Expiry Dates for Commercial and In-House Prepared Reagents In QC Labs

Quality control (QC) laboratories in the pharmaceutical industry depend on the precise use of laboratory reagents (solids, liquids, gases, and solutions) to carry out accurate analytical testing, making the establishment of expiry dates for both commercial and in-house prepared reagents a critical aspect of maintaining testing integrity and consistency.

Understanding their composition, properties, and appropriate storage conditions is essential, particularly in managing the expiration dates to uphold effectiveness and safety in laboratory practices. This article follows OMCL’s guideline on setting expiry dates for reagents in QC labs and explains why expiry dates matter, how they impact testing, and best practices for their management to uphold quality standards.

Why Is the Expiration Date Important for Reagents Used in Laboratories?

The expiration date of laboratory reagents is fundamental for securing the accuracy, reliability, safety, and regulatory compliance of laboratory testing procedures. By managing and adhering to these dates, laboratories can uphold high standards of scientific integrity, safety, and efficiency in their operations.

Key considerations include:

• Accuracy and Reliability: Specific chemical compositions and properties of reagents are essential for their intended analytical functions. Over time reagents can degrade, leading to changes in reactivity or reliability. Using expired reagents can result in inaccurate laboratory results, undermining the validity of scientific findings or quality control assessments in laboratories.

• Consistency: QC labs rely on consistent and reproducible results to validate hypotheses, conduct quality control checks, or ensure product safety. Expired reagents may perform differently than expected, introducing variability into experimental outcomes or test results. This inconsistency can hinder the detection of subtle changes or deviations in analyzed samples.

• Safety: Some reagents may become unstable or generate hazardous by-products as they degrade past expiration. This poses risks to laboratory personnel, potentially leading to accidents or exposure to harmful substances. Adhering to expiration dates helps mitigate these risks by ensuring only reagents with known stability and safety profiles are used in laboratory operations.

• Regulatory Compliance: All laboratories must adhere to strict guidelines, like regarding the use of reagents within their validated shelf life. Compliance with these regulations ensures that laboratories meet industry standards and maintain the integrity of their testing processes.

• Economic Considerations: Proper management of reagent expiration dates also has financial implications. Discarding expired reagents on time avoids wastage and unnecessary costs associated with potentially compromised experiments or retests due to unreliable results.

In the laboratory, the reliability of experimental outcomes heavily depends on the stability and integrity of the reagents used. It is important to carefully determine the shelf life and expiry dates for the reagents used before and after they are opened (put in use). 

Expiry Dates for Commercial Reagents

Reagents produced by specialized manufacturers with stringent quality control measures and standardized documentation guarantee reliability and consistency in routine testing. Laboratories use a variety of commercial reagents based on their analytical requirements and experiments. 

Unopened Reagent Container

Commercial reagents typically have specified shelf lives for their unopened containers provided by manufacturers. When this information is unavailable, guidelines suggest estimating the shelf life as the date of receipt plus up to five years under specific storage conditions detailed in documents like Certificates of Analysis.

After Opening the Reagent Container

Once opened, establishing a suitable expiry period becomes essential, especially without specific stability data. This can involve real-time monitoring during laboratory use to gather empirical data on critical parameters. Sources such as Certificates of Analysis, scientific literature, and manufacturer’s data contribute to informed decisions. 

It’s crucial to verify the expiry period after opening is within the shelf life stated for the unopened reagent container, supported by risk assessments based on scientific literature and experimental findings.

Following Material Safety Data Sheets (MSDS) guidelines for storing reagents after opening is essential. This includes controlling temperature and light exposure and adequately closing the containers. It helps prevent degradation and extends the reagent’s usability. 

Some commonly used commercial reagents in labs, along with their recommended expiry dates, are outlined in the OMCL’s guideline on setting expiry dates for reagents:

By implementing quality assurance practices like regular stability testing and documenting opening and expiry dates, QC labs can comply with regulations and make well-informed decisions about reagent viability. These practices enhance operational efficiency, reduce the risks of compromised reagent performance, and maintain the integrity of analytical results.

Expiry Dates for In-House Prepared Reagents

In-house reagents are substances or solutions prepared within the laboratory rather than being commercially manufactured and purchased ready-to-use. They are tailored to meet specific experimental or analytical requirements aligned with the laboratory’s research or testing protocols. 

This customization allows for precise adjustments such as specific concentrations, purity levels, or unique formulations that may not be readily available commercially. Preparation of reagent solutions adheres strictly to applicable guidelines, compendial methods (e.g., pharmacopoeial texts), test method specifications, and procedures (e.g., Common Technical Documents [CTDs], SOPs), ensuring compliance with rigorous quality standards and regulatory requirements.

