCARE PROVIDERS

Monthly: 5%

Facilities & maintenance

PLATFORMS

USED EACH MONTH:

Professional association websites

Colleagues

Computers & printers

Online reviews

TV & electronics

Medical & surgical

PROVIDER ONLINE PURCHASING:

Daily: 38%

3-YEAR FORECAST 2 – 4 times per week: 31% Weekly: 17%

2 – 3 times per month: 9%

ONLINE PURCHASING

for utilizing a new online platform for business purchases:

57% 39%

More online purchasing

3% Same level of online purchasing

31%

Less online purchasing

34%

Not sure 32%

Five or fewer Six or more

All data derived from results of four surveys of Premier healthcare members conducted between May 2018 and January 2019.

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QA

Confronting the IVIG Shortage:

Q&A with Patrick M. Schmidt

Patrick M. Schmidt is CEO of FFF, the nation’s largest and most-trusted distributor of plasma products, vaccines, and critical-care biopharmaceuticals. Primary immune deficiency diseases (PIDDs) are genetic disorders that compromise the immune system and place patients at risk for debilitating chronic infections.1 Based on data from the National Institute of Allergy and Infectious Diseases, there are over 200 different forms of PIDDs, affecting approximately 500,000 people in the U.S., and the numbers are rising.1,2 The primary treatment for PIDDs is IVIG, a blood product derived from plasma. In addition to PIDDs, IVIG treats neurologic, dermatologic, hematologic, and other disorders.3 Not unexpectedly, there has been a corresponding – and historic – increase in the demand for IVIG.2 In the United States, that demand is growing at an extraordinary rate. According to Grand View Research, which forecast IVIG use through 2022, the global IVIG market size was estimated at $9.09 billion in 2016. It is expected to increase at a CAGR (compound annual growth rate) of 7.1 percent over the forecast period. The challenges of rapidly increasing demand and the need to develop additional IVIG supplies have created a shortage for many providers, and they have been unable to obtain their patients’ preferred IVIG brand, strength, or vial size.4 To help Innovatix members better understand the current IVIG landscape, Patrick M. Schmidt, founder and CEO of FFF Enterprises (FFF), answers some frequently asked questions about the increased demand for IVIG products and its effect on access.

1

Providers across the nation have had to delay or cancel infusions due to a shortage of IVIG products. Understandably, this has caused concern for both providers and the patients who depend on these lifesaving treatments. Can you give us some history and background on IVIG products and explain why IVIG shortages are occurring? Although IVIG was initially approved by the Food and Drug Administration (FDA) in 1981, the process of producing products derived from plasma was a WWII innovation. It was first used 39 years earlier, right after the tragic events of Pearl Harbor, and was credited with saving thousands of lives during that time. The manufacturing process that was used then is the same one used today, and it involves albumin, which was then refined and expanded to produce IVIG. IVIG is a unique product that’s used in more disease states, including primary and secondary immune deficiencies, than almost any other product. That’s one of the main factors contributing to the shortages we’re experiencing today, as is the fact that the list of autoimmune disorders continues to grow. That compounds the problem. To provide some context, when IVIG was first introduced, its market was about 45 million grams per year. Today we’re approaching 100 million grams. These numbers illustrate the growth in IVIG as a treatment and explain why we’re seeing shortages.

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Avoiding IVIG Shortages Does your organization face challenges from the intravenous immune globulin (IVIG) shortage? Do supply interruptions and lack of access to product put your patients at risk?

As IVIG supply and demand change rapidly, partnering with a dependable and experienced supplier has never been more important. While many components of IVIG supply and demand are beyond the power of any single entity, having the right GPO relationship in place can help ensure better access. Innovatix delivers one of the most comprehensive IVIG and fractionated blood programs serving the alternate site healthcare marketplace. In conjunction with FFF Enterprises, our exclusive distributor for plasma and recombinant products, our program improves access to these limited-supply medications while providing opportunities for substantial savings. To learn more about Innovatix’s IVIG/Blood Program, contact your Innovatix representative at 888.258.3273 or email info@innovatix.com.


QA

Additionally, the raw material needed to develop IVIG is derived from human plasma, which is finite in supply and is more costly and complicated than manufacturing from non-living molecules. In IVIG manufacturing, plasma extracted from blood donations is used as the raw material. Both IVIG and albumin are refined from the same plasma. So there is a delicate economic balance between IVIG and albumin production that must be maintained if manufacturers are to invest in increasing the IVIG supply.

2

Why does it take so long to produce an IVIG product? Can you explain its production process? It really starts with plasma collection. While there’s a whole industry that collects plasma intended for further manufacturing, there are only a handful of companies in the world that can actually produce IVIG products. Still, we have made progress in collecting more plasma. In 2007, there were 349 plasma centers in the U.S. that collected 15 million liters of sourced plasma. In 2018, that number almost doubled to 737 centers collecting 49 million liters of plasma. If we are to meet the burgeoning demand for IVIG worldwide, we must collect more plasma in the United States. Producing IVIG is complex and time-consuming. Once the plasma is collected, it goes through multiple steps in the production process, including quality control, FDA approval, and testing. Finally, IVIG goes to large distributors, like FFF, and from there, directly to providers. Given the complexity of production, the time from plasma collection to the time it becomes available for infusion can be anywhere from 7-12 months. IVIG production is unlike pharmaceutical manufacturing. The collection, the quarantine, the long manufacturing cycle, the testing, the FDA approval, and the absolute emphasis on safety and product availability make biological manufacturing all a lengthy process

indicate about 91.2 million grams were distributed in the U.S. from May 2018 to April 2019. However, the manufacturing process does not produce equal monthly increments throughout the year, so the supply into the distribution and infusion provider channels is not consistent. It’s those inconsistencies that may make one product seem to be in short supply or unavailable for a period of time while another brand is not affected. For example, from May 2018 to April 2019, the highest distribution of IVIG in the marketplace was over 9 million grams and the lowest was slightly over 6 million grams. Additionally, in June 2019, one major brand didn’t ship any product in the U.S., and the patients that were prescribed that particular product dealt with access issues. So, timing certainly factors into the response to that question. Overall, the IVIG market is extremely tight. Access is a concern, and there’s much discussion throughout the industry about the contributing factors related to IVIG shortages.

4

Many of our members have shared their concerns about product not being available. What advice or suggestions do you have for them?

Do shortages only involve certain IVIG brands?

If they’re members of Innovatix and not currently taking advantage of our IVIG and plasma blood program, I would suggest they explore the opportunity immediately. Over the past year, Innovatix and Premier have made efforts to increase the amount of IVIG in the U.S. market, as well as to increase access by working directly with manufacturers. As the program’s exclusive distributor for plasma and recombinant products, FFF can also help members manage times of limited availability through our Controlled Volume Measures™ system. At FFF, we use a dynamic allocation process that prioritizes product availability based on actual current needs, shifting units to those that require them before fulfilling standing orders. This dynamic system differs significantly from other wholesalers that typically prioritize allocations based on the size and historic volume of the account, releasing limited supplies to larger customers before all others, regardless of patient needs.

There are three product categories of immune globulin solidify these IVIG, SCIG, and a handful of other products — that can be administered intravenously and subcutaneously. At any given time, the marketplace is very tight. It’s my sincere belief that manufacturers are doing everything they can to collect as much plasma and produce as much IVIG as possible to meet the growing demand. They’re investing time, money, and research to reduce the time it takes to collect a single liter of plasma and extract the most IVIG available. In terms of the brands that are in short supply, I would look at the entire market. Industry data

Other tactics providers can use to conserve IVIG range from using timing of compounding and dose rounding strategies to minimize waste to dosing based on ideal and adjusted body weight over actual body weight. I’d also stress the importance of being flexible when selecting and acquiring available vial sizes as well as matching the preferred IVIG brand to the albumin manufacturer. Lastly, providers should consider developing an immune globulin stewardship program to ensure guideline compliance with appropriate indication and dose.

3

REFERENCES 1. National Institute of Allergy and Infectious Diseases, Primary Immune Deficiency Diseases (PIDDs), June 21, 2016. https://www.niaid.nih.gov/diseasesconditions/primary-immune-deficiency-diseases-pidds. 2. Grand View Research, Intravenous Immunoglobulin (IVIG) Market Size, Share & Trend Analysis Report By Application (Hypogammaglobulinemia, CIDP, Congenital AIDS), By Route of Administration, And Segment Forecasts, 2012 - 2022, February 2018, https://www.grandviewresearch.com/industry-analysis/ intravenous-immunoglobulin-market. 3. S. Jolles, W. Sewell, and S. Misbah, “Clinical uses of intravenous immunoglobulin,” Clin Exp Immunol 142, no. 1 (October 2005): 1–11. doi:10.1111/j.13652249.2005.02834.x. 4. Premier, Inc., Record growth in U.S. IVIG demand and distribution for 2017-18, email communication, December 2018.

Innovatix | innovatix.com 11


Member Success Story: How Northern Light Pharmacy Won Accreditation with the Help of Innovatix Accreditation Advisory Services

Ashlee Rose Perez, Senior Communications Specialist, Corporate Communications, Premier Alternate Site Programs

I

n 2016, Innovatix launched Innovatix Accreditation Advisory Services, a fee-for-service program, to support pharmacies working toward accreditation. Since its launch, the program has partnered with multiple pharmacies to help them gain recognition from various accreditation bodies.

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Why Accreditation is Important for Specialty Pharmacies

BACKGROUND

Pharmacy) was founded in 1957 by Bill

ship led it to choose Innovatix to help

Accreditation can help specialty

Miller and his family in Bangor, ME. In

in this endeavor. To expand its central

pharmacies:

2010, Miller Drug entered into a 50-50

fill location, Northern Light engaged

• Establish clinical services and patient

partnership with Affiliated Pharmacy

Innovatix Accreditation Advisory

Services, a division of Northern Light

Services for:

management offerings; • Provide exceptional value and reliability; and • Distinguish themselves from the competition. Accreditation also verifies compliance with strict guidelines and enhances a pharmacy’s reputation among payers, manufacturers, and patients.

Miller Drug (now Northern Light

Health. By 2014, Miller Drug was wholly owned by a subsidiary of Northern Light Health. The Miller Drug name remained until January 2019, when it changed to Northern Light Pharmacy.

CHALLENGE

To keep up with increasingly high demand and exploding markets for

METHOD The pharmacy’s existing GPO relation-

• Education regarding standards and delivery of department-specific project plans; • Weekly reviews; • Monthly meetings; • Policies and procedures development and review; • Application submission; and

Specialty drug manufacturers and

specialty medications, Northern Light

payers depend upon these pharmacies

Pharmacy began offering world-class

to deliver consistent patient experiences,

specialized clinical services in 2016.

suitable medications, and continuity

Pharmacy management decided to

of care. At the same time, accreditation

pursue URAC accreditation at that

reassures patients that a pharmacy is

time, since it was the highest standard a

guidance through the entire process

safely managing both their medical care

specialty pharmacy could achieve.

played a large role in the accomplishment

• Simulated on-site review and feedback. “Innovatix was a pivotal asset during the URAC accreditation process. Its expertise, knowledge, and lock-step

and their health information. Once accreditation standards are integrated into a specialty pharmacy’s daily operations, consistency and efficacy become the standard. Accreditation from the Utilization Review Accreditation Commission (URAC) is perhaps the most sought-after recognition in the industry. Its Specialty Pharmacy Accreditation helps specialty pharmacies improve their competitive positions while demonstrating their value. Many payers and manufacturers recognize the accreditation not only as a key differentiator but also as an independent validation of quality. In fact, they may include this accreditation as a requirement to participate in their networks. Payer contracts now allow for other accreditations as well. These include the Accreditation Commission for Health Care (ACHC), the Joint Commission, and others. Additionally, payers and manu-

Q&A with Kayla Hines, third-party administrator, Northern Light Pharmacy

Q: A: Q:

After going through the process, how would you advise other pharmacies considering accreditation? We would highly recommend using an advisor, especially for a first accreditation.

What would you have done differently based on your experience with the Innovatix Accreditation Advisory Services program? We’d have more staff dedicated specifically to accreditation tasks – at least one person – to alleviate some of the work from full-time employees. It was very labor-intensive at times, which contributed to some late-night work for us. We’d use the same Level 2 service if we did it again, as Innovatix’s detailed attention and quick response time were great and contributed to the success of the program.

A:

Q: A:

Any other thoughts about accreditation?

In the future, we’d maybe get all seven locations accredited, but for now we have implemented the same high standards and strict processes across the board. Our patient care is held to that high golden standard for all of our pharmacies.

facturers may stipulate dual accreditation as part of their contracts, meaning accreditation by at least two agencies. Innovatix | innovatix.com 13


of our URAC accreditation,” said Kayla

pharmacists, four patient advocates, and

Hines, Third-Party Administrator at

a call center, as well as URAC accredita-

Northern Light Pharmacy.

tion for a second pharmacy location –

RESULT

all in less than one year. According to Hines, “The growth of the

In May 2017, Northern Light

specialty program and the level of care

Pharmacy’s specialty program had just one clinical pharmacist. The engagement with Innovatix was so successful that

that is provided to patients far exceed the upfront investment that Northern Light Pharmacy had to make to achieve URAC

Northern Light Pharmacy’s specialty

accreditation.”

program has since grown to include four

How Can Innovatix Help You? Accreditation has become essential for survival in the pharmacy market, especially in relation to manufacturer and payer access. While this can be daunting, particularly for smaller, independent pharmacies, it is a manageable process with strong leadership and the right assistance. Choosing which accreditation to pursue and the most appropriate advisor for your facility is key. The Innovatix Accreditation Advisory Services program offers hands-on support, customized service, and a “long-term relationship that extends beyond the accreditation process, so it is not a one-size-fits-all scenario. Going through the process and eventually achieving successful accreditation will help your pharmacy assess its strengths, as well as areas that need improvement and how best to utilize resources in an effective way. The ultimate result is greater operational efficiency, increased business opportunities, improved quality of

”

care and better patient outcomes.

- Jennifer Valentine, Program Director, Pharmacy Management Solutions, Premier Alternate Site Programs

Interested in learning how Innovatix Accreditation Advisory Services can help your pharmacy?

Visit

www.innovatix.com/accreditation or call or email

888.258.3273 info@innovatix.com.

