Market Trends in Focus

Connectivity, Sustainability & Large Volume Drug Delivery

Guillaume Lehée, R&D Innovation Leader, BD said several drug formulations and technologies such as RNA vaccines and cell and gene therapies may require storage to very low negative temperatures such as -20 to -196 C.

He said that while the compatibility of vial containers with frozen storage conditions has quite a long and significant history, in contrast, PFS compatibility has been quite poorly documented, with the main example of a glass PFS approved for cold storage being Medimmune’s Fluenz Tetra Nasal flu vaccine with a 20-week shelf life at -25 C.

He said that testing done by BD had shown that glass PFS did not present any risk regarding ensuring key product functions and sub-visible particles performance and maintaining container closure integrity during the thermal cycle when stored one week at -20 C and even down to -40 C.

Large Volume Biologics

Healthcare systems around the world are coming under increasing pressure due to a perfect storm of contributory factors; chronic conditions such as heart disease and diabetes are unfortunately on the rise, patient populations are aging, and the coronavirus pandemic continues to take up the lion’s share of hospital beds.

Self-administration of drugs outside traditional healthcare settings is going a long way to alleviating this stressful combination of events but it is well known that the most simple and convenient route, oral administration, is not suitable for all therapies. Biologics often require subcutaneous delivery; hence the reason why subcutaneous injection is becoming ever more popular as a route of administration for drug delivery.

The use of speciality biologics – high-cost, high-complexity treatments for chronic conditions – is being driven by three main therapy areas: oncology, immunology and antidiabetics.

As Pascale Gauthier, Pharmacist, Faculty of Pharmacy Clermont-Ferrand, Auvergne University says, biologics are specific products sometimes involving very precise manufacturing processes where all steps should be controlled carefully:

“Therefore, all companies in this sector should correctly implement all the stages of the procedures, checking the main points correlated to the products; temperatures, sterility, and conservation.”

The main issue around the administration of biologics remains; speciality biologics often need infusion, or an injectable mode of administration as opposed to traditional oral therapies so to take them into the home setting so that patients and carers can self-administer to help manage their own condition throws up a whole new set of challenges.

Innovation on display at Pharmapack Europe 2021

Standard prefilled syringes and safety devices have been designed to a 1 mL fill volume and typically house therapies with a viscosity of less than 10 cP. These devices are not appropriate for many of the new biologics on the market which tend to be ‘stickier’ i.e. higher in viscosity and therefore requiring dilution and consequently, delivery in higher volumes.

Moving to a higher-viscosity, higher-volume injection (e.g. 5 mL) thus requires an increase in the flow rate in order to maintain the injection time, particularly as needle length and diameter will not usually change due to the need to not adversely impact patient comfort. This results in the need for a much higher injection force.

Sarah Williams, Strategic Programme Manager - Advanced Vaccines Formulation Capability, Centre for Process Innovation (CPI) says the biologics market is continuing to grow, resulting in an increasing number of approved products that are often viscous, concentrated, and complex, requiring higher injection volumes than many of the current products on the market and highlighting the need for drug delivery devices that can handle higher volume and viscosity.

“Lyophilised biotherapeutics also require reconstitution before delivery, calling for systems that make this more convenient for the end-user,” she adds.

With many biologics needing to be administered intravenously by a healthcare professional, which conflicts with the increasing trend towards self-administration and home care, developers are keen to

resolve this particular challenge, while also optimising the patient experience and improving adherence.

Dr. Gauthier says that as IV administration involves nurses or doctors, systems should be correctly designed for both being safe and time-saving, and ready to use ‘all-in-ones’ can simplify administration with the aim of guaranteeing the best use of biologics.

“As self-administration is not possible for IV at any time, systems should avoid or limit the pain for the patient,” she says. “For example, the needles should be as fine as possible and can be hidden in the system. The material should be compatible with the chemical specificities of active substances (or particularity of biologics). Reconstitution or viscosity of the product can also be a key factor for creating or adapting injectable forms."

Ready-to-administer-systems

Ready-to-administer-systems such as pre-fillable syringes can provide benefits to numerous stakeholders, says Sagar Bejalwar, Senior Manager, Global Acute and Specialty Portfolio Marketing at BD Medical - Pharmaceutical Systems.

“There are quite a few benefits that have been documented: the primary benefits are a reduction in medication errors, the reduced risk of contamination, as well as nurse time saving and a reduction in wastage,” he says.

