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Pharmaceutical Commerce - June 2022 Issue (PDF)

Thankfully avoiding pandemic-related postponements and cancellations—as well as any ill-timed personal flare-ups of COVID itself—I was very glad to make it to LogiPharma 2022 in Nice, France in April. (Manchester Airport’s apparent surprise at the very presence of travelers notwithstanding.) Armed with my NHS vaccine passport app, my signed 

 stating I was COVID-free, a printout of my travel insurance documents, and no discernible trace of a dry cough, I arrived at Nice airport… only to be greeted by no checks whatsoever. Getting into LogiPharma itself actually proved trickier, but after one hour of asking to see everyone’s vaccine records on the morning of the first day, the COVID police promptly disappeared from the event, never to be seen again.

Once ensconced inside the Palais dès Congres Acropolis, well… what a difference to the ascetic inertia of the last two years. LogiPharma was bustling with attendees, speakers, and exhibitors, all enthused by the chance to reunite or make contact, or simply be physically present in the face of the conversations and the presentations. There were no masks in sight and people were gleefully shaking hands like the plague had never existed. Like others, I’m sure, I paid for this after the event with a miserable four-day cold, but I wouldn’t say it wasn’t worth it. Just under 1,000 people were in attendance, and all the major pharma companies were represented. Of course, COVID-19 was a dominant subject across the conference sessions, and early reactions to the situation in Ukraine were very much on the radar. But also prominent as a consistent and stimulating theme was that of sustainability.

There is a tendency among some companies and individuals to be fashionably supportive of the idea of sustainability without instigating any meaningful action around it. This posturing has sometimes made me cynical, perhaps to the extent of not taking some of the arguments seriously enough. I put the recycling out like everyone else, but I’ve never been overly sympathetic, say, to extreme cases of eco-activism. But, from the presentations given by some of the LogiPharma speakers, one of the issues that is patently hard to ignore is the problem of waste in the pharma industry.

Ruud van der Geer, head of cold chain EMEA at Merck (known as MSD in Europe), pointed out that only 50% of all the volume that his company ships around the globe actually ends up “in patients.” And of all the material that pharma wastes, around 50% of that is in the form of single-use materials. Think also about all the package inserts that go into each and every box of medication; these millions of sheets of paper, expertly folded as they may be, are routinely ignored and often thrown away without being recycled. And this is all before we get to the problem of CO2 emissions.

Of course, these eco-revelations aren’t new. But, as Marrie Groeneveld of SkyCell asserted, more people are listening these days. She explained, “Twenty years ago, people didn’t care so much… Now we’ve reached a sense of urgency.” Certainly, in the face of the mountains of waste, we can see there is a need to double down on these issues, not just for the sake of the environment, but also for the general health of the industry, now and in the future.

 is well placed to explore and report on the efforts of individual companies and the wider industry to foster and facilitate a true era of sustainability. So, watch this space!

Julian Update is Pharmaceutical Commerce's Editorial Director. He can be reached at

A reflection on the industry's effort to foster and facilitate sustainability

Food for Thought from France 

As the crisis in Ukraine continues, healthcare organizations are facing unprecedented challenges related to manufacturing, access, and supply chain. Naturally, employee safety and patient access to critical medications and supplies are the top priorities for organizations working in or with Ukraine. Beyond that, there is a risk of long-term disruption in global supply chains, such as the increase in the cost of raw materials and logistics. Medical technology companies, especially, are facing headwinds due to rising freight and shipping costs.

To further explore supply chain implications of the conflict, 

sat down with multinational professional services firm EY, whose life sciences and medtech divisions are advising global companies both with connections to and operations within Ukraine. In this conversation, EY’s Global Medtech leader, Jim Welch, and EY Americas Life Sciences Supply Chain Leader, Jay Welsh, outline the industry’s priorities in getting critical medicines and materials to at-risk patients and employees, and discuss the long-term implications of the war for the supply chain landscape.

What are the most pressing concerns about the healthcare supply chain in Ukraine, and how are your clients reacting to the situation there?

The impact of a humanitarian crisis of this size and scale covers a host of different dimensions. But, very simply, getting key medicines, key devices, and key equipment to a population that is incredibly at risk and at the same time completely displaced is very challenging. We’ve seen a whole host of companies working with humanitarian aid organizations, such as UNICEF, the World Health Organization, and the Red Cross, just trying to figure out how to get medicines and devices into Ukraine. Then, once they are in country, it’s a question of how to get them to the population, or the population that remains. At the same time, the companies in our sector are obviously focused on taking care of their own people in the region, ensuring their safety and security, as well as attending to the commercial aspects of the situation.

It’s not just a matter of focusing on Ukraine, but also the countries around it, given the number of refugees that are moving into and across these areas. It’s about supporting the whole region, the whole ecosystem from a healthcare perspective. We’re seeing companies and their distributors who cover the last mile in regions like this doing the best they can, strengthening operations in some of the surrounding countries.

 We’re seeing the impact of some of the conflict-related trauma and worsening conditions around both non-communicable and infectious diseases. There’s certainly a risk of infectious diseases that is starting to emerge or spread, and then there is the ongoing impact of COVID. As of early 2022, I think just 35% of the Ukrainian population was vaccinated.

Clients are trying to make sure that not only COVID vaccines are available, but all the other types of vaccines that people need. There is also an ongoing balancing act when it comes to the Russian side of the equation. The West is boycotting Russian firms and imposing financial sanctions on Russia, but there is still the need to make essential medicines available to people who need them in Russia. It’s a unique situation.

What has been EY’s role in supporting its clients in the face of the conflict?

 It’s a pretty wide range of things. When our clients are faced with business crises of any sort, we facilitate temporary and permanent responses that help with managing their employee base, moving supply chains around, and reconfiguring some of the logistics around these efforts. During this conflict, we’ve done quite a bit of work from a cybersecurity perspective, and more generally in areas of risk management that stem not only from what’s happening in Ukraine, but also following the sanctions imposed on Russia. Companies are either adjusting or winding down their operations in Russia.

 There are lots of discussions and questions around the supply chain implications, as you would expect. What do companies need to think about with respect to their supply network, their supply strategies? What changes do they need to make to domestic production? The pandemic, of course, has significant implications in terms of the need for more domestic production. Another area for us is helping clients think about the risk and resiliency of their supply chains and manufacturing operations; a lot of companies are asking for help with business responses, things like disinvestment, operational closures, the displacement of employees, and the supply chain implications of airspace being closed and ports being impacted, as well as the rising the cost of oil and gas.

How much has your prior experience of preparing for disasters, and particularly the experience of the COVID pandemic, helped in responding to the events in Ukraine?

 It has definitely helped. If you talk to companies about supply chain risk and resiliency and the types of plans that they have in place, companies have been thinking about these things now for two years. Before the pandemic, some of these geopolitical issues would have been way down on the list of priorities that companies were worried about. The pandemic has brought a whole new perspective on what they need to be thinking about, what kind of action plans they have, and what modeling they need to do.

The situation in Ukraine has built on the strategies that companies were implementing during the pandemic. COVID got people thinking about how they would react to a whole host of potential conflicts and issues around the world, and companies are now putting these scenarios into their modeling.

How do you see Russia’s isolation impacting the global pharma and healthcare industry landscape as the war continues?

Between Russia and Ukraine, the global sales from pharma and medtech is less than 3%, so from that perspective, it is not incredibly detrimental for companies worldwide. The challenges are around being able to fly things over the airspace, for example. There is the increased cost of doing that, and there is the macro-economic inflation that is associated with the war.