REFERENCES 1. Robert Rodriguez, “Why Accreditation Makes Sense for Specialty Pharmacies,” AmerisourceBergen Corporation, February 8, 2018, https://www. amerisourcebergen.com/abcnew/insights/pharmacies/why-accreditation-makes-sense-for-specialty-pharmacies. 2. Marsha K. Millonig, “Pharmacy Accreditation: Is It Worth the Effort?,” Wolters Kluwer Clinical Drug Information, June 5, 2017, https://www. wolterskluwercdi.com/blog/pharmacy-accreditation-it-worth-effort/. 3. “Pharmacy Quality Management Programs: Specialty Pharmacy Accreditation,” Utilization Review Accreditation Commission (URAC), https://www.urac. org/programs/specialty-pharmacy-accreditation.

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Food Service Management 101 Annekka Chao, Corporate Communications, Premier Alternate Site Programs

B

oth the population and proportion of older Americans are on the

rise. Over the past half century, the life expectancy of the average American has increased from 69 to 78 years.1 As the baby boomer generation continues to age, roughly one in five Americans will be over the age of 65 by the year 2030.2

Innovatix | innovatix.com 15


Better medical technology and newer treatments have generally led to sustainable improvements in elder health. However, smarter food choices and enhanced nutrition also contribute to healthier older adults.

How Food Service Management Companies Can Help

dining experiences, can save both

Food service companies work

particularly helpful for facilities

primarily with hospitals, senior

that lack capacity or expertise in

living sites, and behavioral health

these areas. And using a food service

As many in the senior living community know, American dining habits have evolved in recent years. Today, aging adults have different expectations for meals, depending on individual needs and preferences. By accommodating this new generation of older adults, senior living facilities can:

care centers. They can serve as

consultant doesn’t have to be an

in-house consultants, managing

all-or-nothing proposition. Food

food service operations from

service management companies

within. Management responsibilities

can tailor their services to meet

include:

specific needs.

• Hiring staff;

If this sounds like an option for

• Developing menus;

your facility, but you’re concerned

• Placing bulk food orders;

about losing all the great benefits

• Entice new residents; • Ease the transition to the facility; and • Keep residents happier and healthier.

time and resources. Food service management companies can be

of the US Foods/Premier distribution

and • Overseeing daily operations. Incorporating their expertise and focusing on other priorities, such as managing and improving

program, there’s no need to worry. Premier has approved a number of food service management companies to receive GPO pricing and benefits.

Senior Living Facility Dining Trends Overview of past characteristics and expectations based on current trends: FOOD VARIETY

FOOD QUALITY

DINING EXPERIENCE

DINING CONVENIENCE

Past

Meals are often prepared in advance and then served during set mealtimes with little or no choice for the diners.

Ingredients are based on what’s easiest to stock, so dining staff can focus on making larger quantities.

Formal dining rooms, banquet-style seating, and a predictable atmosphere and menu contribute to an experience that may come off as stale and tired.4

Regularly scheduled mealtimes can foster a feeling of less individual freedom.

Future

Restaurant style dining becomes more prevalent, allowing residents to choose from different plates based upon their preferences.

Residents are becoming more interested in what they’re consuming.

Dining considerations move beyond what and where food is served to how it is served. Residents expect to be treated like they are dining at a restaurant. Facilities upgrade their equipment, menu, presentation, and service.3

Expanding dining hours plus different menu items allow residents to come and go as they please, eat in, take out, and even bring their families.3

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Facilities use fewer boxed and processed ingredients, replacing them with a “farmto-table” approach with fresher, healthier ingredients.3


Did You Know? Premier has approved a number of food service management companies to receive GPO pricing and benefits. Contact your Innovatix representative at 888.258.3273 for further details.

In this scenario, the food service

Senior living and other non-acute

management company acts as the

care facilities have many options

GPO member, ordering food and

when it comes to staying on top of

food service supplies on contract

the latest food trends and keeping

through the US Foods/Premier

their residents satisfied. Whether

distribution agreement. The food

or not you choose to engage a food

service management company

service management company

then passes along the benefits —

depends on your facility’s needs

including products and selection,

and circumstances. Just remember,

value-added programs, and cost

if you do choose this approach, you

savings — to its client facility.

will be able to keep all the benefits

You continue to receive the same

of the US Foods/Premier program.

contract benefits along with added features, such as trained chefs and special menus, supplied by the food

Who says you can’t have your cake and eat it too?

service company. REFERENCES 1.

The World Bank, World Bank Open Data, “Life expectancy at birth, total (years) - United States,” https://data.worldbank.org/indicator/SP.DYN.LE00.IN?locations=US.

2.

Bethany Runyan Meadows, “Menu Trends in Senior Living” (presentation at Shared Purchasing Solutions IMAGE 2017 conference, Wisconsin Dells, WI, November 1, 2017), https://www.sps-gpo.com/files/cms/image/session_1_eating_trends_in_senior_living.pdf.

3.

Navigator Group Purchasing, Inc., “The Top Five Dining Trends in Senior Housing,” https:// www.mhainc.com/uploadedFiles/Content/Resources/NavigatorGPO_DiningReport.pdf.

4.

Tom Gresham, “11 Trends in Dining Design for the Next Generation,” Senior Living Executive 25, no. 3 (May/June 2018), 12-18.

Is Your Facility Taking Advantage of Our Food Service Program with US Foods? Innovatix and US Foods have one of the strongest food service programs available in the industry today. We offer multiple resources to drive down costs without sacrificing quality. As specialists working with senior living and long-term care communities, we can help you provide your residents with nutritious and satisfying meals that fit your budget. But our program goes far beyond cost savings alone. Our industryleading tools and resources can impact your entire operation by reducing spend and increasing efficiencies in every area of your supply chain. By joining the program, you will gain access to: • Discounted pricing through our committed manufacturer agreements covering in excess of 50,000 high-quality products; • Blueprint Menu Management System®, offering everything needed to plan, customize, and manage menus; • Baseline®, which allows you to compare your financials to industry benchmarks and other facilities nationwide; and • Diagnostic tools and financial reports that break down costs and highlight savings opportunities. To learn more, contact your Innovatix representative at 888.258.3273 or email info@innovatix.com. Innovatix | innovatix.com 17


When Medicare Audits and Pharmacies Collide: What to Expect and How to Handle the Process

Leigh Davitian, JD, Chief Executive Officer, Dumbarton Group & Associates

T

he words audit, inspection, investigation, and data-mining often evoke angst among pharmacies and other Medicare/Medicaid (commonly known as Medi-Medi) providers. One of the consequences of providing supplies and services to Medi-Medi beneficiaries is being subjected to a myriad of government enforcement efforts. Whether you offer long-term care, home infusion, or specialty/retail pharmacy services, chances are that the government will contact you sooner than later. These hyper-focused enforcement efforts, which include complex on-site audits, are not simply scare tactics. They are serious investigative actions that can significantly impact your business. All pharmacy entrepreneurs should expect unannounced Medi-Medi investigations and audits.

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Insight

No pharmacy can assume that overt government policing is a rare occurrence. Unfortunately, many pharmacies are so busy with daily operations and other priorities that they are unable to focus on compliance, and continuously changing program integrity regulations are often overlooked. A lack of serious attention to compliance puts pharmacies at risk for fines, recoupments of past payments, pre- and-post payment reviews, and in-depth, on-site audits.

Why Pharmacies Are Experiencing a Higher Number of Audits

There is more demand than ever before for pharmacies and their services, thanks to the tremendous growth in the aging population over the last five years and the resulting reliance on pharmaceuticals.


Not surprisingly, increases in Medicare Part B and D expenditures have been accompanied by enhanced scrutiny, with continued enforcement activities expected this year. Pharmacies will likely face aggressive policing by the Centers for Medicare & Medicaid (CMS). And the Office of Inspector General (OIG), and the Department of Justice (DOJ) have announced plans to ramp up efforts to address increased fraud, abuse, and vulnerabilities within the pharmacy sector,1 due to non-compliance related to dispensing, billing, over-prescribing, and lack of proper documentation.2

Types of Audits

While Medi-Medi compliance enforcement efforts can’t be avoided, there are preparation strategies that can reduce possible negative outcomes. For example, understanding the various types of Medi-Medi audits is a vital first step. Zone Program Integrity Contractors (ZPICs) ZPICs perform program function integrity checks for Medicare Part A and Part B, durable medical equipment, prosthetics, orthotics, and supplies used by nursing homes, home health providers, and hospice facilities. ZPICs use sophisticated data mining, statistical analysis, and trending activities to identify healthcare providers with utilization, coding, and/or billing practices that are aberrant or suspicious. These audits are not random but based on a belief that non-compliance has occurred. The ZPIC’s goal is to investigate all facets of the business to identify aberrations. Unified Program Integrity Contractors (UPICs) UPICs are the latest program integrity contractors to perform fraud, waste, and abuse detection, deterrence, and prevention activities for Medi-Medi providers. To avoid duplication of program integrity efforts and better integrate the plethora of audits and investigations, CMS has contracted with a number of

new private sector organizations to serve as UPICs. Eventually, UPICs will replace ZPICs and become the preeminent auditing resource, but to date, both remain operational. In the coming months, Medi-Medi providers and suppliers will begin receiving complex UPIC documentation requests and be subjected to on-site UPIC investigations and audits. Even if you have not yet been contacted, your business practices may already be subject to an ongoing review. Recovery Audit Contractors (RACs) RACs identify and correct improper Medicare: • Overpayments made on claims of healthcare services provided to Medicare beneficiaries; and • Underpayments to providers. To complete this audit, RACs review claims on a post-payment basis. They detect and correct past improper payments so that CMS and Medicare Administrative Contractors can implement actions that will prevent future improper payments. The lookback period for RACs to review claims is six months from the date of service. HIPPA Audits In 2016, the Office of Civil Rights (OCR), under the auspices of the DOJ,

increased its scope regarding the Health Insurance Portability and Accountability Act (HIPAA) Audit Program. The program involves the review of policies and procedures by covered entities and their business associates to meet the requirements of HIPAA's Privacy, Security and Breach Notification Rules. One of the enhanced areas of scope is on-site audits. Audits are an important OCR compliance tool and supplement investigations and compliance reviews. They all enable OCR to identify best practices and proactively uncover and address risks and vulnerabilities to protected health information (PHI).

Preparing for the Audit

In a best case scenario, your pharmacy will be given reasonable notice that an announced audit is imminent. Pharmacies that prepare for the inevitable audit are more likely to minimize a potentially lengthily audit process and ultimately secure a positive outcome. Compliance consultants urge pharmacies to take the following steps to prepare for a government audit: Review written notification and confirm audit scope. Once the pharmacy receives formal notification of a pending on-site audit, form an internal committee with responsibility for

Helpful Tips for an On-site Audit • Immediately ask for the auditor’s official identification. Make several photocopies and retain for your record. • Inform senior management and legal counsel, if applicable, that auditors are on the premises. • Ensure pre-designated staff are solely responsible for interacting with the auditors and encourage those employees to demonstrate the utmost courtesy and professionalism. Unprofessionalism will be formally noted and will impact the overall audit. • Prepare a designated physical area for the audit, preferably one that is private and out of view of your pharmacy’s employees and daily operations. • Locate germane operational documents and see that they are readily retrievable for auditors’ review. • Have auditors sign in/out per HIPAA and HITECH regulations before allowing anyone to view confidential records. • Ensure all patient health records are properly secured and that your medical record handling and storage comply with HIPAA standards. • Consider videotaping or recording the audit for your records (and your protection).

Innovatix | innovatix.com 19


dealing directly with audit activities. Be sure to confirm the audit’s intended scope. It is critical that the pharmacy understand the purpose of the audit. Auditors sometimes provide pharmacies with instructions regarding specific claims, requests for documentation, and operational documents. Review audit rules. Become familiar with Medi-Medi checklists, rules, and procedures governing on-site audits. Typically, information about the audit process is contained within the Medicare Integrity Program Manual.2 Gather and review documents. If you are given a detailed list of requested documents, claims, prescriptions, and policies in advance, have them readily available and ensure staff are conversant about said requests. A lack of continuity and organization leads auditors to question a provider’s ability to operate an effective business. Create a master file. Keep a written and contemporaneous log of all telephone conversations with the government representatives that includes the date, time, and brief description of the subject of the call. In addition, maintain a file of all written correspondence pertaining to the audit. If you do this, you can be sure to retain key details, and if there is ever a dispute, you will have the benefit of a written record of what transpired.

Minimizing Negative Audit Outcomes

Most pharmacies that have experienced a government audit agree that audits can be seriously disruptive to the workplace and consume a REFERENCES 1. Centers for Medicare and Medicaid Services,

2019 Program Audit Process Overview: Medicare Parts C and D Oversight and Enforcement Group, Division of Audit Operations, November 2018. https://www. cms.gov/Medicare/Compliance-and-Audits/ Part-C-and-Part-D-Compliance-and-Audits/ Downloads/2019_Program_Audit_Process_ Overview.pdf. 2. Centers for Medicare and Medicaid Services, Medicare Program Integrity Manual. https:// www.cms.gov/Regulations-and-Guidance/ Guidance/Manuals/Internet-Only-ManualsIOMs-Items/CMS019033.html. 3. U.S. Sentencing Guidelines Manual § 8B2.1.

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considerable amount of staff time and energies. Incorporating certain steps can help minimize serious disruption and confusion. Maintain an organic Medicare compliance program. An effective compliance program should be your first line of defense. With such a comprehensive compliance program, a pharmacy can find and correct potential vulnerabilities, which will: • Minimize billing mistakes; • Reduce the chance of an audit; • Increase proper payment of claims; • Decrease the chance of fraud waste, and abuse; and • Promote quality care. Although a compliance program is not a guarantee that fraud, waste, abuse, or inefficiency will not occur, CMS believes that a good compliance program will help you protect yourself from risk of improper conduct. Conduct ongoing education. All staff must receive regular training on how to detect, minimize, and deter Medi-Medi fraud, abuse, waste. and errors. Education can be offered through internal in-service programs, webinars, off-site conferences, and reading timely government materials. It takes constant vigilance to ensure that employees understand and follow all necessary steps to avoid fraudulent and abusive practices.

Perform frequent self-audits. A self-audit is an examination, review, or other inspection performed by a pharmacy management and staff. Self-audits can: • Reduce negligent billing and coding behavior; • Monitor denied claims for patterns that violate Medicare guidelines; • Lower the chances of an external audit; and • Create a robust culture of compliance.

Conclusion

As the growing cost of the Medicare and Medicaid programs continues to be of paramount concern for the government and taxpayers alike, audits will remain a popular enforcement technique to ensure providers comply with state and federal regulations. While government audits seem daunting at first, understanding the different types of audits and how to prepare for them will make the process much less traumatic and minimize the chances of large recoupments or temporary suspensions. Rather than viewing the audit process as an obstructive and potentially threatening measure, pharmacies should see audits as a quality control mechanism to help them identify and correct any hidden gaps in their operational compliance.