He pinpoints savings in labour time and accurate dosing as critical factors, given that the coronavirus pandemic has reinforced the need for healthcare systems – particularly critical care -- to be much more efficient.

“Ready-to-administer systems do play a part in bringing about that efficiency at least on the point of care,” Bejalwar says, adding that they have the most impact in systems of critical care, which are relatively fast-paced and where there is very little room for error during the medication process.

He says around 70% of injectable biologic chronic treatments of 50mL or less are already available and packaged in ready-to-administer formats, with around 50% of vaccines available in this format. This compares to a ready-to-administer penetration of just 2% for acute liquid injectable small molecule drugs, he adds.

As well as the efficiency and time-saving benefits to hospital administrators, Bejalwar says prefilled syringes also present benefits to pharmaceutical players.

“Pharma companies having a generic drug launched in a ready-to-administer system or a prefilled syringe does provide a competitive edge and an opportunity to differentiate in the market that may be dominated by vials and ampoules. The only disadvantage is that the cost of a drug-pre-fillable device combination is much higher than that of a drug in a vial or ampoule.”

Bejalwar says BD had recently launched its BD Hylok glass pre-fillable syringe for intravenous drugs primarily in response to malfunction issues with certain types of pin-activated needleless access devices which essentially led to breakage of the tip of the syringes and ultimately disruption to workflows.

“This really did highlight the aspect of incompatibility of pre-fillable syringes with certain designs of needleless access devices and this was specifically highlighted in emergency care settings,” he says.

Innovation on display at Pharmapack Europe 2021

Bejalwar says that BD’s objective is to position BD Hylok as a solution that meets market needs: “Many pharma companies conduct steam sterilization prior to launching their drug-device combination, and therefore we’ve tested BD Hylok for steam sterilization with water-for-injection to ensure that the pharma companies have that data at hand and are sufficiently equipped to conduct their respective testing processes.”

Needle-free injections

While innovation in injectables technology is focusing on solving the drug delivery administration challenges of large volume biologics, Dr Williams points out that the current pandemic has highlighted the significant need to change the landscape for vaccine technologies, accelerating the accessibility of needle-free vaccines.

“The ability to vaccinate large numbers of people quickly and easily has never been more important, and the global demand has highlighted the requirement for simplified distribution chains,” she says. “Most vaccines are administered via needle and syringe, which poses many challenges such as the need for qualified personnel, needle stick injuries and significant amounts of hazardous waste.”

She says that developing room-temperature stable formulations, which can be reliably and robustly scaled up to produce a consistent product, is essential to enable alternative forms of administration for vaccines.

The benefits of solving the challenge are obvious; the complexity of deployment and distribution currently found with vaccines requiring cold transport and storage can be greatly reduced, she says.

“Reducing needles may also improve the patient experience, increasing uptake of vaccines, therefore, having a positive global impact on preventing avoidable mortality,” she adds. “By developing needle-free room stable vaccines administered via oral, transdermal, or nasal routes, there is an opportunity to increase the speed, availability, and deployment of vaccines, reaching out further to those in need.”

Dr. Williams explains that to solve the need to accelerate needle-free vaccines to market, a partnership between CPI and the Vaccines Manufacturing and Innovation Centre is being developed to provide a foundational capability, with expertise, equipment, and a framework to support a wide range of industry and academic groups involved in the development of needle-free vaccines.

“An Advanced Vaccine Formulation Capability (AVFC) is proposed, building on existing networks to provide a single point of entry to access innovation, development and flexible GMP manufacturing facilities in the UK, which are required for the establishment and supply of such vaccines,” she says.

Pharmapack 2021 Conference Highlights

Pre-filled syringe technology could provide answers to future mass vaccination challenges, says BD

Pre-filled syringes (PFS) could help immensely in solving the challenges of rolling out future mass vaccination campaigns, according to experts at Becton Dickinson (BD).

Speaking at the Pharmapack Europe 2021 online conference in the session Responding to the Vaccine Delivery Challenges, Marie-Liesse Le Corfec, Global Portfolio Marketing Head, BD said that depending on the specificities of vaccines and their intended use situations, PFS technology could increase the efficiency of workflow, increase dose-sparing capabilities compared to vials and have potential to limit random waste volume.

