The pharmaceutical industry is a dynamic, ever-evolving landscape. With the market predicted to grow at a CAGR of around 8% to 20281 , and the number of clinical trials conducted globally increasing each year, outsourcing clinical packaging and supply has emerged as a strategic choice for pharmaceutical companies seeking to optimize their operations and streamline the drug development process, ultimately ensuring speed to market for their life-changing therapies.
Industry-leading CDMOs have witnessed first-hand the transformative and positive impact of outsourcing on clinical packaging, supply, and logistics. By partnering with specialized CDMOs, companies can leverage their expertise, state-of-the-art facilities, and streamlined processes to ensure efficient packaging and labeling of investigational drugs. This, in turn, enables companies to focus their internal resources on core competencies such as research and development. Furthermore, outsourcing clinical packaging provides flexibility, scalability, and cost-effectiveness, allowing companies to adapt to changing market dynamics and manage their budgets more efficiently.
Preparing for Change
In an industry where dynamic growth is the norm, change is inevitable. To prepare for change, a leading CDMO should focus on embracing new technologies, ensuring regulatory compliance, offering customized solutions, building reliable and visible supply chains, and enhancing quality control processes.
It is vital for CDMOs to embrace and integrate the latest technologies and innovations available in the industry. This includes, but is not limited to, smart packaging technologies, eco-friendly materials, personalized packaging solutions, and systems that allow real-time visibility of data, and CDMOs should invest heavily in research and development to stay ahead of the curve and ensure they can offer their clients the most innovative and efficient packaging solutions.
There is a growing demand in the clinical packaging industry for customized and personalized packaging solutions. Such a demand requires building strong partnerships with sponsors to understand their unique requirements, which enables CDMOs to offer tailored solutions that meet the specific needs of each sponsor’s project, such as customized and digital labeling, serialization, and tamper-evident packaging options.
Additionally, clinical trials involving cell-based therapies are becoming more and more common. Whilst many are manufactured and delivered straight to the patient for autologous use and labeled at source, other heterologous products are emerging that are stored in vapour phase nitrogen and are cross matched to patients. These products need to be individually labeled and ‘kitted’ for the patient on demand without thawing the materials. Therefore, operational and QP models need to exist that support the fast turnaround of these materials, with the duration from receipt of order to packaging, QP certification and despatch sometimes being as little as a few days.
It almost goes without saying, but regulatory compliance will continue to be a critical aspect for the industry. To operate at the highest level, CDMOs should ensure they are up-to-date with local and international regulatory requirements, are successfully audited by leading global regulatory bodies, and consistently adhere to Good Manufacturing Practices (GMP). By focusing on being audit-ready at all times, CDMOs are well-prepared for potential regulatory changes and be agile in their approach to adapting their internal processes and procedures to comply with any new regulations.
It is therefore clear that CDMOs need to continue to evolve and adapt, without losing focus on enhancing their quality control and assurance processes to ensure their products meet the highest quality standards. Alongside this, other core concepts remain integral to success, including investment in staff training, equipment, and infrastructure to ensure their processes remain efficient, effective, and ahead of the curve.
Capabilities, Experience, Expertise
A broad yet in-depth range of capabilities, experience, and expertise is crucial for an industry-leading CDMO in the clinical supply arena. This includes packaging design and development, regulatory understanding, robust quality oversight, strong procurement, technical expertise, innovative technologies, and the flexibility and agility to support clinical and packaging operations effectively.
With the expectation from clients that their CDMO has leading speed to market capabilities, technology is paramount to that realization. Speed cannot compromise patient safety and regulatory compliance; technology will be foundational to that success. Smart and reactive inventory management solutions, late stage labelling and packaging customization, and effective digital project management tools are all great examples of solutions that will drive this effort.
Excellent communication between the clients, project managers and operations is essential, and digital platforms which enable access to real-time supply chain data provide an additional benefit (where such systems are available). For example, PCI has developed an in-house digital supply chain management platform; pci | bridge™, which allows clients access to this crucial data in real-time. As most projects are global, providing clients with this platform irrespective of time zone has proven highly valuable.
Being able to offer a wide range of storage temperatures and packaging at cold and frozen temperatures is a requirement, as a greater number of vaccines and gene therapies are being subjected to clinical trials. This capability is best supported by a strong global distribution network which includes depot partners for regions not directly supported by sites within the CDMO’s network. It’s also important to note that global distribution services incur a carbon footprint; it is becoming increasingly important to reduce this where possible, to recommend storage and distribution options and shipping systems that reduce the overall carbon footprint whilst maintaining product integrity.
Common Challenges, and Strategies to Ensure Success
When supplying clinical trial materials, the most complicated packaging solutions occur when the clinical trial is blinded, but the Investigational Medicinal Product (IMP) has not been manufactured to match the material it is blinded against. The complexity may vary, from the manufacturer printing the batch number onto a vial closure which has to be removed before packaging; over encapsulation of tablets and capsules to hide the differences between dosage form and strength; different coloured caps or crimps used on vial or bottle closures compared to the comparators; or different vial sizes used for the IMP compared to the comparator. Ultimately, the blinding solutions must be fit for purpose.
