Big pharma companies who have traditionally focused on chemically developed medicines are investing in biological innovations to have prime mover advantage in a market forecast to be worth $261 billion by 2022. Pfizer, Novartis, Roche and Merck are now the top players, each seeing sales of between $35-45 billion in 2016 alone.
As part of a wider movement to lower the cost of drugs in the U.S., the FDA recently published an action plan on biosimilars, a cheaper yet highly effective alternative to already registered biological drugs. The main aim is to increase access to biosimilars and ensure patients are the primary beneficiaries of this virtuous cycle of drug innovation and competition.
However, packaging is often overlooked in macro-level conversations about the future of biologics and biosimilars, despite it playing an important role in providing patients with safe, effective and more affordable medicine. The fact that the FDA’s action plan fails to mention the word ‘packaging’ even once is a case in point.
The frontier of drug innovation is constantly evolving and so must the design of packaging and delivery systems. However, there are several key challenges the pharma and packaging sector need to overcome in the process or we risk halting progress on these groundbreaking new treatments, ultimately putting health outcomes at risk.
Protecting against degradation
Biologic and biosimilar drugs are a class of medication which aren’t synthesized chemically. Instead, they’re harvested directly from biology as their name suggests, making them very different from traditional small-molecule medicines.
Essentially, biologics and biosimilars are “nano-machines” whose functionality depends on their molecular shape and delicate structure. This has large implications for the design and manufacture of both primary and secondary packaging.
Minimizing exposure to environmental factors that can affect the integrity and efficacy of a product is a top priority for the industry. Even slight changes in temperature or orientation during transportation, storage and usage can affect these sensitive proteins.
With each passing year, the role of the cold chain is becoming more important, keeping sensitive medicines within a designated temperature range as they move through the supply chain. As a result, it’s estimated pharma cold-chain logistics will be worth $16.7 billion by 2020.
Here, effective packaging systems that offer both thermal and refrigerant capabilities are essential to avoiding shipping failure and loss of critical material. A biologic product being shipped domestically in less than 48 hours will need different packaging solutions compared to a product being sent to Europe or Asia, which may need to be kept at a certain temperature range for at least five or 10 days.
Leachables also pose a toxicological and stability concern for biological drugs. An accumulation of leachables often found in metal, glass, plastics and rubber used in packaging can have a profound impact on biological proteins, altering their physico-chemical properties. This contamination has the potential to cause acute toxicity or long-term health issues through chronic exposure.
As such, continued reliance on polyethylenes, polypropylenes and polycarbonates in pharma packaging will mean stakeholders will fail to meet the future efficacy requirements for safe and effective biologic products.
Fluoropolymers are increasingly being used by product design engineers to form a resistant barrier to eliminate contamination. Being chemically inert, fluoropolymers are free of stabilizing additives, so even over time or under intense environmental pressures, medicines remain stable.
As a less brittle, lighter and more flexible alternative to glass, cyclic olefin plastics are also growing in popularity because, like fluoropolymers, they’re intrinsically very inert, composed of just carbon and hydrogen. Almost all are very rigid thermoplastics which can be injection-molded or extruded to produce a wide-range of packaging items.
Re-thinking delivery systems
Biologics are typically made up of much larger molecules than those found in conventional pharmaceuticals. That’s why most biological proteins are formulated as a liquid and delivered via injection rather than tablets.
As patients take a more active role in their own healthcare and the administration of injectable medicines is shifting from health professionals to caregivers and individual patients, prefilled syringes are becoming increasingly popular as a delivery system for biologic drugs.
It’s then, no wonder, the global prefilled syringes market is estimated to be worth $22.5 billion by 2025.
However, as home injection trends rise, pharmaceutical and packaging manufacturers must concentrate not only on how the biologic reacts with its primary container, but also how the container interacts with the delivery device and finally how the patient interacts with the assembled system.
Integrating primary packaging and drug delivery is part of the answer, making products easier to use, reducing the risk of misuse and minimizing overfill waste at the manufacturing stage. Naturally, this also limits the risk of degradation and contamination across the supply chain and during administration.