Looking specifically at Russia, there are questions now around patent and IP protection for drugs and those types of products in that market. If Russia decides it is not going to recognize patents from unfriendly countries, where many of the major companies are based, we have to look at the impact of products going immediately generic in Russia and what that really means for the global markets. Russia will have to increase its manufacturing, so that will have an impact.

Also, there are certain raw materials from Russia, from natural gas to precious metals, that are used especially in the device side in the manufacturing process. We have to look at obtaining alternatives to those materials and at the impact of that economically. In surgical and orthopedic devices and implants, we have aluminum, titanium, nickel, iron, and gas—all those are key components. If the supply base of those materials is severely impacted, which it will be, that in itself creates a challenge in an environment that is already supply-constrained from the pandemic.

 As Jim says, Russia and Ukraine together are relatively small in terms of the pharma and medtech markets. But the area was growing; companies were thinking about expanding there. So, the conflict has put a major dent in those plans. It’s going to be important now for companies to model scenarios around what could happen as the conflict escalates. One of the biggest concerns is, how will this spread to other countries? Russia may enact counter-policy measures to any company or country that they view as unfriendly.

Within Russia, there are a number of things that will happen in regard to the pharma industry and supply chain. There will be opportunities there for smaller domestic pharmas and [active pharmaceutical ingredient] API sellers to produce more products internally. There’s a serious chance that international patents will not be honored, echoing Jim’s point, and so there will be more generic pharma manufacturing in Russia. And we will need to ask how this situation will impact surrounding countries, particularly allies of Russia like Belarus, Armenia, or Kazakhstan.

Concerning supply chain exposure, I think with respect to the situation in Ukraine and also the pandemic, there has been a bigger impact on medical devices than on pharma because of the types of things that are sourced for medtech. Pharma has certainly not been immune though, and as the situation continues, it will get worse as far as obtaining raw materials go. Things like plastics for trays, syringes, pill bottles, etc., will potentially increase in cost and be limited in supply, as well as materials that go into packaging.

If the conflict can be resolved sooner rather than later, do you see things ever getting “back to normal,” as it were?

I don’t think so because of the huge displacement of people. How you deliver medicine and care in those countries surrounding Ukraine is going to be very different. At this point in time, companies are planning for changes in their operating models and their supply chains to account for that. Beyond that, I think it will create a shift in how most large life sciences companies organize themselves in the region commercially and from a supply base perspective. As we said, there isn’t a ton of manufacturing going on in Ukraine and Russia, but there is in the surrounding area, and it’s definitely going to create some changes.

 Certainly, the longer the conflict goes on, the more opportunity there will be within Russia to manufacture generics and start to fill the gap that’s coming from the boycotts of the country. If the war ends relatively soon, there will be less of that and we will perhaps see the return of some western pharmaceuticals back into the market. But whether the war ends tomorrow or way out in the future, supply chain executives are now asking, “What is my risk tolerance for going back into a region where something like this could happen again?” Ultimately, the landscape has been altered and will be for a long time.

A conversation with EY life sciences leaders Jim Welch and Jay Welsh

The Impact of War on Drug Supply Chain 

Diabetes is a pervasive chronic condition that occurs when the pancreas does not produce enough insulin (type 1, often called childhood diabetes, which accounts for 5% to 10% of all diagnosed cases) or when the body cannot effectively process the insulin, it does produce (type 2, often called adult-onset diabetes, which accounts for 90% to 95% of all diagnosed cases). According to the World Health Organization (WHO), roughly 422 million people worldwide have diabetes. In the US, there are currently more than 37 million people living with diabetes (roughly one out of every 10 adults) and 96 million adults (more than one in three) have prediabetes, according to recent data from the Centers for Disease Control (CDC).

 And that only counts those who have received a formal diagnosis.

Over the past 20 years, the number of diagnosed diabetes cases in the US has more than doubled. The most common risk factors, according to the CDC—being overweight, having a family history, being physically inactive, and 45 years of age or older—foreshadow ongoing growth in this public health crisis in years to come.

Successful management of diabetes requires the long-term control of hemoglobin A1c (HbA1c)—a measure of blood glucose levels over time determined with laboratory diagnostic testing. What is so vexing about diabetes is the fact that so many cases could be avoided with changes in lifestyle, and many more cases could be properly managed with diligent adherence to blood glucose monitoring and adherence to complex regimens of glucose-lowering medications and/or insulin. And yet, due to a constellation of reasons and despite increased morbidity and mortality, many patients routinely fail to keep their condition under control. “Diabetes is often paired with comorbidities and/or denial and depression, so it can become even more difficult for patients to manage daily medication regimens and control their diabetes and its progression,” says Vishal Khanna, vice president of marketing communications for HealthPrize Technologies.


Diabetes also imposes an enormous financial toll on healthcare systems worldwide. According to the CDC, the total direct and indirect cost of diagnosed diabetes in the US—medical costs coupled with absenteeism and lost wages—was estimated at $327 billion in 2017. Similarly, according to the agency, medical costs for people with diabetes are more than twice as high as they are for those without diabetes, thanks to the elevated risk of heart disease and stroke, chronic kidney disease, blindness, and limb loss associated with the disease.

With the drug spend in diabetes reaching nearly $170 billion by 2026, it is expected to be the third-largest therapy area globally (after oncology and immunology therapies), with growth estimated to be 6% to 9% a year over the next five years, according to IQVIA’s recent report 

The Global Use of Medicines 2022—Outlook to 2026

. Current drug spending reflects both the consistent use of older (generic) therapies, such as metformin, and, as the patient’s type 2 diabetes progresses, the use of more costly therapies to lower blood glucose levels and eventually regular insulin use. Overall spending is expected to be buffered over time by exclusivity losses on many of today’s branded therapies and with the uptake of biosimilar versions of reference insulin products, the first of which have recently received regulatory approval.

Prescribed medications that are used to help patients manage diabetes can be segmented into therapeutic products (such as insulin, oral glucose-lowering agents, lipid-lowering drugs, and therapies to treat peripheral vascular diseases), and monitoring or testing devices (to track glucose, ketones and microalbumin/albumin in the patient’s blood), according to MarketResearch.com.

 Insulin—administered via multiple daily injections or an insulin pump—is the primary treatment for patients with type 1 diabetes. However, patients with type 2 diabetes are typically treated with a range of glucose-lowering therapies earlier in their disease progression before starting regular insulin administration.

In addition to the widely used generic medication metformin to lower blood glucose, many other novel classes of glucose-lowering medications are available today. Such competing therapies target a variety of different pathological mechanisms implicated in type 2 diabetes, ranging from insulin secretion (i.e., sulfonylureas), peripheral glucose uptake (i.e., biguanides), and glucose reabsorption (i.e., SGLT2 inhibitors).

Industry observers note that as a class, the SGLT2 inhibitors have produced a paradigm shift in the diabetes space. Examples include Invokana (canagliflozin) from Janssen, and Farxiga (dapagliflozin) from AstraZeneca and Bristol Myers Squibb (both approved in 2013); Jardiance (empagliflozin) from Boehringer Ingelheim and Eli Lilly (approved in 2014); and Steglatro (ertugliflozin) from Merck & Co. and Pfizer (approved in 2017). SGLT2 inhibitors are currently the second- largest group of antidiabetic agents in clinical trials (12%) after incretin therapies.

Today’s approved diabetes therapies include 36 new molecular entities (NMEs) as monotherapies—including first-in-class drugs for diabetes management and 23 unique drug combinations that use two or more (non-insulin) glucose-lowering agents. In fact, today, 40% of approved antidiabetic drugs are combination regimens. Meanwhile, there are more than 100 investigational therapies now in the diabetes pipeline (in 375 clinical trials),

 representing a broad mix of mechanisms of action, molecule types, and routes of administration (inhalation, oral, subcutaneous, IV).

