What is a stability test? Stability testing is vital for helping to ensure the quality, efficacy, and safety of dietary supplements. It helps determine how a product’s quality and characteristics may change over time, thereby establishing the product’s shelf-life and proper storage instructions. It also plays a key role in product development, helping manufacturers identify potential issues early in the product development phase, and reducing the risk of commercial interruptions and product recalls.
This article will provide you with an essential understanding of product stability testing and stability testing methods.
What is Stability Testing?
Stability testing includes laboratory methods to determine how nutrients and other nutraceuticals found in dietary supplements will react to standard storage conditions (e.g., on store shelves, warehouse shelves, kitchen cabinets, etc.). Will the supplement maintain its potency? Will it maintain the integrity of its structure? Stability testing plays a key role in answering these important questions.
Stability testing is a crucial part of determining expiration dates that appear on the product’s label. This process plays a key role in identifying the nutrients that are most susceptible to degradation and determining the extent to which their potency is impacted over time. By accounting for such variables as specific ingredients, dosage form, packaging and storage conditions, stability testing can determine the degree of potency needed for a given nutrient to compensate for potency losses over time.
For example, vitamin C was found to be unstable and subject to loss when stored at higher temperatures1Stawny M, Gostyńska A, Olijarczyk R, Dettlaff K, Jelińska A, Ogrodowczyk M. Stability studies of parenteral nutrition with a high dose of vitamin C. J Oncol Pharm Pract. 2020;26(8):1894-1902. doi:10.1177/1078155220904438 2Ribeiro, D.O., Pinto, D.C., Lima, L.M.T. et al. Chemical stability study of vitamins thiamine, riboflavin, pyridoxine and ascorbic acid in parenteral nutrition for neonatal use. Nutr J. 2011; 10:47. https://doi.org/10.1186/1475-2891-10-47.. So, what can be done to mitigate this situation? Avoiding high storage temperatures is recommended, but another thing that can be done is to use a higher overage. Overages refer to adding a higher percentage of the nutraceutical than is required to meet label claim at the time of manufacture. This might range between 3% and 25% for some nutrients, or even higher in the case of probiotics. Adding an appropriate overage helps ensure that 100% of the label claim for a given nutraceutical will be met up to the expiration date.
Factors That Affect Product Stability
There are a variety of factors that can negatively affect product stability. These include:
- Temperature – Temperature is one of the most important factors in a product’s physiochemical stability, and it can have a significant effect on stability testing. For example, a 10°C increase in storage temperature can speed up hydrolytic degradation by up to 500%.3World Health Organization. Annex 5: Guidelines for stability testing of pharmaceutical products containing well-established drug substances in conventional dosage forms. WHO Technical Report Series. 1996; no. 863: 65-80.
- Humidity – Humidity is a key factor in stability testing and storage. For example, tablets stored at high humidity can become more porous and less tensile, especially if they contain a filler like microcrystalline cellulose (MCC).4Maclean N, Khadra I, Mann J, et al. Investigating the role of excipients on the physical stability of directly compressed tablets. Int J Pharm X. 2021;4:100106. Published 2021 Dec 9. doi:10.1016/j.ijpx.2021.100106
- Light – Light exposure can significantly affect the stability of a product, leading to reduced efficacy and/or inactivation.5More HT, Bindra DS, Zumba A, Zhou K, Carvalho T, Mantri R. Effect of light source and UVA quotient on monoclonal antibody stability during ambient light exposure studies. Eur J Pharm Biopharm. 2023;185:177-182. doi:10.1016/j.ejpb.2023.03.001
- Oxygen – Oxygen can cause chemical instability in products, which can lead to degradation and the formation of impurities.6Gabrič A, Hodnik Ž, Pajk S. Oxidation of Drugs during Drug Product Development: Problems and Solutions. Pharmaceutics. 2022;14(2):325. Published 2022 Jan 29. doi:10.3390/pharmaceutics14020325
- pH – pH is an important factor in stability testing since it can trigger chemical reactions that lead to degradation or structural changes in pharmaceutical compounds or release active ingredients from pH-sensitive carriers.7Martins de Oliveira V, Godoi Contessoto V, Bruno da Silva F, Zago Caetano DL, Jurado de Carvalho S, Pereira Leite VB. Effects of pH and Salt Concentration on Stability of a Protein G Variant Using Coarse-Grained Models. Biophys J. 2018;114(1):65-75. doi:10.1016/j.bpj.2017.11.012
How is Stability Testing Done?