“It’s important that all stakeholders understand the benefits in terms of patient safety of PFS but also efficiency,” she said.

Quoting a 2010 study in the Expert Review of Vaccines, she said that it was calculated on the occasion of the last flu pandemic that the use of PFS to vaccinate 300 million people in the US could save over 3 million hours in healthcare worker time.

“The corresponding savings could contribute to making the decision of using PFS instead of multidose vials and disposable syringes cost-neutral,” she added.

In terms of addressing current mass vaccination delivery challenges, Ms Le Corfec said it made more sense to use existing vaccine distribution and administration infrastructures instead of creating new systems from scratch.

“We’ve witnessed that whenever the regular healthcare providers, the regular channels that are used to vaccinate against flu such as nursing homes and employers, were used, things were much smoother in the supply chain,” she explained.

She said another practical recommendation for government and authorities’ taskforces, was to ensure that experts with knowledge of all aspects of planning relative to pandemic response such as pharmacists and supply chain specialists are added to those teams.

“In the real-life clinical environment, before the purchase of massive amounts and release for use in vaccine administration, there were cases when sometimes we were asked for needles that clearly were not the appropriate length for those types of vaccines,” she said. “Having the right experts and practical testing of the disposable syringes that are used in such campaigns is what we really recommend for the future of this vaccination campaign and for future mass vaccination programmes.”

Sustainable Packaging

As the issue of how the world tackles the ever more serious problem of climate change rises to global prominence, more and more companies within the pharmaceutical sector are prioritizing fitting eco-friendliness and sustainability into their manufacturing and distribution processes.

In recognition of this developing trend, Pharmapack Europe launched the inaugural Eco-Design Award for the 2019 edition in Paris, in partnership with Adelphe under the Health Product Category, giving packagers the opportunity to showcase innovative packaging solutions that have made significant contributions in terms of reducing waste and increasing potential recyclability.

Traditionally, much of the scrutiny in this area has fallen on consumer and retail industries since packaging of items such as food and cosmetics has drawn much criticism for single-use plastic and often over-elaborate, excessive design. In contrast, pharmaceutical packagers have not drawn the ire of activists for several good reasons. First of all, the value of medicines dwarfs their packaging and logistics costs, unlike many consumer goods.

Also, the highly regulated sector needs to ensure that its packaging protects and preserves these vital products to ensure efficacy and safety.

“Pressure on the fossil fuel industry as a whole is creating a ripple effect that affects the entire packaging ecosystem.”

Peylina Chu, Vice President, Antea Group and Executive Director, Healthcare Plastics Recycling Council

And last but not least, as a good proportion of pharmaceutical packaging resides behind the counter, it is usually manufactured via a no-frills, pragmatic and cost-effective approach seeing as the end-user – the patient – is not choosing the product because they’ve been drawn in by attractive packaging.

Nonetheless, the volume dial is turning higher for more sustainable pharmaceutical packaging and one of the key drivers is the large volume payers for pharma products, such as drug retailers and hospitals, who are challenging suppliers more and more to demonstrate they are taking sustainability seriously.

Peylina Chu, Vice President, Antea Group and Executive Director, Healthcare Plastics Recycling Council, says procurement departments are definitely raising the bar on sustainability performance, with

stages “can give the best data points that can be synthesised with others as we look at a larger ecosystem of providers and payers to build that foundation around what the best device-type modality may be.”

Nathalie Wardé-Dunoyer, CEO & Founder, D4P pharma said one common problem within healthcare settings for stakeholders such as pharmacists, caregivers or hospitals is that there is no interoperability of the systems: “Everybody is still working in silos; that may be interesting for the information system (IS) providers but for the customers, it is a nightmare because they have to deal with several information systems, it wastes time and introduces the risk of errors.”

She added that the use of standards is key in order to reduce not the amount of IS but to reduce the complexity and allow different systems to talk to each other.

Lionel Jeannin, Group Head Oral Packaging & Delivery Systems, Novartis Pharma AG said that with regard to providing better-quality product information to patients, legacy paper-based product information leaflets are often written in very small fonts, different languages and even folded in a strange way: “It’s not something we could call user-friendly and defeats the purpose of properly informing patients. We should be able to do better.”

Pharmapack 2021 Conference Highlights

Increasing connectivity is the key to patient centricity and simplified access to product information.

