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Pharmaceutical Manufacturing and Packing Sourcer

Up to Standard?

The continuing growth of – and increasing move to – large molecule medicines naturally calls for greater reassurance of temperature-controlled packaging reliability. Across the life sciences and packaging industries, there are benefits to be had from an all-encompassing, standardised measure of performance for the temperature-controlled systems used to transport often high-value assets.

There needs to be a more universal approach. Currently, many vendors demonstrate the performance of temperature-controlled packaging by showing an example of performance – most often carried out with an ambient test profile that shows how the packaging will respond to a particular simulated shipment route. However, this method has its drawbacks.

The 'go-to' industry standard for performance regularity is mainly via the International Safe Transit Association (ISTA), which represents a collaboration of manufacturers, packaging suppliers, testing laboratories and carriers working together to try and ensure responsible packaging. Previously, organisations like ISTA have tried to create a standard profile to capture, in essence, the worstcase scenario of what could happen in any given transport situation. But what that ends up doing is further widening the possibilities of creating packaging that is not always fit for purpose. The customer might end up with packaging that is over-designed for what it is needed for.

ISTA’s initial focus was on the mechanical testing sequences, used to prove the robustness of overpackaging for everyday products such as ovens and washing machines. More recently, the association has established thermal test procedures for insulated packaging: one of the profiles widely adopted in standard qualification is ISTA 7D, while the more recent ISTA 7E is viewed as an industry standard.

With the emergence of the new generation of biopharmaceutical medicinal products – coupled with new, remote and logistically demanding markets – the issue of being able to deploy reliable, high-performing shipping systems is paramount. The rapid rise in biopharmaceuticals, generating global revenues of $163 billion, equates to somewhere in the region of 20% of the pharma market – making it by far the fastest growing part of the industry.

Standardised System

Pharmaceutical products are increasingly having to be transported via challenging shipping routes – facing the risk of being exposed to greater temperature stresses or unplanned hold periods like customs clearance. As a result, the introduction of a new industry-wide standard performance measurement is something that should be at the forefront for decision-makers.

There needs to be a collaborative call for a standardised measurement system that is easy to implement and can be adopted worldwide within the sector. The new generation growth of biopharmaceutical products that are highly temperaturesensitive and must be stored and transported within a specified temperature range give an even greater urgency to this situation. Why not implement a thermal stress score, a standardised procedure, calculated by stress testing with universal acceptance?

Kelvin Hours

For greater reliability, a standardised method such as Kelvin Hours (KH) could be implemented and recognised as a new industry standard for the global temperature-controlled packaging industry. It places the emphasis on the shipping system’s performance capabilities.

The benefits of adopting KH as a standard performance measure is that it does not tie itself to a particular ambient test profile. Rather, it is centred on what the specific selected shipping system is capable of doing; therefore, you can say that a particular shipping system will perform against ambient profile X, Y or Z for a specific number of hours for those different demands. It makes for a less subjective and more measured approach. KH could be collated via a simple equation: average thermal stress (K) x control duration (hrs) = Khrs. Adopting this calculated stress testing, using vendor qualification data, would enable simple, fit for purpose evaluations.

KH could easily be adopted as a tool to select the most appropriate level of performance of packaging. This could be used across the board, with a broad range of performance points for the newer-style phase change material (PCM) systems, which is where the KH measure works particularly well.

A company using temperature-controlled packaging can assess shipping lane data using KH, and select a packaging system that satisfies the minimum performance requirement. Essentially, this matches the shipping system to the challenges it is going to face, as opposed to having one shipper option and then finding only half of its potential performance has been used in a particular shipping lane.

Patient and Industry Reliance

The need for a new, standardised measure of performance was not so pressing before, with the shipping of small molecule products that are potentially less temperature-sensitive. However, the new generation of large molecule products – being developed for relatively rare conditions such as various cancer treatments – rely on high-performance packaging systems to prevent their complex, fragile structures being destroyed.

