Late-Stage Customization in Clinical Supplies by Introducing Just in Time Labeling

Postponement is a concept in supply chain management where the manufacturer produces a generic product, which can be modified at the later stages before the final transport to the customer. So can we transform the clinical supplies environment to maximize the benefits of this concept?

We face daily challenges across our supply chain, surrounding the use of booklet labels and carrying out expiry updates on material already labeled and ready for use, waste, and flexibility. But what if…

We Fade out Patient Unfriendly Multilingual Booklet Labels for Clinical Packages?

Booklet labels are often complex and patient unfriendly; a large percentage of booklets are never opened, which introduces a risk of being non-compliant with the dosage scheme, storage and safety instructions.

Furthermore, often countries are added quite late in the clinical protocol, and as such we need to reorder new booklet labels or add additional labels on the clinical supply package, which increases complexity for the patient.

Shelf life updates often result in relabeling activities, which could create even more confusion for the patient and become an additional cost burden on the organization.

The Concept of ‘Just In Time’ Labeling

The primary objectives of Just in Time (JIT) labeling are to:

• Provide same day delivery: An IxR request will be completed (picked, final label printed and applied, packed, QP-released, and shipped) within 24-36 hours
• Eliminate patient unfriendly multilingual booklet labels for clinical packages
• Reduce relabeling activities to update expiry date
• Reduce complexity and drives a lean process in pack and label
• Reduce packaging campaigns
• Reduce waste and increase utilization of material
• Improve support for pooled supplies
• Ensure local country language is visible and not lost within the booklet

It all starts with Integrated Processes and Validated Systems

Current Process

Packaging and labeling activities occur in the conventional way as the primary and secondary activities are carried out with the output being labeled ‘kits available for shipment.’ Then in the warehouse, a shipping request is received for a specific kit that is picked, packed and shipped to the site.

Future Process

In the future state, primary packaging occurs as it does now, however, bright stock is created. This stock is available for use across a number of protocols and countries.

Single level (blisterpack, bottle) and the use of pre-serialized packaging materials allow for the introduction of a highly automated packaging process. Kits produced in pack and label will no longer have a label on the secondary pack. Instead, the kits will only have a 2D barcode (serial number) which provides a link to the product in the kit and the batch number of the product (as seen in Figure 1):

Figure 1: Michael Stephenson/Ignacio Gomez-Arroyo Bernabeu

The link to the protocol number, kit number and expiry date will only be added during JIT finishing in the distribution center. The current IxR request specifies the kit number to be shipped, which limits the combined use of the finished and bright stock. In the JIT way of working, the IxR request will specify both the kit type and the minimum expected shelf life.

So how does it work in the distribution center after the above request is received?

• The system checks all available batches and automatically selects the one that best fits the supply chain needs, before instructing the operator to pick a kit from the supplies specified in the request
• A 2D bar code of semi-finished kit scanned and system verifies the correct kit selected
• The JIT station then prints the correct label in the correct language and adds variable data
• The most up to date expiry date is printed (linked to country andtrial) on the label
• Each character on the printed label is inspected using a vision system and has the capability to reprint in case of quality defects (Figure 2)
• The label is applied and the correct application is checked by a further scanning operation

Figure 2: Michael Stephenson/Ignacio Gomez-Arroyo Bernabeu

The system will generate a report of all kits processed (including reprints) for QP review and once released, the kit can be shipped to the site. The system then notifies the IxR of the kit number picked and sent to the site. The release process occurs in two stages:

1) Regulatory compliance check (RCC) is completed before the use of bright stock. This includes:

– Country participation for the given trial has been approved

– Bright stock is approved for country/trial combination:

• Manufactured in accordance with cGMP
• Labels are approved

– Country and trial specific expiry date

2) Final QP release after JIT finishing is based upon:

– RCC complete

– Activity log on completion

JIT Finishing will only be Applicable at the Kit Level

But what about the label at the lower level? Let’s look at a simple multilevel pack (e.g. eight vials in a carton – Figure 3). Once a kit is completed in primary, the carton will be tamper sealed to prevent opening kits in the JIT stations. That said, how can you employ the flexibility of pooled stock in this scenario?

Figure 3: Michael Stephenson/Ignacio Gomez-Arroyo Bernabeu

The main change is to replace the booklet on the primary pack by a country agnostic single panel label. The concept of the “untranslatable” label is supported by the ISPE’s “Good Practice Guide: Booklet Labels” © Copyright ISPE 2013, and work is ongoing within the TransCelerate organization on the use of eLabels for use in clinical trials also supporting this approach. The “untranslatable” label ensures:

• All requirements according to Annex 13 are printed on the primary container label, BUT text is replaced by numbers and icons
• Numbers and icons are explained in local language on the kit’s carton label

With the upcoming introduction of Annex 6 and the requirement to print the expiry date on all levels of the kit, the expiry update benefits mentioned previously will be lost. This then moves to the question of kit design and perhaps the necessity to move away from complex kit designs, while keeping kits to the single level, or multiples thereof.

The concept of postponement applied here to the clinical supply chain clearly provides increased efficiencies, better utilization of what can be expensive clinical material, and a flexibility to print the most up to date expiry date at the point of shipping. The addition or removal of countries to a clinical study will no longer create the need to redesign a booklet or package more supplies, simply add the country and apply the label prior to shipping.

 

 

Michael Stephenson

Associate Director, Clinical Supply Chain Technology and Innovation

 

Ignacio Gomez-Arroyo Bernabeu

Senior Associate Engineer, Clinical Supply Chain Technology and Innovation

 

Janssen