Suggested Seven Core Elements for an Effective Compliance Program 3

1. Establish and adopt written policies and procedures to promote the organization’s commitment to compliance. 2. Identify and appoint an individual within the organization to serve as a compliance officer who will be responsible for monitoring compliance efforts and enforcing practice standards. 3. Establish reporting systems to encourage individuals to make complaints regarding compliance issues without fear of retaliation. 4. Commit to conducting formal education and training programs for all levels of employees. 5. Perform ongoing auditing and system monitoring to assess the effectiveness of the compliance program and identify problems. 6. Develop policies to enforce standards of conduct with disciplinary measures for employees who fail to comply with requirements. 7. Implement corrective actions when vulnerabilities and potential violations are identified.


Three Benefits of the Oncology Care Model and Four Recommendations to Advance It Wendy Rossi, Principal, Premier Performance Partners, Premier T. May Pini, MD, MPH, Principal, Population Health Consulting, Premier Aisha Pittman, MPH, Senior Director, Payment and Quality Policy, Premier

Innovatix | innovatix.com 21


I

n July 2016, the Centers for Medicare & Medicaid Services (CMS) launched a payment model for oncology that promoted higher quality care delivered at lower costs. While the Oncology Care Model (OCM) has shown definite promise, some remaining barriers are preventing optimal patient and provider outcomes. Currently, 176 practices and 11 payers are participating in the program, which ends in June 2021. CMS staff will evaluate OCM successes and shortcomings to decide whether to expand the program and launch other oncology payment models. They’ve worked closely with OCM participants and observed three key benefits of the model and four areas for improvement.

OCM is Transforming Provider-led Oncology Practices

The program encourages practices to address patient-focused areas such as quality of care, patient satisfaction, and care coordination. OCM has also emphasized focus on patients and improved access to data that support care delivery and coordination. As a result, providers can: • Become more proactive; • Establish a patient-centered practice culture; and • Leverage robust data to pinpoint improvement opportunities and support value-based payment arrangements. Specifically, OCM has resulted in: 1. Proactive symptom management to avoid emergency department visits. OCM practices have focused on increased patient access to care and addressed the underlying reasons patients seek care on an urgent basis. Providers have implemented same-day appointments, oncology-specific urgent care clinics, nursing triage by phone, and protocols to provide timely, evidence-based care to better manage symptoms such as pain and nausea. This type of 22 |

Insight

practice transformation is supported by OCM’s enhanced services infrastructure payments.

improve the initial design and help providers begin accepting financial risk as they provide high-quality care.

2. The evolution of a patient-centered practice culture. Person-centered care models allow clinicians to strengthen connections with patients and caregivers. OCM requires a focus on patient navigation, survivorship care planning, and conversations with patients to establish care goals and other patient-centered, care-delivery approaches. In addition, the introduction of early palliative care can improve quality of life, and ensure patient wishes and goals of care are known by the care team. OCM has also helped to increase focus on financial toxicity and the need for patient financial counseling.

As CMS evaluates this and future oncology models, it should include these four critical improvements to eliminate barriers to success:

3. The use of robust data to identify improvement opportunities and strategies. Before OCM, oncology practices had little insight into the care their patients received outside of their own clinics. Practices participating in the program receive adjudicated claims data from the entire continuum of care, enabling providers to holistically see all services patients receive. More comprehensive information has helped practices determine areas of overutilization. Identifying and addressing these opportunities simultaneously improves quality while reducing costs. Enhanced data also allow oncology practices to begin discussions with commercial payers about value-based arrangements. Through OCM, some practices are already participating in value-based payment models with commercial payers.

Empowering Providers to Succeed with OCM

While this model has been beneficial in many ways, challenges inherent in the program can limit providers’ abilities to more fully transform oncology care. By addressing these challenges in OCM and future oncology models, CMS can

1. Evaluate the adjustment methodology for rapidly evolving treatment therapies. On average, drug expenditures comprise 40 percent of total episode costs in OCM’s six-month episode of care, significantly affecting whether savings are generated for a single episode. CMS currently uses a novel therapy adjustment factor for new therapies entering the market. The novel therapies adjustment methodology does not appear to sufficiently account for the impact of new cancer drugs, new indications for available drugs, or changes in the cancertype mix of a practice’s attributed population. CMS should explore alternative methods to accommodate escalating drug costs without imposing an undue burden on practices. The current adjustment factor does not accurately account for quickly evolving, evidencebased standards of care or the wide variation of treatment regimens for a specific cancer type. These regimens can fluctuate due to different disease stages and lines of treatment within an episode of care. Possible solutions to address the rising cost of novel therapies include re-evaluating how novel therapies are accounted for (i.e., adjust benchmarks for the additional cost of novel therapies), or not aggregating the novel therapy adjustment and instead applying specific adjustments by cancer type and stage. 2. Refine financial incentives and payments to avoid unintended penalties and promote sustainable clinical transformation. CMS offers OCM reimbursement through a two-part payment system. First is a per-beneficiary Monthly Enhanced Oncology Services (MEOS) payment


that pays for enhanced services provided to patients. This helps build the infrastructure needed to manage and coordinate care. The second is a performance-based payment that allows practices to share in cost-savings generated compared to a target based on historical spending. Once CMS develops target prices, it then applies adjustments for various factors specific to each episode of care. The target price does not include any adjustments for the MEOS payment, which counts as an additional patient care expense in comparison to pre-OCM historical benchmarks. The MEOS payment thus becomes an additional cost barrier that practices must overcome to perform better than the target price. CMS should consider options to lessen the impact of MEOS payments, such as updating the baseline time frame to reflect the most recent performance period. This would ensure that target prices are based on a comparable baseline period (i.e., included MEOS payments), and that they account for new treatments and standards of care upon target prices. Many practices have concerns about sustaining the staff and programs supported by MEOS payments once the program has ended. CMS should incorporate MEOS-type payments in any new oncology alternative payment models. 3. Simplify the attribution process. Providers face challenges in identifying patients who will be attributed to their practices as OCM beneficiaries, particularly those on oral treatment regimens. The current attribution process is retrospective and based on plurality of Evaluation and Management medical billing codes within the episode time period. CMS should provide more frequent data (such as monthly rather than quarterly) to assist practices in identifying attributed beneficiaries.

In addition, the current attribution process is too cumbersome for practices to efficiently submit claims for the MEOS payment recoupment. To simplify the process and reduce administrative burdens, CMS should provide a new option allowing participants to receive the MEOS payment with the semi-annual performance-based payment. This option would permit CMS to determine the number of attributable beneficiaries and calculate the applicable MEOS payment, rather than relying on provider assessments of OCM-eligible beneficiaries. 4. Ensure EHR compatibility with reporting requirements. While the volume of quality measures associated with OCM was initially too high and burdensome to collect, CMS has been responsive to these concerns and has reduced the number of measures. To further decrease reporting burden – and encourage electronic transmission of necessary data – CMS and the Office of the National Coordinator for Health IT need to establish core clinical data for oncology care and measurement. They should also adopt standards for capturing and exchanging the data as part of routine care and business transactions. The goal is to reduce administrative and financial burdens on practices for data collection, file generation, and information reporting.

Continuing the Cycle of Programmatic Improvements

The promise of care transformation under OCM has been advanced through the willingness of CMS to make changes to the program after receiving provider feedback. The findings included here constitute the next phase of lessons learned and provide additional opportunities to improve both the current program and the design of future

oncology models. By remedying these challenges, CMS can: • Enhance model stability; • Encourage more providers to continue their participation and sign up for future oncology models, • Address unintended consequences; and • Reduce provider burdens.

Have You Heard? OncologyExpress is back and steadily expanding its offerings. After 20 years of helping independent oncologists thrive using our robust equipment, supply, and services portfolio, OncologyExpress has been reinvigorated with the help of FFF Enterprises, the program’s newly designated pharmacy wholesaler. OncologyExpress can offer: Cost savings through an extensive purchasing portfolio; Pricing transparency and consistency; Reliable and accurate pharmaceutical distribution services; Complimentary clinical support; and Custom analytics. Whether you’re currently enrolled in the program or are a prospective member, don’t miss out on what’s new at OncologyExpress. Contact us today at 888.258.3273 or email info@innovatix.com.

This article is a slightly modified version of the original version in the Health Affairs Blog on April 22, 2019 10.1377/hblog20190417.733414. Copyright © 2019 Health Affairs by Project HOPE – The People-to-People Health Foundation, Inc.

Innovatix | innovatix.com 23


Snapshot of the 2019 U.S. Biosimilar Market

Liya Davydov, PharmD, BCPS, BCGP, Vice President, Clinical Pharmacy Services, Premier Alternate Site Programs

A

growing number of biosimilar drugs are set to enter the U.S. market in coming years. Understanding the basics of these blockbuster therapeutic agents will be key for providers that treat conditions such as rheumatoid arthritis, anemia, inflammatory bowel disease, skin conditions, and some cancers (to name a few). This look at 24 |

Insight

the U.S. biosimilar market explains the: • Concept of biosimilarity; • Concept and importance of interchangeability; • Regulatory issues involved, as well as other obstacles hindering biosimilar uptake; and • Current pipeline status.


How Biosimilarity and Interchangeability Differ

It’s important to understand the difference between the two terms, since depending on whether the biosimilar agent meets only one or both of these definitions, it would translate into whether or not the biosimilar agent could be substituted at the pharmacy level for the original brand biologic as part of each individual state-governed generic substitution laws. Definition of Biosimilarity According to the Public Health Service 16 Act (PHS Act), section 351(i), for a drug to be considered a biosimilar, both of the following criteria must be met.1-3 • The first criterion is “that the biological product is highly similar to the reference product notwithstanding minor differences in clinically inactive components.”1-3 • The second criterion is that “there are no clinically meaningful differences between the biological product and the reference product in terms of the safety, purity, and potency of the product.” 1-3 Definition of Interchangeability According to section 351(k)(4) of the PHS Act, to receive the designation of interchangeability, the manufacturer of the biosimilar agent “must provide sufficient information to demonstrate biosimilarity and also to demonstrate that the biological product can be expected to produce the same clinical result as the reference product in any given patient and, if the biological product is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between the use of the biological product and the reference product is not greater than the risk of using the reference product without such alternation or switch.” 1-3 Section 351(i)(3) of the PHS Act further stipulates that “interchangeable products may be substituted for the reference

product without the intervention of the prescribing health care provider,” which makes it necessary for the biosimilar agent to obtain the interchangeability designation in order for the state-governed mandatory generic substitution laws to be applicable to a particular biosimilar.1-4

Biosimilar Agents Currently on the Market or Awaiting Launch

September 3, 2015, marked the first time a biosimilar drug was introduced in the U.S.5 That biosimilar, filgrastim-sndz (Zarxio™),5 was manufactured by Sandoz. It was approved by the Food and Drug Administration (FDA) on March 6, 2015, for all of the five indications that its reference branded biologic, (Neupogen® [filgrastim, manufactured by Amgen]), had when filgrastim-sndz received FDA approval.5-7 Since then, 17 biosimilar agents have been approved, and several have launched (see Table 1).5, 6, 8-29

Biosimilar Applications Awaiting FDA Decisions or Already Rejected

The biosimilar pipeline is robust.30, 31 As of January 18, 2019, at least 10 applications for various biosimilars have been accepted for review by the FDA and are awaiting a decision (see Table 2).32-41 Before making a final decision to approve or deny a biosimilar application, the FDA will most likely conduct an advisory meeting to discuss the application’s merits, given the novelty of the approval process and the biosimilars themselves.40, 41 At least three biosimilar applications already have been rejected rejected by the FDA as of January 18, 2019 (see Table 3).42-44

Ongoing Issues and Litigation Affecting the U.S. Biosimilar Market

Originators of reference biologics rely on multiple strategies to delay or prevent the launch of new

biosimilars.45, 46 Some examples of these can include: • Lawsuits pertaining to perceived patent infringements; and • Re-examination of the original biologic’s patents to confirm validity by the U.S. Patent and Trademark Office (USPTO).45, 46 These activities take place not only while products are under FDA review but also after they have been approved (as was the case with Inflectra).45, 46 If decisions from lawsuits, appeals, or USPTO re-examinations favor the originator biologic, there may be additional delays for a biosimilar’s launch.45, 46 On June 12, 2017, the United States Supreme Court overturned a previous ruling requiring a 180-day waiting period between a biosimilar’s FDA approval and its launch.47 If there are no other barriers (e.g., perceived patent infringements, etc.), a biosimilar can, theoretically, at least, launch as soon as the FDA approves it.47

Update on 2019 FDA Biosimilar Guidance

On July 18, 2018, the FDA released a Biosimilars Action Plan (BAP).48, 49 The plan included four core components: • “Improving the efficiency of the biosimilar and interchangeable product development and approval process; • Maximizing scientific and regulatory clarity for the biosimilar product development community; • Developing effective communications to improve understanding of biosimilars among patients, clinicians, and payors; and • Supporting market competition by reducing gaming of FDA requirements or other attempts to unfairly delay market competition to follow-on products.” 48, 49 On December 11, 2018, the FDA expanded the BAP by implementing additional actions, including the release of four guidance publications relating to biosimilars.50 Innovatix | innovatix.com 25


Table 1: Listing of the Biosimilar Agents Approved by the FDA (as of January 18, 2019).5, 6, 8-29 Note: Approved biosimilars are listed in the order they were first approved; those already launched are highlighted in the table.

