Commercial launch is the critical endpoint of the drug development journey, and industry-leading CDMOs know first-hand what it takes to ensure it is achieved as seamlessly as possible.
All roads in pharmaceutical outsourcing lead to one destination: commercial launch. It can take many years to get there, and a recent Deloitte study indicated that the average cost of developing a new drug candidate can exceed $2 billion1. Not only does the drug development process require vast amounts of money, there are patients around the globe who desperately need your drug product to improve their lives and alleviate or even cure their disease. Commercial launch is therefore the critical end-point of the drug development journey, and industry-leading CDMOs know first-hand what it takes to ensure it is achieved as seamlessly as possible.
Trends and Challenges in Commercial Packaging
According to a recent report by IQVIA , oncology is recognized as as the fastest-growing driver of drug development, representing around 38% of the R&D pipeline, or a 10.5% CAGR over the last five years2. Avancements in science and technology, alongside a better understanding of the biology, immunology, and genetics of cancer, has lead to the development and approval of powerful targeted therapies that are capable of causing the complete durable elimination of tumours.
Precision oncology is transforming the way patients are treated. Many patient are receiving precision targeted immunotherapies that are tailored specifically to their disease. By their nature, targeted cancer therapies are more complex than conventional chemotherapies, often classified as being highly potent and requiring more specialized formulation develpoment techniques. As such, they require specialized facilities, equipment, and contained processing technologies, both in terms of commercial manufacturing and packaging.
The growing complexity of commercial pharmaceutical packaging places greater demands on CDMOs to meet the requirements of the end user and the nature of the drug product itself. The reasons for this increased complexity include, but are not limited to:
- Protection and preservation of the drug product;
- Safety concerns (such as child-resistant/senior-friendly/tamper-evident packaging);
- A drive towards reducing the overall environmental impact of packaging operations;
- The need to deliver increasingly complex therapies to patients;
- A shift towards ‘new to market’ products which are injectable, moving away from the Oral Solid Dose bias (although OSD remains a large driver of commercial market growth);
- Ability of the CDMO to scale up manufacturing and packaging from clinical to commercial scale to meet launch and ongoing demand forecasts
- Creating an efficient end-user experience, particularly for patients administering the drug product themselves.
Self-administration of injectable or combination therapies, in and of itself, creates unique challenges in commercial pharma packaging, especially alongside the other trends listed above. When it comes to self-administration, the aim is to make things as clear and simple as possible for the patient, which usually means a much more complex design process for the commercial pack. This is due to the many factors involved, including device protection, thermal impact on the drug product, disposal of the packaging into multiple green channels, and clear direction of use for the patient’s self-administration.
Thermal stability requirements mean that cold- and ultra-cold chain storage conditions are a necessity, particularly for live vaccines. Drug products stored in frozen conditions, usually between -20°C and -80°C, and packaged at refrigerated or ambient conditions require close monitoring. As a result, space becomes a vital factor in commercial pharmaceutical packaging. Not only are the processes for packaging biologics a lot larger and more complex than classic OSD blistering and bottling lines, they can often require storage at between -20°C and -80°C for both bulk and finished products. Therefore, the space required for cold chain storage cannot be underestimated.
When selecting your CDMO partner, you might ask whether they are able to perform semi-automated frozen packaging solutions for vial products that cannot exceed 0°C, with typical temperatures between -20°C and -80°C. Such a process requires a specialized vial labeler which retains ultra-cold conditions, prior to operators manually placing the vials into the final carton. The benefits of semi-automated frozen packaging are:
- Higher operational efficiency;
- Lower quality risks,
- Lower safety risks.
The second and third benefits listed above are critical when it comes to the packaging and storage of high-value frozen drug products. Ideally, your CDMO would have their semi-automated commercial frozen packaging processes adjacent to their clinical packaging processes, as this simplifies the supply chain and therefore mitigates the risk of the drug product being exposed to ambient temperatures.
The demand for increased complexity coexists alongside industry pressure to lower dosage costs, provide resilience in the supply chain, and reduce overall time to market. These opposing forces are driving a technology and mind-set shift within the CDMO space, and is something that will continue into the foreseeable future. But there’s a solution to this inevitable bottleneck which, though apparently simple, involves a mind-set shift within sponsor organizations.
Go Early and Go Deep
Early commercial engagement in the drug product lifecycle is becoming an increasingly important factor in a successful, timely commercial launch. The core message here, therefore, is ‘go early and go deep’. By engaging the advice, expertise and services of your chosen commercial CDMO partner early—ideally during Phase II to III—you ensure that processes involving long lead-times are factored in, alongside adequate research into the drug delivery platforms and their specific technical requirements. However, the hidden message here is partnering with a CDMO early that is able to scale their processes from clinical to commercial supply; all too often, sponsors partner with smaller CDMOs during early phase clinical supply, only to establish processes which need re-engineering at a later stage, increasing costs, delaying timelines and adding a layer of complexity and risk to the drug development process.
Successful commercial packaging relies on the harmonization of Materials, Design and Process. If these three elements to not complement each other, the road ahead for both the CDMO and the sponsor organization will almost certainly be rough. Within each element there are hundreds of questions and considerations to discuss in order to find the optimum balance, and that is only achievable via strong collaboration with a CDMO partner with adequate experience in commercial supply.