During the Innovation in Connectivity Roundtable, experts discussed how digital innovation is shaping industry ambitions to put the patient journey at the heart of drug-device and delivery solutions by simplifying product information via increased connectivity.

Mark Tunkel, Global Category Director for Insight Innovation at Nemera said the primary method his company used was applied ethnography, which he defined as “being in that environment of use through a combination of interviews and observations.”

“We’re looking at these things broadly: the ability to go through the process of using a device successfully but extending that and thinking about all the stuff from when a patient might be diagnosed to receiving their device and again that entire process of preparing, administering and disposing of it,” he said.

He added that an understanding of how “moment-based interactions” might change over time as people go through the process of on-boarding into a new device or going through life

Lise Wagner, Accessibility Specialist and User Expert, OKEENEA said the main issue for blind patients was the huge amount of information on medicines: “When you read by listening to a speech synthesizer you have no idea of the structure of the text and on the amount of information there is. It can take you anywhere between five and 45 minutes to read. It’s very important to give a structure to information with headings. I don’t need to know exactly everything there is in the leaflet but I want to know what I need to know: the effects of the medicines, the possible side effects and in what situation I can take the medicine. I want to know very precise information and if this is lost in a huge amount of topics, it is really difficult.”

She added that it was a huge challenge to standardise the structure of the information and make it understandable with a speech synthesizer or other assisted technologies.

Laurent Tonnelier, CEO, mobiLead – xTag told the webinar that digital technology could be used to tailor product information to language, age, region and even usage.

“This is a way in which the European initiative for electronic product information aims to go, saying that it could be complementary having both paper and digital,” he said. “But to my mind, paper will eventually disappear: we are taking about the information on the box, paper and maybe even the medicine itself, but when you have that digital link, tailored information really helps.”

expectations that companies incorporate more recycled content in packaging materials and eliminate toxic chemicals in products and packaging materials. She cites Vizient, a group purchasing organization (GPO) serving more than half the health care organizations in the US, as a prime example.

“In May 2021, Vizient announced that it would begin implementing environmentally preferred language into virtually all of its medical/surgical contracts to encourage suppliers to eliminate chemicals of concern and reduce waste,” she says.

“Vizient’s Environmentally Preferred Sourcing (EPS) Program, launched in 2017, has 23 sustainability attributes that reduce harmful environmental and human health impacts. Today, the EPS Program has more than 450,000 listed products that meet one or more of the sustainability attributes.”

She adds that while retailers, hospitals, and other supply chain partners play a big part in the push to improve the sustainability of pharmaceutical packaging, it’s important to recognize that pressure is also coming from investors, employees, and the public: “In particular, pressure on the fossil fuel industry as a whole is creating a ripple effect that affects the entire packaging ecosystem.”

Dr. Gauthier says sustainability has emerged as a key element that appears at all levels of pharmaceutical packaging and design: “Materials should present the highest level of recyclability or be

fully sustainable and design is adapted for keeping the highest degree of adaptation (by sometimes decreasing the number of pieces for manufacturing).

“At best, processes should limit energy consumption and design materials must offer a recyclability process that limits energy consumption as much as possible.”

She says, however, that biologics with chemical specificities or stability challenges can be more difficult to adapt.

Greg Anderson, Managing Director at Pharmacentric Solutions says that while awareness of sustainability was starting to build in the pharma sector, much of the momentum has been temporarily lost due to the current COVID-19 pandemic.

“During COVID, essentially anyone who's making medicines has just had to focus on making medicines, because they've obviously lost staff and their supply chains have been challenged,” he says.

“It’s currently all about supply - the problem is that a lot more vials and syringes have been produced, millions of diagnostic testing kits are being thrown away at the moment. Unfortunately, the amount of material that's been incinerated has gone through the roof and then there is all the PPE on top of that.”

However, he adds that with western nations supposedly now turning the corner with regard to managing the pandemic, sustainability is likely to get back on the agenda, not least because of the upcoming COP26 climate change summit in Glasgow later this year.

One major challenge for pharma packaging in terms of sustainability is the disposal of contaminated waste. Is the industry coming up with any solutions to this other than incinerating it or sending it to landfill?

Pharmapack Europe 2021, Paris

Ms Chu makes the point that the value of recycled plastic has steadily increased over the last couple of years due to public pressures on plastic waste and corresponding commitments from big brands to incorporate recycled materials in their products and packaging.