Other common challenges with clinical packaging include:
- Moisture and Contamination: If the packaging material is not sealed properly or is not moisture resistant, it can lead to drug degradation, with the client’s life-changing therapy becoming less effective, or even contaminated. Moisture can also cause the packaging material to deteriorate, which can lead to the loss of the drug’s potency.
- Compatibility Issues: These may arise if the packaging material is not compatible with the drug’s chemical composition. Again, this can lead to drug degradation, loss of potency, or even toxic reactions. It is therefore vital to ensure that the right packaging material is chosen based on the drug’s properties.
- Labeling Errors: Clear, accurate and legible labeling is critical. When the labeling is unclear, illegible, or incomplete, this can lead to confusion about the drug’s dosage, administration, and potential side effects. This can be a substantial challenge with small vials and in scenarios where cold chain packaging is required.
Any problems encountered ultimately result in delays to the project’s clinical and commercial timelines. But there are several key strategies that sponsors may consider, which can help overcome such issues.
- Collaborating closely with packaging suppliers ensures that the packaging materials are designed and manufactured to meet the specific needs of their drug products. This can help to avoid compatibility issues, reduce the risk of contamination and improve efficiency in the supply chain.
- Investing in innovative packaging technologies, such as smart packaging, can help to improve the safety, efficacy, and convenience of drug products. Smart packaging can also help to reduce costs and improve efficiency in the supply chain.
- To ensure the quality and safety of drug products, sponsors should conduct thorough testing of packaging materials and processes. This can include testing for compatibility, stability, and moisture resistance, as well as conducting validation studies to ensure that the packaging meets regulatory requirements.
- Sufficient stability data is vital to enable packaging to take place with minor temperature excursions. This will speed up QP release of product, as there would not be delays where investigations into the excursions are required.
- Where possible, clients should strive to establish product stability at temperatures that are routinely commercially available. For example, routine frozen storage temperature is -15 to -25°C; products requiring storage below -20°C cannot be stored in the same variable freezers, requiring instead the purchase and validation of individual storage units. It’s not unusual for this situation to potentially add months onto the start date for storage and packaging activities.
- Considering commercial pack design earlier in the drug development process. This is usually left until the last minute, with third party design agencies brought in to design a commercial pack. Whereas the third party design may tick the boxes in terms of branding, it often won’t fit on the CDMO’s equipment trains, resulting in expensive capital expenditure purchases or the need to redesign the pack to fit on the commercial lines. Partnering with a CDMO capable of designing prototype packs during clinical phases is the ideal solution here, saving huge amounts of time and money in the process.
- Lastly, sponsors can prioritize sustainability by choosing eco-friendly packaging materials and promoting responsible disposal practices. This helps to reduce the environmental impact of pharmaceutical packaging and improve the company’s reputation among consumers and investors.
Case Studies
It’s not uncommon for clinical trial start dates to be missed due to improper trade compliance planning, as clients are caught off-guard by the requirements for import of product into the US for study start-up. It is crucially important to consider the FDA requirements for IND approval before the drug product is imported for clinical use in humans, including the FDA end use, which must be classified correctly to avoid unnecessary customs holds. Choosing a manufacturer that is located within the country of study start-up is a clear solution, but admittedly this is not always attainable.
One solution is to use a site in Canada (or within the country of manufacture) for pre-IND support to prepare the drug product for clinical use, which can shave valuable time off study start-up and FPI target deadlines. For example, a CDMO with a presence in Canada would be able to pack the drug product whilst awaiting FDA approval, with the product then ready to ship once approval is received. On many occasions, we have seen clients set targets for study start-up that prove impossible to achieve, solely due to the inability to import the drug product into the country where the study is destined to start. Working closely with your supply chain partner and trade compliance experts will allow sponsors to avoid this costly mistake.
Another specific example includes a client whose injectable material was manufactured to match the United States version of the comparator drug. In the EU, it is a requirement that any comparators used are sourced from within the EU; however, in this instance, the EU version of the comparator had a different vial size to the US version. As such, a drug carton had to be designed that contained an internal shelf to lift up the comparator product, so it appeared to be the same size as the IMP; a window was also built into the designed carton to allow the material to be extracted via syringe, whilst ensuring it didn’t compromise the blinding the products. The packaging also needed to be robust enough so the drug product could not easily be removed at the site.
The time and cost of this carton design was an expensive and complicated process, and proved challenging, adding significant time to the packing runs which therefore resulted in increased packaging costs. As it was possible to use the EU drug in the US, the IMP would have been blinded to the correct EU comparator, significantly reducing the time and costs involved.
Summary
Given the ever-increasing number of clinical trials around the globe, and the growing demand for speed to clinic and to market, the need to partner with the right CDMO is becoming more significant. Sponsors should conduct their due diligence with care, asking the right questions of their prospective CDMO partners, and establish an open, honest and collaborative relationship, with the aim of avoiding costly mistakes and hitting those vital clinical and ultimately commercial deadlines.
Reference
Clinical Trial Supply – A Consultative Approach to Pharmaceutical Outsourcing with Rachel Griffiths and Craig LaMarca, PCI Pharma Services. | As seen in a custom ebook presented in partnership with Pharmaceutical Technology.
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