The sheer number of approved therapies and combination therapies continues to grow, showing that drug innovators are trying to capitalize on different pathological pathways associated with this disease, notes Fran Gregory, vice president, payer and pharmaceutical operations for Cardinal Health’s outcomes business.

However, all of this complicates matters at the point of care. With so many competing therapy options and so much heterogeneity among patients calling for a personalized treatment approach, pharma brand teams must frame their positioning and their messaging to help delineate the options for prescribers and patients, and to stand out with payers and ensure strong formulary placement and coverage.

“The No. 1 question from payers is ‘Who’s the right patient?’ There is often rush in the diabetes sector for pharma innovators to say ‘anyone who is not controlled on metformin will benefit from our therapy,’ but that is often not the case from the payer perspective, which must balance providing access and managing costs,” says Aaron Davis, senior managing director, value and access consulting at Syneos Health.

“Not every therapy is right for every person, so determining which patient subset is going to benefit the most from any potential new intervention is the most important piece, because this impacts everything else,” he adds. “If you don’t define who your ideal patients are and how they benefit most 

from your therapy, the payer will then define it for you (based on evidence in literature and market trends), and it won’t likely be the same patients the brand should be targeting.”

Also, according to Davis, more robust planning early in development, especially in Phase II clinical trials and entering into Phase III, will benefit pharma companies the most. “It doesn’t mean you can’t grow from there, but the initial launch needs to have the strongest, data-driven value story, associated with the most well-defined patient cohort,” he says.

The so-called glucagon-like peptide-1 (GLP-1) class of diabetic therapies have also been making headlines. In May, Lilly received FDA approval for the Mounjaro (tirzepatide) injection, which acts on two receptors—glucose-dependent insulinotropic polypeptide (GIP) and GLP-1. The drug’s approval represents the first new class of type 2 diabetes medications in almost a decade, according to Lilly. It is administered using the company’s auto-injector pen for the treatment of type 2 diabetes, and competes with existing injectable medications, including Lilly’s Trulicity (dulaglutide) and Ozempic (semaglutide) from Novo Nordisk.

Ozempic—a GLP-1 receptor protein treatment—was first approved in 2017, and in 2019, Rybelsus (semaglutide) was cleared as the first oral form in that drug class. “The GLP-1 category is one of the biggest drug-spend categories, and payers generally understand their value, but matching them better with specific patients helps to justify the spend,” explains Davis. “Payers have a limited budget, so how do we figure that out?”

He notes that there is an opportunity to address this unmet need by studying real-world data (RWD) from claims databases and other sources to identify uncontrolled patients earlier in the trial process and understand how much they are costing the system, and then designing the trial to demonstrate the benefit of the new intervention on them.

“If payers don’t understand the value—especially in a space with so many overlapping options—they can limit access by not covering it or requiring significant out-of-pocket (OOP) expenses for the patient,” says Davis.

“When it comes to formulary placement, it often comes down to the lowest price,” adds Christine Walton, senior director of Rx marketing for Dr. Reddy’s Laboratories. “The hope is that other competitive factors—such as convenience to patient—also play a role, and can be leveraged to improve access and adherence.”

To date, the insulin market remains highly consolidated among the three top manufacturers—Lilly, Novo Nordisk, and Sanofi—keeping insulin costs artificially high from what industry observers contend is a lack of robust competition.

 A recent survey administered to patients with both type 1 and type 2 diabetes reported cost-related insulin underuse or rationing in 25.5% of patients, which leads to poor glycemic control.

In July 2021, FDA approved the first interchangeable biosimilar insulin product, Semglee (insulin glargine-yfgn), by Biocon/Mylan Pharmaceuticals, which references Sanofi’s long-acting insulin Lantus (insulin glargine). This approval marked “a momentous day” in that this biosimilar “has the potential to greatly reduce healthcare costs,” said then-Acting FDA Commissioner Janet Woodcock, MD, at the time of the announcement (July 28, 2021). Biosimilars marketed in the US in other disease categories typically have launched with initial list prices 15% to 35% lower than the comparative prices of reference products, according to FDA.

“As an interchangeable long-acting biosimilar, Semglee is able to be automatically substituted by a pharmacist without prior approval from the patient’s prescriber, similar to how many generic medications are automatically interchanged today,” says Jeff Baldetti, director of biosimilars, Cardinal Health. “Semglee is available in both a branded and unbranded version, which represents a discount of between 5% and 65%, when compared to the list prices of its reference product Lantus.”

In December 2021, FDA approved the second insulin glargine biosimilar—Rezvoglar (insulin glargine-aglr) from Lilly, which references Sanofi’s insulin glargine. While initial uptake of insulin biosimilars has been slower than expected, payer coverage on formularies is beginning to increase, notes Syneos Health’s Davis. Some stakeholders note that potential misinformation or mistrust among patients may hinder the uptake of biosimilar insulins, so only time will tell.

“Perhaps more so than in other chronic conditions, within diabetes, the success of any biosimilar will be directly linked to the order of market entry—it’s not like the generics market of 20 to 30 years ago, where multiple generics can all be successful,” says Davis. “There may be room for maybe one or two, but not three or more biosimilar versions of any branded product—so it’s all about order of market entry.”

He continues: “At this time, payers are looking to find a few biosimilar partners for cost relief, but do not want to be making a lot of choices in any biosimilar category. If you can’t be first or second biosimilar to market in the disease category, you really should focus your investment and effort elsewhere.”

Meanwhile, the pursuit of insulin in capsule form has received a lot of attention in recent years. Oramed Pharmaceuticals’ investigational therapy ORMD-0801 is now in Phase III trials. If approved, this first-ever oral form of insulin could represent a paradigm shift by eliminating the need for patients to administer insulin via injection, while enabling improved adherence to therapy. The company is also developing an oral GLP-1 analog capsule (dubbed ORMD-0901). In a March survey involving 88 endocrinologists and 82 primary care physicians in the US and Europe (conducted with IQVIA), Oramed found that 76% of the respondents “definitely would” or “probably would” prescribe the oral form of insulin for type 2 diabetes patients.

“With the recent uptick of patients taking their health journey into their own hands and becoming more healthy, the hope is that doctors and patients alike will focus more on preventative care and healthier lifestyles, reducing the need for prescription intervention,” says Walton of Dr. Reddy’s Laboratories. Despite this overall trend in health and wellness and technology options aimed at helping patients overcome their adherence barriers, “the adherence challenge remains a code that has not yet been cracked, and there is absolutely no silver bullet in diabetes or any other chronic condition,” adds Davis. The challenges are further compounded by social determinants, such as access to quality care, poor health literacy, and other factors.

“Some of the adherence challenges can also be addressed better by improving the conversation further upstream,” continues Davis. “Ideally, the brand team must make sure the prescriber has the tools to effectively communicate ‘the why’ to the patient, but typical physician visits continue to get shorter and shorter—so this undermines the likelihood of the patient actually understanding their condition, the role their medication plays, and the overall importance of sustained adherence.”

The coordination of care between a patient’s specialist and their general practitioner is particularly important in diabetes, Cardinal Health’s Gregory contends. Pharmacists can ensure that existing medications the patient may be taking do not interfere with any new drugs for diabetes management, and to provide other forms of support and access to resources.

