With the global personalised medicine market set to be valued at $2450 billion by 2022, and with more than a third (35%) of FDA-approved drugs for cancer being defined as personalised medicines, this trend brings new commercial challenges to the fore, reports Sepha's Business Development Manager Scott Kenny.1,2
Introducing personalised medicine calls for flexible manufacturing processes, particularly if the goal is, one day, to produce a “batch of one.”3
Personalised medicines cannot be brought to market without new, highly agile packaging solutions. Packaging requirements are growing in complexity to accommodate sensitive formulations, fast turnaround times and smaller batches.
To fill and pack personalised medicines, packaging systems need to be able to handle small batch sizes reliably, quickly and safely, all while maintaining product integrity.
What’s more, this small batch packaging depends on flexibility throughout the production process.4 For this reason, the concept of decentralised manufacturing, in which production is managed at local level for responsive product delivery customised to the end user, offers an attractive solution to overcome the challenges facing the supply chain.5
Large pharmaceutical manufacturers and contract manufacturing organisations (CMOs) might not always be best placed to accommodate low volume, small run packaging. Equally, smaller companies rarely have the infrastructure, resources or expertise in place to handle small batch runs, particularly for high potency drugs, in a complex regulated environment.
Shifting to a decentralised model can increase the efficiency of manufacturing and delivery, and offers a practical solution for personalised medicine production. The result is that pharmaceutical organisations are increasingly seeking to outsource activity to specialists.
Why is decentralised manufacturing a promising option?
The future of personalised drug manufacturing lends itself to a decentralised model, particularly in the fast growth sector of cell and gene therapy (CGT). Manufacturing capacity must be able to suit patient-specific therapies that can satisfy the eventual demand.5
This is primarily because of the short shelf-life of these products and the limited options for storage and shipping — particularly within the cold chain, a critical factor highlighted recently by the supply and distribution issues surrounding the COVID-19 vaccine.6
For this reason, when time-to-customer is key, long-distance transit is undesirable and, in many cases, simply does not present a viable option.7
Furthermore, products that require a late-stage customisation, such as bioprinting, are particularly suited to being manufactured close to a clinical setting.8 A decentralised network allows manufacturing to be sited in close proximity to treatment centres.
Outsourcing to the experts: a critical success factor in personalised medicine
Accounting for individual variability in genes, environment and lifestyle requires a sea change from mass production to small-scale, individualised manufacturing.
This change depends on the technology revolution of Industry 4.0 and includes next-generation manufacturing, big data, smart networks and the Internet of Things (IoT) to create an interconnected value chain configured to operate autonomously.
In the future, we are likely to see a decentralised model based on localised production “nodes” rather than a single large-scale manufacturing facility. This is when outsourcing becomes key to success.
In pharmaceutical drug development, the outsourcing model is already well established. This next logical step will follow, wherein major pharmaceutical manufacturers will rely on a series of experts in their respective fields to set up localised nodes. These third-party contractors will take on a key role as partner in the area where they already offer expertise.
Stability testing
Because CGT products are extremely sensitive to uncontrolled variations in the distribution chain, such as temperature, time and humidity, measures must be taken to provide robust quality control during manufacture and shipping.
As a “living drug”, CGTs remain effectively in culture during transport and require active management of the product.9
These specialist, high potency drugs need dedicated packaging that does not fail or compromise on the quality of the drug. For this reason, packaging stability testing is important.
Regulation requires expiration dates to be displayed on all pharmaceutical products. The US Food and Drug Administration (FDA)’s Good Manufacturing Practice for Finished Pharmaceuticals established requirements concerning the expiration date on a drug product and stability testing to ensure the appropriateness of that date.10
Furthermore, each drug will be unique because of differences in chemical and physical properties of the active ingredients or excipients, manufacturing processes, formulations, containers/closures and storage, and will also harness unique characteristics based on each individual’s genetic make-up.10
Stability also depends on the properties of the drug itself to maintain its quality and purity through the use of antioxidants or preservatives. The product’s packaging plays a key role here.
Stability studies are important to test the packaging suitability for regulatory approval and also for new drugs when material selection can also be a challenge.
An expertly managed stability study will measure the effects of variation in temperature, time, humidity, light and partial vapour pressure on the drug. In personalised medicine production, when shelf-life is short, it is critical to get the packaging right.
Drug developers depend on the flexibility and speed of their packaging supplier to accommodate complex and varied stability studies. Non-destructive leak testing, for example, maximises production efficiencies while maintaining the integrity of the product.
Avoiding cross-contamination of highly potent drugs
In small batch production, pharmaceutical manufacturers must frequently switch between batches. This places high importance on process safety and efficiency to avoid cross-contamination and ensure occupation safety.
Outsourcing to experts, who have the necessary lab and cleanroom classifications in place, is particularly important in the high potency drug production sector that characterises the personalised medicine market.
Specialist manufacturers will ensure that fully compliant processes are in place to protect both the drug and the operators.
Personalised medicines are often supplied in prefills, such as syringes or other medical devices that are designed to be self-administered. These sensitive products, particularly in the case of biological medicines, need to be packaged in stable temperature and humidity conditions. Specialist contract packaging companies can advise on the most effective and cost-efficient solutions to optimise packaging.
Avoiding over-specification of materials is important, as personalised medicines are produced in short runs for rapid delivery, so do not need the longer shelf-life requirements of more stable drugs.
Working with specialists ensures efficient and integral pack design to best suit the product. For example, blister packs provide product security for high potency, high sensitivity drugs through the protective barrier of individually packaged tablets.
Most blister packs, however, are currently mass produced on high speed form, fill and seal machines. Experts in this field can provide materials advice and help with a variety of pharmaceutical blistering materials that house the product correctly. Specialists in this field can also offer operational advantages, such as working under modified atmospheric conditions to safeguard product integrity during the packaging process.
In the future landscape as personalised medicine becomes more common, specialist small batch packaging suppliers with a strong track record in compliant drug packaging and the agility to produce batches as small as one will become a key part of the supply chain.
Conclusion
The pharmaceutical outsourcing model is only set to grow in a future that brings personalised medicine to reality.
With advanced CGT attracting new collaborations and significant funding, typified by the UK Catapult model, and with digital transformation poised to deliver the automation, predictive data analytics and collaboration tools needed to support the development of personalised medicine, drug manufacturers need to look to partner with companies who can help bring the vision to practical application.11
References
- https://healthmanagement.org/c/hospital/issuearticle/top-target-treatments-infographic.
- www.bluelatitude.com/how-we-think/mastering-the-precision-medicine-opportunity.
- www.healthcarepackaging.com/markets/pharmaceutical/news/13284409/personalized-medicine-a-batch-of-one.
- https://packagingeurope.com/personalised-medicine-imposes-increasingly-complex-requireme.
- www.sciencedirect.com/science/article/pii/S1465324918305140.
- www.sps.nhs.uk/articles/maintaining-the-covid-19-vaccines-cold-chain.
- N. Medcalf, “Centralized or Decentralized Manufacturing? Key Business Model Considerations for Cell Therapies,” Cell Gene Ther. Insights 2, 95-109 (2016).
- www.sciencedirect.com/science/article/abs/pii/S1748681517302358.
- www.sciencedirect.com/science/article/pii/S1465324918305140.
- www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/inspection-technical-guides/expiration-dating-and-stability-testing-human-drug-products.
- https://ct.catapult.org.uk/news-media/general-news/advanced-therapy-treatment-centre-network-awarded-%C2%A395m-further-investment.
