By Nicholas Basta

Value- or outcomes-based contracting is the buzz of the moment in specialty pharmaceutical marketing. Interest in it is driven by the (typically) high cost of the therapies, and payers’ desire to ensure that they’re getting something for the money expended, In the single-payer systems in Europe, generally speaking, these issues are addressed by health technology assessments; in the US, with its decentralized, pay-as-you-go practices, the value-based contract (VBC) is becoming a viable practice.

Essential to a rational VBC is the ability to track the outcomes or continued health of patients. Where does this outcomes data come from? For the most part, it seems that the payers or health systems engaged in VBCs are using claims records and data from electronic health records (EHRs) to verify outcomes. EHR data figures in many of the prominent efforts to generate real-world data and real-world evidence (RWE) as well.

So far, all good. There are limitations and constraints on RWE from claims and EHRs (mostly, because they’re set up for handling reimbursements, and not for outcomes directly); lots of smart people are working on that. But here’s the twist: apart from the extraordinarily expensive cell/gene therapies, most RWE work seems to be focused on clinical trials, both leading up to and after a drug’s approval. This is due, in part, to the 21st Century Cures Act, which opened the door wider for FDA to consider observational data (which includes RWE) as part of a drug’s application.

We would like to highlight another source of RWE, and one that could play into a much wider range of VBCs: the pharma industry’s hub and patient-support providers. As the 

 details, hubs routinely gather data from patients. In some cases, they are in touch with them daily, not just for medical data, but scads of data on patients’ moods, emotions and concerns.

Surprisingly, all of the outsourced hub providers interviewed for the Overview say that collecting data for VBCs is “not here yet, but coming soon.” We suspect that the reason for this is pharma companies’ siloing of the patient data in commercial or market-access functions; over in the R&D sector, researchers are unaware of the value of these data (or, perhaps, simply don’t recognize it as research-grade).

 from the Institute for Clinical and Economic Review (ICER) is that RWE will become a more central part of their analyses. The RWE contractor that ICER will work with runs a blog on its website named “The Evidence Hub.” That “hub,” and all the RWE researchers, would do well to connect with the actual hubs gathering valuable data every day.

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Hub providers can be the source of the best real-world evidence

CareMetx was founded in 2011 by two longtime industry executives, Bob Dresing and Mark Hansan, who started in the patient support field in the 1980s. Dresing is now chairman; Hansan is CEO. In 2018, it acquired VirMedica, a leading e-services company in the Hub industry, and BioSolutia, an award-winning Hub company in Lake Mary, FL. Today it has five offices and operates as a national patient access company offering turn-key solutions, proprietary e-services and collaborative patient support programs. Most recently, it launched a new business unit, OutcomeRx, designed to provide holistic solutions for new personalized medicines, such as cellular and genetic therapies, that require innovative value-based contracting between manufacturers and payers.

 sat down with Hansan; here’s what he had to say about the evolving hub services/patient support arena.

1. What is the CareMetx origin story? How did you come to concentrate on this part of the healthcare ecosystem?

I was very fortunate to start my career at the Cystic Fibrosis Foundation, just after Bob Dresing became the president and CEO. Bob had a son with CF and he focused the organization on raising money to cure the disease. Over the next 10 years we achieved some remarkable accomplishments including establishing a research framework leading to the discovery of the CF gene in 1989, funding early stage biotech companies for drug development and gene therapy and creating the first disease-specific specialty pharmacy in 1988.

While operating the pharmacy, we saw first-hand the challenges patients and their families faced in accessing the drugs they needed. This was a time of pre-existing conditions, lifetime caps and HMOs and as a result the uninsured rate for CF patients exceeded 15%. This led Bob to push the Pharmaceutical Manufacturers Association (then PMA; now PhRMA) to encourage all member companies to offer patient assistance programs. PMA even dedicated their first PAP guide to Bob for his leadership.

While we worked aggressively to ensure every patient had insurance whether private or government and got the uninsured rate to below 2%, we also witnessed the affordability challenges that all rare disease patients faced. I was inspired and motivated to do something about this issue. When you know the patients and their families, you have a clear view of what they go through just to stay healthy. Why create even more stress in their lives by placing obstacles that create access challenges?

Our response at that time led us to found TheraCom, one of the original Hub providers, in 1996. That company was acquired in the early 2000s, and we subsequently founded CareMetx (after trying to buy TheraCom back) in 2011.

CareMetx is based on two core beliefs — first, the traditional Hub business lacked the technology necessary to improve automation that could reduce the manual processes, and second, there would be an increasing need for payers and manufacturers to move towards more value-based contracts. The initial tagline — “From Intake to Outcomes”—reflects our commitment to our beliefs about the Hub industry.

2. What is CareMetx’ stance in the market in terms of services and capabilities? What are the company’s competitive advantages?

In my opinion, this industry is experiencing a shift from the analog or traditional Hub to a digital-hybrid Hub model. The stakeholders involved in our industry – and healthcare generally – are becoming more digital and reliant on data to make decisions. Partnerships are expanding providing the industry with access to better data capture methodologies and analytics. Tools like APIs are more pervasive and make it easier than ever to access the latest digital transactions. Even patients themselves are cutting the cord and going only mobile. These trends are transforming the Hub business model away from the legacy processes to a more nimble, customized, digital experience for patients, providers and even payers.

To answer the second part of your question about CareMetx, we are comfortable with our market position as a collaborative disruptor. We have all the traditional solutions of a modern Hub, but we have unbundled our proprietary capabilities and provide them to other Hubs, including internal manufacturer Hubs and even our Hub competitors. We have been in the business long enough to know the decision to move a Hub, especially some of the larger ones, is fraught with difficulties and even risk.

We want to minimize these potential issues by allowing others to connect to our tools. Don’t get me wrong, we would love to take over the entire Hub, but in some instances, the best way we can provide immediate value is to leverage our plug-in technologies and e-service transactions.

For the Hub programs we operate, we are proud to support some of the most innovative therapies on the market. We are comfortable with everything from the Hub-lite models to ultra-rare, high-touch Hub programs. Our roots as patient advocates have never left us.

3. What do you mean by “digital-hybrid Hub”? Can you explain more about that?

Sure. There are three aspects of a digital-hybrid Hub: a front-end digital experience; a pathway for manual intervention; and the high-touch services themselves. All of these assets, correctly assembled, create a value proposition in which providers enjoy a more seamless and responsive process, patients start therapy with fewer obstacles, and the manufacturer-sponsor can bring more services to their stakeholders at a lower fee structure than legacy Hub services alone.

A prime example is a pilot program where we are collaborating with a major specialty brand to place our e-service transactions directly into the providers’ EMR system, allowing them to complete an electronic benefit investigation while performing their daily tasks in their EMR. The digital assets support the front-end of the patient onboarding process where tasks such as consent/enrollment, benefit verifications, prior authorizations, and copay support can be performed wholly or partially by our e-service transactions. This not only improves the rate at which these tasks are completed and speeds the patient towards therapy, but it also creates a digital data stream that can improve all aspects of the operation.

When something in the digital process hits an obstacle, whether with an electronic benefit investigations or electronic prior authorization, the partial data from that transaction is captured and automatically sent to an integrated “off-ramp” where a team completes the transaction manually. Once completed, the full result is delivered in a digital format back to the requestor (for example, a provider). The end result enables a closed-loop digital experience for the provider. There is real value in the provider never having to leave their native workflow to reach out to a Hub for service. It’s efficient, cost-effective, and reduces the providers’ workload while moving the patient forward toward therapy.

4. In recent years, CareMetx has made a significant commitment to its IT platform. These days, many hub service providers are touting their platform, which leads to two questions: a) are the various platforms essential to the success of a patient services program? b) are there meaningful differences among the platforms?

This is another area we are disrupting because we think of ourselves as a platform company with technology for the entire process needed to support a patient from the beginning of treatment through achieving the desired outcomes. All parties are seeking a more nimble, digital, self-service model. Stakeholders interface with the platform through different user interfaces (UIs). These could be the EMR, apps, portals, partner software, laptops or maybe a mobile phone. The UI layer—wherever it resides—is now the front door for Hub interactions. Underneath the UI layer, you must have the right technology, tool or platform for whatever the stakeholder is trying to achieve. As an example, you don’t need a big CRM platform to return an electronic benefit verification.

As to meaningful differences among Hub platforms, I would say at this point, there are a lot of strong options available. I believe the CRM system is important for the success of a Hub program, but more so from a flexibility, database, compliance and privacy perspective. We have a proprietary CRM platform called CareMetx Connect supporting all of our traditional Hub programs. But many of our e-service apps are deployed on our clients’ and even some of our competitors’ Salesforce platforms. For CareMetx, we have partnerships for clients that are building their own Salesforce environment. Again, we look at our technology platform through a wide aperture to ensure the right combination of technology and services to produce an optimal result for providers and patients.