“Often, overall care is not coordinated, specifically if the patient does not have access to quality healthcare facilities with integrated care,” says Gregory. Similarly, she notes that “pharmacy teams can help patients access the most cost-effective medications and provide access to financial resources that may be available for underinsured patients through a variety of sources, such as foundations or patient assistance programs.”

Within the realm of diabetes (and other chronic conditions), multiple innovative approaches are being used today to move the needle on adherence. For example, the HealthPrize digital engagement solution uses gamification, health education, and behavioral economics to engage and educate patients; the HealthPrize tool shares clinical information and educational messaging “in small doses, to simplify the complex and create an environment that makes them want to come back and check in every day,” says John Monahan, the company’s CEO. “When patients learn one little thing today, and another tomorrow, the collective information and understanding grows.”

HealthPrize’s Vishal Khanna adds: “Within diabetes, our branded offering gets patients to come back to the platform six or more times per week, spending two minutes or more every day, helping them to learn and ultimately be more adherent.” The HealthPrize platform’s gamification format provides rewards to further motivate users—patients earn points and can convert them to gift cards, health-related products, or charity donations.

HealthPrize recently carried out an analysis of transactional-level claims data with McKesson in a program in the diabetes space that had more than 40,000 users. The study examined what percentage of previously non-adherent users became adherent through HealthPrize—a metric that is particularly important in value-based care.

“The industry considers patients below 80% PDC (proportion of days covered—the gold-standard measure of medication adherence) as non-adherent, so the ability to move non-adherent patients to a state of adherence (reflected by PDC greater than 80%) provides a critical measure of success,” says Monahan.

“We looked at PDC among eligible patients before the HealthPrize intervention and then following utilization of our program and found that 83% of the previously nonadherent cohort—four out of five—became adherent through HealthPrize after 12 months,” adds Khanna. “From the pharma perspective, that translates to about two extra refills per year per patient—a substantial amount, especially given the scale of diabetes prevalence. This enables improved glycemic control, reduced medical interventions, and reduced healthcare expenditures.”

Another solution, from Sempre Health, comes from the cost perspective, in the form of a program that rewards patients every time they pick up and renew their prescriptions. In November 2020, UPMC Health Plan and Sempre Health extended their earlier drug-adherence collaboration to include diabetes medications. The program uses natural-language text reminders and messaging to provide discounts to reduce OOP treatment costs for patients. When participating members fill their eligible prescriptions on time, they receive discounts on their copayments to incentivize improved adherence. The savings realized on the Sempre program are significant—the offering is able to reduce a patient’s OOP costs on their eligible medications by up to 60%.

Unlike traditional coupons, which operate without payer involvement and offer patients one-size-fits-all discounts, Sempre Health allows payers to turn on point-of-sale discounts for their members who have been prescribed specific chronic disease medications. This allows patients to share in the cost savings that their responsible health decisions are generating for insurers, care providers, and pharmaceutical companies.

Meanwhile, Sempre Health also has a collaboration with Sanofi, whereby eligible patients on Lantus (insulin glargine injection), Toujeo (insulin glargine injection), and Soliqua 100/33 (insulin glargine and lixisenatide injection) are able to use the Sempre platform to access discounts to support adherence to therapy. According to the company, a recent analysis of Sempre’s interventions led to an increase of 25% in PDC. On average, in their first year in the program, Sempre patients refilled three more prescriptions than patients in the comparable non-Sempre cohort.

Another company in the adherence space is EveryDose (formerly known as Groove Health). The organization combines its proprietary analytics platform with behavior-modification tactics, and partners with payers, hospital systems, self-insured employers, and Medicare/Medicaid plans. Through these partnerships, EveryDose identifies those patients who are at greatest risk of non-adherence to long-term, chronic medication regimens. The company’s mobile app supports patients in overcoming adherence barriers by combining predictive analytics and personalized engagement. For instance, EveryDose’s web-based app uses a conversational chatbot—dubbed Maxwell—that employs artificial intelligence to help identify the primary reasons for non-adherence, so that tailored follow-up can be provided via targeted content and resources, and through intervention by the patient’s care team.

Finally, Bigfoot Biomedical is using technology to support adherence objectives. In June 2021, the company launched Bigfoot Unity Diabetes Management System and Bigfoot Clinic Hub. The product features connected smart pen caps that recommend insulin doses for people managing multiple daily injections. The pen cap connects to a smart phone app and is integrated with Abbott’s FreeStyle Libre 2 CGM app, according to the company. The cap also works with insulin pens from Lilly, Novo Nordisk, and Sanofi. Bigfoot’s associated cloud-based platform automatically captures and presents insulin therapy data from the Bigfoot Unity System, so an initial number of diabetes clinics and endocrinology practices in select markets across the US can proactively support patients at a distance. Availability will expand to other markets through 2022, says the company.

https://www.cdc.gov/diabetes/data/index.html

2. Diabetes Market Research Reports & Industry Analysis

3. Chaudhury, A., et al., “Clinical Review of Antidiabetic Drugs: Implications for Type 2 Diabetes Mellitus Management,” Front. Endocrinol. (Lausanne) 8, 6 (2017).

https://doi.org/10.3389/fphar.2021.807548

5. Pharmaceutical Care Management Association, “Insulins: managing costs with increasing manufacturer prices,” August 2020.

6. Herkert D, Vijayakumar P, Luo J, et al., “Cost-related insulin underuse among patients with diabetes.” JAMA Intern Med. 2019;179(1):112-14.

8. UPMC Health Plan Further Expands its Sempre Health Partnership to Better Serve Patients with Diabetes, 

Proper control of type 1 and 2 diabetes can greatly reduce the personal impact and economic burden of this pervasive public health condition. To that end, stakeholders are exploring many parallel routes to help individuals and society maintain the upper hand, as the toll of diabetes continues to skyrocket

Controlling Diabetes: Advances & Adherence

Supply chains around the globe should soon be getting an enormous boost thanks to advances in machine-to-machine communications, the internet of things (IoT), artificial intelligence (AI), and immersive networks, which are all part of what is referred to as the Fourth Industrial Revolution, or Industry 4.0.

The concept of a Fourth Industrial Revolution was popularized by the founder of the World Economic Forum, Klaus Schwab, in 2015. The impact on global supply chains and manufacturing should be substantial as self-monitoring systems, intelligent machine-to-machine communications, and a network of networks open a new world of deep and broad process visibility and cross-functional, cross-enterprise communications.

To better appreciate the promise of Industry 4.0, it is helpful to look back at the first three waves of the Industrial Revolution:

Generally delineated as spanning 1760 to 1840, this revolution was powered by steam and advances in manufacturing technologies that reduced the physical labor and time required to create products.

Spanning 1871 to 1914, this revolution was powered by the building of railroads, creation of telegraph networks, the increasing use of electrification, and development of factory production lines.

Sometimes called the Digital Revolution, this era began after World War II, and extends to the present day. This revolution has been powered by the growth of computer technology and all that our ever-more powerful computers have brought to the world.

Without a doubt, Industry 3.0, the Digital Revolution, has carried us to amazing heights. The revolution began with room-filling mainframes, progressed through supercomputers, and along the way gave us what used to be supercomputer capabilities on the smartphones we carry in our pockets.

Given all of the above, why has the birth of the Fourth Industrial Revolution, Industry 4.0, been proclaimed? The answer is both logical and stunning. We are beginning to create networks of networks—with machine learning, expansive communications, and precision process visibility baked in—that will transform how businesses communicate and interoperate.

