USP Regulatory Blog Series

USP <659> Changes are Fast Approaching

The United States Pharmacopeia (USP) is scheduled to make changes to key chapters that may affect life sciences companies such as manufacturers, wholesalers and pharmacists, along with all companies that handle, store and transport pharmaceuticals, including logistics service providers. The changes will be published in August 2020 and made effective by December 2020. In this Sensitech series, we will highlight important changes that will affect life sciences companies’ storage and distribution, and how to plan for those changes.

Difference Between Guidance and Law

Founded in 1820 in Washington, D.C., the USP is a nonprofit scientific organization that develops and disseminates public compendia quality standards for medicines and other articles. The USP product temperature definition was originally in USP <1079> and now resides in chapter, USP <659>. This is significant, because chapters numbered above 1,000 are considered guidance, whereas those numbered below 1,000 are considered law and are enforceable by the U.S. Food and Drug Association (FDA). Moving product temperature definitions to USP <659> has legally mandated that all products with temperature label claims must provide assurance that temperature is maintained.

Controlled Cold Definition Added

The USP has added a new temperature definition called Controlled Cold. Standard Refrigerated temperature is +2°C to +8°C. The added definition of Controlled Cold is +2°C to +15°C with temperature excursion time (above limits) no more than 24 hours and Mean Kinetic Temperature (MKT) not to exceed +8°C. No excursions are allowed below +2°C or above +15°C.

Standard Refrigerated Temperature vs. Controlled Cold

To further understand MKT, it is defined in (USP 35 Chapter <1150>, Pharmaceutical Stability) as: “…a single calculated temperature at which the total amount of degradation over a particular period is equal to the sum of the individual degradations that would occur at various temperatures.” For example, the MKT value is supposed to include the total amount of product degradation for a period of time that is equivalent to the incremental degradation that would occur in separate excursions. MKT is an additional tool that can be used to evaluate a temperature excursion.

This new Controlled Cold definition will allow refrigerated products that experience temperature excursions to be evaluated more quickly. The prior stricter +2°C to +8°C refrigerated definition required more shipments to be quarantined and evaluated. Companies can evaluate potential cost savings by reducing the number of shipments with excursions, thus reducing quality assurance time investigating excursions. TempTale^® dataloggers can be programmed to the expanded +2°C to +15°C with 8°C MKT to potentially reduce the amount of time investigating excursions.

The two changes in USP <659> show that the FDA is continuing to move toward stricter enforcement to protect consumers, while at the same time defining ways to make the process of managing excursions more efficient.

Sensitech Regulatory Experts are Here to Help

Sensitech tracks and maintains extensive information related to regulatory changes and can provide in-depth information to your company related to USP <659>. Sensitech also provides direct support on best practices for temperature controlled storage and transportation. With over 20 years of experience, Sensitech Professional Services conducts more than 100 engagements per year assisting life sciences customers improve their storage and distribution practices with actual data using proven methodologies.

You can read more about the current USP <659> document and the soon to be published USP <1079>. Return to read the next blog in this series: USP <1079> Changes You Need to Know.

USP <1079> Changes You Need to Know

Now we will dive into the changes that affect USP <1079> and how to prepare for risks and mitigation strategies across storage and transportation of finished drug products. The United States Pharmacopeia (USP) is scheduled to make changes in 2020 to key chapters that may affect life sciences companies. It is important that all life sciences companies become aware of the changes and plan how the changes will affect their storage and distribution.

Which Chapter is Changing?

The USP is scheduled to release changes in August 2020 to USP <1079>, which will be made official in December 2020. The new USP <1079> changes are significant and outline the need for all companies who will store, handle or transport products with label temperature requirements to meet a thorough Quality Management System (QMS). USP <1079> outlines good storage and distribution practices for temperature sensitive drugs during all stages of the cold chain. The existing chapter is titled “Good Storage and Distribution for Drug Products.” The new proposed chapter title will be – “Risks and Mitigation Strategies for the Storage and Transportation of Finished Drug Products.”

