How to Choose Serum Vials: Material & Seal Guide

Serum vials play an indispensable role in the highly sophisticated fields of modern pharmaceuticals, biotechnology and vaccine development and storage. It is not only a part of pharmaceutical packaging, but also directly related to the stability, safety and efficacy of drugs. A well-designed serum vials made of good material can ensure the integrity of the drug in the process of storage, transportation and use.

However, if the serum vials are not properly selected, it may change the active ingredient of the medicine, or cause contamination, leakage or even medical accidents. These risks not only bring economic losses, but also may jeopardize the lives of patients. Therefore, the scientific selection of serum vials is a non-negligible part of the entire pharmaceutical and supply chain.

1. Glass serum vials

Borosilicate glass

As the gold standard in pharmaceutical glass, Type I borosilicate glass exhibits excellent chemical stability. Its coefficient of thermal expansion is stabilized in the range of 3.3 x 10-⁶/K, and it is able to withstand sudden temperature changes of more than 200°C. Controlled bottles produced by the modern float process meet USP Class A standards for water resistance on the inner surface and leaching of alkaline oxides of less than 0.1 μg/cm². Of particular note is the material’s excellent resistance to the low ph buffer systems commonly used in biologics, although the risk of attack by hydrofluoric acid-based drugs must be guarded against.

Soda-lime glass (Type III)

Type III glass, which has been surface vulcanized, has alkali metal ion precipitation that can be controlled to less than 5μg/cm², and the cost is 40-60% lower than that of Type I. This economical material is suitable for injectables with ph 5-7.5, but when exposed to alkaline solutions (ph > 8), the Si-O bonds in the glass network structure accelerate hydrolysis. Typical applications include osmolality regulators such as sodium chloride injections and are not recommended for long-term storage of protein-based drugs.

Amber glass

Amber glass with a specific iron and manganese oxide formula effectively blocks UV light in the 300-500nm band, with transmittance controlled to less than 5%. Its optical properties must pass the USP<671> light barrier test, and the difference in wall thickness must be guaranteed within ±0.2mm to avoid uneven shading. Clinical studies have shown that for light-sensitive drugs such as vitamin B12, the use of amber packaging can reduce the degradation rate by more than 70%.

2. Polymer serum vials

Cycloolefin copolymer (COC)

This new engineering plastic has an ultra-low water vapor transmission rate with a surface energy as low as 28 dyn/cm, which effectively prevents protein adsorption. The modulus of elasticity of COC remains stable over a temperature range of -80 degrees Celsius to 120 degrees Celsius, making it suitable for deep cryogenic storage of monoclonal antibodies. However, it should be noted that its tolerance to organic solvents is limited.

Polypropylene

PP serum vials manufactured by injection molding process can maintain 200% elongation at break in -80°C environment. Its disadvantages are gas barrier cross and easy deformation during autoclaving. The newly developed nano-compliant PP material has reduced oxygen permeability by 40%, providing a new option for cell culture media storage.

Key selection recommendations

• Type I glass or COC materials preferred for biologics
• Cryopreserved preparations should consider PP’s low-temperature toughness
• Amber glass must be verified for light-barrier profiles for photosensitive drugs
• Strong acid and base preparations require at least 6 months of compatibility testing

1. Plug Material

As the core component of the sealing system of serum vials, the selection of the gluing plug directly affects the sealing, compatibility and long-term stability of the drug.

Bromobutyl rubber

• • Advantages: very low air and moisture permeability, chemically inert, effective in reducing leachables (e.g. extractables and leachables), suitable for sterile preparations.
  • Applicable scenarios: lyophilized preparations for long-term storage, high value-added biopharmaceuticals.
  • Special treatment: some high-end gel plugs are fluorinated coated to further reduce the risk of protein adsorption.

Chlorobutyl rubber

• • Comparison with bromobutyl: similar sealing properties, but different vulcanization systems, which may affect the leachate profile.
  • Cost advantage: typically 10-20% lower than bromobutyl rubber, suitable for cost-sensitive, high-volume formulations.
  • Limitations: Not recommended for certain halogen-sensitive formulations.

