Shortages are an undesirable, but inevitable, part of the pharmaceutical supply chain. API shortages, recalls, economic factors – even the most well-oiled pharmaceutical machine can be impacted by disruption to one of its many moving parts, and the knock-on effect on a clinical trial in full flow can be significant.

No one wants a shortage to happen – not the manufacturer responsible for producing the commercial drug that you are using as a comparator and certainly not the person responsible for getting that drug to trial sites.

But there are things that we can do. Whilst we can never eliminate 100% of the risk, there are steps we can take to reduce it significantly.

1. Writing flexibility into your protocol

During the study design phase, it can sometimes feel like spending our efforts on Plan B can detract from Plan A, but we need to take this opportunity to build in the flexibility that ‘might’ be needed should a shortage occur. It’s the only sensible time to do it.

When writing a study protocol, it is good practice to list multiple comparator manufacturers, where possible. This is most relevant when using a generic product, as there will be several manufacturers of the same drug, and even if you don’t intend to use them, in the event of a shortage it is best to only be faced with making a slight change to a product label as opposed to re-submitting a protocol listing to a new comparator manufacturer.

Ask your vendor for the top 3 likely candidates and list them all. Submit the generic name of the drug as opposed to a particular brand name. Do not limit yourself to only sourcing from one region or in one language. Allow interchangeability between strengths and presentations.

2. Choosing the right strength and the right presentation from the start

Even after taking point 1 into consideration and allowing for the use of various strengths and presentations, you will still, of course, have a preference and want to supply your trial with a consistent, efficient presentation.

Your vendor, however, should be providing information on which presentation is the most risk mitigating from the outset.

Let’s take Carboplatin as an example, a cornerstone of several chemotherapy regimens and no stranger to shortages. It is commonly manufactured as a 150mg, 300mg, 450mg and 600mg. In many EU countries, we will see hospitals and health services buying the larger vial sizes and using them as multi-dose vials, serving multiple patients. This reduces overall waste for the hospitals.

Whilst your trial design may prefer using a combination of smaller vial sizes, these are manufactured less often and are generally less available – the manufacturers are responding to the demand of the local patient population and producing what is used most.

What this means for a clinical trial is that when a drug goes on shortage it is often the sizes that are in the highest demand that are manufactured as a priority. The 600mg is likely to have more stock on the shelf, more quickly. If your hands are tied to the 150mg or 300mg, you may be waiting longer than necessary.

3. Market Intelligence & Awareness

Every good vendor will be actively monitoring regulatory sites, press releases, and using their industry networks to become aware of shortages as soon as possible, and they should be sharing this with sponsors.

When a shortage happens, there can be a very short window to react and make a purchase of a much-needed comparator, making proactivity essential.

This market intelligence also covers the need to stay close to the right manufacturers during a shortage, so that your trial can be well positioned to receive stock again when normal service resumes.

4. Forecasting

Forecasts are a powerful tool for effective supply planning and whilst it isn’t always easy for a sponsor to provide an accurate outlook for a 12-18 month horizon, even educated assumptions can help with strategizing and manufacturer communication.

A forecast enables you, and your vendor, to put a supply plan in place that will consider all of the variables such as expiry dating, lead times and the likelihood of your comparator being in short supply. The information can also be shared with the manufacturer of your comparator and in some scenarios enable them to adjust their production plans for the year ahead based on your assumptions.

Regularly reviewing the forecast between sponsor and vendor gives everyone the opportunity to share updates, industry insight and other factors, and for the vendor to suggest a more aggressive purchasing plan if they have seen any signs of possible disruption.

5. Maintaining stock levels

A ‘stock out’ is one of the most undesirable scenarios for anyone managing a clinical supply chain, but the risk has to be balanced against overspending and wasting drug that expires before it can be used. Things would be easy if we could simply buy as much drug as possible, but that isn’t the commercial reality that Clinical Supply Managers are faced with, nor should a strategy of excess waste ever be recommended.

Consider how reliant your study is on the low cost, generic medicine with a history of shortages that your study is using, and you may decide it is pragmatic to overstock. The commercial impact of having too much stock would be low when compared to the risk of running out. Conversely, the expensive branded drug your study uses may warrant a more cautious approach to stock levels.

Summary

In some instances, a medicine shortage cannot be avoided but, in most cases, there are a lot of steps that you, and your vendor, can take to prepare and to protect your clinical supply chain. If you have considered each of the five points in this paper during the planning phase of your study, then you will be off to a good start in mitigating the risks posed by shortages.

Midwinter Solutions can help and would be delighted to discuss your plans and share our more detailed insights.

To download a PDF copy of this white paper, please click here.