To confirm the efficacy and reliability of reagent solutions in laboratory analyses, thorough pre-use checks are essential. These checks help confirm that the solutions meet the required properties and maintain quality standards throughout use. Some of the recommended steps for conducting pre-use checks include:

• Perform a visual inspection and discard any reagent exhibiting changes in color, opalescence, or precipitation (unless these changes are deliberate).
• For buffer solutions, perform pH checks as necessary.
• Titrate volumetric solutions to verify their concentration.
• Conduct sensitivity testing on indicators specified in the European Pharmacopoeia (Ph. Eur.).
• Additionally, conduct any other relevant qualification tests specific to the prepared reagents.
• Environmental considerations should guide decisions regarding the adjustment of expiry periods or disposal of reagent solutions.
• Note that while a solution may become unsuitable for a specific analytical procedure, it may still serve other purposes.

Here are some commonly used in-house prepared reagents and their suggested expiry date established on the basis of analytical experience of OMCLs and available literature:

Water

When it comes to the use of water in QC labs, the expiration periods of in-house-prepared reagent solutions are critical for maintaining the accuracy and reliability of physico-chemical tests. The following guidelines, based on analytical experience, method validation, and available literature, outline the maximum expiry periods, risk factors, and recommendations for different types of water used in laboratory settings:

1. Water for Chromatography and Deionised Water (Ph. Eur. 1095503 and Ph. Eur. 1095508):
   • Maximum Expiry Period: 24 hours after production.
   • Risk Factors: High-purity water rapidly picks up contaminants, leading to potential bacterial contamination.
   • Recommendations: Visually inspect the water, and discard if it appears turbid. It is crucial to use water from fresh and closed containers to minimize contamination risks. Additionally, ensure that System Suitability Test (SST) criteria are fulfilled before use.
2. Purified Water (Ph. Eur. 04/2018:0008):
   • Maximum Expiry Period: 3-5 days after production.
   • Risk Factors: Susceptible to bacterial contamination over time.
   • Recommendations: Regularly inspect the water visually, and discard if turbid. Utilize water from fresh containers, and adhere to standard quality practices to ensure its integrity.
3. Water for Injections and Sterilized Water for Injections (Ph. Eur. 04/2017:0169):
   • Maximum Expiry Period: 2 months after production.
   • Risk Factors: Bacterial contamination is a concern, even in sterilized water.
   • Recommendations: Perform visual inspections consistently, and discard the water if it shows any signs of turbidity. Always use water from freshly opened containers to maintain its sterility.

Mobile Phases

For chromatography applications, managing the expiration periods of mobile phases properly is crucial to maintain consistent and accurate results.

1. Pure Organic Solvent (Transferred from Original Container):
   • Suggested Expiry Period: Up to 6 months or until the original expiration date, whichever comes first.
   • Best Practices: Conduct regular visual checks for any signs of degradation and ensure that System Suitability Test (SST) criteria are met to maintain the solvent’s quality.
2. Organic Solvent and Water Mixtures:
   • If Organic Content is ≥ 50%:
     • Suggested Expiry Period: Up to 6 months.
     • Best Practices: Validate the mobile phase by meeting SST criteria before use.
   • If Organic Content is < 50%:
     • Suggested Expiry Period: Up to 3 months.
     • Best Practices: Adhere to SST guidelines to confirm the mixture’s suitability.
3. Organic Solvent with Buffer (HPLC Buffers):
   • Suggested Expiry Period: Up to 2 weeks.
   • Potential Risks: The mixture may suffer from depletion, precipitation, or evaporation.
   • Best Practices: In addition to SST criteria, perform a pH check (if applicable) to ensure the stability and integrity of the mobile phase.
4. Organic Solvent with Acid/Base (e.g., Phosphoric Acid, Perchloric Acid, Methanesulfonic Acid, Trifluoroacetic Acid):
   • Suggested Expiry Period: Up to 3 months.
   • Potential Risks: Exposure to air or light can degrade these mixtures over time.
   • Best Practices: Regular visual inspections and compliance with SST criteria are necessary to maintain the mobile phase’s effectiveness.

Acid Solutions

When managing acid solutions in QC laboratories, it is essential to adhere to specific expiration periods to ensure the accuracy and safety of chemical processes. For acids used in pH adjustment, a general expiration period of 12 months is recommended. However, more reactive acids, such as hydrochloric and sulfuric acid, require shorter expiration periods, especially at lower concentrations, with suggested expiry times ranging from 2 to 7 months. Perchloric acid, due to its instability, should be used within one month of preparation. Regular visual inspections are necessary to detect any signs of degradation, and System Suitability Test (SST) criteria must always be met before use to ensure the integrity and effectiveness of these acid solutions.