These sophisticated medicines are a lifeline for huge numbers of patients, helping them overcome or manage certain diseases, so it is vital they arrive intact and perform properly. At the same time, pharma companies developing products to treat such conditions rely on shipper performance when supplying for clinical trials. It is at this early, risk-heavy stage, when there is no stability data for the medicines being trialled and it must not go outside a temperature window, that a robust shipping system is required. The safe transportation of both the medicines being trialled and the supply of comparator drugs is crucial.

Comparator Supply

New products being developed have to be tested against similar drugs on the market, usually manufactured and sold by a competitor. Pharma companies have to buy these products at market value, which is often very expensive. Coupled with the fact these companies do not have access to any stability data, they have to ship the payload within a strict temperature range to know it is going to be as effective as it should be. Indeed, the cost implications related to this comparator drug testing can be extremely high, and can constitute up to half of the total budget allocation of a clinical trial.

If the comparator drug goes to waste because the packaging selected for the transportation is substandard, due to a lack of a well-defined performance measure, the costs can be unbelievably high. For example, a 10ml vial could cost tens of thousands of euros for a single dose.

Product Scoring

An industry-wide standardised performance measure such as KH is being driven by the development of large molecule products, as well as the growth of gene therapies and manipulating proteins in research into certain conditions like cystic fibrosis. The reassurance in packaging provided would be particularly relevant in the clinical trial sector, where Big Pharma is focusing more R&D in high-value niche application products.

If a new KH approach was adopted across the industry, there would be different levels/points of performance, or KH scores. This, in turn, would make it easier to match the score with the appropriate shipping system required.

Technically speaking, a KH scoring system could be used to appraise performance at the actual stage of preparing the packaging. This could revolutionise the packaging industry. Rather than selecting a shipper for a particular duration, it would be a case of choosing the appropriate shipper with the relevant KH score attached to it. For further ease of use, a customer could describe the challenges of their specific shipping lane and receive a score that would help them pick the best packaging product for their their needs. This would also have signifi cant cost benefits as it would help to avoid using a product that is over-engineered for its purpose.

Speed and Simplicity

This proposed approach would make it much easier to compare one set of products against another. At the moment, because there are so many different ambient test profi les being used in the industry, performance – or the appreciation or perception of performance – can be skewed. KH scoring would work especially well with newer PCM systems; the area in which it probably needs a little more development is in older water-based technology.

Most of the new product development being seen in the temperaturecontrolled packaging industry incorporates newer, more advanced materials, but there is still a signifi cant proportion of the market using these older water systems, purely due to the cost restraints.

Packaging suppliers often have ambient profi les against which they qualify their packaging. Also, some customers have their own profi les which they request suppliers to qualify against – they see these as indicative of what they would expect during distribution of their product. Each customer will have a different view on what that looks like.

Given that the whole qualification process can be extremely time-consuming, a new industry-wide performance measurement would introduce speed and simplicity – benefiting not just packaging suppliers but also those who have to specify the packaging. When aware of the temperature challenges expected in a shipping lane, it can be used to create a KH score: in theory, whichever suppliers have packaging tested to the standardised score should have the shipper most appropriate for the job.

Passing the Test

Over the last five years, there has been a notable rise in the temperature monitoring of pharmaceutical products. Depending on which region a product is being shipped to – for example, emerging markets such as the Middle East – customs control may open a temperature-sensitive package with a data logger inside it, in order to inspect the data logger and check it is still within temperature. If it has not been maintained at the correct temperature up to that point, the package could be sent back.

The industry needs to change in order for the ever-more sophisticated medicines being produced to be effective and to reach their destinations. If they get too hot or cold, and if they are protein-based, the proteins can denature and lose efficacy – jeopardising what could be life-saving treatments for patients. It remains to be seen whether changing to a standardised method, such as KH, can truly allow companies to significantly enhance their performance.

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Richard Wood, Design Manager at Peli BioThermal, has worked in various design and manufacture engineering functions during his career. He has been part of the company since 2005 and has been involved in hundreds of cold chain packaging projects. Richard’s current role is focused on standardising development, qualification and manufacturing practices across the Peli BioThermal network, supporting its global customer base and leading the new product development programme.
Richard Wood
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