BRAND NAME FOR THE BIOSIMILAR AGENT

GENERIC NAME FOR THE BIOSIMILAR AGENT

MANUFACTURER OF THE BIOSIMILAR

REFERENCE BIOLOGIC (BRAND & GENERIC NAMES)

MANUFACTURER OF THE REFERENCE BIOLOGIC

DATE APPROVED

LAUNCH STATUS

Zarxio

filgrastim-sndz

Sandoz

Neupogen (filgrastim)

Amgen

3/6/15

9/3/15

Inflectra

infliximab-dyyb

Celltrion/Pfizer

Remicade (infliximab)

Janssen Biotech

4/5/16

Late November 2016

Erelzi

etanercept-szzs

Sandoz

Enbrel (etanercept)

Amgen

8/30/16

Not yet launched

Amjevita

adalimumabatto

Amgen

Humira (adalimumab)

Abbvie

9/23/16

Not yet launched

Renflexis

infliximab-abda

Merck/Samsung Bioepis

Remicade (infliximab)

Janssen Biotech

4/21/17

7/24/17

Cyltezo

adalimumabadbm

Boehringer Ingelheim

Humira (adalimumab)

Abbvie

8/29/17

Not yet launched

Mvasi

bevacizumabawwb

Amgen/ Allergan

Avastin (bevacizumab)

Genentech

9/14/17

Not yet launched

Ogivri

trastuzumabdkst

Mylan/Biocon

Herceptin (trastuzumab)

Genentech

12/1/17

Not yet launched

Ixifi

infliximab-qbtx

Pfizer

Remicade (infliximab)

Janssen Biotech

12/13/17

No plans to launch

Retacrit

epoetin alfaepbx

Pfizer

• Epogen (epoetin alfa) • Procrit (epoetin alfa)

• Amgen

5/15/18

11/14/18

Fulphila

pegfilgrastimjmdb

Mylan/Biocon

Neulasta (pegfilgrastim)

Amgen

6/4/18

7/26/18

Nivestym

filgrastim-aafi

Pfizer

Neupogen (filgrastim)

Amgen

7/20/18

10/1/18

Hyrimoz

adalimumabadaz

Sandoz

Humira (adalimumab)

Abbvie

10/31/18

Not yet launched

Udenyca

pegfilgrastimcbqv

Coherus BioSciences

Neulasta (pegfilgrastim)

Amgen

11/2/18

1/3/19

Truxima

rituximab-abbs

Celltrion/Teva

Rituxan (rituximab)

Genentech

11/28/18

Not yet launched

Herzuma

trastuzumabpkrb

Celltrion/Teva

Herceptin (trastuzumab)

Genentech

12/14/18

Not yet launched

Ontruzant

trastuzumabdttb

Samsung Bioepis/ Merck

Herceptin (trastuzumab)

Genentech

1/18/19

Not yet launched

While approved biosimilar agents demonstrate biosimilarity to the reference biologic, they have not been labeled as “interchangeable” with the reference biologic. This is, in large part, because there are currently no finalized guidelines that biosimilar manufacturers must 26 |

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• Janssen Products

follow in order to demonstrate interchangeability of their biosimilars to the reference biologics.8,51 A draft guidance (“Considerations in Demonstrating Interchangeability with a Reference Product”) was released on January 17, 2017, but it has yet to be finalized.52, 53

The FDA indicated it will strive to publish the final interchangeability guidance within two years after the comment period for the draft guidance (that was released on January 17, 2017) ends.41, 53 Therefore, the earliest possible release date for the final guidance is likely to be in the second quarter of 2019.41, 53


As an example, Sandoz’ Zarxio, the first biosimilar approved in the U.S., received designation of biosimilarity but did not apply for and did not receive the designation of interchangeability, thus preventing its mandatory generic substitution at the pharmacy level.54 Without clear guidelines for interchangeability – and biosimilar products having a distinction that they are indeed interchangeable with the reference biologic – no mandatory substitution of biosimilars for the reference biologic can take place, even in states that have mandatory generic substitution laws. That means that if the prescriber wants the patient to receive a biosimilar agent, then the prescription must be written specifically for a biosimilar agent in question, rather than for the original biologic. In today’s regulatory environment, due to the lack of interchangeability designation, the biosimilar agent would not be automatically substituted at the pharmacy

if the prescription is written for a reference biologic. A final guidance (“Labeling for Biosimilar Products”) was released on July 18, 2018.55, 56 This document provides industry with recommendations for creating labeling content for biosimilar agents.55, 56

Challenges for Physicians, Payers, Patients, and Pharmacies

Surveys reveal that physicians do not have the same degree of familiarity with biosimilars as they generally tend to have with traditional generic drugs.57-63 A majority of physicians surveyed felt additional and continuing biosimilar education would be necessary in order for them to develop sufficient competence and comfort with accepting and prescribing biosimilars rather than reference biologics.58,59 For payers, regardless of whether they manage commercial, Medicaid

or Medicare lives, adoption of biosimilars largely centers on overall cost benefit achieved through increased use of biosimilars versus reference biologics.64,65 Patients’ lack of knowledge regarding biosimilars has been revealed in a recent survey.66 Additional education is needed to increase patient acceptance of biosimilars as safe, clinically effective and cost-effective substitutes for original reference biologics.65-67 Patients should also be made aware that while biosimilars will have similar efficacy of the reference biologic, the delivery device may differ from that of the reference drug.68 While specialty pharmacies have been successfully dealing with dispensing of original reference biologics, as they are gearing up to dispense biosimilars, issues surrounding dispensing biosimilars remain.69 One of the issues specifically to be faced in the future is

Table 2: Listing of Biosimilar Agents Currently Awaiting FDA Decision (as of January 18, 2019).32-41

BIOSIMILAR NAME

MANUFACTURER OF THE BIOSIMILAR

REFERENCE BIOLOGIC

MANUFACTURER OF THE REFERENCE BIOLOGIC

PROJECTED BsUFA* TARGET DATE OR LAUNCH DATE

Lapelga

Apotex

Pegfilgrastim (Neulasta)

Amgen

Unclear – Pending

Grastofil

Apotex

Filgrastim (Neupogen)

Amgen

Unclear - Pending

Filgrastim Adello

Adello Biologics

Filgrastim (Neupogen)

Amgen

Unclear - Pending

TX01

Tanvex

Filgrastim (Neupogen)

Amgen

September 2019

ABP 710

Amgen

Remicade (infliximab)

Janssen Biotech

December 2019

SB5

Samsung Bioepis/ Merck

Humira (adalimumab)

Abbvie

July 2019

PF-05280014

Pfizer

Herceptin (trastuzumab)

Genentech

1Q:2019

PF-06439535

Pfizer

Avastin (bevacizumab)

Genentech

2Q:2019

PF-05280586

Pfizer

Rituxan (rituximab)

Genentech

3Q:2019

PF-06410293

Pfizer

Humira (adalimumab)

Abbvie

4Q:2019

Note: BsUFA - Biosimilar User Fee Act

Innovatix | innovatix.com 27


biosimilar substitution for the reference biologic (once interchangeable biosimilar products are available). Anticipating arrival of biosimilars to the market, especially once they achieve the interchangeability status, each individual state has been challenged with establishing guidelines to delineate biosimilar substitution for branded biologic agents at the pharmacy level.4 To that end, bills or resolutions have been filed in 49 states as of October 22, 2018,

regarding biosimilar substitution, with 45 states and Puerto Rico already enacting a biosimilar substitution-related law.4 For up-to-date information on each state-specific laws, guidelines, and/or policies regarding biosimilar substitution, please visit http:// www.ncsl.org/research/health/ state-laws-and-legislation-related-to-biologic-medications-and-substitution-of-biosimilars. aspx#Mandatory.4

Conclusion

As of January 18, 2019, 17 biosimilars have been approved in the United States, and seven of them are already on the market. The resolution of pending litigation and logistical issues should pave the way for increased biosimilar acceptance and adoption in the U.S. Note: the information in this article is up-to-date as of January 18, 2019. For clinical updates from Innovatix, please visit: https://members.innovatix.com/.

Table 3: Listing of Rejected Biosimilars (as of January 18, 2019).42-44

BIOSIMILAR NAME

MANUFACTURER OF THE BIOSIMILAR

REFERENCE BIOLOGIC

MANUFACTURER OF THE REFERENCE BIOLOGIC

STATUS

LA-EP2006

Sandoz

Neulasta (Pegfilgrastim)

Amgen

CRL in late June 2016

GP2013

Sandoz/Novartis

Rituxan (rituximab)

Genentech

CRL on 5/2/18

ABP 980

Amgen/Allergan

Herceptin (trastuzumab)

Genentech

CRL on 5/31/18

Note: CRL – complete response letter; BsUFA - Biosimilar User Fee Act

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S. Mehr, “FDA Approves Second Infliximab Biosimilar,” Biosimilars Review and Report, April 24, 2017, https://biosimilarsrr.com/2017/04/24/ fda-approves-second-infliximab-biosimilar/.

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U.S. Food and Drug Administration, FDA approves first biosimilar for treatment of adult patients with non-Hodgkin’s lymphoma, November 28, 2018, https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm627009.htm.

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29.

S. DiGrande, “FDA Approves Third Trastuzumab Biosimilar, Ontruzant,” The Center for Biosimilars, January 18, 2019, https://www.centerforbiosimilars.com/news/fda-approves-third-trastuzumab-biosimilar-ontruzant.

30.

U.S. Food and Drug Administration, Testimony on Biosimilars Implementation by Janet Woodcock, M.D., Director, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, before the Committee on Energy and Commerce, Subcommittee on Health, United States House of Representatives, February 4, 2016, http://www.fda.gov/NewsEvents/Testimony/ucm485042.htm.

31.

T. Reinke, “Biosimilars: The Pipeline Seams Seem to be Bursting,” Managed Care, March 9, 2017, https://www.managedcaremag.com/ archives/2017/3/biosimilars-pipeline-seams-seem-be-bursting.

32.

Apotex Inc., Apotex Announces FDA Has Accepted For Filing its Biosimilar Application for Filgrastim (Grastofil™), February 17, 2015, https://www.prnewswire.com/news-releases/apotex-announces-fda-has-accepted-for-filing-its-biosimilar-application-for-filgrastim-grastofil-292257431.html.

33.

Apotex Inc., Apotex Announces FDA Has Accepted For Filing its Biosimilar Application for Pegfilgrastim, December 17, 2014, https://www.prnewswire.com/news-releases/apotex-announces-fda-has-accepted-for-filing-its-biosimilar-application-for-pegfilgrastim-286092751.html.

34.

IPD Analytics, Clinical Pipeline, www.ipdanalytics.com (accessed March 6, 2019).

35.

Generics and Biosimilars Initiative (GaBI), “FDA accepts application for Adello’s filgrastim biosimilar,” October 6, 2017, http://www.gabionline. net/Biosimilars/News/FDA-accepts-application-for-Adello-s-filgrastim-biosimilar.

36.

Generics and Biosimilars Initiative (GaBI), “Tanvex BioPharma submits filgrastim biosimilar to FDA,” November 23, 2018, http://www.gabionline.net/Biosimilars/News/Tanvex-BioPharma-submits-filgrastim-biosimilar-to-FDA.

37.

Amgen, Amgen Submits Biologics License Application for ABP 710 (Biosimilar Infliximab) To US Food And Drug Administration, December 17, 2018, https://www.amgen.com/media/news-releases/2018/12/amgen-submits-biologics-license-application-for-abp-710-biosimilar-infliximab-to-us-food-and-drug-administration/.

38.

S. DiGrande, “FDA Accepts Samsung Bioepis' BLA for Adalimumab Biosimilar SB5,” The Center for Biosimilars, September 27, 2018, https://www.centerforbiosimilars.com/news/fda-accepts-samsung-bioepis-bla-for-adalimumab-biosimilar-sb5.

39.

Pfizer Inc., Pfizer reports third-quarter 2018 results, October 30, 2018, https://www.businesswire.com/news/home/20181030005339/en/PFIZERREPORTS-THIRD-QUARTER-2018-RESULTS/.

40.

U.S. Food and Drug Administration, Biosimilar biological product authorization performance goals and procedures fiscal years 2013 through 2017, https://wayback.archive-it.org/7993/20170111191425/http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/Biosimilars/UCM281991.pdf (accessed March 6, 2019).

41.

U.S. Food and Drug Administration, Biosimilar biological product reauthorization performance goals and procedures fiscal years 2018 through 2022, https://www.fda.gov/downloads/ForIndustry/UserFees/BiosimilarUserFeeActBsUFA/UCM521121.pdf (accessed March 6, 2019).

42.

Generics and Biosimilars Initiative (GaBI), “FDA rejects Sandoz’s biosimilar pegfilgrastim application,” August 5, 2016, http://www.gabionline. net/Biosimilars/News/FDA-rejects-Sandoz-s-biosimilar-pegfilgrastim-application.

43.

K. Davio, “FDA Rejects Sandoz's Proposed Rituximab Biosimilar,” The Center for Biosimilars, May 2, 2018, https://www.centerforbiosimilars.com/ news/fda-rejects-sandozs-proposed-rituximab-biosimilar.

44.

K. Davio, “FDA Rejects Amgen's Trastuzumab Biosimilar, ABP 980,” The Center for Biosimilars, June 1, 2018, https://www.centerforbiosimilars. com/news/fda-rejects-amgens-trastuzumab-biosimilar-abp-980.

Innovatix | innovatix.com 29


45.

N. Walsh, “A Rocky Start for Biosimilar Inflectra? Infliximab biosimilar approved, but obstacles remain,” MedPage Today, April 7, 2016, http://www.medpagetoday.com/rheumatology/arthritis/57239.

46.

C. Suzuki, D. Yellin, B. Ryland, et al, “The Long And Winding Road For Biosimilars: Charting a Pathway through Patent, FDA, Antitrust, Prescription Filling, Reimbursement and Liability Law,” Bloomberg BNA Pharmaceutical Law and Industry Report 13, no. 1354 (September 18, 2015), https://www.crowell.com/files/The-Long-and-Winding-Road-for-BIOSIMILARS-Charting-a-Pathway-through-Patent-FDA-Antitrust-Prescription-Filling-Reimbursement-and-Liability-Law.pdf.

47.

Decision Resources Group, “U.S. Supreme Court Rules 180-Day Delay Will Not Be Required for Biosimilars After FDA Approval,” June 16, 2017, https://decisionresourcesgroup.com/drg-blog/u-s-supreme-court-rules-180-day-delay-will-not-required-biosimilars-fda-approval/.

48.

S. DiGrande, “FDA Releases Biosimilar Action Plan,” The Center for Biosimilars, July 18, 2018, https://www.centerforbiosimilars.com/news/ fda-releases-biosimilar-action-plan.

49.

U.S. Food and Drug Administration, Dynamic Regulation: Key to Maintaining Balance Between Biosimilars Innovation and Competition. Remarks by Scott Gottlieb, Commissioner of Food and Drugs, at The Brookings Institution, Washington, D.C., July 18, 2018, https://www.fda.gov/NewsEvents/ Speeches/ucm613452.htm.

50.

U.S. Food and Drug Administration, Statement from FDA Commissioner Scott Gottlieb, M.D., on new actions advancing the agency’s biosimilars policy framework, December 11, 2018, https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm628121.htm.

51.

G. Macdonald, “Biosimilar not interchangeable: Sandoz and Pfenex call for US FDA guidelines,” BioPharma-Reporter, September 4, 2015, http://www.biopharma-reporter.com/Markets-Regulations/Biosimilar-not-interchangeable-Sandoz-and-Pfenex-call-for-US-FDA-guidelines.

52.

U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research, Considerations in Demonstrating Interchangeability With a Reference Product: Guidance for Industry (Draft guidance) (Silver Spring, MD, 2017), https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM537135.pdf.