There are two types of stability testing:
- Accelerated stability
- Ambient stability
Types of Stability Testing
Accelerated Stability
During accelerated stability, a dietary supplement in its intended packaging is placed inside an environmental chamber that controls both temperature and humidity. This chamber will create temperature and humidity conditions which are designed to accelerate the normal aging of a product. For example, if a product spends one month in the accelerated machine, it may be the approximate equivalent of six months of aging time. When the product is removed, it can then be tested for potency loss and other effects.
Ambient Stability
What is a real-time stability study? Ambient or “real-time” stability is determined by taking a sample of the packaged product we manufacture and holding it in a retain room under controlled, ambient temperature and humidity conditions. The retain room is used to correlate and confirm shelf-life results from accelerated testing. At regular intervals during its shelf life, a product is pulled from the retain room and tested for potency which is then compared to the accelerated aging studies.
Most brand owners prefer not to wait until stability testing is completed to launch a product since, even with accelerated stability, that will result in a delay of a few months after the product is manufactured to bring it to the market. In this situation, a brand owner may rely on the contract development and manufacturing organization’s (CDMO’s) expertise with the ingredients in the supplement to establish expiration dating, and then make any adjustments deemed necessary on the subsequent production run.
Analytical Methods Used
As previously mentioned, once a product has completed its stability testing, it can then be tested for potency loss and other effects. The most common analytical methods used for these purposes include:
- High-Performance Liquid Chromatography (HPLC) – HPLC can be used to separate the constituents of a compound, tell you how much of each compound is found within the mixture, and help to identify what each compound is. HPLC is the technique of choice when analyzing materials for a wide range of organic compounds.
- Mass Spectrometry (MS) – MS is an analytical tool useful for calculating the exact molecular weight of the sample components, as well as the chemical identity or structure of molecules and other chemical compounds. This can be useful in identifying unknown degradation products.
- Spectrophotometry – Spectrophotometry is a method to measure how much a chemical substance absorbs light by measuring the intensity of light as a beam of light passes through sample solution. This can be particularly useful in identifying minerals.
Common Tests Conducted
Other tests that can be conducted in association with stability testing include:
- Sensory/Organoleptic Evaluation – Physical attributes like taste, flavor, color, odor, and appearance are vitally important for consumer acceptability. Sensory/organoleptic testing is performed by lab technicians and others to assess these attributes, which also assesses any potential degradation of the supplement.
- Chemical Analysis – The analytical methods previously discussed—HPLC, MS, and spectrophotometry—are used to quantify active ingredients and ensure they meet labeled amounts after stability testing has been completed.
- Physical Analysis – Laboratory devices are used to evaluate certain physical properties of a supplement such as tablet hardness, friability (broken tablets or loss of tablet mass through chipping), and powder flowability. Dissolution testing measures how effectively tablets and capsules dissolve in a solution, emulating breakdown during digestion. Each of these methods of physical analysis may be affected by storage conditions.
- Microbiological Examination – Supplements must be tested for microbiological compliance to verify they don’t contain dangerous levels of microorganisms such as E. coli. Special equipment is required for this purpose. As with the other types of analysis, micro-testing may be impacted by storage conditions.
How Often Should Stability Testing Be Conducted?