Change is Defined

The new USP <1079> chapter focuses on product and process knowledge, risk identification, mitigation strategies, documentation, training, resources, and qualification/validation, all leading to a well-designed Quality Management System (QMS). One of the significant changes is a new chapter outlining the Roles of Organizations within the Supply Chain. It specifically defines the responsibilities of manufacturers, wholesalers, distributors, pharmacies, compounding pharmacies, hospitals, healthcare providers, brokers and logistics providers. The new USP <1079> defines the requirements of all partners within the supply chain, from manufacturer to last-mile pharmacy, and the responsibilities that all must follow to protect product and ensure patient success. The responsibilities relate to qualification and validation such as temperature mapping, shipping package qualification, monitoring systems and alarms, software validation, calibration, excursion handling and training.

The product temperature definition that was in USP <1079> now resides in chapter, USP <659>. See blog: Why are USP <659> Packaging and Storage Requirements Important?

New Sub-Chapter USP <1079.2>

The USP has also written a new sub-chapter to USP <1079> called USP <1079.2> “Mean Kinetic Temperature in the Evaluation of Temperature Excursions during Storage and Transportation of Drug Products.” The USP plans to add new sub-chapters to supplement the new USP <1079>, and they are:

• USP <1079.1> Storage and Transportation of Investigational Drug Products
• USP <1079.2> Mean Kinetic Temperature in the Evaluation of Temperature Excursions during Storage and Transportation of Drug Products
• USP <1079.3> Monitoring Devices – Time, Temperature, and Humidity will replace USP <1118>
• USP <1079.4> Qualification of Storage Areas
• USP <1079.5> Qualification of Shipping Systems
• USP <1079.6> Transport Route Profiling Qualification
• USP <1079.7> Information Systems for Distribution Validation / Verification Studies

USP <1079.2> Mean Kinetic Temperature More Clearly Defined; Storage and Transportation of Drug Products

In this final section, we will clearly define sub-chapter USP <1079.2> Mean Kinetic Temperature. The United States Pharmacopeia (USP) is scheduled to make changes to key chapters that may affect life sciences companies. It is important that all life sciences companies become aware of the changes and plan how the changes will affect their storage and distribution.

USP <1079.2> Mean Kinetic Temperature Defined

The United States Pharmacopeia (USP) is scheduled to release changes in August 2020, to sub-chapter USP <1079.2>, which will be made official in December 2020. USP <1079> outlines good storage and distribution practices for temperature-sensitive drugs across all stages of the supply chain. USP <1079.2> is a new sub-chapter providing more guidance around Mean Kinetic Temperature (MKT). Mean Kinetic Temperature expresses the cumulative thermal variability experienced by a product during storage and distribution. Excessive thermal variability will result in an unacceptable MKT value.

Mean Kinetic Temperature Challenges

Challenges with the use of Mean Kinetic Temperature over the years and within the pharmaceutical industry have centered around three main topics:

1. How much temperature data is too much when calculating MKT?
2. Can MKT only be used for storage or can it also be used within transportation?
3. Can MKT only be used for Controlled Room Temperature (CRT) products or can it also be used for refrigerated products?

This new sub-chapter USP <1079.2> defines limiting how much data to use when calculating MKT, along with an explanation of its use for transportation and refrigerated shipments.

Many organizations still use 52 weeks of temperature data to calculate MKT. For the Storage of CRT products, this new chapter defines that a maximum of 30 days of temperature data may be used for the calculation of MKT. Similarly, for the new refrigerated temperature category called “Controlled Cold Temperature,” only 24 hours of data during transportation may be used to calculate MKT. For more information about the new definition Controlled Cold, see Why are USP <659> Packaging and Storage Requirements Important?

The Benefit of USP <1079.2>

The goal of this new sub-chapter is to limit the amount of data used and the time period in the MKT calculation -- calculating over a longer time period increases the amount of data used, which can potentially dilute results and create acceptable MKT values, when the product actually may have been temperature abused. By limiting the timeframe of data used to calculate MKT (maximum of 30 days), it will result in MKT values that better depict the actual temperature a product may experience during storage or transportation.

Read more about USP <1079.2> and the revised USP <1079.2>. This concludes the USP <659> and <1079> series. Return often to learn about other regulatory changes that Sensitech experts are monitoring to help customers become compliant while improving quality and cost to their supply chain.

If you would like more information on Sensitech’s thermal mapping studies, contact us.