She says that starting with the 2017 China National Sword ban on contaminated waste and accelerating during the pandemic, the recycling industry is responding with more creative ways to manage contaminated waste streams.

“Traditional mechanical recycling technologies are not well-suited for a mixed plastics waste stream or multiple materials within a single packaging material (e.g., polyethylene + nylon + foil); these materials are usually sent to landfills or waste-to-energy facilities,” she says. “However, the emerging advanced recycling technologies are better equipped to process multi-material packaging waste and extract plastic components.”

She says the Healthcare Plastics Recycling Council has been evaluating several advanced recycling technologies over the past year, including an industry survey assessing the suitability of medical plastics as a feedstock for different advanced recycling technologies. HPRC is currently working with several advanced recycling companies to test different types of medical packaging materials for technical and economic feasibility as a feedstock, the results of which are due to be published in Q1 2022.

“While advanced recycling is not a ‘silver bullet,’ it does provide a new tool in the sustainability toolkit to capture valuable plastics in a mixed medical packaging waste stream,” she adds.

Dr. Nazneen Rahman, Director at the Sustainable Medicines Partnership says that in part, one barrier to packaging innovation in the pharma industry is that the disposal of pharmaceutical products and therefore the packaging around them, are subject to legislation. She says that in the UK, for example, this can include The Controlled Waste Regulations 2012; The Hazardous Waste Regulations 2005; and The Environment Protection Act, 1990 (including duty of care regulations).

“These legislations are in place to protect people and the planet from pharmaceutical toxins; therefore changes to the disposal of pharmaceutical waste, should consider the broader implications,” she says.

She adds that the industry is exploring new waste disposal methods, and where appropriate, e.g. advanced (chemical) recycling that enables closed-loop recycling (blisters back to blisters) and/or employing more environmentally-friendly incineration processes.

“It is essential that the industry engages in articulating the trade-offs of different solutions and has a more holistic approach based on end-to-end considerations,” she says. “Packaging being recyclable does not necessarily mean it is recycled and may have knock-on negatives in terms of

performance, shelf life, or re-certification costs. The pharmaceutical sector should invest in, develop and adopt processes to reduce medicines waste prior to disposal, which will ultimately contribute towards reducing the overall volumes of pharmaceutical waste that end up going to incineration, landfill or other.”

So how should small- to medium-sized pharma packaging companies go about devising a strategy on sustainability?

Anderson recommends that companies at the smaller end of the scale hire an external expert to come in and do an audit and essentially, create a green guide: “It stops you essentially being embarrassed and means when your customer comes to you and asks you what you’re doing about sustainability, you've actually got a document in place and an actionable (and measurable) plan.”

He says that a solid sustainability plan can be divided into three main parts, the first of which is a review of structural operations to identify the ‘quick wins’: “Have you bought the most fuel-efficient machines? Have you stopped using disposable cutlery in your canteen? Have you installed solar panels?

Anderson believes companies should then examine how they are handling their waste: “What are you doing about waste in your manufacturing capability and do you monitor it? Are you looking to reduce it?”

He adds that the third and final part concerns the actual products, including their manufacturing and design processes: “Are you using the right materials while using the right process? Have you done an audit on everything including all your stock-keeping units (SKUs)?

Dividends can be realised by taking such an approach, Anderson argues: “if you get a CO2 saving by saving energy and materials, by default you get a financial saving.” He says that in the past, many companies were losing out by not claiming CO2 savings from cost reduction exercises.

When packaging companies decide to take firm action on sustainability, Ms Chu says the greatest risk for them is expending too much effort and not making a real impact.

“To avoid this problem, companies need to identify which areas – also known as ‘material topics’ – are critical to their business and important to their stakeholders, both internally and externally,” she says.

She adds that transparency and stakeholder engagement should be key pillars of any company’s sustainability strategy: “Stakeholder engagement

is a two-way process – companies transparently communicate strategies, goals, progress, and impacts; stakeholders provide valuable feedback, which companies incorporate into materiality assessments and corresponding strategies. It is a virtuous circle that drives improvement and accountability.”

Despite the progress that has undoubtedly been made thus far, Anderson warns that there is still much room for improvement when it comes to the packaging sector incorporating sustainability into its business practices and communicating the benefits of such initiatives to a wider audience.

