Title: Evaluation Process Supporting Elimination of Defined Shipment Temperature Range for Solid Oral Dosage Forms
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| Guidance Number: 87 | |||||
| Prepared by: | Date: | Supersedes: | |||
| Checked by: | Date: | Date Issued: | |||
| Approved by: | Date: | Review Date: | |||
Evaluation Process Supporting Elimination of Defined Shipment Temperature Range for Solid Oral Dosage Forms
Introduction
Some GMP sites may be practicing to ship some oral dosage form products from manufacturing facilities to Distribution Centers under controlled (defined temperature range) temperature conditions. Given the characteristics and stability performance of many solid oral dosage form products, shipment under a defined temperature range is not necessary. This document provides the scientific and risk management assessment process to support the evaluation and, where appropriate, discontinuation of solid oral dosage form shipment under defined temperature range conditions, dependent upon the results of individual product analyses.
Assumptions
- During summer months and in tropical climates, pharmaceutical products being shipped under ambient conditions have the potential to be exposed to elevated temperatures reaching an approximate maximum temperature of 50ºC (122ºF).
- Review of central America to United States Distribution Centres shipment time indicates that the typical shipment time for these pharmaceutical products from manufacturing facilities to distribution centers is less than two weeks. The presented rationale may be applied to discontinue defined temperature range shipments for other shipping routes if the shipment time is known and falls within the assumptions of this model.
- Since the maximum exposure to elevated temperatures occurs during day time hours (approximately 12 hours per day), for a two week shipment time the actual exposure to elevated temperatures is estimated to be a maximum of one week as a worst case scenario.
- Applicability of this document is limited to solid oral dosage forms (e.g. tablets, hard gelatin capsules, powders, etc.). Given dosage form characteristics, shipment of other dosage forms (e.g. soft gelatin capsules, liquid products, etc.) should be performed under temperature conditions in accordance with product labeling.
Requirements
- A minimum of 3 months stability data at 40ºC/75%RH or 40ºC exists for product to be evaluated.
- Prior to implementation of ambient shipment of a product currently shipped under defined temperature range conditions, a documented assessment confirming satisfactory (compliance with specifications) 3 month stability performance at the 40oC/75%RH or the 40oC condition is to be prepared. If available, the required stability information may be obtained from previously executed studies, protocols or regulatory filings performed on the same product formulation. If the product formulation is equivalent, the stability information may be obtained from another site or location. There is no requirement to repeat stability studies if this information is already available.
- The documented assessment should also take into consideration any relevant distribution (e.g. typical shipping duration or anticipated maximum load temperature) or product-specific information that could impact the decision to ship under ambient conditions. This document must be approved by the Site Quality Team.
Recommendations and Rationale
An evaluation using the Arrhenius Equation was conducted to determine if stability data generated at 40ºC would support the elevated temperature excursion potentially affecting the potency and/or degradation of the product during shipment under ambient conditions. As part of this exercise the humidity was not considered a factor and was solely based on temperature.
The Arrhenius Equation relates rate (k) of reaction to temperature (T) and is described by the following equation:
Conclusion
This document provides the scientific and risk management assessment to demonstrate that solid oral dosage forms with acceptable (compliance with specifications) 3 month stability data at 40oC/75%RH or 40oC may be shipped under ambient temperature conditions. Additionally, it provides the requirements to implement ambient shipping for those applicable products that currently are shipped under defined temperature range conditions.