Silicone Plugs

• • High purity advantage: virtually no organic leachate, suitable for very high purity biologics (e.g., gene therapy vectors, cell therapy products).
  • Mechanical defects: composite gel plugs can

2. Type of aluminum cover

The mechanical design and surface finish of the aluminum cap is critical to the integrity of the seal, and different applications require different configurations.

Standard Aluminum Caps

• • General Purpose: Suitable for most vials and ensures an airtight seal by mechanical pressure sealing.
  • Finish: Epoxy coated or anodized to prevent corrosion (especially for high salt preparations).

Flip-top aluminum caps

• • Convenient design: Integrated plastic flip-top cap for multiple puncture sampling.
  • Risk control: to be used in conjunction with pre-scored adhesive plugs to avoid dislodging of particles due to multiple punctures.

Easy Pull Aluminum Caps

• • Optimized for emergency scenarios: one-touch tear-open design for emergency medications (e.g., epinephrine injection).
  • Sealing challenge: need to verify its initial sealing after opening by ISO 8362-6 standard.

3. Sealing test methods

Validation of the sealing system requires a combination of physical, chemical and microbiological methods to ensure compliance with USP<1207> and FDA guidelines.

Vacuum Attenuation Testing

• • Principle: Monitoring the change of vacuum level inside the container with a sensitivity of up to 0.05 cc/min (for lyophilized preparations).

Microbiological Challenge Test

• • Method: Enter the container into a high concentration of bacterial solution, incubate and then test the contents for bacterial contamination.
  • Industry requirements: PNSU (Probable Sterility Assurance Level) <0.1% needs to be met.

Helium Leak Detection

• • Highly accurate applications: Detection limits as low as 10-⁹ mbar-L/s for high-risk agents (e.g., cell therapy products).
  • Equipment requirements: Mass Spectrometer Leak Detector (MSLD) required.

Key selection recommendations

• Biologicals: Prefer fluoride-coated bromobutyl rubber stoppers + flip-top aluminum caps and perform helium checks.
• Lyophilized products: the permeability of the rubber stopper needs to be verified (water vapor transmission rate <0.01 g/day).
• Terminal sterilized preparations: the rubber stopper should be resistant to steam sterilization at 121 degrees Celsius and have no vulcanization reversion.

In order to ensure the stability and safety of drugs, reagents or chemicals during storage, transportation and use, it is necessary to select the appropriate type of serum vials and accessories (e.g., stoppers, caps) according to different application scenarios.

1. Biopharmaceuticals and vaccines

Applicable objects: recombinant proteins, biological antibodies, mRNA vaccines, inactivated vaccines, viral vectors, etc.

It is recommended to use Type I borosilicate glass vials with brominated butyl rubber stoppers to ensure that the vials will not react with the active ingredients, and at the same time have good sealing performance to organize microbial invasion. For serum vials, aseptic filling systems are adapted to simplify the process and significantly improve product consistency.

2. Lyophilized pharmaceutical products

Applicable objects: lyophilized antibiotics, vaccine powder, lyophilized proteins, peptide preparations, etc.

When used for lyophilized powder formulations, serum vials need to withstand extremely low temperatures (typically up to -80°C) while avoiding protein adsorption or aggregation due to silicone oil particles, so low-silicone oil or silicone-controlled design vials are recommended. The special bottle bottom structure can improve the heat transfer efficiency during the lyophilization process, and the water can be sublimated quickly, so as to improve the stability and efficiency of the whole lyophilization process. In addition, bottle size that matches the lyophilization equipment and a low-precipitation stopper suitable for secondary capping are also key considerations.

3. Technical specifications for the packaging of diagnostic reagents

Core requirements: anti-evaporation, low adsorption, chemical compatibility

For diagnostic kit laboratory sample storage, plastic serum vials, especially those made of COC (cyclic olefin copolymer) or COP (cyclic olefin polymer) are more commonly used. These materials offer good clarity, dimensional accuracy and chemical stability, making them suitable for high-throughput automated analysis platforms. Meanwhile, to prevent reagent evaporation and ensure analytical data stability, PTFE (polytetrafluoroethylene) coated stoppers are often used to effectively block gas permeation and adsorption of components, enhancing long-term storage performance.