“No single pharma company is going to solve problems like recycling so there's definitely more of an opportunity for the industry to work together to try and standardize more around the materials that it uses,” he argues. “We also have to invest in some of the challenges around contamination, biological and medicinal.”

He says that while many companies are making commendable individual achievements, “there's a bigger prize if we all work together and also work more with our suppliers on recycling; don't forget pharma companies don't actually make any packaging materials or devices, they just specify them and put the drugs in them.”

Anderson feels the “last piece of the puzzle” is successful incentivisation of the public to return used or unused materials such as inhalers and EpiPens via product recycling schemes.

“I don't think it's up to the pharma companies alone because the products have already been purchased at that point,” he explains. “It's more up to the healthcare providers, along with advice, assistance and partnership with the people who specify the materials; if you can get all of those things aligned, I do think that there's a huge opportunity, but it's not down to one company. It has to be an industry that does this and we have to look at it globally.”

Dr. Gauthier says the pharma packaging industry certainly needs to do more to communicate its commitment to social and environmental issues. She says numerous clever systems or breakthrough innovative packs still remain largely unknown by the wider public.

“All too often, users see packaging as a polluting element; a better knowledge of how useful packaging can be and how sustainability is studied by health industries is fundamental,” she says.

She adds that much has been done to improve the sustainability of materials and manufacturing processes.

“What is important now is to improve communication on how packaging is

conceived in the interest of the patient and the product,” she says.

Dr. Rahman says she believes the pharmaceutical packaging industry lags behind other industries, such as FCGM for example, in articulating its commitment to social and environmental issues: “However, awareness is increasing as is the drive to improve communication and engagement across the pharmaceutical packaging supply chain.”

She adds that some companies are embedding sustainability CSR into their annual reports, which are publicly available.
“These showcase the targets and work undertaken by sustainability leaders in the sector,” she says. “It should be standard for all companies to report on sustainability commitments and achievements, annually.”

Listen to our podcast on sustainability from Polymeris

Developing a Sustainability Strategy:
Where to Start?

Peylina Chu, Executive Director of the Healthcare Plastics Recycling Council recommends the following seven-step process to pharma packaging who may be unsure where to begin when devising a sustainability strategy:

Conduct a Materiality Assessment, a formal process to capture and map information so companies can identify areas to prioritize for their sustainability strategy. – Hone in on key sustainability issues, and opportunities, that are most likely to affect business operations and stakeholders.
Assess Current State (Baseline) – Work with cross-functional stakeholders to identify existing programs, policies, metrics, and other systems already in place for material topics.
Set Objectives and Goals (Future State) – Identify areas where efforts just need to be maintained or communicated, where improvement is needed, and where your company can take a leadership position – and use this information to set objectives and goals.
Analyse Gaps to Achieving Future State – Identify the gaps between Baseline and Future State to set the foundation for your sustainability strategy.
Develop a Strategic Roadmap and Framework – Identify key actions and milestones to develop the roadmap, build a framework to communicate expectations to key stakeholders, and gain agreement on accountabilities.
Set Action Plans and Measure Key Performance Indicators – Work with key stakeholders to develop and integrate sustainability action plans and KPIs into business practices and processes.
Report Progress – Use multiple communication channels to share strategy, goals, and progress with your stakeholders.

It is best practice to refresh the materiality assessment regularly to accommodate changes in the industry.

Pharmapack 2021 Conference Highlights

Barriers to healthcare adoption of growing sustainable packaging trend still exist, say experts

The panel discussed how healthcare institutions are adapting to calls for more sustainability in various processes in the value chain.

While the sustainability of pharmaceutical packaging is growing in prominence, barriers to effectively implementing materials recycling processes across the value chain remain, according to experts speaking at the online Pharmapack 2021 conference.

During the live Sustainability in Packaging Roundtable, chaired by Yasemin Karanis, Consultant, Thought Leadership, IQVIA, the experts discussed how healthcare institutions are adapting to calls for more sustainability in various processes in the value chain.

Andrew Green, Market Development Manager, Rigid Medical Packaging, Eastman said one of the main key barriers regarding the improvement of recycling and waste management was the difficulty in creating space for the activity to occur within healthcare institutions.