53.

T. Sullivan, “FDA Extends Wait for Biosimilar Interchangeability Guidance,” Policy and Medicine, May 5, 2018, https://www.policymed. com/2017/01/fda-extends-wait-for-biosimilar-interchangeability-guidance.html.

54.

J. Wechsler, “Further Guidance on Biosimilars Needed from FDA,” Pharmaceutical Executive, March 9, 2015, http://www.pharmexec.com/ further-guidance-biosimilars-needed-fda.

55.

“FDA Finalizes Guidance on Labeling for Biosimilars,” The Center for Biosimilars, July 18, 2018, https://www.centerforbiosimilars.com/news/ fda-finalizes-guidance-on-labeling-for-biosimilars?utm_medium=email&utm_campaign=Biosimilars%20enews%207-25-18&utm_content=Biosimilars%20enews%207-25-18+CID_567ba687005ec338321c29d9fb5335be&utm_source=CM%20BioSim&utm_term=FDA%20Finalizes%20Guidance%20 on%20Labeling%20for%20Biosimilars.

56.

U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research, Labeling for Biosimilar Products: Guidance for Industry (Silver Spring, MD, 2018), http://www.fda.gov/downloads/Drugs/ GuidanceComplianceRegulatoryInformation/Guidances/UCM493439.pdf?source=govdelivery&utm_medium=email&utm_source=govdelivery.

57.

A. D. Zelenetz, I. Ahmed, E. L. Braud, et al, “NCCN Biosimilars White Paper: regulatory, scientific, and patient safety perspectives,” J Natl Compr Canc Netw 9, Suppl. 4 (September 2011): S1-22.

58.

North American Center for Continuing Medical Education, “CME Survey: Biosimilars,” May 24, 2013, http://www.naccme.com/sites/naccme. com/files/biosimilar-survey-results.pdf.

59.

Quantia, Inc., New Quantia Report Reveals Physician Attitudes toward Biosimilars, August 18, 2015, https://www.businesswire.com/news/ home/20150818005839/en/New-Quantia-Report-Reveals-Physician-Attitudes-Biosimilars.

60.

Z. Schwartz, J. Schulz, A. Vinther, et al, “Uncovering clinicians’ gaps and attitudes toward biosimilars: impact of a 2-phase educational program” (paper presented at the 2018 American College of Rheumatology/Association of Rheumatology Health Professionals Annual Meeting, Chicago, IL, October 23, 2018), https://acrabstracts.org/abstract/uncovering-clinicians-gaps-and-attitudes-toward-biosimilars-impact-of-a-2-phase-educational-program/.

61.

K. Robinson and R. Esgro, “Revealing and addressing knowledge gaps regarding biosimilars in rheumatology practice with targeted continuing education and patient surveys” (paper presented at the 2018 American College of Rheumatology/Association of Rheumatology Health Professionals Annual Meeting, Chicago, IL, October 23, 2018), https://acrabstracts.org/abstract/revealing-and-addressing-knowledge-gaps-regarding-biosimilars-in-rheumatology-practice-with-targeted-continuing-education-and-patient-surveys/.

62.

K. Davio, “Despite Educational Efforts, Providers Still Lack Knowledge on Biosimilars,” The Center for Biosimilars, October 18, 2018, https://www. centerforbiosimilars.com/conferences/acr-2018/despite-educational-efforts-providers-still-lack-knowledge-on-biosimilars.

63.

A. Gaffney, “How comfortable are physicians with biosimilars? Not very (yet),” PwC Health Research Institute, October 24, 2018, https://www.pwc. com/us/en/industries/health-industries/library/physicians-with-biosimilars.html.

64.

“As Patents Expire, Payers Are Bullish on Price-Reducing Potential of Biosimilars,” Specialty Pharmacy News 13, no. 1 (2016): 1-4.

65.

S. D. Lucio, “Adoption of biosimilars: Prescribers, pharmacy, and payer perspectives,” American Journal of Pharmacy Benefits 8, no. 2 (2016): 67-76.

66.

I. Jacobs, E. Singh, K. L. Sewell, et al, “Patient attitudes and understanding about biosimilars: an international cross-sectional survey,” Patient Preference and Adherence 10 (2016): 937-948. https://doi.org/10.2147/PPA.S104891.

67. D. Stanton, “Patient groups express safety concerns about US FDA's biosimilar guidance,” BioPharma-Reporter, June 10, 2015, http://www.

biopharma-reporter.com/Markets-Regulations/FDA-biosimilar-guidance-leaves-patient-groups-with-safety-concerns.

68.

“Next Generation of Biosimilars and Biobetters: Challenges and Opportunities,” R&D Magazine, October 22, 2018, https://www.rdmag.com/ article/2018/10/next-generation-biosimilars-and-biobetters-challenges-and-opportunities.

69.

D. Steiber, “Biosimilars: The Perfect Fit for Specialty!” Specialty Pharmacy Times, April 15, 2015, http://www.specialtypharmacytimes.com/publications/specialty-pharmacy-times/2015/april-2015/biosimilars-the-perfect-fit-for-specialty.

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Continuing Education Prevention and Management of Clostridioides Difficile Infection (CDI) in Adults Renee Hofman, MS, RPh, Senior Director, Clinical Pharmacy Services, Premier Alternate Site Programs

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CONTINUING EDUCATION

Prevention and Management of Clostridioides Difficile Infection (CDI) in Adults This CE activity has been produced by Innovatix Institute, an educational program offered by Innovatix, LLC (“Innovatix”). This activity is accredited for pharmacists, pharmacy technicians, and nurses.

Goal Statement

The purpose of this activity is to provide the participant with the knowledge needed to prevent and treat Clostridioides difficile infection in adults.

Learning Objectives – Pharmacists and Nurses

At the completion of this activity, the participant will be able to: 1. Describe the pathogenesis and risk factors for developing Clostridioides difficile infection (CDI) in adults. 2. List and recognize strategies for the prevention of CDI. 3. Recommend treatment options for CDI in adults as per current IDSA/SHEA guidelines. 4. Identify and recognize notable adverse reactions associated with medications used to treat CDI.

Learning Objectives – Pharmacy Technicians

At the completion of this activity, the participant will be able to: 1. Identify risk factors for developing Clostridioides difficile infection (CDI) in adults. 2. Recognize strategies for the prevention of CDI. 3. Name three medications for the treatment of CDI

Target Audience

Pharmacy and nursing staff involved in managing patients with Clostridioides difficile infection (CDI).

Type of activity Knowledge-based

Cost

This activity is free of charge.

Disclosures

This continuing education activity is managed and accredited by Innovatix in cooperation with Affinity CE. Ms. Hofman, Innovatix, and Affinity CE have no relevant or apparent financial interests or relationships to disclose. The material presented for this article has been reviewed by the Innovatix Institute CE Committee and Affinity CE, and has been found to be free of any content influenced or supported by industry. Commercial support was not received for this activity.

Pharmacy Accreditation

Innovatix, LLC is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. This activity has been approved for 1 contact hour for pharmacists and pharmacy technicians. Universal Activity Number: 0409-0000-19-004-H01-P (Pharmacists) and 0409-0000-19-004-H01-T (Technicians)

Nursing Accreditation AffinityCE is accredited as a provider of nursing continuing professional development by the American Nurses Credentialing Center’s Commission on Accreditation. This activity provides 1 contact hour of continuing nursing education for learners who successfully complete this continuing nursing education activity, read the article, pass a post-test, and evaluate the educational content of the activity on-line at innovatix.cds.pesgce.com For technical support with this nursing activity, please contact cds_support+innovatix@affinityced.com

To receive CE credit, Pharmacists and Technicians must go to www.innovatix.com/evaluations. Click on Insight Magazine and scroll to find the title of this CE article. Complete the evaluation form. A score of 70% or higher is required to receive credit. Statements of Credit will be available from CPE Monitor within eight weeks, upon successful completion and submission of the verification of Continuing Education and Program Evaluation online forms and obtaining a passing score on the test. This lesson will not be valid for CE credit after 4/15/2022.

To Receive Nursing CE Credit, Nurses must go to innovatix.cds.pesgce.com. Scroll to find title of this CE article and click “Take Exam.” A score of 70% or higher on the post-test is required to receive credit. Continuing nursing education credit will be available from AffinityCE upon obtaining a passing score on the test and submission of the program evaluation online form. This lesson will not be valid for CE credit after 4/15/2022.

Legal Disclaimer The materials in this CE activity do not necessarily reflect the views of Innovatix or its affiliates. A qualified healthcare professional should be consulted before using any therapeutic product referenced as part of the program. Readers should verify all information and data before treating patients or employing any therapies described in the activity materials. As a condition to participating in this program, you acknowledge and agree that Innovatix is not providing any medical conclusions or advice, but is rather summarizing publicly available clinical information. The activity and corresponding materials may contain statements that may appear to be recommendations or advisory in nature, however, such statements are merely being recounted by Innovatix from the literature cited and do not constitute the recommendations or advice of Innovatix. Accordingly, Innovatix hereby disclaims all warranties, express or implied, as to the accuracy of any of the materials or information contained in the activity, or their fitness for any particular use or purpose. Clinical information and comments contained in the activity are for general guidance only. Mention of specific products in the activity or corresponding materials do not constitute an endorsement or advertisement. The activity provided is intended to provide you with information and is not intended to be used as a substitute for clinical or medical judgment. You agree that Innovatix shall not be responsible to you or any other third party for any clinical advice rendered by you, including advice related in any way to the activity. You agree to indemnify, defend, and hold Innovatix and its officers, directors, affiliates, employees, and agents (the “Innovatix Indemnitees”), harmless from and against any liability, costs, expenses, or damages, including attorneys’ fees and other costs of defense, incurred by any Innovatix Indemnitee in any action, proceeding, claim, or demand that is caused by, relates to, or arises out of your acts or omissions, or that in any way relate to your use of the information contained in the program or program materials. You agree that the activity and corresponding materials will be used for educational purposes only, and will not otherwise be copied or distributed without the prior written consent of Innovatix.

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Prevention and Management of Clostridioides Difficile Infection (CDI) in Adults Introduction Clostridioides difficile (formerly known as Clostridium difficile [C. difficile or C. diff]) is a Gram-positive, anaerobic, sporeforming bacillus bacterium usually spread by the fecal-oral route. It is non-invasive, remaining in the colon where it produces exotoxins, toxins A and B that cause diseases such as asymptomatic carriage, mild diarrhea, colitis, and pseudomembranous colitis.1 C. difficile was first detected more than 75 years ago in the stool of healthy infants,2 but the organism was not associated with human disease until 1978, when it was identified as the source of cytotoxin in the stool of patients with pseudomembranous colitis.3 The Centers for Disease Control and Prevention reports that in the United States, Clostridioides difficile bacteria causes almost half a million infections annually, with a higher incidence in females, whites, and those patients 65 years of age or older.4 Once a CDI is diagnosed, roughly 83,000 patients will experience at least one recurrence and 29,000 will die within 30 days of the initial CDI diagnosis.4 Clostridioides difficile infection is the most common cause of hospital-acquired illness reported. This puts an undue burden on the healthcare system and accounts for more than $4.8 billion in additional inpatient healthcare costs.5 Not surprisingly, major efforts have been directed at the control and prevention of CDI.

Pathogenesis C. difficile spores are shed in feces and can contaminate materials, surfaces, and equipment (including commodes, bathtubs, and medical devices) with which patients routinely come in contact. Infection occurs when these spores are ingested. Spores are often transmitted from one patient to another through the hands of healthcare personnel or the environment.6 The spores are resistant to heat, stomach acid, and many antibiotics, and will colonize in the large intestine. The colonized patient will demonstrate no clinical symptoms but will test positive for C. difficile or its toxin.6 Disturbances

of the gut flora, often due to antibiotic exposure, cause the proliferation of the vegetative C. difficile and the expression of clinical symptoms 7 (see Figure 1). Figure 1: Pathogenesis of CDI7 NORMAL MICROBIOTA

SUSCEPTIBLE MICROBIOTA

C. DIFFICILE SPORES

ANTIBIOTICS loss of colonization resistance

C. DIFFICILE INFECTION

germination

toxin production

VEGETATIVE C. DIFFICILE

The protein exotoxins, toxins A (tcdA) and B (tcdB), and the host's immune response are primarily responsible for the pathogenicity of the CDI. The endotoxins cause widespread inflammation in the colon and damage the epithelial tissue, causing fluid loss into the intestinal lumen and resulting in severe diarrhea.8 Some strains also produce a third toxin, binary toxin. While its role in CDI is unclear, when it is present with the current BI/NAP1/027 epidemic strain of CDI (also called ribotype 027), it may cause severe colitis.9

T E S T YO U R K N O W L E D G E Q U E ST I O N # 1:

What is the current epidemic strain of C. difficile?

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CONTINUING EDUCATION Figure 2: Risk Factors for Clostridioides difficile Infection (CDI)11,12,13,14,16 AGE GREATER THAN 65

LENGTH OF

Exposure to antibiotics

immunosuppression-

COMORBID DISEASE STATES

chemotherapy or HIV

HOSPITAL STAY Exposure to acidsuppressing drugs (PPI/H2RA)

Manipulation of GI system/ tube feeders/ GI surgery

EXPOSURE TO CDI IN A HEALTHCARE SETTING

human immunodeficiency virus (HIV) are at greater risk for CDI, apparently related to their immunosuppressed state.13 Other patients at risk are those who have had gastrointestinal surgery or nasogastric tube placement, as they are often of advanced age and/or have taken antibiotics and PPIs. 13

T E S T YO U R K N O W L E D G E Q U E ST I O N # 2:

What is the greatest risk factor for developing C. difficile infection?