The textbook example for Industry 4.0 is supply chain management (SCM). How many partners does an organization have? This can range from dozens to hundreds to thousands. In turn, each of those partners have their own partners and suppliers. Now imagine the Industry 4.0 concept of creating a network of networks, securely connecting all of these participants, each permitted to see the data relative to their own needs.

This brings extreme visibility to all supply chain participants. With such a network of networks, one could see an overview of not just their own supply chain needs, but dive deeper to ensure their partner supply chains were also flowing properly. Add to this, machine-to-machine communication, AI, and you can understand how significantly supply chain operations can be enhanced by the network of networks of Industry 4.0.

TraceLink’s traceability and compliance solution for the pharmaceutical industry is a prime example of Industry 4.0 connectivity. Our network of networks links 286,000 members to supply chain partners and manages 31.3 billion serial numbers, providing a digital twin for the life science industry.

The foundation: Creating a network of networks

The challenge, of course, is to actually 

 a network of networks, especially when unifying communications across multiple companies, each with their own enterprise resource planning (ERP) and SCM systems, their own custom applications, and work processes. How do we integrate these disparate entities into a network of networks that lets us access information in a manner that enables us to develop intelligence, share execution, and work as an integrated organism?

The answer is to create a central network platform on which organizations can create a digital twin of their networks without changing their internal architecture. Such a network platform would enable the creation and running of multi-enterprise applications with business objects and business processes as a harmonizing layer—essentially translating between disparate applications to allow seamless communications and processes across and between organizations.

Basic elements of such a network of networks would include:

Creating a standardized digital representation of a firm’s own processes that can be extended to partners.

Sharing processes and applications across the network, including appropriate security and access controls among partners.

Supporting cross-functional and cross-company execution with a shared, but customized, application that enables the company and its partners to participate based on their own workflow and data requirements.

Providing a common data model for information in the network, with a system that auto-translates each other’s data into a common language.

Generating collective intelligence from across the network to predict shortages, anticipate supply disruptions, and identify shifts in demand.

Such an Industry 4.0 network of networks would connect people, processes, data, and systems with digital networks that could break down the barriers to digital supply chain transformation. The results could help us meet some of the major challenges supply chains face, including:

 A network of networks will enhance traceability and provenance to defend against counterfeiting and diversion in pharmaceuticals and a spectrum of other industries.

 Recent supply chain disruptions underscore the need to adapt and adjust to fluctuations at a very rapid rate, made possible by the visibility and communications inherent in a network of networks.

 Environmental concerns require traceability. For example, the US Environmental Protection Agency’s Scope 3 on carbon emissions basically says that you need to not only be able to certify that your own products meet certain sustainability requirements, but that all the raw materials that your suppliers are using also meet the requirements.

A network of networks provides the transparency companies require to work in a more orchestrated manner and to ensure accountability to each other in order to achieve goals—and mandates—for social responsibility.

These are exciting days. We are witnessing the dawn of the Fourth Industrial Revolution, and because of the network of networks that is forming such a foundational element of this revolution, supply chain management will be one of the earliest beneficiaries of Industry 4.0. This capability is no longer theoretical, but in action today and providing immeasurable value to customers and their patients. To ensure availability and visibility to critical drugs, TraceLink’s network, for example, is able to successfully predict product shortages 90 days in advance with over 80% accuracy. This is the kind of revolutionary impact interoperability and end-to-end digitalization can have on society.

Shabbir Dahod is President and CEO of TraceLink.

Pharma supply chain management will be one of the earliest beneficiaries of the Fourth Industrial Revolution, and the potential of ‘networks of networks’

The Promise of Industry 4.0

Today’s technology-driven, “Amazonized” economy demandslevels of agility that enable companies to flex, respond, and innovate faster than ever to market and supply chain dynamics. A significant challenge to optimizing agility is that the flow of information often comes from systems that are set up for longer-term planning cycles, not plans that change by the hour, or even second. The cost of inaction is huge—a single prolonged production-only shock is likely to wipe out up to 50% of one year’s earnings before interest, taxes, and amortization (EBITA). However, pivoting from “point-in-time” to “real-time” supply chain operations requires a different way of thinking. It requires a method of continuous realignment between planning and real-time operations, constantly ingesting data, and updating what’s happening on the ground with what was initially desired.

This shift is more urgent than ever for pharma and life sciences companies, and not only is it needed, it’s mandated for patient safety. As a result, many areas of the supply chain, such as shipment delivery and integrity, cannot be taken lightly. Whereas in many industries, product delivery may result in unhappy customers or reduced revenue, the magnitude of importance for delivery, as promised, is greatly compounded in these industries. Given the volatility of some methods such as air transportation for cold-chain shipments, the challenge is more acute. When excursions happen, they present a cascade of repercussions—unhappy customers, financial implications and in worst-case scenarios, loss of patient lives.

Customer satisfaction, while important, can pale in comparison to the other factors at stake. These include loss of life for patients, public health risks, and even tarnished company reputation. The challenge of minimizing risk in pharma/life sciences is that to do it well, many factors must be considered and each of them needs to work together seamlessly to deliver outcomes that cannot be deviated from or compromised unless carefully executed.

The mass rollout of COVID-19 vaccines showed us that we are not prepared to deal with the many obstacles that present themselves in times of greatest need. The mismatch between vaccine availability and last-mile delivery consistently highlighted the need for all constituents—pharmaceutical manufacturers; government at the national, regional, and local levels; shipping and distributors; even airlines—to work together to deliver appropriately.

It’s an ongoing process and clearly one that’s not easy to solve: although efforts began at scale over a year ago, they are still working on how to execute best. Recognizing the depth of the challenge and how to solve it most effectively requires an appreciation and understanding of the factors that cause it.

Pharma and life sciences industries are heavily regulated and for good reason: any error risks lives. Ensuring compliance with these regulations is most often focused on the manufacturing of the drug. This, however, is short-sighted. Regulatory scrutiny occurs across operations, sales and marketing, price transparency, patients, clinical operations, and even transport and delivery. To ensure that risk of breach is minimized and managed, every aspect must be visible, tracked, and traced regardless of workflow stage. Pharma companies have huge regulatory affairs teams to ensure compliance. The challenge for them, however, is that they are often not able to see the full journey of the drug from development to patient, and all steps in between. To achieve this, there must be a shift away from a siloed view of regulatory compliance to one that is not only enterprise wide, but also extends to every element in the supply chain, that is, all hands/organizations and teams that have a hand in successful market delivery.

If a drug goes through years of research, and finally is ready to ship (after clearing the many regulatory hurdles), but then never gets to the medical facility so it can be effective for the patient, it’s a huge loss. Sadly, this is often the case. More than $35 billion is lost in the biopharma industry annually due to failures in temperature-controlled logistics. Products must be transported so they arrive not only on time, but also, in many instances, at a controlled temperature for maximum effectiveness. Seven of the top 200 most prescribed drugs in the US require 2–8°C storage and freeze protection, and this number increases each year. Fighting COVID now requires delivery of temperature-controlled vaccines 

 and if they aren’t delivered in a timely fashion, they simply cannot be used, and this is something state and federal agencies strive to avoid at all costs. Oregon is just one state of many that has struggled: as of March, it had over $700,000’s worth of doses it was working to get into the hands of providers before they went to waste due to shipping mishaps, refrigeration issues, breakage, and expiration.

Simply knowing what’s working, or isn’t, in your supply chain operations doesn’t help fix the problem. Many planning applications give insight based on goals, prior results, or industry benchmarks. They often don’t consider what’s really going on, the “ground truth,” and thus may unintentionally contribute to the challenges. It’s vital to have a central system to predict at-risk situations in the supply chain for all companies involved—from manufacturer to intermediaries, to the end-customer or patient. With ~$440 billion in product moving through pharma cold chains by 2024, simply knowing where the product is along the way won’t be enough.