5. You have mentioned insource, outsource, hybrid, hub-lite and traditional Hubs. What’s your position on how best a pharma company should structure its programs?

This question has been asked for the last two decades and the answer remains the same—it depends. What I mean is the manufacturer needs to first decide whether they want to take on the responsibility for an internal Hub. There is no doubt we are seeing many major manufacturers invest in an internal Hub with the goal of owning their data and system infrastructure. In doing so, they are able to better define workflows, specify which technologies add value for their brands and improve access to program data and performance metrics.

However, internal Hubs also face a range of competing priorities within a manufacturer and as a result, compliance may be challenging. In fact, executives from one manufacturer were just convicted in part because their internal Hub fell out of compliance.

Structuring a Hub program begins with the product driving the program strategy and understanding the dynamics of the disease including the patient and their providers. We believe the digital-hybrid model with its combination of e-services and complementary manual support systems holds the most promise and value in today’s marketplace.

There is no longer a one-size-fits-all solution. Manu-facturers want significant input and more control over how their brands are accessed and consumed. That’s why our technologies have been designed to support a variety of use cases. For example, we have developed a family of “bolt on” apps around our most common e-services transactions that enable the trans-action to be quickly activated with-in a manufacturers own CRM Sales-force environment. These apps deliver a turn-key product in that the workflows, user interface, and connectivity are already enabled in the solution.

6. What’s your take on the current level of per-formance of pharma com-panies in running their patient-support programs? What could the industry be doing better?

Many manufacturers do an outstanding job running their patient-support programs. I think this is due in part to executives realizing the importance of understanding the challenges the patient is facing. Also, manufacturers know access and affordability can be a brand advantage or disadvantage but patients are sophisticated and know whether there is a genuine commitment by the manufacturer. I believe this is why we are even starting to see C-suite level roles focused on the patient.

In terms of what they can be doing better, well, I think we all can do more to eliminate the access and affordability barriers which still exist. Hubs remain viable because considerable process friction remains in healthcare related to access and delivery of specialty medicines. Isn’t it time to solve some of the foundational problems? For example, CareMetx has been working for the past few years to advance a collaborative agenda that brings together manufacturers and payers to find common ground to ensure no patient waits for a life-saving treatment due to ineffective business practices or lack of information.

Specifically, we believe the increasing number of cell and gene therapies will accelerate the need for these new approaches. Is it realistic for a patient to have a copay when a one-time cell or gene therapy can cost millions of dollars? The industry is challenged to create a new model that is focused on meeting stakeholder needs. We are embracing this challenge. In 2019, we launched OutcomeRx, which is an entirely new business infrastructure that contemplates 360-degree solutions for manufacturers and payers. We’ve been pleased with the response from manufacturers and payers. The key to these efforts is a focus on payer collaboration in the form of innovative financial contracts that change how drugs are paid for by tying payments to predetermined clinical outcomes and long-term patient results.

7. So as you look ahead to the next decade, how do you see Hub services evolving?

Well, over 20 years ago we used to be called “hotline providers.” I doubt in 10 years, we will be using the term “Hub” to describe what we do. The name emerged due to the access challenges and the need to navigate issues and solve problems among stakeholders.

As access challenges are managed more effectively with technology, I believe the next focal point will be to ensure the patient achieves the results expected from the treatment. Frankly, outcomes matter more than ever. Manufacturers and payers will be working together to ensure the patient gets the appropriate treatment which achieves the desired results. And our industry will be right in the middle, helping all parties work in the patients’ best interests to get them healthy again. On second thought, maybe Hub is the right name, but in the next decade, we will play an expanded role and the name will have a different meaning.

A Conversation with Mark Hansan, CareMetx

Patient support services—supported directly or indirectly by pharma companies—have gone from a ‘nice to have’ feature to a ‘must have’ one in recent years. The reasons are not hard to find: the growth of specialty pharmaceuticals (now representing nearly half of the drug-spending dollar in the US); the complexity of treatment, requiring administration by infusion (for example), and genetic and diagnostic testing; and the high cost of those specialty products, making successful treatment a high-stakes commitment by patients and payers.

 has been tracking the evolution of this field for nearly a decade. In this year’s review, several trends have become apparent: more extensive digitization of the services, including mobile interaction; a stronger push toward in-field services (at patients’ homes, or at doctors’ offices); and a stronger drive toward providing so-called “end to end” services, ranging from patient acquisition, through drug dispensing, and on to followup care. That drive is compelling a wave of acquisitions, as various organizations build out a more complete suite of services. However, at the same time, new organizations are springing up, swelling the slate of service providers and service options.

All that being said, it remains remarkable how disparate the field is, with software developers, data aggregators, nursing and clinical education providers, and call-center case managers all playing a role. Pharmaceutical Commerce prefers the term “hub provider” for those organizations that bring all these and more services together; even so, numerous organizations shy away from the term. Meanwhile, specialty pharmacies continue to raise their profile with pharma manufacturers as a viable alternative to patient support.

One reason for the lack of clarity is how pharma itself looks on the topic. According to a broad survey by Helio Health, a consulting firm for commercial compliance, pharma companies differ in where patient support is located in the organization, including whether or not it is carried out internally. As Fig. 1 shows, “patient engagement” ranges from a dedicated corporate function to a subsidiary of brand/commercial teams, managed markets, or medical affairs.

That same Helio Health survey also provides revealing data on trends in patient support. Fig. 2 shows that outsourced hub providers are most heavily utilized for managing prior authorization (PA), benefit verification (BV) and reimbursement support/patient assistance programs and copay assistance—all areas with significant regulatory risks when not properly handled. the Helio Health data show an increasing involvement of specialty pharmacies (SPs) in these areas, as well as adherence programs.

As numerous sources interviewed for this report state, PA and BV support are “table stakes” for the patient support field. Automation in this area, as will be shown later, is a big driver.

A recurring theme among service providers is the goal of “end to end” solutions. The meaning changes slightly from one vendor to another; in some cases, it includes patient support in clinical trials; in other cases it includes providing field sales support. This comprehensive approach has driven significant M&A activity in the past year:

TrialCard, long known has a leading provider of copay support programs, acquired a closed-door pharmacy, PC Scripts in late 2018; it is now licensed inall 50 states to support free-drug programs and PAPs. In 2019, it acquired Rx Solutions, which offered both copay programs and support for clinical trial patients; Mango Health, a mobile-app developer in support programs, and Policy Reporter, a database developer of insurance and hospital formulary-practice data, used by pharma for market access research.

Eversana, already a conglomeration of distribution, channel management and patient services, added Cornerstone Research Group, a Canadian specialist in health economics and outcomes research (HEOR) in October, Alamo Pharma Services and BexR Logistix Telesales, for field sales, in May, and Seeker Health, an analytics firm for identifying potential patients for trials, in late 2018. It also opened a new consulting practice early this year, Eversana Consulting, and a marketing services agency, Eversana Engage.

Diligent Health Solutions, roughly a year old now, acquired WRB Communications, a patient-support call center, from Diplomat Pharmacy late last year; the acquisition returns a business that one of the principals of Diligent had sold to Diplomat in 2017. Diplomat itself, once the leading unaffiliated specialty pharmacy, was absorbed into Optum, one of the leading pharmacy benefit managers, earlier this year. (It’s also worth noting here that Optum also acquired another leading specialty pharmacy, Avella, in 2018.)

“End-to-end solutions provide benefits to the pharma sponsor as well as to the patient,” says Joe Abdalla, chief commercial officer at TrialCard. “It’s one point of contact for the pharma company, and the patient has a better experience from enrollment, financial support, dispensing and longterm engagement. The better experience from this can result in better outcomes.”

Bhaskar Sambasivan, President of Patient Services and Chief Strategy Officer at Eversana, notes that an integrated solution is a powerful benefit for small to mid-size companies, who might not have the investments needed to get products out of the lab. Eversana’s ability to provide complete commercialization support – innovative programs that combine patient access, distribution, 3PL, agency services, field solutions – end-to-end – is a game-changer, he believes.

Eversana scored something of a coup with a pharma client, Evoke Pharma, at the beginning of this year. Under a comprehensive, multi-year agreement, Eversana is taking on a full range of commercialization services for Evoke’s Gimoti, a nasal spray formulation of metoclopramide, for the relief of symptoms associated with acute and recurrent diabetic gastroparesis. Evoke expects FDA approval in June.