PPI=proton pump inhibitor, H2RA=histamine 2 receptor antagonist, HIV=human immunodeficiency virus, GI=gastrointestinal

Risk Factors (See Figure 2) Although individuals with no risk factors can contract CDI, the most important nonmodifiable risk factors associated with disease development are advanced age (greater than 65 years) and length of hospitalization.11 Older age is also associated with increased risk of disease with the virulent strain BI/NAPI/027 and recurrent CDI. The risk associated with advanced age may be related to the increase in comorbid conditions and severity of illness in those individuals. The longer the hospital stay, the greater the risk of CDI, as the potential for exposure to infection and the need for antibiotics increases.12 Antibiotic use is by far the greatest risk factor for the development of CDI.12 All antibiotics have the potential to disrupt the normal gut microflora, providing an environment for C. difficile to flourish. Even one dose of an antibiotic prior to surgery can pose a risk of colonization with no symptoms but subsequent CDI.13 The antibiotics with the highest risk for causing CDI are third/fourth generation cephalosporins, fluoroquinolones, carbapenems, and clindamycin.13 Exposure to multiple antibiotics and longer duration of antibiotic therapy will increase the risk of developing CDI.14 Antibiotic cycling was once thought to decrease the development of CDI and decrease the emergence of antimicrobial resistance, but a recent study suggested otherwise, showing CDI rates did not change while healthcare-associated methicillinresistant Staphylococcus aureus (MRSA) increased significantly.15 Several studies have shown that patients taking acid-suppressing drugs (ASD), proton pump inhibitors (PPIs), or histamine 2 receptor antagonists (H2RA) are at increased risk for developing CDI.16 Proton pump inhibitors seem to pose a greater risk than H2RA, and this may be related to the degree of acid suppression and duration of therapy.16 The Food and Drug Administration (FDA) required that the package inserts for PPIs carry the warning that PPI therapy may be associated with an increased risk of Clostridioides difficile-associated diarrhea, especially in hospitalized patients.17 34 |

Cancer patients receiving chemotherapy and those with Insight

Diagnosis The diagnosis of CDI must be made using both clinical and laboratory findings.13 Clinical symptoms observed with CDI include diarrhea, which is defined as: • The passage of three or more unformed/watery stools in 24 or fewer consecutive hours; • Fever; • Loss of appetite; • Nausea; and • Abdominal pain, tenderness, and cramping.10 In non-severe and severe cases, leukocytosis – with a white blood cell (WBC) count ≤ 15,000 cells/mL and a serum creatinine (SCr) level ≤ 1.5mg/dL or a WBC > 15,000 cells/mL and a SCr level > 1.5mg/dL, respectively – is supportive of diagnosis.13 The condition is considered fulminant if the patient is hypotensive or in shock with ileus or megacolon.13 Also needed for diagnosis is a positive stool test for the presence of toxigenic C. difficile or its toxins or colonoscopy or histopathologic findings demonstrating pseudomembranous colitis.11 The challenge remains in differentiating between infection and colonization as molecular tests, such as nucleic acid amplification tests (NAATs), do not discriminate between the two, leading to misdiagnosis.13 It may be necessary to do a glutamine dehydrogenase (GDH) or toxigenic testing as well.13 This highlights the weight of looking to the clinical findings and testing only appropriate candidates.13 The guidelines caution against repeat testing of patients with negative findings for at least seven days, with only those that have multiple episodes of shapeless stool considered for testing.13 Repeat testing to establish if the patient is cured is of no value, as 60 percent of patients will remain C. difficile positive even after successful treatment.13 When diagnosing recurrent CDI, the same criteria should be followed.

CDI Prevention The first action that healthcare practitioners can take to reduce the risk of CDI is to initiate an antibiotic stewardship program, promoting judicious use of antibiotics, whereby the number and duration of the antimicrobials prescribed are


CONTINUING EDUCATION diminished. Restriction of fluoroquinolones, clindamycin, and cephalosporins should be considered, as they pose the greatest risk of triggering CDI.13 Use of PPIs and H2RA also should be assessed, and when deemed unnecessary, be discontinued.6

scopes, left in the patient's room. If this is not possible, ensure thorough cleaning of any shared devices using a sporicidal agent. Patients should be encouraged to wash their hands and shower to reduce the burden of spores on their skin.

The use of probiotics has been suggested as a means of reducing the development of CDI by preventing C. difficile overgrowth when given with antibiotics. They are low cost, readily available, and easy to administer. A recent systematic review of probiotics found evidence for their use to reduce CDI in hospitalized patients taking antibiotics.18 However, the current guidelines do not support their use due to the many limitations in the studies.13 Probiotics also lack standardization.13 In studies, there were differences in formulation and disparities in the duration of therapy as well as reports of probiotics causing infections in hospitalized patients.13 More probiotic studies will be needed to demonstrate beneficial outcomes.

Precautions should remain in place for at least a few days after diarrhea has stopped, as the patient continues to shed spores. Some facilities maintain precautions until discharge.19 A recent study documented skin contamination and environmental shedding of C. difficile for one to four weeks after resolution of diarrhea, supporting contact precautions remain in place until discharge.20 Upon discharge, the room surfaces should be disinfected with a sporicidal agent, such as chlorine bleach in proper dilution to prevent infecting the next occupant.19

Patients with known or suspected CDI must be placed on contact precautions to prevent the spread of infection.6 Where possible, patients with CDI should be placed in a private room with a dedicated toilet or be cohorted with other patients with CDI. Gloves and gowns should be worn when entering the room and while giving care to a CDI patient and hand hygiene performed before and when gloves are removed. It is best to use soap and water for cleaning as alcohol hand rubs do not kill C. difficile spores. Efficient washing of the hands remains the most effective way to prevent the transmission of CDI to others. If possible, disposable equipment should be used or medical equipment, such as blood pressure cuffs or stetho-

Treatment Guidelines for CDI

(see Figure 3)13 The Infectious Disease Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) released updated guidelines for the treatment of CDI in 2018.13 If a patient is suspected of having CDI, all laxatives must be stopped, the offending antibiotic, where possible, discontinued, and antibiotic therapy for CDI started. Antimotility agents such as loperamide (Imodium®) or diphenoxylate with atropine (Lomotil®) should be used with caution, as they can mask symptoms and lead to megacolon. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.13

Figure 3: Treatment of Adult Clostridium difficile Infection (CDI) CLINICAL DEFINITION

SUPPORTIVE CLINICAL DATA

RECOMMENDED TREATMENT

Initial episode, Non severe

Leukocytosis with WBC ≤ 15,000 cells/mL and SCr level ≤ 1.5mg/dL

1. Vancomycin 125mg QID orally x 10 days or 2. Fidaxomicin 200mg orally BID x 10 days — if above options are not available, then 3. Metronidazole 500mg orally TID x 10 days

Initial episode, severe

Leukocytosis with WBC > 15,000 cells/mL and SCr level > 1.5mg/dL

1. Vancomycin 125mg QID orally x 10 days or 2. Fidaxomicin 200mg orally BID x 10 days

Initial episode, fulminant

Hypotension or shock, ileus, megacolon

1. Vancomycin 500mg by mouth/NG tube QID 2. If ileus, may consider rectal vancomycin and add metronidazole 500mg IV Q8H

First recurrence

1. Vancomycin 125mg orally QID x 10 days if metronidazole used initially or 2. Vancomycin in a prolonged taper and pulse regimen (vancomycin 125mg orally QID x 10-14 days; 125mg bid x seven days; 125mg daily x seven days and then 125mg every two-three days x two-eight weeks) if vancomycin 125mg QID used initially or 3. Fidaxomicin 200mg orally BID x 10 days if vancomycin was used initially

Second or subsequent recurrence

1. Vancomycin in a prolonged taper and pulse regimen or 2. Vancomycin 125mg orally x 10 days followed by rifaximin 400mg orally TID x 20 days or 3. Fidaxomicin 200mg orally BID x 10 days or 4. Fecal microbiota transplant

Adapted from the Infectious Disease Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) Recommendations for Treatment of C. difficile.13 Note: QID=four times a day, TID=three times a day, BID=two times a day, Q8h=every eight hours, WBC=white blood cells, SCr=serum creatinine, NG=nasogastric, IV=intravenous

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CONTINUING EDUCATION

T E S T YO U R K N O W L E D G E QUESTION #3:

What steps can healthcare providers take to prevent the spread of C. difficile? Treatment choice for CDI is based on the severity of the infection and the patient's risk for recurrence.13 The guideline-recommended treatment for the initial episode of CDI is with either oral vancomycin (Vancocin®) 125mg orally four times a day for 10 days or fidaxomicin (Dificid®) 200mg orally twice daily for 10 days over previously recommended firstline metronidazole (Flagyl®) 500mg orally three times a day for 10 days.13 This more aggressive approach is associated with a decreased recurrence of CDI. In situations where a contraindication exists or obtaining vancomycin or fidaxomicin is an issue due to high cost, metronidazole may be used for the first episode of non-severe CDI.13 A study conducted at the Veterans Affairs Medical Center indicated that patients younger than 65 and in general good health who used metronidazole and vancomycin presented similar success rates in the treatment of mild CDI.21 Other treatment option that may be effective but are not FDA-approved for initial CDI are nitazoxanide (Alinia®) 500mg orally twice daily for 10 days and fusidic acid (Fucidin Suspension®) 250mg orally three times a day for 10 days (not marketed in the United States).13 Rifaximin (Xifaxan®), tigecycline (Tygacil®), and oral bacitracin have also been suggested, but the evidence does not support their use for initial occurrences of CDI.13 For fulminant CDI, an increased dose of vancomycin at 500mg four times a day is used orally or via nasogastric tube.13 It can also be administered via the rectum as a retention enema (in 100mL of normal saline with the addition of metronidazole 500mg intravenously every eight hours) if the patient presents with ileus.13

36 |

days for as many as eight weeks) can be used if vancomycin 125mg orally four times a day was given initially.13 Taper and pulse administration is used to diminish the vegetative C. difficile organisms and allow the normal microbiota to come back. A course of fidaxomicin 200mg orally twice daily can also be considered if vancomycin was the initial therapy.13 Approximately 25 percent of those treated with vancomycin will have a recurrent episode, and of that group, 40 percent will have an additional recurrence leaving the patient in a viscious cycle due to the depletion and disruption of the microbiome.13 Fidaxomicin usage initially versus vancomycin was associated with a lower risk of CDI recurrence supporting its initial use.13 For the second or subsequent recurrence, the guidelines recommend vancomycin in a prolonged tapered and pulse regimen or vancomycin 125mg orally four times a day for 10 days, followed by a course of rifaximin (Xifaxan®) 400mg orally three times a day for 20 days, or fidaxomicin 200mg orally twice daily for 10 days.13 Addition of probiotics has not proven to be efficacious.13 Empirical antibiotic treatment of patients who require antibiotics for an infection after treatment for CDI has been completed is another option that is not recommended at this time, as there is insufficient evidence to support this therapy.13 Fecal microbiota transplantation is also a possibility for patients with multiple recurrent episodes of CDI who have not responded to antibiotic treatment13. Not addressed in the guidelines newUtreatment option T E SisTtheYO R KNO W Lfor E Drecurrent G E CDI, bezlotoxumab (Zinplava®), a monoclonal antibody that binds Q U22E ST I O N # 4: to toxin B . It is used in conjunction with antibiotics and was Which medication is no longer shown to reduce the recurrence of CDI22.

considered the first line treatment for C. difficile infection according to the IDSA/SHEA guidelines?

Medications Used to Treat CDI Metronidazole

23

Metronidazole, while not approved by the Food and Drug

Still another option, if the vancomycin/metronidazole combination is ineffective, is the addition of tigecycline to the vancomycin therapy, with a loading dose of intravenous tigecycline100mg, followed by 50mg twice daily.13 Surgical management may be indicated for those severely affected, requiring a colectomy. Additionally, it may be necessary to do a diverting loop ileostomy, with colonic lavage and vancomycin flushes, to provide better patient outcomes.13

Administration for the treatment of CDI, was once considered

With recurrent CDI a regimen other than that used initially should be considred.13 Oral vancomycin is recommended if metronidazole was the original treatment agent or a prolonged oral taper and pulse regimen (vancomycin 125mg four times a day for 10 to 14 days, followed by 125mg twice daily for seven days, then 125mg every two to three

via nasogastric tube), and administered intraveneously. It is

Insight

a first-line therapy for the infection. The exact mechanism of action of metronidazole is unclear, but it interacts with deoxyribonucleic acid (DNA), leading to inhibition of DNA synthesis and DNA degradation. This results in the death of the bacteria. Today it is considered for treatment if vancomycin or fidaxomicin is contraindicated or unavailable.13 It can be administered orally (tablets also may be crushed and administered an inexpensive option for first episodes of mild CDI or as an adjunct when treating a fulminant case with ileus.13

Treatment should be limited to one course, as neurotox-

icity has been reported with lengthy or repeated usage.13 In


CONTINUING EDUCATION patients with severe hepatic impairment or end-stage renal disease, the dose may need to be reduced. Patients receiving

Rifaximin

27

Rifaximin is a semi-synthetic derivative of rifampin

the medication should be cautioned against consuming

and acts by binding to the beta-subunit of bacterial

alcohol or propylene glycol during treatment and for three

DNA-dependent RNA polymerase, blocking one of the steps

days following therapy, as a disulfiram-like reaction may

in transcription and causing inhibition of protein synthesis

occur. This can lead to cramps, nausea, vomiting, headaches,

and bacterial death. It is FDA-approved for the treatment of

and flushing. The medication may enhance the effects of

traveler’s diarrhea, hepatic encephalopathy, and irritable

warfarin (Coumadin®), increasing the prothrombin time and

bowel syndrome with diarrhea.

INR, thus requiring additional monitoring and possible dose

reduction of the warfarin. The most common side effects include nausea, headache, and a metallic taste. 23 24,25

Vancomycin was the first antibiotic to be FDA-approved

for treating CDI and is one of the antibiotics considered as first-line therapy in the IDSA/SHEA guidelines.13 It is bactericidal and works by inhibiting cell-wall biosynthesis as well as altering cell membrane permeability and ribonucleic acid (RNA) synthesis. The medication can be given orally, via nasogastric tube, and rectally as a retention enema in severe cases of CDI.

after therapy with vancomycin.13 It has not been studied in those with renal issues and should be used with caution in

Vancomycin

It has been used off-label as an alternative for initial

treatment of CDI and as an adjunct in treating recurrent CDI

those with hepatic impairment. One concern with the use of rifaximin is the potential for resistance. The most common adverse events reported with its use are peripheral edema, nausea, dizziness, fatigue, and ascites.7

Nitazoxanide

28

Nitazoxanide, an oral synthetic antiprotozoal that should

be administered with food, is indicated for the treatment of diarrhea caused by Giardia lamblia or Cryptosporidium

The intravenous route is not appropriate for the treat-

parvum. It works by disrupting anaerobic energy metabolism

ment of CDI. When given orally, it is not absorbed systemi-

and has been considered as an off-label treatment option for

cally so clinical monitoring of serum concentrations is not

CDI.13 The most common adverse reactions are abdominal

generally necessary. In cases of renal insufficiency, in the

pain, headache, chromaturia, and nausea.28

elderly, and at high doses for prolonged periods, clinical monitoring may be warranted to avoid nephrotoxicity

Tigecycline

and ototoxicity. The most common side effects noted are

nausea, abdominal pain, and hypokalemia. Vancomycin is

in patients 18 years of age and older for complicated skin

available as a capsule, as an injectable powder (that also can

and skin structure infections, intra-abdominal infections,

be compounded and used for oral administration as a cost-

and community-acquired bacterial pneumonia. It has

saving alternative), and as the newly approved vancomycin

been considered in combination with oral vancomycin

oral solution (Firvanq®).

as an off-label treatment option for CDI when the

24-25

Fidaxomicin

26

Fidaxomicin is a macrolide antibiotic that was approved

by the FDA in 2011 for the treatment of CDI in adults. It is bactericidal and works by inhibiting RNA synthesis by RNA polymerases. It is also considered a first-line option in the treatment of CDI and has demonstrated superiority in sustained clinical response when compared to vancomycin.13 It is given orally with food and has minimal systemic absorption and requires no renal or hepatic dose adjustment.