This isn’t an easy question to answer since it depends on multiple factors, including the type of stability testing being performed:
- Ambient stability – For products with a shelf life of at least 12-24 months, the frequency of testing is typically every 3 months for the first year, every 6 months for the second year, and annually after that. However, if the product is expected to have a longer shelf life, testing may be done at longer intervals, such as 36, 48, or 60 months.
- Accelerated stability – The frequency is usually 0, 3, and 6 months in an environmental chamber. Six months of accelerated testing is equivalent to about 2 years of ambient (real-time) testing.
- Highly stable formulations – For products that are highly stable, testing may only be done after the first 12 months and then at the end of the shelf life.
Why is Stability Testing Important for Supplement Brands?
Having read to this point in the article, it is likely that you can confidently answer the question of “Why is stability testing important for supplement brands?” Nevertheless, here is a brief overview of the answers:
- Ensures Consumer Safety and Product Efficacy – Both active and inactive ingredients in a supplement may degrade over time, which in turn may result in reduced potency (impacting efficacy) and possibly in undesirable metabolites and/or tablet/capsule frailty as well (impacting safety). Stability testing assures that the supplement maintains its original safety and efficacy.
- Sets a Scientifically Backed Expiration – It is important that nutraceuticals in a supplement maintain their potency through their expiration date. Stability testing is the best way to help ensure that this takes place vis-à-vis scientific validation.
- Reduces Risk of Product Recalls and Lawsuits – Although product recalls are relatively rare, they are more likely to occur in association with the degradation of active and inactive ingredients. As noted, stability testing assures that the supplement maintains its original safety and efficacy.
- Provides Data for Optimizing Packaging and Storage Recommendations – Since stability testing is conducted by placing the supplement tablets/capsules/etc., in their actual commercial packaging, this allows for an accurate determination of whether that packing is suitable for the product in question, and if the storage conditions are likewise appropriate.
- Builds Brand Trust and Consumer Confidence – Stability testing, and the assurances it provides for both supplement safety and efficacy, bestows consumers with a sense of confidence in your products. This builds brand trust, not to mention brand loyalty.
What to Consider When Planning Stability Testing
There are a few key factors to consider when planning stability testing. These include selecting a CDMO, the importance of following cGMPs, and factors influencing stability testing design.
Selecting a Contract Development and Manufacturing Organization
While all CDMOs can manufacture products, not all of them have the in-house capabilities to conduct stability testing. While this testing can be outsourced, it is preferable to conduct stability testing with the CDMO who manufactured your supplement since they have access to all the documentation and knowledge associated with the product’s development and can more easily assess any issues that may arise. Consequently, it is recommended that you choose a CDMO with in-house stability testing capabilities and expertise.
Importance of Following cGMPs
Regulations dictate the dietary supplement industry must current Good Manufacturing Practices (cGMPs). These regulations stipulate cGMPs for dietary supplements which require that proper controls are in place, ensuring all products are processed in a consistent manner to meet identity, purity, strength, and composition quality standards.
Of course, that doesn’t necessarily mean that all CDMOs actually follow cGMPs. A good way to ensure that cGMPs are being followed is to choose a CDMO that has been audited for cGMPs by a credible third-party agency (e.g., NSF), ensuring compliance with industry standards.
Factors Influencing Stability Testing Design
There are a few key factors that influence the design of a stability testing program:
- Dosage Form – Capsules, tablets, and powders each require different types of excipients. Those excipients (e.g., binders, sweeteners, etc.) may have interactions that impact stability. Understanding this in advance allows the CDMO to make adjustments before stability testing begins.
- Ingredient Types – Different vitamins, minerals, herbs, or other nutraceuticals may have properties that make them more sensitive to temperature, humidity, or light. These properties may have an impact on testing parameters.
- Packaging Materials – As with ingredient types, packaging materials—such as bottle type, blister packs, etc.—may also influence product stability. This may necessitate the need for special packaging (e.g., light-protective bottles) to be factored into testing design.