Not only is Eversana handling patient support services after the drug is approved; it is also managing launch, distribution and sales. (As distinct from many companies involved in patient support services, Eversana has substantial—and recently expanded—third-part logistics facilities.) The company will receive reimbursement of certain costs and a percentage of product profits in the mid to high teens when Gimoti net sales reach a preset milestone. Eversana is also providing a $5-million revolving credit to Evoke, subject to FDA approval.

“Eversana has been built up over time to provide exactly this sort of integrated service to a pharma manufacturer,” says Greg Skalicky, chief revenue officer at Eversana. “Most small pharma companies, if they’re not planning to commercialize themselves, look either to out-licensing, or being acquired. We’re providing an alternative option.”

Connecting early with an emerging pharma company is also an objective of PharmaCord, a relatively young (two-year-old) hub provider based in Louisville, KY. “We’re willing to make bets [on an emerging company’s eventual success],” says Nitin Sahney, CEO, who says that the company’s current mix of clients is half existing brands, and half companies involved in product launches. “We’ve been getting engaged 12-14 months before launch.” That willingness to take on risk might be part of the company’s success: Sahney says the firm is on track to nearly double its staff (to 400) by the end of this year; it is also planning to double again by 2023—and is building its own operations center in Jeffersonville, IN, to accommodate that future growth.

Each of the Big 3 wholesalers has a comprehensive patient services function; AmerisourceBergen’s is arguably the oldest, centered on Lash Group, complemented by third-party logistics, specialty product distribution to physician offices, and specialty drug pharmacy. Cardinal Specialty Solutions is centered on its Sonexus hub service (acquired in 2014), along with specialty distribution services. McKesson Life Sciences was restructured in 2018, bringing together the acquisitions Biologics (a specialty pharmacy), RxCrossroads (a hub service provider) and existing businesses in patient support.

“My first job in McKesson in 2003—my first general manager job—was running our specialty pharmaceutical business … and candidly, we probably weren’t too relevant,” Brian Tyler, McKesson CEO, told attendees of the JPMorgan Healthcare Conference in January. “But over the course of the last years, we’ve very systematically built great franchises in these markets.” Tyler used the occasion to tout a new McKesson product, Access for More Patients (AMP), which combines patient support with the data and service offerings of CoverMyMeds (a $1.3-billion, 2017 acquisition). (More about AMP later.) Tyler noted that specialty is among the “key channels that we’re in and our key manufacturer service business that leverages off those channels.”

There’s no question that an end-to-end solution provides simplicity in project management; nevertheless, there can be significant reasons to pick and choose among service offerings from multiple vendors. For one, a manufacturer might choose to retain some part of the patient-service offering internally, while outsourcing other parts—the so-called hybrid solution. For another, pharma management might prefer a best-of-breed solution in several distinct areas of patient service.

And while most patient support vendors offer a broad range of services, some of them put an emphasis on one or another of their capabilities. “We do everything except field services,” notes Anthony Bianchini, VP and GM, pharmaceuticals and life sciences, at Conduent. As befits its historical roots as part of Xerox business services, the company has resources and expertise to process “millions” of documents or transactions across a range of industries, he says. That capability works well for handling patient enrollment, benefits verification and prior authorization paperwork—all key components of getting patients on therapy quickly. Conduent also has the advantage of being a global organization, thus able to conduct patient outreach in multiple geographies. And while it does have staffing in nurse educators for patient interaction, Bianchini touts the company’s IT system, branded as IntelliHealth, to digitize many interactions (for example, email or text), and then direct case managers more toward exception management.

Another benefit of Conduent’s broad reach, says Bianchini, is its substantial business with healthcare providers. The company is developing a network that would quickly link patients who need diagnostic services (a common element in dispensing specialty pharmaceuticals) with the laboratories that provide such testing. “Driving service costs down, while providing a better patient experience,” he sums up.

The flip side of that capability, perhaps, is seen at Covance, which has long experience in patient support in both research and clinical settings. “We have field teams for clinical education, reimbursement support at doctors’ offices, and even field training of other field personnel,” says Adrienne Stofko, senior director in the Patient Services Group. “Some of our field personnel transition to the client pharma company” while performing this role.

To be sure, Covance also has internal staffing, IT systems that collect data and other features of a hub provider. The driving force in its offering, she says, “is to move beyond the current paradigm” of responding to a query in a certain number of minutes, “to measuring outcomes, patient quality of life—a more holistic view of the patient experience.” To that end, the Patient Services Group also taps into a health economics and outcomes research (HEOR) group, which can provide guidance to pharma clients in program design and operation.

Yet another perspective is offered by Human Care Systems, where the emphasis is on the combination of a comprehensive IT system, branded as Resilix, and what it calls “treatment experience nurses” who work with patients (usually electronically) to improve adherence. The cloud-based Resilix platform, says Thom Doyle, CEO, is designed to provide a 360° view of the patient experience by interfacing with both electronic health record (EHR) systems at health systems, and the relationship-management systems at hub providers or at the pharma clients themselves.

Mention of relationship-management software highlights a powerful driver of hub service evolution: the development of IT platforms for collecting, recording and analyzing data from channel partners, health systems, pharmacies and even patients themselves. Within the hub service, the IT platform manages workflow for case managers and care coordinators themselves.

When it comes to these enterprise systems, there are those that are built on SalesForce software and the SalesForce Health Cloud; and then everyone else with home-grown systems. Deloitte’s ConvergeHealth software-development company, as well as Accenture, Cognizant and other systems integrators, take the SalesForce platform and configure it to the requirements of each client (which are the hub services, and the pharma manufacturers themselves). The process is said to be expensive and time-consuming—but the systems work.

Cardinal Health Specialty was an early adopter of the SalesForce.com platform for patient support; in its case, it hired Deloitte ConvergeHealth the build the system, and then customized it and branded it as ConnectSource. “We’ve been stable in our implementation now for a couple years,” says Steve Jansen, VP of technology at Cardinal, “but we continue to evolve it.” A key benefit, he says, is that a new client can be onboarded with a tailored ConnectSource system in a matter of a few weeks—a vital consideration given that the company has had some success, it says, in winning switchovers from one hub service to Cardinal’s.

 on one such switchover, noting that the disruption in moving patients from one set of case managers to another, along with all the data collection and interfacing can lead to a 5-10% loss in revenue for the manufacturer if not handled well.

Eversana is in the process of building out its SalesForce implementation; Conduent is up and running with its version. But other hub providers interviewed for this report—TrialCard, PharmaCord, CareMetx—pride themselves on their home-grown systems. Human Care Systems Resilix platform uses a “document-based” database program, MongoDB, said to streamline extracting data from other data sources. CareMetx says that it has built numerous application programming interfaces (APIs) in its CareMetx Connect platform, to work with Salesforce and other systems; it also licenses its software out to other parties. PharmaCord’s CorSend platform has its own API tools.

“We wanted to be agnostic in the IT platform we provide,” says Trialcard’s Scott Dulitz, chief strategy officer. “Building our own platform enables us to work with many EHR systems at healthcare providers, and pharmacy management systems at pharmacies. In fact, we’ve had multiple integrations with the SalesForce systems at pharma clients.”

McKesson has combined IT, data and services in the aforementioned Access for More Patients (AMP) service, which went live late last year. The offering is based on CoverMyMeds software and data, which automate the processing of prior authorizations paperwork, together with the patient care services of RxCrossroads. According to the company, patients have been shown to gain access to prescriptions (after the PA work) 27% faster than industry norms, among other benefits.

CoverMyMeds has the capability to interface with common EHR systems, both to provide PA documentation and a real-time benefit check at the point of prescribing.

“AMP is a new approach to patient intake by transitioning data electronically, then bringing in case managers as needed,” says Heather Morel, VP of Access & Adherence. “It can eliminate hours of non-value-added work” by case managers and healthcare providers. AMP is also helpful, she says, in cases where outsourced hub services are bypassed entirely by working with the specialty pharmacy that dispenses the drug.

Another significant feature of AMP touted by Morel is that it can interface directly with a specialty pharmacy, so that a physician using it can write a prescription and direct it to the specific pharmacy (SP) where the drug is dispensed. (Many specialty products have a limited or exclusive distribution with SPs, and the difficulty of locating the right SP is a common obstacle to getting drug to the patient.) “Today, some manufacturers want to engage SPs directly, and the ability to use the ePA environment of CoverMyMeds to speed access to therapy benefits both the provider and the patient.”

Mention of direct linkage to SPs raises a contested area of patient support services: whether the assistance is provided by a hub service that coordinates the various activities, or the SPs themselves, many of whom have built up staffing and resources to support patients themselves.