“Rightly so, there is an emphasis on patient health and ensuring that

you put that first and it can feel perhaps immoral or improper to prioritise waste management over spending time and effort to ensure that you’re doing the best for the patients,” he said. “But it can’t be forgotten that there’s a connection between environmental health and human health generally. The key element is how do you create space for that both physically in the hospital facility but also within how you allocate the time of the hospital staff i.e., who’s going to be responsible for sorting out materials and see if they can be sorted out for recycling and how can you make that process easier so that there’s not a cost to the quality of your patient care?”

Steven Meun, Executive Director, Healthcare Plastics Recycling Council said he believed hospitals were facing challenges in engaging with waste processes: “In many cases they see the plastic waste generated at hospitals as potentially contaminated and they don’t want to take the risk even if the hospital staff is really capable of segregating contaminated and non-contaminated waste.”

Jean-Jacques Legat, Projects and Innovation Director, Polymeris said that in contrast to product users in markets of other industries, “maybe there is a reluctance on the part of patients to be ready to use products which contain recycled materials such as alternative polymers.”

He said that adding traceability to materials used in packaging was a challenge:

“We have to be sure, depending on the defined sources of the material, on the percentage of the material to be used in the new product with the same properties of the aging material. That means we have to work on the specifications of the material to ensure we have the same properties of the aging one.”

Romane Osadnick, Key Account Manager, Adelphe said one major hurdle for pharma laboratories who are in essence international companies is that have to find solutions that satisfy all the regional markets they send their products to.

“Recyclability means packaging compatible with the sorting and recycling system in the country the package will be managed for the end-of-life,” she said. “The difference between household packaging and professional hospital and medical packaging is that for household packaging, at least in France, we separate the unused medicines from the packaging. Household packaging for medicines has to be collected in the collection bin when it is empty, without any unused medicines and without any sanitary issues.”

She added that a decision to eco-design packaging invariably involves a change in concept, elements and materials of packaging, which would undoubtedly have a knock-on effect on the Marketing Authorisation.

“Companies working on eco-designing pharma packaging need to have this point in mind and work with regulatory agencies or partner organisations to make sure it is included in the global approach,” she said.

Connected Devices and Smart Packaging

Connected smart devices have transformed everyday life in many ways over the last few years. This is particularly evident in the consumer space, where on top of the ‘must-have’ smartphones, computers and wearables, there are now also solutions for recharging, home lighting, managing appliances and energy saving.

However, when it comes to connected drug delivery, the ecosystem is undoubtedly much more complex, not least because it operates under the spotlight of increased regulatory scrutiny. Also, healthcare systems around the world can differ greatly, in terms of clinical practice, pricing and competition and can also be subject to sudden changes brought on by new governmental policy or funding.

Taking all this into account, it is nevertheless an extremely exciting time for product innovators in the drug delivery sector. Digital technology has to all intents and purposes been a real game changer and companies working in this space are finely balancing the opportunity that harnessing the power of this technology can present with the pressing challenge of addressing unmet needs such as patient adherence and compliance.

Connected devices such as smart inhalers, auto-injectors and closed-loop solutions offer tremendous opportunities to improve patient adherence and reduce the risk of dosage errors when delivering drugs, particularly as they can be used in the home setting.

“The digital era is a reality with computers and smartphones fully integrated into everyday life for all products including healthcare products,” says Dr. Gauthier. “Now, we have arrived at the second generation of products that offer great adaptation without enslaving people to machines too much.”

She says connected device developers need to focus on creating devices that can be used easily and intuitively, while design should never lose sight of the device’s primary purpose, while balancing this with addressing safety, improving compliance, offering therapeutic education, and providing useful knowledge on the treatment or disease.

One important current trend in the drug delivery space is interoperability – the ability of devices to not only capture data but also make effective use of it by processing and analysing it to improve outcomes.

The technology to connect healthcare devices and applications and transmit and receive data exists but so far, the focus has been mainly on collecting information. The crucial thing going forward is how devices are integrated into complex health systems and whether the next step of the

connected device revolution is achieved: making optimal use of the data that is gathered from an analytical perspective.

With this in mind, what kind of developments and innovations are we likely to see in connected devices over the coming years that address interoperability?

Dr. Gauthier says interoperability is a key element for a device to be easily used by all systems whatever the country or technology, otherwise they are likely to fail: “One example can be seen with apps that offered a huge number of benefits only ever being used once or for a short time and in the end, not really integrated and accepted.”