Hypersensitivity reactions such as angioedema of the

29

Tigecycline is an intravenous tetracycline indicated

combination of oral vancomycin and intravenous metronidazole has failed.13

Patients who develop abnormal liver function while

receiving therapy should be monitored for evidence of worsening hepatic function and evaluated for the risk/benefit of continuing the tigecycline. Its use has also been associated with pancreatitis. If this is suspected, consider discontinuing the medication. The most common adverse reactions are nausea, vomiting, diarrhea, abdominal pain, headache, and increased serum glutamate pyruvate transaminase (SGPT).29

Bezlotoxumab

30

mouth and throat, dyspnea, pruritus, and rash have been

In 2016 bezlotoxumab – an intravenous monoclonal anti-

reported, requiring the medication be discontinued and

body that binds to C. difficile toxin B and neutralizes its effects

rescue therapy administered. Patients with known macrolide

– was approved for use in patients 18 years of age and older.

allergy should be observed for cross-sensitivity. The most

It is administered in conjunction with CDI antibiotic therapy

common adverse effects are nausea, vomiting, abdominal

to patients at risk for recurrence. It is not an antibiotic and

pain, gastrointestinal hemorrhage, anemia,

should not be used alone. The recommended dose is 10mg/kg

and neutropenia.26

given once as an intravenous infusion. Innovatix | innovatix.com 37


CONTINUING EDUCATION

In clinical trials, patients who received antibiotic

Studies have shown FMT cure rates of greater than 80

treatment for primary or recurrent C. difficile infection

percent for recurrent CDI with a single dose and repeated

and bezlotoxumab had outcomes associated with a substan-

doses of FMT show cure rates over 90 percent.32 Some limiting

tially lower rate of recurrent infection than placebos

factors to physician adoption of FMT use are stringent

while having a safety profile similar to that of a placebo.22

requirements by the FDA (as it is still an experimental

Caution should be used in patients with heart failure. The

therapy) and issues with insurance reimbursement.31,32

most common adverse reactions reported included nausea,

More work needs to be done to determine the optimal dose,

pyrexia, and headache.

protocols for donor screening, recipient preparation, and who

Bezlotoxumab is available as an injection: 1,000 mg/40 mL

could most benefit from the therapy.31,32

(25 mg/mL) solution in a single-dose vial that should be stored

Summary

in the refrigerator and protected from light. The vial can be stored at room temperature protected from light for up to 24 hours. The vial should not be shaken, and it must be diluted prior to infusion with sodium chloride 0.9 percent or 5 percent dextrose to a final concentration ranging from 1mg/mL to 10mg/mL. The dilution solution should be mixed by gentle inversion and any unused contents of the vial discarded.

The diluted solution may be stored at room temperature

Clostridioides difficile infection is one of the most common

hospital-acquired infections in the United States. The overgrowth of the vegetative bacteria alters the normal microbiome and produces toxins A and B, killing cells and causing inflammation resulting in multiple episodes of diarrhea, nausea, and abdominal pain. A few significant risk factors for developing CDI are antibiotic exposure, gastric acid suppression, and advanced age. The infection has been reported

for up to 16 hours or under refrigeration for up to 24 hours.

with the use of almost all antibiotics. Transmission of the

If it has been refrigerated, bring the infusion up to room

disease is often through the contaminated hands of healthcare

temperature before use. The infusion should be administered

personnel or soiled surfaces. Key to the reduction of CDI is

over a 60-minute period using a sterile non-pyrogenic,

prudent prescribing of antibiotics and good hand hygiene.

low-protein-binding 0.2 micron to 5 micron in-line or add-on

filter. It should not be given as an intravenous push or bolus or co-administered with any other drugs.30

Fecal Microbiota Transplant (FMT)

31,32

Fecal Microbiota Transplant (FMT) is an investigational

therapy for recurrent CDI that has not responded to conventional antibiotic therapy. The IDSA/SHEA guidelines

First-line treatment of CDI is with the oral antibiotics

vancomycin and fidaxomicin. If they are not available, then metronidazole may be considered for an initial non-severe case. Recurrence of CDI is seen in 20 percent of patients, and the risk of recurrence increases with each subsequent episode. A different antibiotic from the one used to treat the first episode should be used to treat a recurrence.

recommend it be considered after multiple recurrences of

CDI. Fecal matter from a healthy, well-screened donor is

keeping the C. difficile overgrowth in check while permit-

transplanted into the colon of the CDI patient. This reintro-

ting the restoration of the microbiome. The addition of

duction of normal flora from the healthy donor helps restore

bezlotoxumab, a monoclonal antibody that binds to the

the patient's microbiome.31

toxin B produced by C. difficile, has been helpful to prevent

13

Initially, FMT was done by retention enema, but other

Often vancomycin taper and pulse dosing can aid in

recurrence when used with standard antibiotic therapy.

methods have been developed. The stool sample can be

introduced by colonoscopy, via nasogastric tube, and even

may be considered in those patients with multiple recur-

Fecal microbiota transplant with healthy donor stool

with oral capsules.31 The risk associated with FMT includes

rent episodes of CDI who have not responded to antibiotics.

the potential for infection from the donor sample (dictating

In some patients with unresponsive severe CDI, surgery is

rigorous screening of the donor) and potential procedural

necessary using colectomy or diverting loop ileostomy with

risks such as upper gastric bleed after nasogastric tube

colonic lavage. Effective prevention and management of

insertion or colon perforation during colonoscopy.13

CDI are crucial to diminish the burden of the disease.

REFERENCES 1. Taber's Medical Dictionary Online, s.v. “Clostridium,” accessed December 21, 2018, https://www.tabers.com/tabersonline/view/Tabers-Dic-

tionary/750171/all/Clostridium.

2. I. C. Hall and E. O’Toole, “Intestinal flora in newborn infants with a description of a new pathogenic anaerobe, Bacillus difficile,” Am J Dis

Child 49 (1935): 390–402.

3. R. H. George, J. M. Symonds, F. Dimock, et al, “Identification of Clostridium difficile as a cause of pseudomembranous colitis,” Br Med J 1, no.

6114 (March 18, 1978): 695.

4. Centers for Disease Control and Prevention, Clostridioides difficile (C. diff), December 17, 2018. https://www.cdc.gov/hai/organisms/cdiff/

Cdiff-patient.html.

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CONTINUING EDUCATION 5. Erik R. Dubberke and Margaret A. Olsen, “Burden of Clostridium difficile on the Healthcare System,” Clinical Infectious Diseases 55, Issue

suppl_2 (August 2012): S88–S92. https://doi.org/10.1093/cid/cis335.

6. Centers for Disease Control and Prevention, FAQs for Clinicians about C. diff, December 17, 2018. https://www.cdc.gov/cdiff/clinicians/faq.html. 7. The Young Lab, Department of Internal Medicine/Infectious Diseases Division and the Department of Microbiology and Immunology at the

University of Michigan, Ann Arbor, Research interests: Clostridium difficile and the indigenous gut microbiota. https://sites.google.com/a/ umich.edu/younglab/research-interests.

8. G. P. Carter, A. Chakravorty, T. A. Pham Nguyen, et al, “Defining the Roles of TcdA and TcdB in Localized Gastrointestinal Disease, Systemic

Organ Damage, and the Host Response during Clostridium difficile Infections,” MBio 6, no. 3 (June 2, 2015): 00551-15.

9. F. C. Lessa, C. V. Gould, and L. C. McDonald, “Current status of Clostridium difficile infection epidemiology,” Clin Infect Dis 55, Suppl 2 (2012):

S65-70.

10. West Virginia Bureau for Public Health, Division of Infectious Disease Epidemiology, “Guidelines for Clostridium difficile (C. diff) Outbreaks

in Long-Term Care Facilities,” February 2012. http://dhhr.wv.gov/oeps/disease/AtoZ/Documents/CDiff%20Guidelines.pdf.

11. S. H. Cohen, D. N. Gerding, S. Johnson, et al, “Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the

Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA),” Infect Control and Hosp Epidemiol 31 (2010): 431–455.

12. P. Eze, E. Balsells, M. H. Kyaw, et al, “Risk factors for Clostridium difficile infections - an overview of the evidence base and challenges in data

synthesis,” J Glob Health 7, no. 1 (2017): 010417.

13. L. C. McDonald, D. N. Gerding, S. Johnson, et al, “Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017

update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA),” Clin Infect Disease 66, no. 7 (March 19, 2018): e1–e48.

14. J. Pépin, N. Saheb, M. A. Coulombe, et al, “Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile-associated

diarrhea: a cohort study during an epidemic in Quebec,” Clin Infect Disease 41 (2005): 1254–60.

15. G. Conlon-Bingham, M. Aldeyab, M. Scott, et al, “Effects of Antibiotic Cycling Policy on Incidence of Healthcare-Associated MRSA and

Clostridioides difficile Infection in Secondary Healthcare Settings,” Emerging Infectious Diseases 25, no. 1 (2019): 52-62.

16. L. Fisher and A. Fisher, “Acid‐suppressive therapy and risk of infections: pros and cons,” Clin Drug Investig 37, no. 7 (July 2017): 587–624.

https://doi.org/10.1007/s40261-017-0519-y.

17. Daily Med (NIH National Library of Medicine), s.v. “Prevacid,” https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=71ba78cb-7e46-

43eb-9425-fa130f537f84 (accessed December 27, 2018).

18. Nicole T. Shen, Anna Maw, Lyubov L. Tmanova, et al, “Timely Use of Probiotics in Hospitalized Adults Prevents Clostridium difficile

Infection: A Systematic Review With Meta-Regression Analysis,” Gastroenterology 152, no. 8 (June 2017): 1889 - 1900. https://doi.org/10.1053/j. gastro.2017.02.003.

19. N. Macleod-Glover and C. Sadowski, “Efficacy of cleaning products for C. difficile: environmental strategies to reduce the spread of

Clostridium difficile-associated diarrhea in geriatric rehabilitation,” Can Fam Physician 56, no. 5 (2010): 417-23.

20. A. K. Sethi, W. N. Al-Nassir, M. M. Nerandzic, et al, “Persistence of Skin Contamination and Environmental Shedding of Clostridium difficile

during and after Treatment of C. difficile Infection,” Infection Control & Hospital Epidemiology 31, no. 1 (2010): 21-27. https://doi.org/10.1086/649016.

21. Haley J. Appaneal, Aisling R. Caffrey, and Kerry L. LaPlante, “What is the role for metronidazole in the treatment of Clostridium difficile

infection? Results from a national cohort study of veterans with initial mild disease,” Clinical Infectious Diseases (December 18, 2018). https://doi.org/10.1093/cid/ciy1077.

22. M. H. Wilcox, D. N. Gerding, I. R. Poxton, et al, “Bezlotoxumab for prevention of recurrent Clostridium difficile infection,” N Engl J Med 376,

no. 4 (January 26, 2017): 305-317. doi: 10.1056/NEJMoa1602615.

23. Daily Med (NIH National Library of Medicine), s.v. “Flagyl,” https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b39cc0e4-57ad-

4d70-a105-44ebccf201f8 (accessed January 2, 2019).

24. Daily Med (NIH National Library of Medicine), s.v. “Vancocin,” https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a078d9c2-f89c-

4f9f-8ded-60ffb2983c3f (accessed January 2, 2019).

25. Daily Med (NIH National Library of Medicine), s.v. “Firvanq,” https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5aca5508-b577-

446c-9980-ab4c7582b4b9 (accessed January 2, 2019).

26. Daily Med (NIH National Library of Medicine), s.v. “Dificid,” https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=dd966338-c820-

4270-b704-09ef75fa3ceb (accessed January 2, 2019).

27. Daily Med (NIH National Library of Medicine), s.v. “Xifaxan,” https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c5e8e2fd-7087-

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28. Daily Med (NIH National Library of Medicine), s.v. Alinia,” https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=56b1575a-dff4-4c5a-

a159-2f858e7a0cb8 (accessed January 8, 2019).

29. Daily Med (NIH National Library of Medicine), s.v. “Tygacil,” https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2ccdb48e-c14a-

4eeb-348c-4920ccfd7465 (accessed January 8, 2019).

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4cc5-9aee-1357364480b0 (accessed January 8, 2019).

31. L. J. Brandt, “American Journal of Gastroenterology lecture: Intestinal microbiota and the role of fecal microbiota transplant (FMT) in

treatment of C. difficile infection,” Am J Gastroenterol 108, no. 2 (February 2013): 177–185. doi: 10.1038/ajg.2012.450.

32. B. J. Kelly and P. Tebas, “Clinical Practice and Infrastructure Review of Fecal Microbiota Transplantation for Clostridium difficile Infection,”

Chest 153, no. 1 (January 2018): 266-277. doi: 10.1016/j.chest.2017.09.002.

Innovatix | innovatix.com 39


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CATEGORY SPOTLIGHT

Category Spotlight: Room Refresh Portfolio

The healthcare industry today is riding a patient consumerism wave. As patients increasingly become empowered consumers, providers must adapt to meet their expectations.

To encourage preference and inspire loyalty, providers must consistently deliver patient experiences that go beyond achieving better outcomes. While there is no silver-bullet solution to improve the patient experience, room refresh projects are a great starting place.

the perception of your facility among green conscious

Room refresh projects can include making minor repairs, installing new fixtures, or even reworking an entire space. In the past, these initiatives may have seemed like a drain on resources, but it’s time to rethink that notion. The benefits associated with investing in small-scale room upgrades directly impacts the patient experience by:

Enhancing Operations

Green upgrades provide a great example. A simple refresh

project like replacing lights in rooms with new energy efficient LED bulbs can improve patient comfort, decrease the likelihood for errors, lower energy costs, and enhance consumers. This type of refresh project also allows existing patient care to continue while rooms are upgraded.

Boost the ROI of Room Refresh with Innovatix

Whether you’re operating a senior living facility with

long-term residents or an infusion pharmacy with visits from multiple patients a day, Innovatix’s portfolio has a full array of suppliers and contracts that can lower your supply costs and boost the ROI of your room refresh initiatives.