Many companies have interfaces to see the results, but few have a platform that allows for action. If temperature-controlled medicines are baking in the heat, or freezing in the snow, it’s vital that action be taken as soon as possible to prevent them from being rendered useless. Those platforms that have moved from predictive to proactive will be the winners, as they are able to monitor every aspect of the supply chain—even at the item level—to flag quality and compliance risks.

It’s vital that these important requirements can be addressed in real time and in a central platform that addresses complexity, and the ever-changing need to stay on top of the unique requirements you have—whether it’s how to address cold chain issues, handling problems, transportation-planning issues, or regulatory affairs. The good news is that these challenges are not insurmountable, and many can be mitigated through real-time monitoring and analytics, which drives the ability to act to salvage valuable product and profit before it’s too late.

Enabling the end-to-end supply chain to be modeled and adapted identifies potential points of weakness and drives strategic initiatives to reduce cycle time and mitigate risks. So, whether transporting plasma, vaccines, insulin, or even cell therapy treatments for patients, removing data and organizational silos with a central system to monitor every collection, transit point, storage facility, and temperature gauge, including systems, sensors, warehouses, ports, and packages—even at the item level—must be considered. Collecting data from all sources and tracking it in an extensible platform that can model current and future outcomes via digital twins, 

orchestrating intelligence, and extending it to all relevant partners in the supply chain process is done by automating workflow via a low code workbench to resolve excursions that must be addressed immediately or differently. This ensures that the supply-chain system recognizes and addresses cases that must take the highest priority based on ground truth and real-time data. Digital twin functionality is a vital way to pivot for success; should one link in the supply chain break, it enables virtual modeling of the physical impact before it happens and provide recommendations on how to best reduce risk. This allows you to reduce waste, improve quality assurance, and protect your patents and brand at every step of the journey.

The last few years have seen unprecedented shocks to the biopharma supply chain that have forced the industry to face some harsh realities. Resilience, the ability to anticipate adverse factors, course correct in real time, and recover quickly are now critically important in continuing to meet increasing customer demands for faster delivery and more therapeutic personalization.

The speed and scale of disruptions reinforces the need for real-time operations.

Technology innovations are moving the biopharma supply chain beyond simply visibility into a much richer, more contextual “real-time-all-the-time” dynamic, enabling intelligent digitization across every enterprise in the supply-chain ecosystem. By modeling and adapting, embedding intelligence into operations, and deploying digital twins for collective insight and collaboration, we are now able to continuously align planning and execution with ground truths to improve service levels by increasing on-time and in-full delivery (OTIF), and line-item fill rate (LIFR). This helps maintain security, quality, and compliance standards, and provides specific measures of increased environmental, social, and governance (ESG) goals and achievements across the entire supply chain to boost customer satisfaction, patient outcomes, and revenue.

Mahesh Veerina is President and CEO of ParkourSC.

Why ‘real-time-all-the-time’ supply chain operations are fundamental to         biopharma success

From Point-in-time to Real-time

High demand for pharmaceutical goods existed prior to the start of the COVID-19 pandemic. Since that time, demand has only increased in tandem with increased supply chain woes. This has put pharmaceutical manufacturers under added pressure to expedite the shipment process, especially given the urgent need for safe, fast, and reliable transport of specimens, vaccines, medicines, and medical devices around the globe. Many of these are classified as DG, and, as a result, bring additional regulatory requirements and supply chain challenges.

In addition to the material shortages and shipping delays impacting businesses around the world, drug manufacturers face unique issues that make transport harder and more complicated.

The fact that infectious substance classifications differ between countries creates a challenge for manufacturers. This is compounded by differences in packaging requirements and shipping regulations that exist between countries. Ensuring that HAZMAT shipments are fully compliant requires that the item being shipped (e.g., vaccine, specimen) and what those items are shipped with (e.g., data logger containing a lithium battery, dry ice) comply with regulations of the origin and destination countries.

Not only do rules and requirements differ by country, but they also vary based on transportation mode. While the requirements and restrictions that work for ground shipment apply to sea as well, the complexity ramps up shipping by air. When shipping DG, you cannot simply transfer ground or sea cargo to planes because air transport is far more restrictive in terms of allowable quantities, packaging requirements, documentation, and labels. Some items cannot be shipped via air at all.

Vaccines, specimens, and pharmaceutical devices are all delicate, and all come with their own specific temperature maintenance requirements. The temperature requirements for goods sitting in a warehouse may differ from the acceptable range while that item is in transport. Shipping these materials in certain locations or by certain modes (particularly planes) increases vulnerabilities due to air pressure fluctuations and temperature fluctuations on the tarmac, although shipping by ground or boat can also impact temperature. Improper packaging could lead to heat or cold exposure outside of acceptable temperature ranges and compromise the integrity of the product.

The lithium battery market has grown significantly in recent years, particularly in the pharma/healthcare industry, as many medical devices run on lithium batteries, as do temperature monitoring or location tracking devices shipped with pharmaceutical goods. The classification of lithium batteries as DG further complicates the transport process, and many shippers may be unaware that these batteries are classified as DG or the specific requirements that come with transporting them, which could lead to shipments being stopped. And just like with other DG, the rules vary by transportation mode. For example, lithium battery exceptions that apply to truck or train transport may not translate to air transport. Additionally, state-of-charge issues might also arise for manufacturers required to ship a product to end users with a specific state of charge, given that 30% is the maximum allowable for plane transport.

While a wide range of factors can impact the transport of temperature-controlled pharmaceutical goods, packaging plays a particularly important role. Incorrect or non-compliant packaging, labels, or markings can result in costly fines and delays. For pharma companies, delays can cause specimens and medications to be ruined, while putting patients at the end of the supply chain at risk. For this reason, consistency is critical in pharma transport. Without controls, test samples could be ruined or generate false readings, and vaccines could spoil. That’s why manufacturers must take the necessary steps to ensure every shipment, regardless of origin or destination, is kept within the correct temperature range and arrives in a certain condition.

To support consistent temperatures throughout the shipment journey, pharma manufacturers want to use the same tested and approved packaging, with specific dimensions, performance expectation, and insolation properties, anywhere in the world. But it’s important to remember that the emphasis on proper packaging doesn’t come from only individual organizations, it also comes from governing and regulatory bodies.

Mitigating the risk of shipping noncompliance

Being found non-compliant in terms of packaging, documentation, or any other DG shipping requirement can result in delays, especially when dealing with multiple supply chain partners. And in the pharma industry, delays or other shipping or handling mishaps can impact the health of those waiting for those products and the integrity of the product itself. It could also result in steep financial fines or exposure to byproducts that are harmful to the environment and people. Keep these strategies in mind to support shipping success and ensure you have the right tools, packaging, and procedures in place:

 Many factors impact how goods are shipped, so it’s critical to know what exactly you’re shipping, and which items are classified as DG. Be aware of the rules and regulations that govern the transport of those items (especially any shipping restrictions), and then ensure you have the proper processes and infrastructure in place to guarantee compliance across the supply chain. DG shipping regulations continue to change, so it’s important to stay up to date on any regulatory changes, both in the US and globally, and have processes in place to communicate information across your organization and implement any necessary changes within your supply chain operations.

DG shipping regulations can be complex and confusing. Consult with attorneys and compliance experts to ensure you follow the specific regulatory mandates for shipping pharma products across all transport modes—land, sea, and air. They can also assist with assessing your facilities and compliance programs to identify any gaps and better integrate compliance into other parts of your organization.

