For registering novel pharmacological ingredients and medicinal products, the minimal requirements for stability data package Stability studies are carried out in several temperatures and Humidity chambers manufacturers to offer data for determining the medicinal product’s or biologic’s commercial expiry date.
Although medical devices are not included in the scope of the ICH paper, many of the principles can be applied to medical device stability studies. Representative stability samples are held and removed in these conditions according to a pre-approved testing plan or technique.
Testing is performed on these samples using proven analytical processes to support the expiration dating of pharmaceutical items, and data are compared to relevant product specifications.
These storage conditions require that the temperature and humidity of the stability chambers be controlled within two °C and 5% Relative Humidity, according to guidance from the Food and Drug Administration (FDA), the World Health Organization (WHO), the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH), and various global health authorities (RH).
Excursions that aren’t covered by these variants must be handled and researched. 1,2,3 The temperature of injectables or biologics stored frozen may need to be kept within five °C or ten °C, with no required humidity.
How carefully stability chambers are built and maintained, inevitable deviations will occur, including power outages, chamber component failures, and even human error (for example, a technician failing to close the chamber door completely). As a result, a temperature and humidity deviation occur, which must be addressed to evaluate the impact.
Consider the case of a technician who leaves a chamber door open in the afternoon; the excursion may easily last longer than 24 hours, prompting an investigation. Knowing precisely what samples are held in the chamber is a critical first step in conducting the inquiry. As a result, preserving accurate and up-to-date chamber sample inventories is vital of the trip (as determined by the environmental monitoring system).
It’s also crucial to be aware of current inventory, particularly for temperature-sensitive items. A weekend getaway, for example, may not be necessary for a 12-month sample, but it may have a significant influence on a 1-month selection.
The relative humidityis a function of temperature, and it’s also necessary to evaluate the impact on humidity if any samples are in permeable packaging. These three details (length, worst-case temperature, and presence of permeable packaging) will aid in the inquiry, corrective action, and, if necessary, rapid remedial action.
The product’s stability qualities are also important in determining the impact of these excursions; hence, labile products may be subjected to a more significant effect than stable products and should be assessed on a case-by-case basis.
Create a Risk Assessment
Understanding the physical and chemical features of the impacted sample material is crucial. This understanding will serve as the foundation for assessing the risks and consequences of deviations from the stability program and adopting and prioritizing appropriate actions..
Temperature/moisture-sensitive items should be given special attention. Excessive excursions are often not tolerated by biologics, as they risk losing their therapeutic effects entirely. Due to the loss of time and product and the danger of creating conflicting results, repeating a stability study due to an excursion is not a desirable alternative.
Furthermore, some biologic degradation processes are only detectable at higher stress temperatures, making the shelf-life determination to be utilized for the temperature excursion evaluation meaningless. Appropriate controls and due diligence provide a scientific and technically sound method to ensure any ongoing project’s ongoing integrity.
Excursion Scenarios and Recommendations in the Stability Chamber.
Several suggestions are made based on the nature of the excursion and the impacted Humidity chambers manufacturers (Controlled Real-Time (CRT) or Accelerated). It should be emphasized that this study does not handle refrigerated or frozen situations. In many circumstances, Mean Kinetic Temperature (MKT) can be used to explain the performance of a chamber over a longer length of time (30 days or more). This information would apply to all of the products kept in these rooms.
Use data from accelerated and stress studies to your advantage.
Stability risks can be identified using forced degradation experiments. Examining degradation products at severe temperatures and humidity levels aids in the identification of degradation pathways and the development of appropriate stability-indicating analytical methods.
If a previous stress study had been conducted at 50°C for up to a week for each type of product sample contained in the chamber, we would have a good idea of the type of degradation that the models would experience, as well as how the critical quality attributes might be impacted in the case where a 40°C accelerated aging knowing how Having this information before going on a chamber expedition will be beneficial.
While the focus of this article is on temperature and humidity variations, the photostability of the drug substance and drug derivatives should also be considered. Many stability samples may be held in main packages in stability chambers and exposed to light. Any contaminants should be identified as resulting from storage (aging) or light excursions if degradation occurs. As a result, forced degradation studies can be helpful in the study of a Humidity chambers manufacturers excursion and provide extra information to assess the risk to sample integrity.
Stability chambers that are well-maintained are an essential part of any well-run Stability Program. A temperature and Humidity chambers manufacturers excursion will occur at some point, regardless of vigilance. The impact of the expedition on the stability samples can be assessed using a variety of methods. Depending on the duration and extent of the excursions, changes in the samples’ chemical or physical (and even geometric) features occur.
To assess the impact risk of the excursions on the quality and integrity of the samples stored in that chamber, tools such as the Mean Kinetic Temperature (MKT) concept, stress testing/forced degradation studies, accelerated condition studies, and additional post-excursion extra sample testing can be used. Once the effect risk has been identified, mitigating measures such as protocol testing enhancements or enhanced aging can be determined.