samedan logo
 
 
spacer
home > pmps > winter 2011 > the impact of ista 7e
PUBLICATIONS
Pharmaceutical Manufacturing and Packing Sourcer

The Impact of ISTA 7E

The recently published ISTA 7E aims to function as a universal test profile for insulated shipping systems. But how can the standard best be used by the shippers themselves?

Regulatory pressures and the use of third parties to manufacture and distribute drug products has attracted the attention of global regulators as well as quality assurance groups in pharmaceutical companies. Active and passive devices designed for the shipment of temperature-sensitive medicinal products have not been standardised due to the dynamic nature of the supply chain. The International Safe Transit Association (ISTA) is publishing a data-based standard to assist pharmaceutical companies in the qualification of temperature-controlled systems. This article considers the pros, cons and potential impact of a universally accepted global thermal test profile for the qualification of insulated shipping systems.

ISTA 7E

International Safe Transit Association 7E is a thermal test standard being published by the ISTA. It is designed to recommend a standard for the qualification of temperature-controlled product packaging (TCPs) for the transport of temperature sensitive medicinal products. TCPs are defined as any active or passive packaging system designed to maintain designated temperatures during the transport of temperature sensitive medicinal products. First, it is important to understand that no globally accepted standard exists for the qualification of TCPs. The development of this standard is controversial within the Parental Drug Association (PDA), global regulatory bodies and the pharmaceutical industry for a number of reasons.The goal of this article is to identify facts, explore positive attributes, along with negative impacts, and, finally, to speculate on how ISTA 7E may be employed.

Why the Debate?

ISTA’s previous thermal profile recommendation was called ISTA 5B, which is meant to be an example of how a thermal profile might be constructed and recommended monitoring supply chain temperatures. Since the development of ISTA 5B, thermal test profiles have been a source of discussion amongst regulatory bodies as well as pharmaceutical manufacturers. The primary reason for this debate is the lack of data. When taking into consideration geographic zones, seasonal variance and anticipated temperatures throughout the shipping process, many pharmaceutical companies lack sufficient temperature data within their supply chain. This hinders their development of a data-based profile. As a result, many companies adopted the example profile provided in 5B. Other engineers adopted a ‘worst case’ approach; engineering to extreme geographic ambient highs and lows. The use of a ‘worst case’ methodology in the design of TCPs leads to higher packaging and logistics spends. Higher levels of thermal or physical stress require additional packaging materials in order to protect products. The added materials lead to heavier systems, higher costs and increased freight spends. Despite these engineering attempts, temperature excursions still plagued the industry.

In recent years, data loggers have become smaller, more affordable and easier to use. The data collected from these devices shows that temperatures within the supply chain do not match the extreme geographic highs or lows on any given day (see Figure 1).

Several key observations can be made:

  • Temperature is a moving target
  • It is difficult to capture extreme temperatures over 35ºC or under 0ºC
  • When extreme temperatures are captured they single out events which do not last long in duration

This information provided an opportunity for larger pharmaceutical companies to develop new thermal test profiles developed from data within their supply chain. This approach is in line with Six Sigma or risk-based approaches often used in the pharmaceutical industry.Using data in the development of thermal test profiles is a significant step forward.

Facing the Facts

ISTA 7E is the International Safe Transit Association’s attempt to update their test methodology for the testing of TCPs, specifically for the pharmaceutical industry. ISTA 7E is the first data-based thermal profile published by a packaging standards organisation. ISTA accomplishes this using the Center for Drug Evaluation and Research (CDER) guideline for process validation. Process validation is defined as the collection and evaluation of data, though the process of design and production (IQ/OQ) which establishes scientific evidence that a process is capable of producing consistent results (1). ISTA partnered with several pharmaceutical companies, a packaging supplier and a global logistics provider in order to conduct this study.Temperature, vibration and pressure data were collected during a summer and winter test campaign. Data were collected during round-trip shipments over 82 different lanes within the US. Statistical confidence intervals were used in order to develop test criteria for TCPs. ISTA notes a difference between geographic and shipping lane temperatures. Geographic temperatures are defined as the extreme outdoor seasonal highs or lows in a given region verses a shipping lane temperature which are the seasonal highs or lows within trucks, warehouses and planes within the supply chain (2). ISTA 7E will contain a qualification manual called Standard 20 which will instruct customers on exactly how to develop a test protocol, which contains information on test procedures, responsibilities, data analysis techniques and how to format data (2). Standard 20 includes detailed information about thermal lab audit requirements, personnel training, design testing (installation qualification), thermal and physical qualification (operational qualification), nomenclature and document formatting. The ISTA 7E data package will include raw data, formatted graphs, ‘qualified air temperatures’ (Delta T between air and product temperatures), drawings, packing instructions and calibration certificates in triplicate (2).

