What Is Shelf Life Testing Of A Pharmaceutical Product?

Posted by Michelle Puglielli

Find me on:

chamberShelf-life testing of a drug product is a means of assessing the functionality, effectiveness, and stability of a pharmaceutical product over a period of time to either establish a new expiry date for a new product, or to collect data in ongoing support of an already-existing expiry date for a commercial/marketed product.

To challenge the lifespan of either a new or commercial drug product, it is exposed to various extremes of regulated temperature and humidity conditions for specified lengths of time, inside what are known as “stability chambers”. At periods throughout the study, known as “time points”, samples are removed from their storage conditions, and their integrity is assessed by conducting laboratory testing against an approved, stability product specification.

Shelf life is the period of time, from the date of manufacture, that a drug product is expected to remain within its approved product specification while stored under defined conditions. Shelf life is typically expressed in units of months, i.e. 24 months, 36 months, to a maximum of 60 months. The phrase “shelf life” and “expiry date” is often interchangeably used in the industry, as both terms reflect the same concept: there is a period of time where a product is stable and safe for use, but is made limited based on thorough stability research. Shelf life/expiry dates reflect the time where a product will work both safely and effectively. This is why “shelf life testing” is also referred to as “stability testing”. The amount of time a product can stay stable under certain environmental conditions, equates to its shelf life.

Common Stability Chamber Storage Conditions Used For Product Shelf Life Testing

Long Term Stability Storage

Typically, this is when a product is stored at a temperature range of 25°C +/- 2°C, with humidity set at 60%RH +/- 5%RH (RH – stands for “Relative Humidity”) for up to 60 months. Testing against the product’s stability specification will take place at designated time points. “Time points” reflect the duration of time that the product has been exposed in the set temperature/humidity storage condition. Usual time points for testing are at 0, 3, 6, 9, 12, 18, 24, 36 months, etc. It’s also a good idea to ensure testing is conducted at the actual (proposed or established) expiry date. You should put a minimum of one lot per year of marketed product onto long-term stability; for each dosage strength, each size, and from each type of container/closure, to support the product’s existing expiry date. New products must also be placed on long-term stability to collect pertinent data that will help advise an expiry date.

Accelerated Stability Storage

Determining-Best-Manufacturing-Processes-Guide-For-Pharmaceutical-Products This is when a product is stored at a temperature range of 40°C +/- 2°C, with humidity set at 75%RH +/- 5%RH for up to 6 months. It is referred as “accelerated” because high temperature/humidity exposure to the product over a short period of time accelerates product degradation. In other words, it stresses and challenges the product’s chemical composition to the extreme. Typical time points for testing under this condition are 0, 3, and 6 month milestones. It’s always a good idea to assess the stability of your product at 1 and 2 month time points if possible - more data is better than less data. Accelerated conditions are important to determine the stability of a drug product prior to marketing, and prior to adoption of significant changes in formulation, manufacturing, procedures, or packaging materials that may affect the shelf life of the product.

Intermediate Stability Storage

This condition is usually referred as a “back-up” storage condition in the event that an out-of-specification (OOS) result or significant stability change is identified during testing at the accelerated level. Intermediate storage is generally set at a temperature and humidity range of 30°C +/- 2°C, 65%RH +/- 5%RH. It is called “intermediate” because the storage condition is situated at slightly higher settings than a long-term program, but not as harsh as the settings for the accelerated program. There should be an intermediate study time point coinciding with each accelerated time point up to 6 months. Some intermediate studies allow for product to remain in storage up to 12 months. When a significant change in the product’s stability is observed at the accelerated level, intermediate-study samples can be used for further investigation and assessment as a back-up testing condition.

Stability Product Specifications Must Challenge “The Three P’s” Of Your Product

Your stability product specifications will vary depending on the nature of the product, i.e. tablet, liquid/gel, capsule, cream/ointment, etc.), but three major parameters, regardless of product type, will be challenged. These parameters are the Three P’s:

  • Potency
  • Physical Characteristics
  • Purity

WS-12-2013_47Challenging potency means assaying for all active ingredients and related substances, in addition to preservatives and antioxidants, if applicable. Assessing physical characteristics includes evaluation of the packaging/closure system, product colour, odour, hardness, dissolution, disintegration, pH, viscosity, etc. (again, depends on the nature of the product being tested). Challenging purity of the product at each time point means investigating factors like moisture content, possible migrations between drug and packaging container, corrosion, microbial testing, sterility (if applicable). Maintaining a data/analysis trend record is also important, so that you can closely observe if significant variability exists in the product's performance from time point to time point. The key is to catch atypical results or trends immediately, so that an investigation can be initiated to dig deeper into the issue at hand.

Shelf life testing must challenge the Three P’s at all specified time points, under the appropriate storage conditions, to provide the data and insight necessary for supporting a product shelf-life or expiration date. 

The data collected from challenging Potency, Physical Characteristics, and Purity is a tell-all read of how your product handles. You want to see unwavering results during the proposed shelf life, to ensure consumers have a safe, reliable, and effective product.

Like What You've Read? Click to Subscribe to This Blog ››

Topics: Quality Control Testing

Michelle is a Project Manager of Pharma Services in WellSpring’s Business Development Department, with previous roles in Stability and Research Development as a Program Coordinator, and Quality Control positions in the Chemistry and Microbiology laboratories. Michelle has been with WellSpring since graduating from the University of Waterloo, where she earned her Bachelor of Science Undergraduate Degree. She is currently responsible for managing commercial and clinical CMO projects.

Find me on:

About The Author