 Many pharmaceutical products must maintain a specific and consistent temperature, and ensure safety, as they move through the supply chain. Proper packaging is critical to ensuring these goods aren’t compromised during this process. Be mindful to use only materials that are UN-certified for DG packaging. And, if your go-to suppliers are out of stock, remember that any alternate materials you use must also meet certification requirements.

 Training plays a critical role in ensuring goods are shipped safely and compliantly. Make sure all employees involved in shipping and handling DG receive the necessary training—not only to comply with training mandates but to prepare them to do their jobs correctly. Incorporating digital and eLearning tools helps train new employees remotely and are often more interactive and effective than more traditional methods.

Pharma companies create and distribute products that directly impact people’s lives. That’s why it’s important to remain accountable and uphold the highest standards. Any inkling that you are cutting corners or don’t have the necessary processes in place could have a negative impact on your customers, your brand reputation, and your business.

Supply chain issues and the increased demand for pharmaceutical goods will continue. Manufacturers must expedite shipments to keep pace, but not at the cost of compliance and proper packaging. As the challenges of the past two years continue to impact daily life, quality control remains more vital than ever.

Jay Johnson is Senior Manager for Labelmaster Services, Labelmaster.

The packaging and shipping of dangerous goods (DG) adds further challenges 
to the distribution pressures brought about by the pandemic

Dealing with Dangerous Goods

Over the past year—and in the face of a pandemic that has snarled supply chains and work schedules—the US pharma industry has made measurable progress in its march to the November 2023 deadline for compliance with the Drug Supply Chain Security Act (DSCSA). DSCSA, passed in 2013, set out a 10-year process for creating “interoperable, electronic tracing of products at the package level to identify and trace certain prescription drugs as they are distributed in the United States.” Although both industry and FDA have marked some key steps, there is a lot yet to be done, and not all of the pharma supply chain (from manufacturers to dispensing pharmacies and hospitals, with distributors and contractors in between) is moving at the same pace.

In the past 12 months, FDA issued a batch of guidance documents that detailed its view of product verification processes (clarifying what a “suspect” product is) and procedures for handling product returns that are salable. One guidance, “Enhanced Drug Distribution Security at the Package Level,” however, elicited a sharp reaction from the Healthcare Distribution Alliance (HDA), which said that the document should be withdrawn since it proposes a system that 

“does not exist, cannot be built by 2023, and poses unacceptable security and compliance risks.”

HDA objected, among other things, to the recommendation that a trading partner, FDA, or a state official, could get a rapid response to trace a suspect product with one request; HDA suggests that because the data of such transactions are stored across multiple databases, that quick response is not possible. FDA has been quiet about revising or withdrawing the guidance.

Another key guidance, issued early this year, was the long-awaited proposal for managing the licensure of drug wholesalers and third-party logistics providers (3PLs) by FDA—superseding the many state-level procedures already in place. This guidance represents the first time that FDA officially will oversee wholesaler and 3PL activities, and will be issuing operating licenses and inspecting facilities going forward. (At press time, the comment period on this guidance was still open.)

On the industry-collaboration front, there are at least three significant activities going on: the Partnership for DSCSA Governance (PDG); the Open Credentialing Initiative (OCI), and HDA’s ongoing surveying and codifying of industry practices and readiness. None of these organizations has force of law or regulation, but all of them, one way or another, are trying to establish agreed-on industry practices to make both interoperability and understandable data file transfers happen.

In early 2022, HDA published an updated Guidelines for Barcoding, superseding pre-DSCSA guidance and essentially defining what the barcodes will look like for fast data collection at distribution centers. The organization is also surveying its members (most recently, to determine how extensively the electronic product code information services, or EPCIS standard for electronic communication, is being adopted) and providing feedback to FDA on its guidances. In the recent past, HDA took a leadership role in establishing the concept of a “verification router service” (VRS), which will serve as a phone book for how queries on product identifiers will be directed from the query source to the information source.

Partnership for DSCSA Governance (PDG), set up intentionally to bring together manufacturers, wholesalers, and dispensers to represent the full breadth of the supply chain, issued the first chapter of a “Foundational Blueprint for 2023 Interoperability” last year. The document is fairly technical and detailed around file descriptions; the next step is to take the output of four working groups to set up how connections will be made between trading partners. The working groups are Credentialing and User Authentication; Serialized TI/TS Data Exchange; Verification Architecture; and Tracing Architecture.

OCI is organized by the Center for Supply Chain Studies, a Pennsylvania nonprofit, and skews toward software vendors of blockchain-related technology (see OCI’s 

 on interoperable electronic credentialing). So far, it has published several proof-of-concept projects that demonstrate how the technology could function.

“It’s pretty clear that there will not be one communication technique, or one software application, that will connect all trading partners to each other,” says Perry Fri, EVP, industry relations, at HDA. “Industry standards will help.”

“Manufacturers have one answer to interoperability, and wholesalers have another,” notes Greg Cathcart, president of Excellis Health Solutions. He agrees that “multiple systems and standards will be written,” but that “the ultimate question is, ‘Who owns the data?’”

), generally regarded as the most widely used IT system for DSCSA compliance, has gone in a direction of creating a network of trading partners across the supply chain, and setting up communication processes within that network for connectivity. There will always be outsiders to the network, or special cases, though, and so Shabbir Dahod, CEO of the company, says that the Opus platform, the company’s newly announced software version, will be set up to provide interfaces to other software tools. “Other companies have already layered applications on Opus, and we can support that,” says Dahod.

The solution provider landscape has changed in recent years. Most notably, Antares Vision, an Italian provider of packaging line equipment and software, has acquired rfXcel, Tradeticity (a Croatian traceability software vendor), Acsis, a software provider oriented toward warehouse management, and the assets of Adents, a French firm. Systech, an early innovator in packaging serialization, was acquired by Dover Industries and linked to the Dover subsidiary Markem-Imaje, a marking/labeling firm. Movilitas, a European consulting and systems integration firm, has been acquired by Engineering Group, a global IT provider; similarly, Excellis Health Solutions, based in the US, is now owned by NNIT, a Danish IT firm.

According to industry sources, the great majority of manufacturers are now routinely barcoding their products with unique serial numbers (this was an early DSCSA milestone). Packaging vendors benefited from the business driven by that requirement. However, those numbers are not being routinely shared and verified up and down the supply chain—that requirement has been delayed to 2023. A key element of serial code transmission is aggregation—the ability to infer what codes are inside a case of product (which might have dozens or hundreds of individual units), from the “parent-child” relationship established by the packager when the case was composed.

Lacking aggregation, wholesalers and distributors will be compelled to break down pallets and open cases, and perform a manual serial code check.

FDA’s 2022 proposed guidance, for the first time, explicitly permits inference from aggregated cases; however, this puts the onus on the packager to collect the unit data to create the parent-child relations. “While essentially everything we receive is barcoded, only half of it, at best, is aggregated,” comments Pat McGinn, SVP of supply chain integration at Eversana, a 3PL and commercial-services provider to life sciences. “While the aggregation levels are improving, it’s a problem, especially for generic manufacturers.”

McGinn has some good advice for industry supply chain managers, regardless of how rapidly they’re aggregating: pay close attention to how your products enter the supply chain, and where it’s best to compose larger or smaller aggregated containers. An example of this is the use of inner packs—the bundles of product (say, four bundles of 12 in a case of 48); if used, these need to be aggregated as well. But it’s conceivable that the packager might do better with shipping cases of 12 rather than 48. “You might spend a little more on the packaging, but you could save substantially on service requirements or product damage across the supply chain,” he says. Eversana offers to consult with its clients in this matter.