4. Cosmetic active ingredients and specialty chemicals

Applicable objects: highly active extracts, plant extracts, direction there, organic acids, volatile solvents, etc.

In the packaging of cosmetics and special chemicals, serum vials not only assume the storage function, but also need to take into account the stability of ingredients and user experience. For products containing light-sensitive ingredients (e.g. Vitamin C, essential oils, etc.), amber glass bottles can effectively shield UV rays and prevent formula degradation. For formulations containing strong acids and alkalis or organic solvents, HDPE (High Density Polyethylene) plastic bottles are preferred for their excellent chemical resistance. Different closure designs such as droppers, pump heads or screw caps can also enhance ease of use and market acceptance.

The selection of serum vials in the supply chain decision-making of pharmaceutical packaging systems requires a multidimensional comprehensive evaluation system that incorporates technical parameters, regulatory requirements, supplier capabilities and economic benefits into a unified analysis model.

Playing a role in compliance forms the basis of decision-making and requires simultaneous fulfillment of the differentiated requirements of the three major pharmacopoeial systems: the USP standard focuses on the glass water resistance index, the EP specification additionally requires verification of the stability of the inner surface after autoclaving at 121°C, and the Japanese Pharmacopoeia has even stricter limitations on the amount of heavy metals that can migrate. For biologics packaging, the FDA’s CCS validation guidelines require the establishment of a system for the validation of the stability of raw materials to finished products.

Supplier evaluation should go beyond the appearance of certification, in-depth production quality system of the core links. The differentiation ability of high-quality suppliers is reflected in the following: the glass tube drawing process can maintain ≤ 0.05mm concentricity deviation, the production environment of rubber plugs has reached ISO 5 cleanliness, the life of the aluminum cap stamping die is more than 500,000 times and still be able to stabilize the opening force in the range of 15-30N.

Batch size and costs need to be evaluated in relation to the stage of the project: small batch R&D allows for more flexibility in the choice of packaging, while large-scale commercial production requires consideration of supply chain stability and unit cost control.

Some enterprises may have customized needs, such as non-standard bottle types, special labels, anti-UV or anti-sorption coatings, etc., in the selection of the feasibility of the selection should be communicated in advance with the supplier to ensure that the product in the actual application of the functional integrity and compliance with the output.

Problem 1: Serum vials break after cryopreservation

• Possible cause: Ordinary glass vials are not resistant to very low temperatures, and thermal stress at low temperatures leads to structural rupture.
• Solution: Replace serum vials with Type I borosilicate glass vials that are resistant to deep freezing, or use plastic serum vials made of COP/COC material, which have stronger low-temperature toughness.

Problem 2: Adsorption of drug ingredients on the bottle wall.

• Possible cause: Physical adsorption of proteins or active molecules on the inner wall of glass or plastic, resulting in measurement deviation or decreased potency.
• Solution: Use glass vials with a low protein adsorption coating and switch to COC material vials, which have very low adsorption properties themselves.

Problem 3: Plugs react with medicines

• Possible cause: additives or ingredients in the stopper dissolve and chemically react with the drug, affecting stability or introducing impurities.
• Solution: Choose bromobutyl rubber stoppers, whose chemical inertness is better than that of natural rubber or chlorobutyl. Conduct stopper-drug compatibility testing to identify potential risks and screen for optimal combinations in advance.

The selection of pharmaceutical packaging system is a precise science that needs to balance material properties, quality requirements and economic benefits. In the selection process of serum vials, core considerations should be centered around three dimensions: firstly, material matching is the basis for selecting suitable packaging materials for different drug characteristics, such as giving priority to Type I borosilicate glass for biological preparations, considering COP materials for lyophilized preparations, and matching with fluoride stoppers for protein drugs; secondly, it is crucial to set up a preventive quality system, including rigorous extract research, Dual-source supply verification and customized design for special applications; finally, the application of innovative technologies is reshaping industry standards, with cutting-edge technologies such as smart monitoring, blockchain traceability and computational simulation bringing brand new possibilities for pharmaceutical packaging.

Last Updated: 2025/04/25

More about serum bottles