The SP business is one that has undergone tremendous growth, commensurate with the growth of specialty pharmaceuticals themselves. The big integrated health providers (Cigna/Express Scripts; CVS/Aetna, United Health/Optum) dominate the SP world (as they do traditional pharmaceuticals), but the ability to provide a higher level of personalized attention at independent SPs has helped their growth. Traditionally, a hub service helps to “triage” a prescription by directing it to the appropriate SP; but if SPs themselves are connected to prescribers, that loop becomes less necessary.

A look at some of the biggest independent SPs shows how they are positioning themselves to manufacturers. The “Soleo Health Difference” at Soleo Pharmacy includes a “dedicated account team from pre-launch through program implementation and ongoing support … Preferred relationships with nationally recognized prescribers, healthcare systems and accountable care organizations (ACOs) [and] Reimbursement specialists dedicated to timely insurance verification and authorizations to expedite patient start of care and assistance with manufacturer copay programs.” The company also offers a data service, branded as SoleMetrics, that provides details on “prescriber utilization and clinical outcomes management.”

“As a manufacturer-focused, patient-centric rare pharmacy, we consistently exceed our partners’ expectations,” says PantheRx, a fast-growing SP in Pittsburgh.

“Carepoint is a nationwide specialty pharmacy helping manufacturers bring new products into the marketplace by keeping in step with every stage of the process. From research and development to clinical trials and educational programs, our clinical staff will work alongside you with one goal in mind … to offer our patients the best treatment available,” is how CarePoint Pharmacy describes its capabilities.

This SP-manufacturer relationship was brought to prominence by Diplomat Specialty Pharmacy, whose annual revenue approached $5 billion until last year, when a series of missteps caused its stock to tank; it is now absorbed into Optum. Another high-flying SP, Avella, also belongs to Optum now.

“We’re not competing with SPs,” maintains Nitin Sahney, CEO of PharmaCord. “SPs can have a difficult time maintaining their margins while providing patient services, and from the manufacturer perspective, SPs are usually not brand-specific [i.e., offering only one of what might be several brands for a particular disease state]. We are.”

Meanwhile, among wholesalers, in line with being all things to all pharma manufacturers, McKesson and AmerisourceBergen provide both hub services and SPs of their own: Biologics at McKesson; United Bioservices at ABC. Cardinal Health does not have an SP business. “We’ve carried out some hub switches from an SP to us,” says Tara Herrington at Cardinal Health Specialty. “SPs need very solid firewalls between their dispensing and their contractual relationships with manufacturers,” she notes.

Despite the growth that many SPs are experiencing, all is not sweetness and light. A 

* (a subsidiary of Intalere GPO, which in turn is a unit of the Intermountain Healthcare system) found that half of SPs surveyed are constrained by insurance networks and PBM practices on the one hand, while 17% were constrained by an inability to enter limited distribution contracts on the other. At the same time, manufacturers responding to the survey said, by an 80% margin, that their patients had some sort of issue being serviced by their partner specialty pharmacies (Fig 5.)

The CSI survey also asked manufacturers about their hub-provider relationships, and here there were similar perceived shortcomings, with 83% of manufacturers reporting that “there was room for improvement in their current third-party vendor hub model,” and that “17% indicated they are not pleased and are pursuing other options.” (The implication here is that the percentage of manufacturers happy with their current hub provider across the board is zero.) Two-thirds of respondents “would like to see improvement with respect to communication between patients and providers, and half of manufacturers seek enhancements in process/workflow, technology solutions, and FTE/resource review.”

Despite this potential friction, SPs and hub providers have worked out complementary roles, and most hub providers emphasize how the “get along with” the SPs with which they interact.

(There can be some confusion for participants in specialty pharmaceutical dispensing, in that numerous hub providers have so-called “closed door” pharmacies, from which free-drug, patient assistance program, or quick-fill scrips can be fulfilled. In fact, it is a competitive advantage for the hub provider to be able to provide this service. These programs, however, do not pertain to routine prescribing.)

There is more to the IT question than what enterprise system is chosen, or who is managing the patient interaction. The entire patient-support field is colored by gathering data from diverse sources, and presenting it in useful form to patients, providers and payers—and ultimately manufacturers.

There is a growing trend toward use of mobile technology to interface with patients, both as a means of communicating messages to them, and to gather patient-reported outcomes (PROs) from them. Use of conventional SMS texting has been commonplace for years, especially for refill reminders; now, there are efforts to communicate the status of reimbursement applications, status queries and the like.

“We’ve known we wanted to develop a virtual copay card for quite a while,” says TrialCard’s Scott Dulitz, “then the opportunity to acquire a market-leading app developer, Mango Health, came up late last year. Now, we’re working with the Mango platform to provide transparency to patients—they will be able to track enrollment applications, reimbursement actions and the like. This will be rolled out later this year.”

There are hundreds if not thousands of apps available to smartphone that have health information; the distinction here is to have an app closely tied to a hub service provider like TrialCard. Human Care Systems, developers of the Resilix CRM platform for managing the patient journey, uses text, email and click-to-chat to connect with patients even in a pre-treatment phase. The company says that a “rules-driven automatic cadences” of messages and communications both inform the patient, as well as collect responses that in turn guide adherence programs or other actions.

HelpAround, which styles itself as a “mobile concierge platform,” has had some success with improving adherence and streamlining patient communications via its app. Behind the messages and notifications sent by the system to patients, it has what it calls “hyperpersonalized” AI-based technology to tailor messages and their timing to the patient. As shown in Fig. 4, it has provided a boost for adherence for an unspecified pharmaceutical, according to the company.

Eversana’s Bhaskar Sambasivan touts the company’s recent partnership with Noom, as an example of digital patient engagement and part of Eversana’s next generation of “Patient Services 2.0” solutions that include technology and data. The goal to combining Noom’s digital therapeutic platform with Eversana’s integrated patient services model is to improve therapy adherence and patient engagement for complex therapies. Sambasivan notes that his company is working to include other behavioral data in its CRM, such as financial ratings, to help predict the level of financial assistance patients need.

There is widespread agreement that mobile communications, both from and to patients, is transforming not only patient support programs for specialty pharmacueticals, but all pharmaceutical patient interactions. In the patient-support context, though, there is thought to bringing in another element: the community of peer groups of patients taking the same drug, or suffering the same disease state. “Imagine if patients on a therapy could join a group of their peers, moderated by experts from a pharma company, to talk about their treatment,” says Valerie Sullivan, an industry consultant and former president, inVentiv Patient Access Solutions. “In general, the pharma industry is petrified of the potential liabilities of such interactions, but this kind of communication should be a more meaningful way to engage.”

Direct interaction with patients in open forums might be a bridge too far for most pharma companies; they are continually balancing their interactions with patients with the restrictions imposed by governments. In past years, there were instances of violations in sharing protected health information of patients directly with the sales and marketing teams; this is one of the reasons for hub providers to exist in the first place—to be a clear buffer between the manufacturer and the patient.

In the past year, FDA, CMS and the US Dept. of Justice have mostly been focused on the workarounds used by some companies to provide financial support to Medicare, Medicaid and related government-insured patients; those patients are not eligible, in most cases, for copay or other financial assistance. Settlements between DoJ and manufacturers include Aegerion, Alexion, Amgen, Insys, Jazz Pharma, Lundbeck and US WorldMeds, who collectively paid hundreds of millions in fines for alleged violations of the False Claims Act and its Anti-Kickback statute. In all these cases, the government alleges, the companies paid funds into patient assistance foundations, who then reimbursed federaly insured patients’ copays. (Privately insured patients are legally allowed to receive copay assistance a manufacturer, usually through the intercession of a hub provider or copay-assistance provider.) In some of the cases, the foundation support was structured such that only one drug (of that manufacturer) was eligible for the assistance.

At least one foundation, Patient Services Inc., was also penalized for alleged violations in these patient-support efforts.

“When pharmaceutical companies use foundations to create funds that are used improperly to subsidize the copays of only their own drugs, it violates the law and undercuts a key safeguard against rising drug costs,” said Assistant Attorney General Jody Hunt of the Department of Justice’s Civil Division. “These enforcement actions make clear that the government will hold accountable drug companies that directly or indirectly pay illegal kickbacks.”