Global Supply Chain in Flux

Since shipping lane temperatures differ from geographic temperatures, to some degree ISTA is measuring the capabilities of the US supply chain for one carrier. The US supply chain differs significantly from other global regions in that other logistic providers have less control of their packages. Shipping the same distance in the European region would be considered international shipping. Therefore, these European shipments will endure an increase in scrutiny in the international environment and affect the data collected. Delays due to customs or other problems associated with international shipping, especially to under developed countries, may increase the probability of extreme thermal and physical exposure.

The global supply chain is in a state of evolution. The advent of affordable miniature-sized data loggers is a key factor in the ability of the industry to gather data from their supply chain. While this development gives ISTA the ability to develop a data-based thermal profile, it also gives logistics providers the opportunity to take better control over their supply chain. In an effort to differentiate themselves in a competitive market, large freight companies have spent millions of dollars developing specialised service divisions which cater to the pharmaceutical industry. These companies are not only collecting data, but experimenting with RFID in order to measure thermal and physical events, while also gaining control during transit. A higher degree of control over the shipping process and real-time information is a competitive advantage for the life science freight company. Areas of risk can be identified and gaps in the process can be addressed. These activities will decrease the thermal and physical stress packages within shipping lanes.

The primary reason stated by the ISTA as to why pharmaceutical and regulatory bodies should adopt the ISTA 7E profile for the qualification of insulated shipping containers (ISC) is that it removes the subjectivity to the ISC qualification process and allows for “an intercomparable common standard” (3). Once 7E was published, discussion amongst pharma companies and services providers will in all likelihood ensue. As mentioned previously, ISTA 5B gave a suggested thermal test profile and recommended periodic monitoring. It appears that ISTA is taking a stronger stance this time around.

The cost to become Standard 20 compliant and sanctioned as an ISTA qualified thermal lab is $25,000. The fee is paid to ISTA for qualification and does not include additional equipment, report writing, component testing or labour costs. On 13 April 2010 at the annual Pharmaceutical Cold Chain Interest Group (PCCIG) meeting in Bethesda, industry members asked the ISTA what cost will be passed down to end users as a result of the new qualification process. ISTA responded at IQPC’s 8th Cold Chain Distribution of Pharmaceuticals Global Forum that the cost to become Standard 20 compliant will not impact the cost of ISCs, because “interviews with manufacturers confirm that there will not likely be a mark-up for an ISTA certification of a shipper” (2). If the pharmaceutical manufactures and regulatory groups accept 7E universally, this premise may become reality and testing to customer-specific thermal profiles could be greatly diminished or eliminated.

While thermal labs trying to assess industry acceptance may struggle to develop a standard return on investment (ROI), analysis shows the financial gain on the investment is tied directly to the degree of industry sanction. Independent ISTA qualified test labs, which perform both physical and thermal testing,may not be able to justify the expense due to their mix of business and risk a loss in revenue. A lab must have a great deal of thermal test business in order to recoup the ISTA fee; as a result the supply of ISTA licensed thermal labs may diminish. Conversely, manufacturers of ISC who seek ISTA qualification first risk the loss of profit dollars in their labs, as they work to recover dollars paid to become Standard 20 compliant. How the market will react is still uncertain, but if it can be shown that ISTA-qualified ISCs make drugs safer by significantly reducing temperature excursions, customers can make decisions based upon their profit margins and risk associated with product loss. Detailed information can be obtained by contacting ISTA.

Conclusion

Standard 20 is well intentioned and designed in a way which is compatible with the industry it is attempting to serve. High marks can be given to its science-based approach. What is difficult to measure is cost versus benefit; in the world of regulation and good manufacturing practice (GMP), it is often easy to lose sight of who we are serving. Ultimately, the two most important groups, in order of importance, are the patients and shareholders. Product safety and efficacy must be placed before profit; however, drug products could not be developed, tested and approved without shareholder benefit and corporate profit. The current economic climate places high demands on business in order to survive. The pharmaceutical company not only faces economic uncertainty, but also political pressure to provide more products to more people for less money. This makes it difficult to embrace a suggested standard which may or may not make products safer and meet political and consumer pressures to lower prices.

