Margaret Radford is unlicensed medicine services manager at Almac Clinical Services.

Margaret Radford

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In the era of patient centricity, managed access programs (MAPs) are coming of age. While this program type was previously considered a more reactive tactic, sponsors today are increasingly harnessing MAPs—also known as compassionate use programs or early access programs—to provide patients with an unmet medical need with access to unlicensed medication. Used as a strategic tool, MAPs can facilitate optimized, patient-centric, and cost-effective access to investigational drugs outside of a trial setting.

As use of MAPs matures, the potential they represent is becoming more universally acknowledged. As MAPs are designed to deliver treatment access, rather than facilitate research and commercialization, they can be simpler and more cost-effective to operate. MAPs can also support the expansion of patient demographics, strengthen relationships with patient advocacy groups, increase exposure to more healthcare professionals prior to commercialization, and support corporate social responsibility agendas.

There are, however, several key challenges that can prevent sponsors realizing the full potential of MAPs. Many of which can be overcome by embracing a just-in-time manufacturing (JTM) strategy.

Specific challenges vary depending upon the pathway chosen (named patient or patient cohort) but relate to regulatory oversight, product presentation, and supply chain.

Where regulatory activity is concerned, a patient cohort pathway will place full responsibility on the sponsor. This pathway can increase the burden of operating a MAP, especially in regions like Europe, where each member state has its own legislation relating to how European Medicines Agency recommendations are implemented.

Likewise, the nuanced supply chain challenges relating to MAPs are significant. Due to the reactive nature of the program type, demand forecasting is particularly difficult. This difficulty increases the risk of waste or rework if supplies surpass expiry dates while awaiting patient allocation, which can be particularly costly when dealing with biologics and advanced therapies. It also increases the risk of negative patient impact if insufficient drug is available when the patient need arises. In either scenario, a sponsor’s ability to start-up and respond quickly once demand is known is seriously hindered.

To overcome these challenges, the industry is seeking better solutions for MAPs delivery. Solutions that deliver an improved service to patients and healthcare providers (HCPs), while driving improved operational efficiency. JTM is proving useful in this respect by increasing flexibility for packaging and labeling to meet both geographical and forecasting complexities and providing sponsors with more effective management of supplies across both MAPs and clinical trials.

JTM refers to the late-stage customization of clinical kits. It’s a demand-led production technique designed to put patients first and deliver an adaptive supply strategy to meet expanding challenges, including concurrent clinical trial and MAP delivery. JTM achieves all this by delaying secondary packaging and labeling activity until patient or site need arises.

And it really comes into its own where MAPs are concerned. For instance, late-stage customization means unlicensed medicines can be directed to where they are needed, both in terms of geography and volume, helping to reduce cost by conserving drugs. Supply also becomes more flexible when using JTM, as supplies can be used for any country without the need for booklet labels.

Similarly, JTM supports supply pooling, empowering sponsors to use the same bulk supply across clinical trials and MAPs and, through standardizing key elements across pooled lots, benefit from economies of scale without sacrificing the flexibility required to share the product. And because products are only packaged and labeled when needed, JTM reduces exposure to expiry date events. Not only is there less date labeled stock at risk of expiry update loss in the field, but there is also no depot stock requiring relabeling.

Where patient centricity is concerned, JTM supports MAP sponsors to deliver patient specific packaging, helping to lower overheads and improve patient understanding and compliance.

MAPs are typically subject to significant change. Timelines can shift. Participating countries can alter. Regulation and ongoing clinical trial activity can influence supply requirements. While operating a traditional batch manufacturing approach can leave sponsors restricted in their ability to respond to these kinds of changes, JTM supports sponsors to adapt, achieve earlier start-ups, improve reaction time to demand changes, and realize more sustainable supply chains.

To realize these benefits, reduce waste and optimize supplies, JTM must be approached correctly at the time of MAP development. Proactive planning to incorporate JTM can make the process faster, easier, and increase the likelihood of achieving optimal results.

Furthermore, a robust pre-production phase is needed to establish a quick pack, label, and quality release cycle for unlicenced medication. This means developing blueprints for receipt of unlicensed medication at packaging and labeling facilities, agreeing on pack design details, procuring kit components, and translating label text for initial participating countries.

Master packaging specifications will also need to be created within an enterprise resource planning (ERP) system to define each finished good by country, expiration date known at the time, and unique lot number. The ERP will also need to maintain the components required to make future kits, including the assigned bulk drug lot, the approved master label and label variables.

If appropriate planning takes place during pre-production, JTM production and distribution can be completed rapidly, with orders received, validated, and translated to a label work order and assembly work order via the ERP. Labels can then be printed, checked, and approved by quality control for use in the JTM pack and label operation.

MAPs represent an opportunity for sponsors to uphold ethical and regulatory responsibilities to patients with an unmet medical need. More than this, they have the potential to support sponsors to expand their own horizons by driving cost-efficiencies, capturing real-world data in support of commercialization goals, and building strong relationships with a range of key stakeholders. By harnessing JTM as a supply chain solution for MAPs, sponsors can look to maximize these opportunities and deliver production strategies that support speed, agility, and patient centricity.

Margaret Radford is unlicensed medicine services manager, and Lyn McNeill is Just in Time Manufacturing Solutions manager, both at Almac Clinical Services.

Articles

Challenges that can prevent sponsors realizing the full potential of managed access programs can be overcome by embracing a just-in-time manufacturing strategy.   