But fraud or misuse of patient support funds can come from other directions. TrialCard, which has years’ experience in managing copay programs, has been able to return roughly $10 million back to pharma companies in 2019 when it found pharmacies fraudulently claiming copay reimbursement for drugs that were never dispensed, or patients that never existed. “In the course of performing analytics on how we manage manufacturers’ copay programs, we noticed irregularities in where some of the reimbursement claims were coming from,” says Jason Zemcik, a senior director at the firm. Those irregularities were then investigated by an internal team at the company, and TrialCard was able to block reimbursement to some of the pharmacies, eventually returning the funds to the pharma client. The service has now been formalized as a TrialCard offering, RxSpotlight, and Zemcik says that the company is deepening the analytical tools it uses for this purpose.

Dramatic growth tracks the flood of new specialty    pharmaceuticals entering the market

2020 Patient Support / Hub  Services Report

At this point, the state of the art for managing commercial-operations data in the US life sciences industry is pretty clear.

It is cloud-based, to accommodate the vast increase in the volume of data (and their sources, which are themselves often cloud-based). The relatively low cost of data storage allows for as much data tracking to be enabled as users could want, especially for purposes of audit trails, regulatory submissions and the like.

It is a platform with various specialized applications, so that data can flow relatively effortlessly from one function (say, master data on prescribers) to another (say, rep call plans)

It allows for dashboards to be designed and implemented—sometimes with the user’s own efforts—to provide management-level views of what’s going on in the organization.

Interoperability is claimed almost across the board by IT vendors: Whatever system they are offering, the claim is made that it can be connected to legacy software or other applications. How well this is carried out in reality is an open question, both because of how the software is written and because of how well vendors can carry through on their claims, so buyer beware.

Year after year, the pharma industry gets hit with new regulatory frameworks that place demands on data-collection and -collation systems, which luckily are in place (most of the time) as the regulations come into force. Pharma marketing organizations had some heavy lifting a couple years ago as aggregate-spending rules came into force, requiring the industry to tote up—by HCP—how much money or “transfers of value” are spent by that company annually. Now, the Open Payments System, where HHS publishes these annual reports, has been humming along relatively quietly.

In fact, the 2018 Open Payments report, summarizing spending and activity for calendar-year 2017, showed the first decline in aggregate spending since the reporting started in 2013: In 2017, industry spent $8.4 billion as recorded in 11.54 million transactions, as compared to $8.81 billion and 12.4 million transactions in the prior year. There are undoubtedly a number of factors causing the decline, such as the number of product launches or new indications for approved drugs—but one factor might be the higher scrutiny the industry is getting, with debates on drug pricing and reimbursement policies rising in intensity.

A more recent development affects sample accountability and reconciliation, monitoring the industry’s longstanding practice of handing out free samples of drugs to prescribers. Starting last year, the state of Ohio requires a license as a “terminal distributor of dangerous drugs” (TDDD) when certain classes of prescribers receive most types of Rx drugs. (The law came into being in part as a response to the ongoing opioid crisis, which has hit Ohio particularly hard, but was written to pertain to most Rx drugs.) In red highlighted letters, the instructions from the Ohio Board of Pharmacy states: “This includes drug samples.”

Providers of sample accountability systems have had to adjust their data-collection systems, which already track DEA licenses of prescribers, and record signatures when prescribers receive a sample (a requirement under the Prescription Drug Marketing Act). “Our Titanium platform, which includes sample accountability and practitioner validation, was written to include TDDD” by auto-detecting an Ohio address and then sending out a notification for the license information, says John Cunningham, EVP at QPharma. “On their own, pharma manufacturers are struggling with the TDDD requirement, piecing together a solution that requires a lot of manual intervention.”

The Titanium suite is one example of how IT systems have grown to encompass more sales operations functions. Separate modules handle KOL engagement, call center interactions, product launch processes and more; CRM is but one of many other modules. QPharma asserts that the integrated suite (for which individual modules can be acquired by pharma clients) allows for rapid data dissemination between functions, so that, for example, sales reps’ calls can be informed by prescriber’s sampling history.

Controlling sales and marketing practices remains something of a blood sport between the industry and state or federal regulators. The industry has been hit with fines ranging from millions to billions of dollars; new, tighter controls always seem to be in the offing (most of which require additional reporting by industry, and become a burdensome data-management task); at the same time, software systems get more sophisticated in what data can be extracted for interacting with patients, monitoring prescribing practices and anticipating changing market conditions.

“Today’s software systems are both an ‘offensive’ tool, to improve market position, and a ‘defensive’ tool, to maintain compliant practices,” says Ramon Chen, chief product officer at Reltio. Reltio has been offering the Reltio Cloud, a master data-management (MDM) system for, among other things, compiling trustable data on physicians and their prescribing and communication preferences.

While there are still pharma companies operating with on-premises software, necessitating IT staffs to maintain the hardware of data centers and communication networks, much of sales, marketing and commercial operations has moved to the cloud. Amazon Web Services, Microsoft Azure, Google Cloud and others offer on-demand data storage capacity, and are differentiating their cloud offerings with a variety of software applications or programming environments that enable easier use of large datasets.

To a considerable degree, Veeva pioneered the commercial-pharma march into the cloud, and Matt Wallach, Veeva president, touts the fact that Veeva adapted to modern cloud-based IT processes from its beginning, as opposed to switching on-premises applications to a hosted environment, and then into the cloud.

In a recent investor-day presentation, Veeva officers outlined its future direction, and the structure of how its cloud-based offerings will evolve.

A key next phase, according to Paul Shawah, SVP, Commercial Cloud, is to upgrade industry’s data-warehouse capabilities. Today, most companies have multiple data repositories (on-premises or cloud-based); these create or hold data that then flows into a data warehouse if an integrated data-management approach is to be taken. The problem is keeping the various applications (which are continually updating) in synch with how the data warehouse operates; a lack of synchronization means that data won’t flow into the warehouse for effective use. As shown in Fig. 2, there are many internal processes in the data warehouse that need to be coordinated.

Now, Veeva is beginning the introduction of Nitro, a packaged commercial data warehouse (and built, coincidentally, on a database infrastructure” from Amazon called Amazon Redshift). “We’re turning [data warehousing] into a standard industry product, something that’s been messy and custom with lots of services for a long, long time,” Shawah told his audience. “That will establish an ecosystem of partners and services providers that are able to all work on the same system, the same product, the same data model.”

Specific benefits of using Nitro, says the company, will be to enable the analytics and AI processes that it and others are developing to access curated data quickly and easily.

The big guns in dedicated, life-sciences IT systems for commercial operations are Veeva and IQVIA, the former with its Veeva Commercial Cloud and the latter with OCE, the Orchestrated Customer Engagement platform. Point-to-point comparisons are difficult, in part because Veeva is primarily a software developer, while IQVIA provides a host of operational and advisory services, in addition to its software offering. (And, continuing the distinction into the clinical realm, Veeva is now making a strong push into software for clinical research, while IQVIA, through its merger with Quintiles, is a major contract research organization.)

Interestingly, both companies use the SalesForce.com IT resources as the underlying foundation of their systems, and SalesForce.com (the company itself) has considerable play as a life sciences CRM provider.

An area of direct competition between the two has been over master data management (MDM) and the reference data on HCPs that both maintain—IQVIA’s OneKey database, and Veeva’s OpenData offering. Since January 2017, there has been litigation between the two, with IQVIA claiming improper use of its data, and Veeva claiming anticompetitive behavior. Based on the court docket (2:17-cv-00177-CCC-MF IQVIA Inc. et al v. Veeva Systems, Inc., in the District Court of New Jersey), the case is going hot and heavy, with claims, counterclaims and special master rulings happening almost weekly. Even with all this, the case is still at the discovery phase.

IQVIA, in its former incarnation as IMS Health, has been a longstanding provider of physicians’ master data; Veeva built up its offering over the past few years, with a couple acquisitions along the way. According to Veeva, it is able to continue offering commercially successful services to pharma clients, in part through the data stewardship services it provides. The stewardship function, in turn, highlights the dynamic and time-sensitive nature of reference data, which starts with physicians’ names, addresses and contact information, but now goes well beyond that to include affiliations (i.e., the health systems that HCPs are employed by or affiliated with and, in turn, the insurance providers those health systems use), and a host of professional activities (conference attendance, speaking engagements and so on) that HCPs participate in. Affiliations change at a fairly rapid clip; insurer policies (and their formularies) do the same. Data elements like the recently adopted Ohio TDDD simply add yet more fields to include.

Several other organizations compete in the MDM/reference data space, notably MedPro Systems, whose MedProID database is used by a number of life sciences CRM vendors, such as StayInFront and Synergistix, as well as sample-accountability providers like RxS (which, in turn, offers a dedicated sample-accountability and -management system, LinkedRx).