It is still uncertain if ISTA 7E will be accepted globally; conversely, the pharmaceutical industry is global. Harmonisation from a process perspective is difficult. Years ago, being global meant operating a facility in a foreign country, but in 2010 it means operating all facilities in unison, in order to benefit the entire firm. This is extremely difficult to accomplish given legacy procedures, different cultures, language barriers and time zone differences. The present economic situation and high levels of flux in foreign currency exchange add layers of complexity to global firms. The chances that regulatory bodies worldwide will accept an ISTA certified system, without additional data to substantiate its use, is challenging. Comparing temperatures within your supply chain to the thermal test profile used to qualify your package will still be significant moving forward. Collecting performance data is critical in supporting any qualification methodology in a regulatory audit. Many larger pharmaceutical organisations have internal validation plans for the implementation of ISCs. These standard approaches are still relevant from a regulatory point of view in the evaluation of a prequalified ISC package. Customers will compare the thermal profile provided in any given pre-qualified package against the data they have collected within their supply chain in order to establish a proof-of-concept.

Ideally, if all pharmaceutical companies and package providers adopted ISTA’s testing methodology, pharmaceutical companies could more easily bid out ISC providers and select one, or multiple providers, that can provide the supply, pricing and performance against the ISTA test methodology. ISTA announced that the 7E profile and Standard 20 were scheduled to be released on 22 September 2010 at IQPC’s 8th Cold Chain Distribution of Pharmaceuticals Global Forum, in Philadelphia, but would not be published until later in 2010. Ultimately, this standard will be used by those that require the attributes it offers and rejected by those who have been vigilant in thermally protecting their temperature sensitive shipments and have already developed measurable standards specific to their needs.

References

1. Food and Drug Administration (FDA), Guideline on General Principles of Process Validation, www.fda.gov/Drugs/GuidanceComplia nceRegulatoryInformation/Guidances/ ucm124720.htm, October 2010
2. International Safety Transit Association (ISTA) Brochure, ISTA 7E + Standard 20 p3, September 2010
3. Cox J, IQPC 8th Cold Chain: Distribution for Pharmaceuticals Global Forum, afternoon session Track B, 22 September 2010

 


Read full article from PDF >>

Rate this article You must be a member of the site to make a vote.  
Average rating:
0
     

There are no comments in regards to this article.

spacer
Kenneth L Lukes is Business Development Manager of Inmark’s Temperature Control Packaging (TCP) line within its Life Sciences Division. From 2003 to 2007, Kenneth was the Sales Manager for EnviroCooler. His experience includes TCP package design, thermal laboratory testing, process development, data analysis, package validation, and TCP implementation in a GMP environment. Kenneth is a member of The Parenteral Drug Association and has participated in the Pharmaceutical Cold Chain Interest Group since 2003. He holds an MBA, with an emphasis on global business, from the University of Redlands in California.
spacer
Kenneth L Lukes
spacer
spacer
Print this page
Send to a friend
Privacy statement
News and Press Releases

Syntegon and Vetter win PDA Drug Delivery Innovation Award for Versynta microBatch

Waiblingen/Germany, October 6, 2021. Together with Vetter, an international pharmaceutical service provider for injectables, Syntegon (formerly Bosch Packaging Technology) has won the PDA Drug Delivery Innovation Award. In the "Partnership Innovation" category, the Parental Drug Association (PDA) honors development projects by pharmaceutical and machine manufacturers that advance the production of (bio)pharmaceuticals. The collaboration between Vetter and Syntegon resulted in Versynta microBatch, a highly flexible and fully automated production cell with a gloveless isolator, the smallest possible dimensions and a complete batch-to-batch changeover of less than two hours.
More info >>

White Papers

Challenges of Analytical Method Transfer in the Pharmaceutical Industry

RSSL

The development and validation of suitable analytical methods is a critical part of the overall drug-development life-cycle. For the majority of products, particularly those that are clinically successful, the transfer of the analytical method between laboratories will be required. This process is designed to verify that a given laboratory is capable of performing a test method for its intended purpose. This can be performed either internally (at the same company), or, with the on-going increasing trend in outsourcing, to an external Contract Research or Development organisation (CRO or CDO).
More info >>

 

 

 

©2000-2011 Samedan Ltd.
Add to favourites

Print this page

Send to a friend
Privacy statement