Alkaline Solutions

Alkaline solutions, particularly those used for pH adjustment in QC labs, have a recommended shelf life of 6 months. Sodium hydroxide solutions, which are prone to CO2 absorption, require careful handling as this can alter their concentration and effectiveness. Depending on the molarity, sodium hydroxide solutions have a suggested expiration period ranging from 1 to 5 months. To maintain the stability and reliability of these solutions, it is crucial to store them in tightly sealed containers, preferably plastic, to prevent CO2 absorption. Regular visual inspections and adherence to SST criteria before use are also necessary to ensure the solutions remain suitable for their intended applications.

Volumetric Solutions

The expiration periods for volumetric solutions vary depending on their composition and susceptibility to factors like precipitation, photochemical degradation, and volatility.

For EDTA solutions, a 0.1M solution has a recommended shelf life of 7.5 months, while a 0.01M solution should be used within 2 months. Precipitation is a common issue, so after visual inspection, it is necessary to determine the titration value before use. It is also recommended to store these solutions in plastic containers to avoid contamination.

Argentometry solutions, such as 0.1M AgNO3, have a suggested expiration period of 7 months due to potential photochemical degradation. This solution should be protected from light, and the titration value should be checked after a visual inspection. The 0.01M AgNO3 solution is stable for up to 5 months, while 0.1M NH4SCN also has a recommended shelf life of 7 months.

In Redoxometry, the stability of solutions like 0.1M I2 is influenced by volatility and air-oxidation processes, with a recommended expiration period of 7.5 months. It is crucial to store these solutions in tightly closed containers and to determine the titration value after visual inspection. The 0.01M I2 solution remains stable for 5 months, while 0.1M Na2S2O3 has a 5-month shelf life but should be prepared at least 2 weeks before use to ensure stability. Additionally, 0.1 M KMnO4 should be used within 1 month, and it is advisable to filter it before use and verify the titration value after a visual check.

Indicators

When it comes to indicators used in laboratory settings, a general expiration period of 2 to 3 years is recommended to ensure their accuracy and effectiveness. Common indicators such as Ferroin, Phenolphthalein solution, Phenol red solution, Methylene blue, Methylthymol blue mixture, and Methyl red solution are stable within this timeframe. However, it is essential to perform sensitivity tests periodically (as specified in Ph. Eur.) and conduct regular visual inspections to verify their integrity. Additionally, protecting these indicators from light can help maintain their stability throughout their shelf life.

Microbiological and Cell-Based Methods

The stability and storage of growth media used in microbiological and cell-based methods are essential for maintaining accurate and reliable test results. Listed below are specific recommendations based on the type of storage:

1. Solid or Liquid Growth Media (Stored in Tightly Sealed Containers):
   • Maximum Expiry Period: 6 months.
   • Recommendation: These media should be stored below 25°C or at 2-8°C, depending on the specific medium, and in tightly sealed containers like screw-capped flasks to preserve their sterility and effectiveness over time.
2. Solid or Liquid Growth Media (Stored in Unsealed Containers):
   • Maximum Expiry Period: 1 month.
   • Recommendation: For media stored in unsealed containers, such as bottles with a cellulose plug and aluminum foil, it is recommended to use them within 1 month to reduce the risk of contamination and ensure the media’s reliability.

Factors Influencing Expiry Periods and Considerations for Reagents

Upon opening, reagents are susceptible to various environmental factors that can impact their integrity and, consequently, the reliability of experimental results. Factors such as reagent purity, storage conditions, handling practices, and intended use are crucial in determining the appropriate expiry period post-opening.

Purity of the Reagent

The purity of a reagent significantly influences its stability after opening. Higher-purity reagents tend to exhibit shorter expiry periods due to increased susceptibility to degradation. For example, while standard-grade sodium chloride may have a longer shelf life post-opening compared to ultra-pure variants, the purity level should be selected to align with the specific analytical requirements to ensure accurate and reproducible results.

Environmental Conditions

Strict control over environmental conditions is paramount to maintaining reagent stability. Temperature and humidity levels must adhere to manufacturer-provided guidelines or internal Standard Operating Procedures (SOPs) to minimize degradation risks. Exposure to light and potential contamination during handling requires meticulous attention to storage and usage protocols.

Handling Practices

Reagents should always be managed with clean equipment and stored in clean, dry conditions to maintain their integrity. Ensuring that reagent containers are properly sealed is equally important to avoid exposure to air and moisture, which can compromise the stability of the reagent. Careful attention to these practices helps safeguard the quality and reliability of the reagents used in laboratory processes.