The AI and MDM company Reltio occupies an interesting position in all this. Reltio is one of the underlying technologies to support IQVIA’s OCE; it is also a relationship partner with MedPro. Reltio’s Chen notes that many pharma clients deal with it directly (and not just through its business partners). Reltio started out as a more sophisticated way of identifying and scoring relationships among HCPs and their affiliations; its algorithms and machine learning technology has now evolved where the output of Reltio, when applied to a dataset, results in a measurable level of “trust” (in the sense of, being accurate) in data relating to HCP characteristics. This degree of trust can then produce more actionable insights, such as a suggestion to contact a physician who might have become more active in handling a certain disease state.

Reltio has just announced an update to Reltio Cloud: Key new features include Reltio Rank and Reltio Data Quality IQ. Reltio Rank can be compared to what is commonly understood about Google Page Rank—the process of analyzing how frequently a page is linked or viewed by users, says Chen. “How often does the information on a profiled change, and how often is that record referenced by users? This tells the pharma company that, for example, certain HCPs need to have closer attention paid to them.”

Reltio Data Quality IQ builds on an existing feature of Reltio, Reltio IQ, which is a method for evaluating the quality and usefulness (to the user) of data sources. “Together, Rank and Data Quality IQ allow the pharma company to decide what information is worth spending more time cleansing and updating, based on the importance of the profile that that data define, avoiding wasted time and effort.”

AI is the leading next-generation step being taken for MDM, and indirectly for sales and commercial operations platforms. Veeva is building AI functionality into its Commercial Cloud with an offering branded as Andi, to be released in 2019. IQVIA has Ada, designed to offer recommendations to field sales reps or marketing teams, based on analytics of the stored information. SalesForce.com is in the process of implementing its AI offering, Einstein.

There are also dedicated analytics firms, not touting their AI expertise, but rather depending on skills in “network analytics” and related business-intelligence methods, to arrive at similar benefits claimed by Reltio and others. Zephyr Health is one; Shyft Analytics is another. (Shyft is now owned by Medidata, a clinical-research software firm, and Zephyr has been acquired by Anju Software, a clinical and medical-affairs software provider.)

Both claim to offer value in MDM analytics, among other applications, and in using large datasets to create clearer pictures of customer relationships, and then recommended actions to be taken in such activities as product launch. Shyft touts is value in analyzing real-world evidence (see p. 22) for drug-development purposes (undoubtedly why it became a target of Medidata). Zephyr has a relationship with Veeva, to provide recommendations for sales activities.

Amazon Web Services Seattle, WA; www.AWS.amazon.com

Microsoft Azure Redmond, WA; www.azure.microsoft.com

QPharma Morristown, NJ; www.QPharmaCorp.com

Salesforce.com San Francisco; www.SalesForce.com

Shyft Analytics Waltahm, MA; www.ShyftAnalytics.com

StayInFront Fairfield, NJ; www.StayInFront.com

Synergistix Sunrise, FL; www.Synergistix.com

Veeva Systems Pleasanton, CA; www.VeevaSystems.com

Zephyr Health San Francisco; www.ZephyrHealth.com

Multi-faceted software platforms seek to unify salesforce automation with commercial and compliance activity

Merging data for managing  pharma commercialization

A good way to get vendors involved in pharma cold-chain services and equipment looking sideways is to ask them to provide the data they collect during shipments and deliveries. In the frictionless, IoT (Internet of Things) world we are entering, everyone is supposed to know everything, all the time. The reality is that dataloggers often require manual data retrieval (as does the datalogger itself); and moreover, only some of the data (such as internal temperature of a parcel or pallet) is known. That’s like being told a partial baseball score is: home team, 2 (riffing on an old George Carlin joke here!).

More data is being collected all the time—but it comes from different sources, and there are different claims over ownership of it. A datalogger owned by a pharma manufacturer, put into a shipment and delivered back at the end of a trip is pretty clear-cut, but these days the data is often automatically transmitted to a carrier’s database. Meanwhile, the 3PLs or freight forwarders involved in managing logistics have their own data systems. More and more, packaging vendors are providing containers with some form of embedded sensors and communications, so they’re asserting their ownership of data, too.

Finally, there are independent communication and data-gathering services (many of which are listed in the “Instrumentation and Data Collection” section of the 

) who will provide as comprehensive a data service as the client is willing to pay for. The biggest pharma companies might have their own control tower that oversees shipments zooming around the world; smaller companies depend on their 3PL partners, or carriers that they have a relationship with, or simply hand it off to wholesalers (who have their own tangled relationship with data providers).

All this is heading in a good direction: more data, combined with smart analytics, will lead to more efficient supply chains and safer deliveries of temperature-sensitive products. But there are going to be some bumpy and/or costly roads to travel to get to this point, with various data collectors looking for a fee for tracking a manufacturer’s product. The latest iteration of this activity is to set up a blockchain to deliver data—and that might happen in a way that rationalizes the data-gathering process.

Meanwhile, before we all get carried away with IoT and blockchain buzz, here’s a cautionary note: in 2018, it is still a topic of lively discussion among pharmacists on how to interpret the handwritten scrips of physicians. (E-prescribing, which is in growing use throughout healthcare, is making this go away. Still…) At least one pharmacy publication still devotes a page per issue to the topic, which is usually looked on as a fun puzzle to figure out, until you realize that misinterpreted prescriptions could have deadly consequences. To quote another writer/thinker (William Gibson): “The future is already here; it’s just not very evenly distributed.”

Ownership of supply chain data is becoming contentious

Gimme my data

Pharma manufacturers have been able to deliver refrigerated products to patients almost since the time when mechanical refrigeration was invented—the 

 cites instructions from Parke, Davis & Co. in 1919 to keep smallpox vaccine refrigerated. Over the past decade or so, however, the pharma cold chain has become a focus of most industry supply chain managers and—equally significantly—product and service developers in packaging, logistics and transportation. Now, after waves of (packaging) product innovation, investment by logistics service providers, and a thorough effort by pharma brand owners to rationalize their delivery practices, a new pharma cold chain is emerging. Its features:

The most worry-free form of long-distance (international) shipping remains air freight and the active (powered) unit load devices (ULDs). As the most expensive form of high-volume delivery, supply chain managers are continually evaluating new containers and alternative modes of transport like ocean shipping.

Airports, air carriers and many third-party logistics providers (3PLs) have substantially upgraded and expanded their refrigeration storage capacity, so much so that shipments can depend more on moving from one temperature-controlled storage facility to another in the supply chain, rather than express deliveries from the manufacturer to a dispensing endpoint.

Reuse of parcel and pallet shipping containers is more of a reality today, meeting some of the sustainability goals of manufacturers that have been talked about for years. At the same time, the reuse “loop” is transforming the business of temperature-sensitive packaging from the purchase of single-use packaging, to the pay-per-use rental or leasing model.

Innovation continues both at the “upper end” of temperature-controlled shipping—managing controlled room-temperature products in the 5-30°C regime—and at the “lower end” of temperature-controlled shipping—cryogenic containers and delivery services for the introduction of cellular and genetic therapies (CGTs) to the market.

More attention is being paid to the front end of the biopharma supply chain—laboratories and manufacturing facilities—and the back end or last mile—including delivery of individual dosages to patients’ homes.

CGTs, in that some of them involve the patient’s own cells being extracted, transported to a pharma facility and manipulated, then returned to the patient for infusion, represents both the crowning achievement of personalized medicine, and a radically different supply chain. Commercial delivery to patients is very similar to clinical trial logistics, and in fact, the clinical trial logistics leaders are moving aggressively into managing this on behalf of pharma clients.

Finally, data—of the shipment’s condition in transit, and of the overall logistics process—is becoming a more sought-after element of supply chain management. Geolocation of the shipment is a reality; the “internet of things” (IoT) philosophy is taking hold via smart devices that automatically report their status in real time. At the farther ends of the digitization, developers are looking at applying blockchain technology to the cold chain.

Perhaps the broadest-based change going on in the pharma cold chain is the adoption of the CEIV Pharma certification, which now has nearly 300 organizations globally involved in renewing or receiving this designation. The Center of Excellence for Independent Validators – Pharma is an effort undertaken by the International Air Transport Assn. (IATA) to standardize (to the degree possible) global practices for any shipment or trade lane that involves air freight. But it goes well beyond air carriers: airport ground handling providers; warehouses that store pharma products for delivery to an airport; trucking companies that make such transfers into and out of airports; and freight forwarders and 3PLs that manage pharma shipments are all within scope. Arguably, the only parts of global logistics that don’t fit are seaports, and ground carriers that never deliver to an airport.