As there are limitations on how rapidly any volume of drug can be injected subcutaneously, there’s also a growing interest in wearable injectors—or on-body delivery devices—to improve biologics’ bioavailability and patient experience.
By their nature, biologics are highly viscous and often require large doses to be injected slowly over time. This can make it difficult to deliver a consistent dose at regular intervals, potentially impacting medication adherence and health outcomes.
The most advanced on-body systems incorporate discreet cyclic olefin polymer containers with smart electronic injectors to avoid calling undue attention to the system while performing automated dose delivery.
Most devices are now also equipped with a microprocessor capable of giving immediate feedback via a dose confirmation window and audible cues to indicate whether the prescribed medication was delivered successfully.
Quality by design
While innovation has traditionally been synonymous with new drug discovery, the next generation of packaging and delivery systems warrant the same attention.
Precision engineering is becoming a priority as innovations in biologics place increasing and complex demands on the pharma supply chain. So too is collaboration at the early stages of new product development between pharma and packaging manufacturers.
It’s fair to say there’s a steep learning curve ahead to build transferable knowledge across the global pharma industry. Quality by design (QbD), a well-known standard of practice in other industries such as automotive, chemical and electronics is now being widely adopted in pharma.
According to PwC, by 2020 a QbD approach is likely to be the norm in the pharma industry. The FDA has already published a draft guidance in which it proposes replacing ‘three-batch validation’ with a three-stage methodology that involves designing a suitable process, using the knowledge gained in development and scale-up; ensuring the process is capable of reproducibly manufacturing commercial batches; and validating it continuously during routine production.
As our understanding of the fundamentals of biologic behavior grows, so too does the requirement to dig deeper for data to support further progress and inform best practice.
Through increased knowledge integration, the impact of raw materials on product quality and optimal storage conditions will become clearer, allowing packaging and delivery systems to be designed to meet exact patient needs and performance requirements. QbD can also eliminate waste and reduce overall costs of supply.
For example, a self-injection system needs to function consistently and reliably for patients using them at home. QbD-designed components can significantly reduce plunger variation, facilitate more efficient manufacturing processes and boost patient confidence. They can also enable larger-size delivery systems and greater dose volumes to encourage accurate self-administration and reduce wastage.
Standing out from the crowd
Biologics promise new avenues for doctors to better treat patients and for drug companies to widen their profit margins. Although biologics are prescribed less frequently than the most popular small-molecule drugs, they’re worth a lot more in terms of ROI capabilities.
However, while biologics cannot be copied exactly, unlike small molecule medicines, near-copycat biosimilar drugs can be developed to compete with originators. This places pressure on pharma manufacturers to keep hold of their market position and differentiate their brand.
Patients are understandably concerned that a switch to a biosimilar from an originator biologic drug could disrupt the effectiveness of their treatment regime, notwithstanding the fact that a biosimilar will only be approved by regulatory authorities after a robust and detailed evidence-based assessment.
Like with all consumer products, packaging is a key marketing tool. As biologic players can now expect a fiercely competitive playing field, we’re likely to see packaging designs with value-added features.
For example, more exclusive deals will be struck to secure access to enhanced delivery devices; vacuum insulated panels added to cut cold chain risks and hibernation capabilities to extend a product’s shelf life if unexpected delays occur.
It’s clear, biologics and biosimilars are the future of medicine, offering huge rewards for pharmaceutical and packaging manufacturers who get it right and better quality of life for patients living with chronic diseases.
However, before their full potential can be realized, there are many challenges to overcome, not least the design of primary packaging and delivery systems.
Rich Quelch is global head of marketing at Origin. He is an experienced global marketer within the healthcare and pharmaceutical sector. He has led the development of the Origin brand, positioning it as a world-leading supplier of innovative and ground-breaking pharmaceutical packaging devices, as well as offering a unique supply chain model which is disrupting the pharma industry.