- Cost Considerations – While undoubtedly important for the many reasons previously outlined, the cost of stability testing should also be considered. It is important to find a balance between thoroughness and budgetary constraints.
Conclusion
Stability testing is vitally important for ensuring the quality, safety, and efficacy of dietary supplements. Furthermore, stability testing plays a key role in building brand trust and consumer confidence.
A good CDMO can do a great deal to help ensure effective stability testing for your brand. Vitaquest is a CDMO that has provided nutraceutical businesses with exceptional supplement formulation design, contract manufacturing, particle and powder, and engineering solutions using fluid bed, oscillation, and roll compaction technologies, packaging design, testing (including stability testing), and fulfillment services for over 45 years.
Whether you’re a newcomer to the industry or aiming to diversify your product range, Vitaquest possesses the expertise, cutting-edge facilities, and solutions needed to swiftly and effectively turn your dietary supplement concept into reality. Vitaquest offers a variety of dosage forms, including capsules, tablets, and powders.
Vitaquest also has expertise in domestic and international regulatory standards. We are GMP-certified by NSF, assuring brand owners and consumers about compliance with industry regulations and standards. In addition, Vitaquest can offer Kosher, Halal, and certified organic products, and FSSC 22000 certification for food safety.
Are you ready to move forward with creating high-quality dietary supplements with appropriate stability for your brand? If so, call 800-526-9095 to speak with one of our knowledgeable sales executives or request a competitive nutraceutical manufacturing price quote if you’ve already finalized your project requirements!
Frequently Asked Questions About Supplement Stability Testing
Q: What are the two types of stability testing?
The two types of stability testing are accelerated stability and ambient stability. During accelerated stability, conditions are created to accelerate the normal aging of a product. Ambient or “real-time” stability is determined by taking a sample of the packaged product we manufacture and holding it in a retain room under controlled, ambient temperature and humidity conditions. In both cases, testing can be done intermittently to determine results.
Q: What is an example of stability testing?
An example of stability testing is accelerated stability, during which conditions are created to accelerate the normal aging of a product. Testing can be done intermittently to determine results.
Q: What is the difference between reliability testing and stability testing?
Reliability testing assesses the ability of manufacturing and testing equipment to consistently perform its intended functions over time, without errors or failures. Stability testing determines how nutrients and other nutraceuticals found in dietary supplements will stand up to standard storage conditions and maintain safety and efficacy.
Q: How do you verify supplement quality?
Supplement quality is a multifaceted process involving adherence to current Good Manufacturing Practices (cGMPs). These include the testing of ingredients and the finished supplement product, including stability testing to determine how nutrients and other nutraceuticals found in dietary supplements will stand up to standard storage conditions and maintain safety and efficacy.
Q: What is the FDA guidance on in-use stability testing?
The FDA doesn’t require dietary supplements to have expiration dates, shelf lives, or “best if used by” dates, and doesn’t require stability testing for these dates in Part 111. However, if a product does have an expiration date, the FDA recommends that the manufacturer have data to support that date and a written testing program to assess the product’s stability.
Q: Is stability required for dietary supplements?
The FDA doesn’t require dietary supplements to have expiration dates, shelf lives, or “best if used by” dates, and doesn’t require stability testing for these dates in Part 111. However, if a product does have an expiration date, the FDA recommends that the manufacturer have data to support that date and a written testing program to assess the product’s stability.
Q: Is shelf life testing the same as stability testing?
No. Stability testing determines how nutrients and other nutraceuticals found in dietary supplements will stand up to standard storage conditions and maintain safety and efficacy, making it possible to determine and verify shelf life.
Q: What are the stability parameters?
Stability parameters include temperature, humidity, and light. In association with this, purity and potency testing can be done intermittently to determine results.
Q: What are you testing for with stability tests?
Stability testing determines how nutrients and other nutraceuticals found in dietary supplements will stand up to standard storage conditions and maintain safety and efficacy.