“A chain is only as strong as its weakest link,” notes Andrea Gruber, head of special cargo at IATA, under which the CEIV Pharma program operates. Besides getting many other logistics players involved beyond air carriers (who are the only formal members of IATA), the effort’s focus is to “harmonize practices and requirements to a uniform level globally, thus providing assurance to the pharma industry.”

IATA started the CEIV Pharma program in 2014 in part for clearly competitive reasons: it didn’t want to lose market share relative to ground and ocean transportation. IATA has some standards that, in effect, have force of law (such as regulations for cargo container construction), but CEIV Pharma is voluntary. Certification can be provided for an individual business (and by location); for a “community” (an international airport and its associated service providers) or a “coalition” (a regional grouping of airports, facilities and providers).

CEIV certification involves a two-step audit by IATA-approved (but independent) validators, who bring a 300-item list of criteria; the full program can take as long as six months and usually involves training personnel in addition to reviewing facilities and procedures. There are 10 validators currently; one company that touts the approved auditors within its staff is 4advice, based in Mechelen, the Netherlands.

Although the goal is global harmonization, IATA’s Gruber concedes that there will be national variations in practices; Saudi Arabia, for example, requires all refrigerated pharma deliveries to be temperature-monitored, something that is recommended but not required elsewhere. The main standards involved are the EU Good Distribution Practices (GDP) document, in place since 2013, and World Health Organization requirements; national standards are followed where applicable.

The list of organizations with CEIV Pharma validation is long. Some highlights: Kuehne + Nagel validated its entire air-freight network (86 locations) in 2017; DHL has validated nearly all of its North American operations; and the airports of Brussels, Miami, Singapore, Sharjah (Saudi Arabia) have community validation. Delta Air Cargo was the first US passenger-based airline to be validated, in 2017. But the program is not by any means universal; World Courier, a leading clinical trial logistics provider, opted for GDP certification (by a consulting firm called DQS) for its global network of offices early this year.

Meanwhile, standards-setting is not a done deal by any means. The US Pharmacopeia, which has a variety of standards relevant to cold chain logistics, issued a draft version of USP <1079> this summer, and is soliciting comments with a goal of finalizing the standard in early 2019. USP <1079> is being nearly totally rewritten; the new standard is focused primarily on setting up quality management systems to oversee logistics processes; it also refers to other USP standards for stability testing and packaging.

Standards will continue to evolve, just as industry practices have. “The industry has studied temperature and humidity and how it affects medicines for many years,” notes Rafik Bishara, a leading voice in pharma cold chain practices and member of USP expert committees (see p. 14). “Now, with new therapies such as personalized, genetically engineered pharmaceuticals appearing, additional factors such as shock, drop, shake, vibration and pressure should be investigated.”

Traditionally, bulk air shipments have been in pallet-sized unit-load devices (ULDs) pioneered by Envirotainer, which introduced a powered version containing its own heating and cooling unit in the mid-2000s. CSafe, DoKaSch and a few others have similar units, and in most cases, they are leased or rented, for a set period of time or for individual trips. (Since the units rarely leave airplanes or airports, there’s little incentive for pharma companies to have their own stock of the units.)

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The world of parcel containers, whether for air or ground transportation, has been a different matter. There, the boxes are inexpensive (relative to the value of the pharma products they are protecting); and most of the materials (cardboard, foamed-plastic insulation, gel packs) are disposed after a single use.

Two factors are changing this traditional dynamic: one, client companies are calling on packaging suppliers to provide a more integrated service, starting with the design and specs of the container, preconditioning to deliver them at an appropriate temperature, and helping manage the logistics processes and data collection. Second, risk-based analysis of higher-value pharma products calls for employing higher-quality containers, such as using vacuum insulated panels instead of expanded polystyrene, or advanced phase-change materials (PCMs) in gel packs. Together, these factors make a reuse program based on renting or leasing the containers, rather than a single-use purchase, more feasible.

“We are promoting the concept of ‘cold chain as a service,’” says Jay McHarg, CEO of AeroSafe Global. “Clients should tell us what level of service they need, and we provide the appropriate container, manage its reverse logistics, and handle the client’s variations in container inventory.” Pharma companies should not, in his opinion, devote substantial warehouse space to storing and prepping containers; by working with AeroSafe’s network of locations and service partners, these issues can be taken off the table.

AeroSafe is best known for its vacuum panels based on a proprietary form of open-cell, carbon-based aerogels, but it now offers a more economical line of EPS containers as well.

“Our pay-per-use reuse program is the fastest-growing part of our business,” says Ron Haub, commercial director of Sonoco ThermoSafe, the leading pharma cold-chain packaging vendor. “In the past, this was viewed as something of a fad for ‘greenness’, but now the growth of high-value products that require reliable temperature control, plus the cost advantages that are available when a container can be reused multiple times are making it a reality.” Haub says that the success of the program for a client depends on a well-characterized trade lane including reverse-logistics capabilities (to improve the probability of getting the box back), and accurately understanding the environmental conditions of the lane. Vishal Khushalani, global business development and marketing manager at Sonoco ThermoSafe, notes that his company is unusual in that it offers both bulk containers (pallet shippers) and parcels, in five distinct insulation materials ranging from EPS to vacuum panels. These degrees of freedom enable the company to dial in the appropriate packaging materials and designs, while evaluating the economics of reuse. “Reuse isn’t going to work in all instances,” he says, “we want to be proactive to provide options to clients.”

“Reuse/rental systems are another example of pharma companies getting back to core competencies—which is not packaging operations, asset management or logistics,” notes Jamie Chasteen, sr. product manager at Cold Chain Technologies (CCT). “We do conditioning and setup of shipping systems, both parcel and pallet, from our facilities, show up at your door, your product is placed inside, and the container goes right out the door.” CCT has facilities in the US, Latin America, and SE Asia as well as a longstanding partnership with Topa Thermal Packaging in the Netherlands for a European footprint facilitating reuse.

Pelican Biothermal, another provider of a range of containers and materials, is investing heavily in its reuse program. “We started the year with around 20 locations that could accept our containers after use,” says Adam Tetz, director of worldwide marketing. “By the end of this year, we will have 100 around the world. Our clients ship globally, so we have to be a global provider.” Tetz says that a rental or leasing program reduces the worries of clients whose shipment volumes vary from month to month, besides reducing the complexity caused by preconditioning, container packout, and managing the logistics of the out- and return-trips.

While the reuse programs are most suited to high-performance packaging solutions, providers of conventional parcels (EPS insulation plus a gel pack) have not been standing still. EFP, marketers of the PharmaTuff brand of EPS containers, has done two things to address the market, according to Keith Arentz, EFP president: It is building out a network of other shaped-plastic foam manufacturers to provide national coverage; and it is actively promoting the recycling of EPS through membership in the EPS-Industry Alliance, a network of foam processors that accept used material for recycling. EPS recycling remains a challenge (among other things, EPS is 98% air—a tough material to transport economically), but EPS manufacturers note that the volume of EPS in all applications continues to rise, so the industry needs to continue developing a recycling pathway.

The reuse model, having been developed for bulk, air shipments employing ULDs, is now being used against those ULDs by vendors of passive shipping systems. This active vs. passive debate has been going on for years in the industry; on the one hand, active systems offer the best assurance of keeping a shipment within its temperature limits, but at higher cost; on the other, passive systems provide economical air-freight rates while, say their proponents, offering temperature control as reliably as the active systems.

“Active and passive systems will both have a place in the industry going forward,” says Sonoco ThermoSafe’s Haub. “The deciding factor will be how to take risk out of the equation—what is the best solution for a given trade lane.”

Envirotainer, known for its active systems announced earlier this year that it now has over 1,000 RKN (active units) in circulation around the world. (Envirotainer blurs the distinction between active and passive by claiming that its “t”-type units, which use dry ice rather than a powered refrigerator, are still an “active” system.) CSafe, a competitor, has just come out with a RAP-designated active unit (“RAP” is airline-code lingo for size and refrigerative capability), that can carry four US-size pallets or five Euro-size, to compete with the RAP-e2 unit Envirotainer has had on the market for several years.

Meanwhile, passive systems vendors have been upping their game for several years now, overcoming the relatively poor reputation they had when first offering pallet-size air-freight containers. Pelican Biothermal has just introduced its CoolPall Flex line (Fig. 2), featuring modularized components and variations on PCM configurations for both refrigerated (2-8°C) and CRT (15-25°C) shipping, and claiming in-spec performance under nominal operating conditions for up to 144 hours. Many other vendors have similar designs.

Sonoco ThermoSafe now straddles the active/passive debate, having acquired the PharmaPort technology two years ago, and is now re-introducing it to the market (Fig. 3). PharmaPort “uses a different active technology, involving eutectic plates, fans and compressors to maintain a constant +5°C temperature (“eutectic” material changes its physical orientation as it warms).

