Stability Testing Methods and Protocols in Pharmaceuticals - A Recent Update

Introduction:

Stability testing is an integral part of pharmaceutical science. It is more crucial to existing pharmaceuticals and developing new pharmaceutical products with their active ingredients to determine their shelf life and so the expiry date. As for the newly developing products, stability testing is equally essential for ongoing manufacturing to assess the quality of the product as a function of time. For any drug product, stability testing establishes the shelf-life of that particular product by determining the duration for which the drug product would be safe to administer and preserves therapeutic value depending upon the rate and degree of active ingredients.

What Is Stability Testing?

Generally, stability testing is the process of discerning and assessing the products over a predetermined time interval in certain environmental conditions. This process is aimed at detecting any change in the quality with respect to time and environmental changes. The stability testing process in the pharmaceutical industry is a similar process where the manufacturers gather data on their drug product over the premediated length of time in specific conditions to establish whether there is any change in active ingredients and the final drug product. The data collected through this process is then proclaimed to the Food and Drug Administration (FDA). So, the drug product could be designated an appropriate shelf-life and receives its approval for public release.

What Are the Stability Testing Methods and Protocols in Pharmaceuticals?

Stability testing is an integral part of the pharmaceutical industry, as it serves an essential purpose in ensuring the safety, quality, and drug products over their shelf life. There are a range of methods and protocols employed for stability testing. The following are a few crucial methods:

• Real-Time Stability Testing: Real-time stability testing is a chief method where the samples of the drug products are stored under approved storage conditions for a lengthened period, mostly until the date of the product’s expiration. Then, the stored samples are tested periodically for their dispositions, such as potency, efficacy, impurity levels, degradation, and physical changes.

• Accelerated Stability Testing: The method of accelerated stability testing treats drug products to more crucial and severe conditions like increased temperature and humidity. This accelerates the degradation mechanisms that would happen over time. This testing helps determine and assess the shelf-life of the drug product even in a shorter timeline. Accelerated stability testing studies are generally directed eventually with real-time stability testing.

• Forced Degradation Studies: In the forced-degradation study approach, the drug products or ingredients are exposed to certain stressful or forced conditions, including light, heat, humidity, oxidation, and acid and base hydrolysis. The significance of this method is to determine and characterize the possible degradation pathways and their inherent stability.

• Stability-Indicating Assays: Stability-indicating assays are analytical-based methods that are implemented during stability testing to determine the stability of the drug. It is also used to determine any changes or degradation that might happen over time. This approach is strong enough for isolating and weighing the active pharmaceutical ingredients and their impurities.

• Photostability Testing: Photostability testing help evaluate the product’s susceptibility of getting degradation when induced by exposure to light. Here, the drug samples are exposed to a distinct range of light sources, such as ultraviolet (UV) light and visible light. They are then observed for changes and degradation in the quality consideration.

• Container Closure Integrity Testing: This testing approach is used to ensure that the product packaging contributes to a potent barrier against common environmental determinants. These include light, oxygen, heat, and moisture. The routine methods in container closure integrity testing include dye ingress, microbial ingress, visual inspection, and headspace gas inspection.

What Are the Guidelines for a Pharmaceutical Stability Test?

The following includes the pivotal guidelines for stability study testing for new drug products:

• The stability study should be inclusive of augmented and long-term stability testing on a minimum of two primary drug production batches. Consideration is to be taken for a minimum of three primary production batches in the case of any susceptible product.

• At the event of submission for the drug product application, The augmented stability testing data at 40 degrees Celsius for at least six months and long-term stability readying at 30 degree Celsius must be available.

• The drug product that is stable for six months at 104 degrees Fahrenheit and 75 %, then the shelf-life for that product can be designated as 24 months.

• Nevertheless, if the drug products extending over 24 months are to be designated to the product, then the actual time stability testing input should be at hand.

• According to the internal policy decision, a shelf life of 36 months can be given if the drug product is recognized as stable at the augmented stability testing conditions. But this is not accepted by international means.

• The shelf life status of 36 months can be labeled to the drug product that has completed the long-term stability testing period of 36 months and more.

• If a change is implemented in the primary packaging material, the drug product should be addressed and treated as a new drug product for stability study testing.

• The stability studies are to be executed on every individual strength of the product until bracketing is applied.

• If the same product has different doses, strengths, and production processes but similar production formulations, then each product should be addressed and treated as a new drug product. These products should carry out separate stability studies for each of their doses.

• The frequency of the long-term stability testing includes every three months over the first year, every six months for the second year, and annually for the entire proposed shelf-life.

Conclusion:

Pharmaceutical stability testing is essential to a greater extent in the manufacturing and distribution of drug products since it is assigned a shelf-life and approval for release. In addition, it is more important for determining the determinants like optimal storage conditions, restored time, and overall quality. During stability testing in the pharmaceutical industry, drug manufacturers examine their products for any susceptible changes in the physical, biological, chemical, and microbiological properties of the drug substance. Moreover, these elements are known to influence the safety and efficacy of the drug product for consumers. Therefore, it is essential to undergo effective and extensive stability testing prior to displaying the drug product in the market.