Sponsor organizations regularly work in isolation with design agencies for their commercial pack design without the input or knowledge of their CDMO partner. The core issue here is that, whereas the pack might tick the boxes in terms of branding and general ‘look’, there is little or no thought of how that pack will be manufactured, the protection it will provide, or the end-of-use disposal. The result: a clever, novel design which requires hand-packaging at a much greater cost, because automation costs are prohibitive when the product is not provided with the level of protection it needs.
Case Study #1: Short-Term Solutions, Long-Term Loss
During the early clinical phases of a sponsor’s drug product lifecycle, their CDMO partner at the time advised them to use stock tooling to blister pack their oral solid dosage form to place on stability. The reason was simple enough: they wanted to save money. However, whereas this is understandable to a degree, the cost saving at the time was only around £2,000. The sponsor went ahead with the stock tooling, which created a blister cavity that was oversized in comparison to the drug product. They placed the blister pack on stability in cold form only, and the product eventually received Fast Track approval from the FDA.
Later, when the sponsor engaged with PCI to establish a commercial packaging process ahead of their drug product’s launch, the pressure was on. Due to the Fast Track approval, and the suboptimal blister packaging process established with the previous CDMO partner, PCI was handcuffed to the same process. When packaging the drug product into this large, oversized cold form cavity, it naturally resulted in a large blister pack. The result was a maximum of two blister packs per cycle, and a lower output alongside the pack being too large for a standard cartoner ultimately resulted a higher Cost of Goods (COGs) for the client.
Had the sponsor engaged with PCI during Phase II to III, a Value Engineering Program would have been conducted to produce an optimized blister pocket. This would have resulted in PCI being able to produce an additional blister pack per cycle for the sponsor and a higher CPM with the added benefit of automated cartoning. By making these changes, the sponsor would have benefited from:
- Reduced lead times;
- Reduced cost of goods, and;
- Reduced environmental impact of their overall commercial packaging process.
Case Study #2: Dual Sourcing with an Integrated CDMO
Sponsors benefit hugely when partnering with a CDMO that is able to integrate commercial packaging and manufacturing services, particularly when it comes to establishing a dual sourcing strategy for a commercial drug product. FDA draft guidance released in 2022 recommends that “stakeholders develop, maintain, and implement risk management plans (RMPs) to proactively assist in the prevention of human drug product and biological product shortages. RMPs can provide stakeholders with a framework to proactively identify, prioritize, and implement strategies to mitigate hazards that can cause a supply disruption. Such a supply disruption may lead to a drug shortage.1
A global biopharma company approached PCI to secure the supply of a high value, highly potent drug product. It was emphasised that an integrated solution was an essential part of their risk mitigation strategy, with the dual sourcing partner required to absorb up to 100% of their annual demand. A key consideration was PCI’s UK-based Contained Manufacturing Facility (CMF), which is able to handle potent products to an OEL of 0.01 µg/m3. The combination of potent manufacturing capabilities and the global network of commercial packaging sites was fundamental to the sponsor’s needs, with the complexity of vendor management reduced by selecting a single dual sourcing partner.
Through their due diligence, and through PCI’s integrated outsourcing solutions, the sponsor benefitted in a number of ways, such as:
- Risk mitigation, via immediate continuity of supply for their high value, life-saving therapy;
- Agility and flexibility of supply, as a second source provides additional capacity to absorb any unexpected increases in demand;
- Geopolitical benefits, with additional manufacturing and packaging locations leading to more local supply, therefore reducing distribution costs and carbon footprint;
- Added product value—in the event a drug product is out-licensed, or sold to another owner, a robust dual sourcing strategy adds significant value to that drug product itself.
Elements of Successful CDMO Partnership
There are three main aspects to a successful partnership between the sponsor company and their CDMO partner:
- Working with one CDMO throughout the drug product life cycle ensures a deep understanding of the product and maintains the necessary level of knowledge and experience. Transferring between CDMOs is not a straightforward task and so working together to deliver an end-to-end solution and navigate challenges along the way leads to success.
- The process by which a CDMO is chosen is also critical. The assessment criteria should not only take into account the CDMO’s technical capabilities, but also the more subjective factors such as how the company communicates, how they approach a problem, their proactivity and the emphasis placed on building a true partnership, whereby the CDMO becomes a seamless extension of the sponsor team.
- Thirdly, the continual education of employees about the nature of the actual drug product itself is more vital than ever. It elevates care and ownership to a different level, as it encourages staff to truly understand the impact of their role within the CDMO in human terms, i.e. improving or even saving lives.
Sponsors should view their CDMO partner as a travel companion, someone they’ll journey with throughout the drug product’s lifecycle. Challenges are inevitable, but partnering with the right CDMO, at the right time, ensures that challenges are met with industry-leading technology, experience and expertise. It is therefore strongly advisable to find the right CDMO partner for your needs, and taking the right care to consider the broader aspects of how a CDMO operates.
References
- Genetic Engineering & Biotechnology News. The unbearable cost of drug development: Deloitte report shows 15% jump in R&D to $2.3billion.
- IQVIA Institute for Human Data Science. Global trends in R&D 2023: activity, productivity, and
enablers. Published online February 15, 2023. - FDA. Risk management plans to mitigate the potential for drug shortages guidance
for industry. Published online May 2022.
Commercial Packaging – A Consultative Approach to Pharmaceutical Outsourcing with Paul Smallman, PCI Pharma Services. | As seen in a custom ebook presented in partnership with Pharmaceutical Technology.
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