Type of Reagent

Different types of reagents require specific storage and handling practices to maintain their effectiveness. Liquid reagents, for example, can separate or change concentration over time, so it is important to regularly inspect these solutions for any changes in appearance, such as precipitation or discoloration. Solid reagents, on the other hand, are prone to absorbing moisture or becoming brittle. To prevent this, they should be stored in airtight containers. Buffer solutions also require special attention, as they can experience pH shifts or microbial contamination if not stored under the recommended conditions. By following these guidelines, the stability and accuracy of reagents can be preserved, ensuring consistent results in laboratory work.

Conducting Stability Studies for Reagents Used in Quantitative Analysis

Stability studies for reagents used in quantitative analysis are essential for maintaining the reliability and accuracy of results over time. These studies evaluate how reagents retain critical attributes, such as concentration and purity, under specific storage conditions. By conducting stability testing, laboratories can determine appropriate shelf lives and storage practices, helping to keep reagents effective throughout their intended use. 

Retesting Reagents to Set New Expiry Dates

Setting clear retesting protocols should be based on comprehensive stability data, manufacturer recommendations as outlined in the Certificate of Analysis (CoA), and relevant regulatory requirements. It’s important to define both the frequency and conditions for retesting to ensure reagents continue to meet established quality standards. 

Retesting intervals should account for the original shelf life and any potential accelerated degradation from extended storage. For reagents critical to high-precision procedures, more frequent retesting might be necessary. Detailed documentation, including sample preparation, analytical methods, and acceptance criteria, is essential to maintain data integrity and ensure compliance with regulatory standards.

Labeling and Storage of Reagents

According to the guidelines outlined in OMCL Management of Reagents, reagent labelling should include the expiry period for an opened container whenever feasible. This practice is crucial for maintaining the efficacy and reliability of reagents throughout their usage period. Proper labelling ensures that reagents are utilized within their validated lifespan, thereby upholding the accuracy and integrity of analytical results.

Storage Conditions for Reagent Solutions

Reagent solutions must be stored under conditions that are appropriate for their specific chemical properties. Adhering to the prescribed storage conditions—such as controlling temperature, and protecting from light and moisture – is essential to maintaining reagent stability and performance. The following storage guidelines are recommended:

• Temperature Control: Reagents should be stored at temperatures specified in their stability data. Depending on the reagent, this may involve refrigeration (2 – 8 °C), freezing (below – 15 °C), or specialized storage conditions such as under vacuum or in liquid nitrogen.

• Protection from Light: Reagents sensitive to light should be stored in containers that provide adequate protection to prevent photodegradation.

• Protection from Moisture: For reagents vulnerable to moisture, it is imperative to store them in a dry environment and ensure that containers are effectively sealed to prevent moisture ingress.

• Container Types: Alkaline solutions should be stored in plastic containers to avoid potential interactions with glass. Additionally, flammable liquids should be stored in minimal quantities to reduce risk.

Key Elements of Reagent Labelling

Clear and consistent labels provide essential information, such as the chemical’s identity, concentration, expiration date, and storage conditions, which are crucial for maintaining the integrity of experiments and ensuring compliance with regulatory standards.

• Expiry Date: The label on a reagent container should prominently display the expiry date, which indicates the end of the period during which the reagent is expected to maintain its intended performance characteristics. For opened containers, it is critical to include the date on which the container was opened, as the expiry period may be shorter than that for unopened reagents. This information helps in tracking the usability of the reagent and ensures that it is used within its validated lifespan.
• Storage Instructions: Labels should provide specific storage instructions tailored to the chemical properties of the reagent. These instructions may include temperature requirements, such as refrigeration or freezing, and any need for protection from light or moisture. Accurate storage conditions are essential for preserving the reagent’s stability and efficacy.
• Chemical Name and Concentration: The chemical name of the reagent and its concentration should be clearly stated on the label. This information is crucial for ensuring the correct usage and dilution of the reagent in experimental procedures.
• Handling Instructions: Labels should include any special handling instructions necessary to ensure the safe use of the reagent. This may involve instructions for using personal protective equipment, specific precautions to avoid contamination, or guidelines for safe disposal.
• Batch Number and Manufacturer Information: The batch number and information about the manufacturer should be included to facilitate traceability. The batch number helps in tracking the reagent’s origin and any associated quality control data, while manufacturer information assists in obtaining technical support or additional product details if required.
• Hazard Warnings: If applicable, the label should include hazard warnings as per the Safety Data Sheet (SDS). This includes any potential hazards associated with the reagent, such as flammability, toxicity, or corrosiveness, as well as appropriate safety measures to mitigate these risks. 
• Date of Receipt: For reagents received from suppliers, it is advisable to include the date of receipt on the label. This allows for better management of reagent inventory and helps in scheduling retesting or replacement based on the date of acquisition.