Back on the software side of the DSCSA compliance march, there is some industry buzz around a recent product offering of LSPediA, which provides serialization and supply chain software. When fully implemented, DSCSA will require the documentation of a shipment (in digital form) actually match up with the physical shipment; ideally, the documentation arrives prior to the shipment, and then the receiver verifies the identity of the two. But errors are rampant in both the documentation (where an errant “0” or hyphen could throw off an identification field) and in the physical shipments, where a nominal case of 48 might have 47—or 49—units.

LSPediA has introduced the Investigator application, a tool that automatically (and with some programmed intelligence) goes through an EPCIS or similar file and identifies errors in the documentation. Without such an automated tool, the checking needs to be performed manually. According to Michael Ventura, a VP at the firm, some companies have spent hours looking for an error, which Investigator found in minutes. In recent months, both AmerisourceBergen and Cardinal Health—which together represents roughly two-thirds of primary distribution of pharmaceuticals in the US—have adopted Investigator, as well as numerous small distributors and some manufacturers.

One unexpected outcome of the COVID-19 pandemic is the intense focus, these days, on supply chain practices and problems (think of how the suppliers of baby formula are currently dealing with that issue). “We don’t have to explain to outsiders what the importance of supply chains is anymore,” notes HDA’s Fri. For all the disputes for and against the value of DSCSA in its early days, the industry is benefiting from the new capabilities that serialization and traceability are beginning to provide to the industry.

TraceLink’s Dahod says that traceability is foundational to what the industry will be able to accomplish going forward. An example of this is a newly announced capability to predict product shortages in TraceLink’s Opus platform. The company claims that shortages can be predicted 90 days out, with 80% accuracy. Similar supply chain improvements are expected from a newly announced partnership between TraceLink and Kinaxis, a company that specializes in supply chain and logistics analytics and optimization.

Other companies have adapted traceability to specialized applications: rfXcel, for example, demonstrated the utility of tracking cold chain shipments via its software (cold chain products need to have documentation of the temperature and environmental conditions of the shipment, when the shipment arrives).

And then there is anti-counterfeiting, which, from a legislative perspective, was the driving force to DSCSA passage in 2013. Although most US observers note that counterfeit product is at worst a minor factor in US distribution, there have been some recent, startling instances. The worst example, arguably, was 

 that some $250 million worth of its HIV and other products was allegedly diverted or counterfeited in the past two years. Gilead brought civil suits against a wholesaler and pharmacy ring that crossed 10 states. The US Dept. of Justice is reportedly now looking into the matter.

While DSCSA barcodes figured in the Gilead and other counterfeiting discoveries recently, industry experts agree that the serial codes alone won’t be unbeatable countermeasures. The use of authentication technologies—holograms, security inks, microprinting, and the like—will also figure. A few vendors working in the DSCSA environment, notably Systech and Covectra, are offering authentication technologies that use the same label as where the serial codes are printed.

Recently, Covectra updated its previously announced StellaGuard technology, which enables an investigator (or, a consumer) to use a smartphone camera and internet connection to verify a label, based on the precise positioning of star-shaped particles in the label (the positioning is unique to each unique serial code).

Systech is promoting its e-Fingerprint technology, which uses a similar logic based on the fine details (flaws) in a printed label. Both technologies depend on accessing a database of the labels’ original features that the smartphone compares; both have the utility of enabling consumers to do their own, on-the-spot authentication.

Yet another direction being taken in the traceability path (but not necessarily DSCSA-compliance-driven) is the use of radio-frequency identification (RFID) labels in addition to the 2D barcodes. RFID scanners in place at a hospital pharmacy can be integrated into an inventory- and security-management process, as well as to ensure the right medication is being received by the right patient. Kit Check has been a pioneering firm in this effort, and there is now an industry group, the DoseID Consortium, that brings together the labeling service providers and suppliers of RFID technology. Last fall, ears perked up when AmerisourceBergen announced it would offer RFID labeling for medication trays (which hold multiple doses of medicines) used in hospitals.

These new applications are not only instances of how technologies can find places in niches of the overall pharma supply chain, but also how technology has continued to move on over the near decade that DSCSA has been in place. Nevertheless, the DSCSA mandate is in place for all parties in the pharma supply chain, and time is running short. “Manufacturers need to be working now on finalizing their connections with their wholesalers,” says Fri. “Next year, those wholesalers will be busy getting aligned with the downstream pharmacies and hospitals, who have big hurdles to get over.” To that end, HDA is generating content and pooling together resources for the pharmacy community on its website, 

The clock is ticking on a massive effort to bring interoperable, electronic tracking of pharma shipments in the US

Countdown to 2023 DSCSA Compliance

Requirements and implementation activities stemming from a phased rollout of the Drug Supply Chain Security Act (DSCSA) will be coming to a close on Nov. 27, 2023, barring a last-minute reprieve from FDA. At times, it has seemed as if the final phase of the DSCSA may never come to fruition, given the interim milestone timeline delays and a decade-long runway. But now, the finish line is finally in view, with less than 18 months until the DSCSA legislation’s goal of having complete traceability of the US pharma market.

Recently, there has been an increasing focus on this hot topic, highlighting the importance of DSCSA and the significant confusion still present in the market. Many manufacturers cite the lack of clarity, formal education, and official resources as the key drivers for not having a serialization solution in place today. This may also be why the upcoming DSCSA timelines create such confusion and frenzy. Whether companies were hoping to see additional timeline delays from FDA or simply lost track of time during the pandemic-induced void of 2020–2021, the time to act is now for companies without a full serialization solution in place.

DSCSA stipulates that by November 2023, the US will have an electronic, interoperable system that will monitor the movement of prescription drugs from manufacturing to dispensation.

There’s still time to implement solutions before November 2023, but not much. How much time is needed depends on what strides have already been taken toward preparation. When considering the breadth of manufacturers impacted by the DSCSA requirements and the limited resources available to implement such software connectivity, what time is left is precious. As heightened awareness cascades throughout the market, the backlog of manufacturers waiting to implement with distributor partners and third-party logistics (3PL) solution providers continues to grow. This backlog is not likely to diminish between now and November 2023.

According to the distributor serialization teams engaged with for this article, if a product isn’t yet aggregated, the “oh no!” moment is here. For manufacturers with inventory that is aggregated and serialized but who haven’t yet launched a total serialization solution with their trading partners, there is agreement that they should aim to begin implementation activities no later than this summer.

Some manufacturers question if the sense of urgency to aggregate inventory and implement end-to-end serialization programs is real—or if, instead, the haste is fabricated by trading partners for their own benefit. Manufacturers need to understand that the deadline and urgency are real. Companies’ aversion to risk may soon be a contributing factor to action over inaction.

A recommended checklist for manufacturers as they enlist distributor and 3PL support—and the important questions they should be asking themselves  

Pharmaceutical Commerce - June 2022

Pharmaceutical Commerce - June 2022 Issue (PDF)

Food for Thought from France

The Impact of War on Drug Supply Chain

Controlling Diabetes: Advances & Adherence

The Promise of Industry 4.0

From Point-in-time to Real-time

Dealing with Dangerous Goods

Countdown to 2023 DSCSA Compliance

The Key Steps Ahead of DSCSA D-Day

New Serialization Mandates Inch Closer

Closing a Key Gap in DSCSA Compliance

Navigating Uneven Terrain in Labeling

Positioning the Patient in Drug Trials

What Makes Hub Programs Successful?

Setting Science Free