Our room refresh portfolio consists of more than 30

product and service categories representing over 120 manufacturers, distributors, and service providers. The

Driving Efficiencies

contracts cover virtually every conceivable room refresh project need – from interior and exterior signage to flooring products and services.

Improving Quality of Care Innovatix | innovatix.com 41


CATEGORY SPOTLIGHT

Innovatix Room Refresh Portfolio CONTRACT NAME

SUPPLIER

CONTRACT NUMBER

END DATE

FACILITY MANAGEMENT & MAINTENANCE Air Filtration Products

Ceiling Tiles, Panels and Systems

Clinical Headwalls

Cubicle Curtains, Tracks, and Privacy Screens

Doors, Frames, and Hardware Flooring Products and Services

Furniture and Systems, Casegoods, Seating and Accessories

42 |

Insight

AAF INTERNATIONAL

PP-FA-686

08/31/21

CAMFIL USA, INC

PP-FA-687

08/31/21

KOCH FILTER CORPORATION

PP-FA-688

08/31/21

TRI-DIM FILTER CORP.

PP-FA-689

08/31/21

ARMSTRONG WORLD INDUSTRIES, INC.

PP-FA-555

08/31/19

ARMSTRONG WORLD INDUSTRIES, INC.

PP-FA-745

08/31/22

CERTAINTEED CORPORATION

PP-FA-554

08/31/19

USG CORPORATION

PP-FA-538

08/31/19

AMICO CORPORATION

PP-FA-730

03/31/22

HOSPITAL SYSTEMS, INC.

PP-FA-731

03/31/22

WITTROCK HEALTHCARE

PP-FA-732

03/31/22

CUBE CARE COMPANY

PP-FA-711

11/30/21

ENCOMPASS GROUP LLC

PP-FA-712

11/30/21

HYGENICA, INC.

PP-FA-710

11/30/21

ICP MEDICAL

PP-FA-713

11/30/21

PHOENIX TEXTILE CORPORATION

PP-FA-714

11/30/21

S2S GLOBAL

PP-FA-715

11/30/21

SILENTIA INC.

PP-FA-716

11/30/21

STANDARD TEXTILE CO., INC

PP-FA-717

11/30/21

WELMED, INC

PP-FA-718

11/30/21

ASSA ABLOY SALES AND MARKETING GROUP, INC

PP-FA-663

12/31/21

ARMSTRONG FLOORING, INC.

PP-FA-692

11/30/21

ECORE INTERNATIONAL

PP-FA-693

11/30/21

FORBO FLOORING INC

PP-FA-694

11/30/21

MANNINGTON COMMERCIAL, INC.

PP-FA-695

11/30/21

MOHAWK INDUSTRIES

PP-FA-696

11/30/21

SHANNON SPECIALTY FLOORS

PP-FA-697

11/30/21

SHAW INDUSTRIES, INC.

PP-FA-698

11/30/21

TANDUS CENTIVA US LLC

PP-FA-700

11/30/21

TARKETT

PP-FA-699

11/30/21

ALLSEATING CORPORATION

PP-FA-631

12/31/20

DURFOLD CORPORATION

PP-FA-625

12/31/20

EXEMPLIS LLC

PP-FA-626

12/31/20

HAWORTH, INC.

PP-FA-617

12/31/20

HERMAN MILLER INC.

PP-FA-614

12/31/20

HILLROM COMPANY, INC.

PP-FA-616

12/31/20

KIMBALL INTERNATIONAL

PP-FA-623

12/31/20

KNOLL, INC.

PP-FA-624

12/31/20

KRUEGER INTERNATIONAL, INC (KI)

PP-FA-618

12/31/20

LA-Z-BOY CONTRACT FURNITURE

PP-FA-627

12/31/20

NATIONAL BUSINESS FURNITURE

PP-FA-622

12/31/20

NATIONAL OFFICE FURNITURE

PP-FA-620

12/31/20

NOVUM MEDICAL PRODUCTS

PP-FA-632

12/31/20


CATEGORY SPOTLIGHT

CONTRACT NAME

SUPPLIER

CONTRACT NUMBER

END DATE

OFS BRANDS HOLDINGS, INC.

PP-FA-621

12/31/20

STANCE HEALTHCARE INC

PP-FA-629

12/31/20

STEELCASE INC.

PP-FA-615

12/31/20

STRYKER CORPORATION

PP-FA-619

12/31/20

SUMMER CLASSICS

PP-FA-628

12/31/20

Gypsum Board and Drywall

USG CORPORATION

PP-FA-531

08/31/19

USG CORPORATION

PP-FA-747

08/31/22

HVAC Equipment, Controls and Services

CARRIER CORPORATION

PP-FA-613

10/31/19

DAIKIN APPLIED

PP-FA-512

10/31/19

TRANE U.S. INC.

PP-FA-513

10/31/19

Ice Machines and Water Dispensing Products and Services

FOLLETT LLC

PP-FA-596

06/30/20

SCOTSMAN ICE SYSTEMS

PP-FA-597

06/30/20

Interior and Exterior Signage

2/90 SIGN SYSTEMS

PP-FA-575

02/29/20

LOC8 SOLUTIONS, LLC

PP-FA-762

02/29/20

MANDEVILLE SIGN

PP-FA-577

02/29/20

MDM COMMERCIAL ENTERPRISES INC

PP-FA-578

02/29/20

SOUTH WATER SIGNS

PP-FA-579

02/29/20

AIRSUPPLY TOOLS, INC

PP-FA-590

04/30/22

THE PART WORKS

PP-FA-594

04/30/22

WW GRAINGER

PP-FA-591

04/30/22

AMERICAN DAWN INC

PP-FA-654

01/31/21

ARAMARK UNIFORM AND CAREER APPAREL

PP-FA-690

01/31/21

CINTAS CORPORATION

PP-FA-656

01/31/21

CONTEC

PP-FA-657

01/31/21

ENCOMPASS GROUP LLC

PP-FA-658

01/31/21

PHOENIX TEXTILE CORPORATION

PP-FA-659

01/31/21

S2S GLOBAL

PP-FA-605

01/31/21

STANDARD TEXTILE CO., INC

PP-FA-660

01/31/21

UNIFIRST CORPORATION

PP-FA-691

01/31/21

CUSTOM COMFORT MEDTEK

PP-FA-678

06/30/21

GROUPE LACASSE LLC

PP-FA-679

06/30/21

HERMAN MILLER INC.

PP-FA-680

06/30/21

INTERMETRO INDUSTRIES, CORP.

PP-FA-681

06/30/21

MASS MEDICAL STORAGE, LLC

PP-FA-682

06/30/21

QC STORAGE, LLC

PP-FA-683

06/30/21

SOLAIRE MEDICAL

PP-FA-684

06/30/21

BENJAMIN MOORE & COMPANY

PP-FA-733

02/28/22

NATIONAL PAINT ALLIANCE

PP-FA-734

02/28/22

PPG INDUSTRIES

PP-FA-735

02/28/22

AFFLINK, INC.

PP-FA-606

10/31/20

NETWORK SERVICES COMPANY

PP-FA-607

10/31/20

OFFICE DEPOT

PP-FA-608

10/31/20

STRATEGIC MARKET ALLIANCE

PP-FA-609

10/31/20

TRIPLE S

PP-FA-611

10/31/20

VERITIV CORPORATION

PP-FA-612

10/31/20

Furniture and Systems, Casegoods, Seating and Accessories (continued)

Maintenance, Repair and Operations Microfiber Products, Mats, and Accessories

Modular Casework, Storage Systems and Mobile Carts

Paint and Related Sundries Paper and Janitorial Supply Distribution

Innovatix | innovatix.com 43


CATEGORY SPOTLIGHT

CONTRACT NAME Rental Equipment and Specialty Solutions

SUPPLIER

CONTRACT NUMBER

END DATE

HERC RENTALS INC.

PP-FA-751

03/31/22

AMERICAN DAWN INC

PP-FA-702

11/30/21

CALDERON TEXTILES, LLC

PP-FA-703

11/30/21

CAREANDWEAR II, INC.

PP-FA-704

11/30/21

ENCOMPASS GROUP LLC

PP-FA-705

11/30/21

HINSON & HALE MEDICAL TECHNOLOGIES, INC.

PP-FA-706

11/30/21

MEDLINE INDUSTRIES, INC.

PP-FA-707

11/30/21

PHOENIX TEXTILE CORPORATION

PP-FA-708

11/30/21

STANDARD TEXTILE CO., INC

PP-FA-709

11/30/21

Synchronized Monitoring

SAPLING, INC

PP-FA-662

11/30/20

Television Systems and Services

D&L COMMUNICATION SYSTEMS

PP-FA-569

02/29/20

MDM COMMERCIAL ENTERPRISES INC

PP-FA-563

02/29/20

TELEHEALTH SERVICES

PP-FA-565

02/29/20

UNITED MEDIA SOLUTIONS

PP-FA-701

02/29/20

INPRO CORPORATION

PP-FA-726

01/31/22

KOROSEAL INTERIOR PRODUCTS

PP-FA-727

01/31/22

PAWLING CORPORATION

PP-FA-728

01/31/22

WALLPROTEX

PP-FA-729

01/31/22

GREAT AMERICAN ART

PP-FA-737

04/30/22

PHOENIX TEXTILE CORPORATION

PP-FA-738

04/30/22

RAO CONTRACT SALES, INC

PP-FA-739

04/30/22

THE AMBIANCE GROUP

PP-FA-736

04/30/22

DURACELL INDUSTRIAL OPERATIONS, INC.

PP-MM-685

11/30/21

ENERGIZER BATTERY COMPANY

PP-MM-684

11/30/21

RAYOVAC CORPORATION

PP-MM-687

11/30/21

S2S GLOBAL

PP-MM-688

11/30/21

Blood Pressure Cuffs and Accessories

GE MEDICAL SYSTEMS INFORMATION TECHNOLOGIES, INC.

PP-MM-632

05/31/21

WELCH ALLYN INC

PP-MM-631

05/31/21

Chart Paper and Related Products

CARDINAL HEALTH 200, LLC

PP-MM-482

08/31/20

PRINT MEDIA, INC.

PP-MM-483

08/31/20

Cribs, Bassinets, Youth Beds and Related Products

ATOM MEDICAL USA, LLC

PP-MM-714

03/31/22

HARD MANUFACTURING CO INC

PP-MM-713

03/31/22

NOVUM MEDICAL PRODUCTS

PP-MM-715

03/31/22

Custom Whiteboards

CHAMELEON CORPORATION

PP-MM-598

08/31/20

CLARUS GLASSBOARDS

PP-MM-599

08/31/20

DIGITAL DESIGNED SOLUTIONS, LLC

PP-MM-689

08/31/20

TAYLOR HEALTHCARE

PP-MM-690

08/31/20

VISCOT MEDICAL LLC

PP-MM-600

08/31/20

AIRGAS, INC.

PP-MM-608

10/31/20

PRAXAIR INC

PP-MM-610

10/31/20

BREWER COMPANY, LLC

PP-MM-462

03/31/20

FIRST HEALTHCARE PRODUCTS, INC.

PP-MM-459

03/31/20

MEDICAL TECHNOLOGY INDUSTRIES, INC. (MTI)

PP-MM-461

03/31/20

MIDMARK SALES CORPORATION

PP-MM-460

03/31/20

TRANSMOTION MEDICAL, A DIVISION OF WINCO MFG., LLC

PP-MM-463

03/31/20

Reusable Textiles and Textile Services

Wall and Door Covering and Protection

Wall Art and Mirrors

MATERIALS MANAGEMENT Batteries and Battery Products

Cylinder Gases Exam Room Furniture Equipment

44 |

Insight


CATEGORY SPOTLIGHT

CONTRACT NAME High Density Mobile Storage Systems Patient Beds, Mattresses and Therapeutic Surfaces Patient Scales

Physical Therapy Products and Exercise Equipment Stainless Steel Equipment, Storage Systems and Mobile Carts (Medical and NonMedical)

SUPPLIER

CONTRACT NUMBER

END DATE

LOGIQUIP LLC

PP-MM-638

06/30/21

QUANTUM MEDICAL

PP-MM-640

06/30/21

SPACESAVER CORPORATION

PP-MM-639

06/30/21

HILLROM COMPANY, INC.

PP-MM-717

02/28/22

LINET AMERICAS

PP-MM-718

02/28/22

STRYKER MEDICAL

PP-MM-716

02/28/22

HEALTH O METER PROFESSIONAL

PP-MM-602

09/30/20

RICE LAKE WEIGHING SYSTEMS

PP-MM-488

09/30/20

SECA CORPORATION

PP-MM-603

09/30/20

WELCH ALLYN INC

PP-MM-489

09/30/20

CYMEDICA ORTHOPEDICS, INC.

PP-MM-720

02/29/20

PERFORMANCE HEALTH SUPPLY, INC.

PP-MM-456

02/29/20

THE MEDCOM GROUP LTD

PP-MM-457

02/29/20

ALIMED, INC.

PP-MM-634

06/30/21

BLICKMAN INDUSTRIES

PP-MM-635

06/30/21

LAKESIDE MANUFACTURING, INC.

PP-MM-636

06/30/21

PEDIGO PRODUCTS INC

PP-MM-637

06/30/21

STERIS CORPORATION

PP-MM-725

06/30/21

NURSING Auditory and Visual Exam Diagnostics and Systems

SONIC INNOVATIONS, INC.

PP-NS-1142

04/30/21

WELCH ALLYN INC

PP-NS-1141

04/30/21

Fall Management Footwear

CARDINAL HEALTH 200, LLC

PP-NS-1055

07/31/20

ENCOMPASS GROUP LLC

PP-NS-1054

07/31/20

S2S GLOBAL

PP-NS-1056

07/31/20

BECTON, DICKINSON AND COMPANY

PP-NS-1002

04/30/20

CARDINAL HEALTH 200, LLC

PP-NS-1001

04/30/20

ARMSTRONG RELOCATION

PP-SV-156

07/04/20

BELTMANN INTEGRATED LOGISTICS

PP-SV-158

07/04/20

EWING MOVING SERVICE

PP-SV-159

07/04/20

HEALTH CARE RELOCATIONS OF AMERICA

PP-SV-161

07/04/20

SIRVA WORLDWIDE, INC.

PP-SV-162

07/04/20

Sharps Disposal Containers

PURCHASED SERVICES Moving Services

Innovatix | innovatix.com 45


Meeting & Expo

Save the Date Arizona Biltmore October 11 - 15, 2020 Phoenix, Arizona

46 |

Insight


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