Dr. Williams is of the view that for connected devices, we do not just need to consider interoperability but also simplicity of use:

“Requiring patients/users to connect their device to Wi-Fi or Bluetooth will instantly marginalise some of the population which either may not have the required infrastructure or may not be digitally savvy enough to perform the task.”

She says that ideally, devices that will seamlessly connect to wireless infrastructure, for example through mobile phone networks including LTE-M and NB-IOT or through low powered wireless networks such as LPWAN are desired.

“This wireless infrastructure is growing and enables designers to have low powered IoT enabled/connected devices whilst making connectivity simpler for patients,” she says. “Also, these wireless connectivity protocols are low power, requiring the patient or user to charge their devices less frequently.”

In terms of smart pharmaceutical packaging, more and more solutions are now hitting the market in an increasingly competitive market, although the jury is out on how far they go to fully address the more pressing issues they have been designed to solve.

Dr. Williams says there are many technologies available in the smart packaging toolkit including adherence packs (that will measure and report when a pill is removed) as well as unique identification technologies (UID) such as RFID and NFC: “Use of these technologies is still generally rather niche even though they have significant potential to improve patient adherence and enhance supply chain security respectively.”

Daniele Giorgi, Head of Global Indirect Procurement, Ferring Pharmaceuticals, says that despite enormous progress within the development of smart packaging solutions, the products out on the market are “not yet fully satisfying the patient needs when it comes to adherence to the therapy.”

He says that adherence rates to therapies can sometimes drop by 40% after the initial period of therapy, with reminders to take daily pills not being followed up for several reasons, ranging from a lack of discipline to a perceived lack of freedom and choice in being told when to administer medication.

The adverse effects of such events are well-known; not only is the patient’s condition not improving due to the compromised course of treatment but money is being wasted all along the supply chain.
Giorgi says that one of the biggest challenges to solve is creating a smart packaging solution that can accurately measure whether a drug has been taken or not, in the same way that a digital pill can. Digital or ‘smart’ pills contain ingestible sensors that can start transmitting medical data after they are consumed.

“Smart packaging can nudge you towards taking a pill by making the connection between you and the box a little bit stronger, so you feel the need to go back to that packaging,” he says. “As of now, I have not seen that famous ‘wow’ factor in packaging which really makes you go back to that packaging and take the pill.”

He says that while the eventual solutions should remain within the remit of digital developers, he suggests that packaging digitally connected to apps on mobile phones may provide the best opportunities for improvement for adherence through gamification and incentivisation.

“If we always stick to this reminder alarm concept, it is alarming by definition,” Giorgi adds. “The smart packaging solution has to be not necessarily only playful, but also something which is tailored to that specific person. I would like to see packaging, which is modern, sustainable, and which is – whether it’s linked to a mobile phone or a smartwatch, it doesn't matter - engaging with you to make you take the medication.”

One area where smart packaging is gaining traction is in supply chain and logistics, says Dr. Williams: “Dataloggers have been used for many years to provide information on location as well as monitor the environment of shipments. Historically this was often simply historical data, that is, the data logger would be interrogated at the end of the journey to understand what conditions the products had been exposed to.”

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She says that this information could be used to verify that the product had been under the correct conditions through its transport but did not enable any timely interventions to be made.

“Technology is advancing, and pharma is working closely with solution providers and supply chain partners to provide real-time logging and environmental monitoring information,” she adds. “This is enabling informed decision making to be made, rapidly enhancing supply chain efficiency and reducing wastage. However, the current direction of travel for the pharma industry is towards single data loggers per pallet or case.”

Dr. Williams says that driven by regulations such as the EU Falsified Medicines Directive, pharma has invested heavily in authentication features with a datamatrix symbol chosen as the digital authentication method in many jurisdictions including Europe.

This symbol is unique at an item level which means that every pack of medicines sold in Europe now has a unique identity and pharmaceutical companies are investigating how to gain more value from this and the investment they have already made.

“The opportunities are significant, from item level tracking (through aggregation with dataloggers) through to enabling patients to connect to cloud-based systems which could support adherence,” says Dr Williams, noting that one project to note is the Pharmaledger project in which a number of large pharma companies are working with solution providers to

harness the power of blockchain and the datamatrix symbols to enhance supply chain security and efficiency.

“If we are designing smart packaging then we need to consider the value, ideally right across the supply chain from pharma to the patient,” says Dr Williams. “Full system-based approaches are needed as quantification of value is key.”

Symbioze, by Nemera