Another element playing into passive ís favor is that transportation providers, airports and air cargo companies have substantially expanded their temperature-controlled infrastructure around the world: shipments can now hopscotch from one reefer space to another; active containers can get a power recharge, and passive systems can stay within a designated temperature, and sometimes even have their PCM packs “recharged,” so to speak.

This PCM recharging takes a more sophisticated knowledge of thermodynamics, says CCT’s Chasteen. “Some vendors claim that by having their PCM system in refrigerated storage, it is ‘hibernating’ and stopping the qualification clock,” he says. “But what is really necessary to accomplish this is to have a PCM whose freezing point is higher than the refrigerator. The industry’s standard 5°C PCM will not truly hibernate, rather it will lose some amount of ‘cold energy’ which reduces the remaining time the shipper has left.” For this reason, CCT has developed a proprietary family of gelled PCMs, including 3, 5, and 7°C versions. The 7°C PCM provides 2-8°C protection, allows for single step conditioning in refrigerators, and recharges during extended refrigerated storage while in transit.

When the EU GDP standards were promulgated in 2013, there was considerable attention paid to the requirement that all pharmaceuticals—not just 2-8°C ones—be transported within the temperature specified on the product’s label. Result: controlled room-temperature products (essentially, the other 90%+ of pharmaceuticals that are not refrigerated) need temperature control, possibly including CRT packaging.

The first industry response to this has been to tighten up the data and procedures for determining the stability budget of a pharma product—how long it can be outside its label temperature and retain efficacy. Many products (especially oral solids) are relatively immune to temperature. But the situation creates ambiguity: some customs inspectors or health authorities are rigorous about the matter; others, less so.

The most direct way to address CRT temperature control is to adopt the same technology as refrigerated containers—insulated boxes with gel packs. The challenge here is that it can be more difficult to keep a product at room temperature (because of the mass of PCM material necessary) than a refrigerated product, whose PCM can pack more cooling into a given mass). Packaging vendors have also engineered two-component PCMs, to protect against both the upper end and the lower end of the temperature range (this can also turn into a winter packout for cold, and a summer packout for heat).

In many cases, determining the necessary protection is a combination of stability budget and the characteristics of the trade lane—it might be necessary only to protect against extreme heat (such as when product pallets are sitting on a runway tarmac); the rest of the time, more moderate temperatures can exist. This, in turn, is opening up the use of thermal blanketing—a wrap that encloses a pallet, and offers several hours of protection against temperature extremes. Q Products, a blanketing manufacturer, has marketed its products successfully in such applications, including wrapping pallets that go into ocean-borne reefer containers. The blanketing can protect product while the container is being loaded or unloaded; the reefer container provides protection during the transit. The forms of blanketing have multiplied, with some including fiberfill layers, bubble wrap, and aluminized films to turn away sunlight.

Cold Chain Technologies expects to make significant headway in this market with its KoolTemp GTS Enshield pallet blanket product, which incorporates its advanced PCM Gel. The gel, says Chasteen, is shape stableóthe PCM remains a flexible solid even at its thawed temperature, said to be the first of its kind. (If the PCM packet were cut open, he says, it would not leak fluid. Conventional PCM ìbricksî are often an open-cell plastic foam with PCM suffused within it and if breached PCM will leak.) The Enshield knits together multiple packets of the gel, thus providing the temperature-sustaining properties of PCMs in a blanket form. CCT has multiple versions intended for frozen, refrigerated, and CRT applications.

Cost savings is the big driver of blanketing. CCT claims a 50% savings when using its blankets, relative to a fully equipped shipping container, depending on the specifics of a shipping lane; other manufacturers note that the lighter weight, ease of application and reuse all combine to lower shipping costs, and thus making temperature control for CRT products, in particular, cost-effective.

Clinical trial logistics is its own sub-specialty where, because of how critical trial results are to a drug’s approval, essentially no cost is spared to ensure safe and effective delivery, to and from the trial site. Well-insulated containers, often transported via courier services, are common. The practices of PCI Pharmaceutical Services (which recently acquired Pharmaceutical Packaging Professionals, a Melbourne, Australia service provider, to expand its global reach) are an example: “PCI performs the tertiary packaging, but based on the needs of the study it is not necessarily done right after secondary packaging. Due to the fact that we hold material and ship on an as-needed basis to investigational sites, PCI chooses the optimal temperature-controlled shipping solution after considering the amount of material being shipped, the shipping lane, and environmental conditions during transit. Most often PCI will perform this packaging but in some special circumstances, PCI will use a third party specialty logistics carrier to bring a pre-charged active system for transit.”

 Cold Chain Sourcebook estimates the 2017 clinical trial logistics market at $3.4 billion overall (with much of it requiring temperature-controlled services regardless of the compound being investigated). Within that, however, there is a boomlet around cellular and genetic therapies (CGTs) that involve the latest gene-editing techniques. The fact that many of these therapies are tied to a patient’s own cells (the ultimate in “personalized medicine”) puts a heavier burden on the logistics component of the process: the right cells have to be delivered, within narrow timespans.

“The challenge is that fresh cells, from and back to the patient, are best; this puts constraints on how the trials are performed, or how commercial therapy is carried out,” says Simon Ellison, CGT service director at World Courier. “Cryopreservation is often necessary for the processed cells, but it’s a balancing act to preserve as much cell viability as possible.”

Ellison, who notes that his company has been involved with CGT since 2005 and currently handles half of the growing number of trials around the world, says that the researchers are so focused in their early stages on finding a therapeutic pathway, they lose sight of the logistics obstacles in their way. “Many of the CGTs are targeted initially for rare diseases, and of necessity, finding patients with those diseases is often a global undertaking.”

The CGT field is already affecting logistics technology. Earlier, says Ellison, drug developers didn’t realize that some conventional laboratory dewars (which are used for cryogenic storage) didn’t fit or couldn’t be used for air freight. World Courier has now partnered with two of the firms offering tailored solutions: Savsu (Fig. 1) and Cryoport. Evidence of how the CGT boomlet is benefiting logistics service providers can also be seen at BioLife Solutions, which manufactures cryopreservation fluids used in both clinical and commercial development: the company saw a doubling of revenue in Q2 2018 over the year before, and then garnered a $20-million capital investment from a private equity firm. (BioLife is part owner of Savsu.)

While all these materials and process innovations are occurring, the most dynamic part of cold chain logistics is data collection. Data has long been a part of the process, to ensure that standards are being met, but increasingly, data are being used to rationalize the entire logistics process. An example of this is seen with Sonoco ThermoSafe’s PharmaPort 360, which features FAA-approved communications that include geolocation along with internal and external environmental conditions, as well as status checks of the container’s components. “Aside from the temperature control technology, we have clients that are as interested in the data gathering capabilities of PharmaPort,” says Sonoco’s Khushalani. The GPS capability means that the shipment can be tracked in real time (at least, while a plane is on the ground, since in-flight communications are forbidden by air regs); when matched with the temperature data, a more complete picture of a transit is created. The equipment status capability is of value to DHL Global Forwarding, which is partnering with Sonoco ThermoSafe in providing the service. “Getting equipment status enables us to anticipate potential problems, rather than simply reacted to what has occurred,” says Dave Bang, global head of temperature management solutions at DHL.

“If you’re collecting internal condition data only, that is for compliance,” says AeroSafe’s McHarg. “With external data and location, now you’re not just checking on the status of a box; you’re evaluating your entire supply chain.”

Bringing all the data together is an example of the “internet of things” (IoT) approach, with multiple sensors providing information and intelligence. But, as IoT advocates are finding in other industries, getting all the data from multiple supply chain participants is not straightforward. One potential solution to this is adopting blockchain technology, wherein various parties would share information on purpose-built network. This is the subject of study at the Center for Supply Chain Studies, which has 20-odd organizations participating in a proof-of-concept. At least one cold-chain equipment vendor, SkyCell, says that it has already built a blockchain network to provide clients data access with its pallet-scale shipping containers.

Ultimately, manufacturers will have to decide how much control and oversight they want to exert on their logistics services and equipment providers, and how much they want to leave in the hands of their providers. Robert Coyle, recently appointed SVP for planning and strategy at Kuehne + Nagel, says that it is striving to be the trusted advisor to its pharma clients, handling not only shipments but also contracted logistics services (including being a 4PL, or manager of various 3PLs serving global pharma). “We want to be the critical glue bringing data to provide an integrated, end-to-end supply chain,” he says.

Pharma supply chain managers now have options for dealing with cryogenic to room-temperature ranges