Calibrators and quality control materials are only as reliable as the container that holds them. A calibrator's assigned value assumes that the analyte concentration stays unchanged from filling to last use, and a control is expected to behave predictably over its whole shelf life. The primary container influences both: it can lose water, admit oxygen, release substances into the matrix, bind the analyte to its surface or simply break in transit.
This article compares glass vials with plastic vials and bottles for liquid and lyophilised calibrators and controls. It does not declare a universal winner. Both materials have well-understood strengths and weaknesses, and the right choice for a given product is ultimately confirmed by stability data, not by material preference.
What the container has to do
Before comparing materials, it helps to list the functions a calibrator or control container must fulfil:
- Protect concentration: limit water loss and evaporation that would shift assigned values.
- Protect the analyte: limit oxygen ingress, light exposure and surface interactions.
- Stay inert: release as little as possible into the matrix, especially substances that can interfere with the assay.
- Survive the supply chain: withstand transport, refrigeration, freezing and handling in the laboratory.
- Support use: allow clean reconstitution, accurate pipetting and, where needed, reclosure.
Glass vials: barrier and lyophilisation compatibility
In general terms, pharmaceutical glass is classified by its hydrolytic resistance. Type I borosilicate glass releases very little alkali and is the usual choice for sensitive or weakly buffered solutions. Soda-lime glass (Type III, or surface-treated Type II) is less expensive but releases more alkali ions, which can raise the pH of weakly buffered solutions over time. Clear glass allows visual inspection of the contents; amber glass filters ultraviolet and much of the short-wavelength visible light.
The glass wall itself is practically impermeable to oxygen and water vapour, so the closure becomes the limiting barrier. Glass vials are typically closed with a rubber stopper secured by an aluminium crimp or a flip-off cap. Stopper formulation matters: elastomers can release extractables and can also transfer moisture into a dry cake, so coated or low-moisture stoppers are often specified for lyophilised products.
Glass remains the conventional container for lyophilisation. Flat-bottomed vials transfer heat well on the freeze-dryer shelf, slotted lyophilisation stoppers let vapour escape during drying, and the vials can be stoppered under vacuum or dry nitrogen inside the chamber before crimping.
The drawbacks are equally well known: glass is heavier, can break or chip, needs protective trays in shipping, and can crack if an overfilled liquid freezes. Proteins also adsorb to glass surfaces, so glass is not automatically inert towards low-concentration analytes.
Plastic vials and bottles: robustness and design freedom
The plastics most often used for IVD liquids are polypropylene (PP), high-density polyethylene (HDPE) and polyethylene terephthalate (PET). Their properties vary by grade and supplier, but some general patterns hold:
- PP: good chemical resistance and stiffness, autoclavable in many grades, good water vapour barrier, relatively high oxygen permeability. Homopolymer grades can become brittle below freezing; copolymer grades usually perform better in the cold.
- HDPE: very good water vapour barrier and good toughness at low temperatures, but a poor oxygen barrier and limited transparency.
- PET: clear, with a better oxygen barrier than polyolefins and a moderate water vapour barrier; generally not suitable for autoclaving.
Plastic containers are shatter-resistant and light, which reduces breakage and freight weight. Screw caps and dropper inserts make opening, dispensing and reclosure simple for multi-use controls. Moulded parts also offer freedom in shape, neck finish and colour.
The main technical risks lie in interactions with the contents. Proteins adsorb to polymer surfaces, and small hydrophobic molecules, such as some steroid hormones and drugs, can sorb into polyolefins. Additives such as antioxidants, slip agents and colourants may appear as extractables. Over a long shelf life, permeation of water vapour and oxygen through the wall can change concentration or oxidise sensitive components.
Side-by-side comparison
The table summarises typical behaviour. Actual performance depends on glass type, resin grade, wall thickness, closure design and fill volume.
| Criterion | Glass vial | Plastic vial or bottle |
|---|---|---|
| Oxygen and water vapour barrier | Wall practically impermeable; the closure is the limiting path | Depends on resin and wall thickness; PP and HDPE good moisture barrier but poor oxygen barrier; PET better oxygen barrier |
| Breakage and weight | Fragile and heavier; needs protective trays | Shatter-resistant and light |
| Surface interaction | Protein adsorption; alkali release, lowest with Type I | Protein adsorption; sorption of small hydrophobic molecules into the polymer |
| Extractables | Very low from the glass; mainly from the rubber stopper | Antioxidants, slip agents, colourants; grade-dependent |
| Lyophilisation | Conventional choice; works with lyophilisation stoppers and crimp seals | Limited; only special polymers, requires validation |
| Light protection | Amber glass filters UV and blue light | Amber or opaque grades, or secondary packaging |
| Freezing | Risk of cracking if overfilled | HDPE stays tough; PP homopolymer may become brittle |
| Opening and reclosure | Stopper with crimp or flip-off cap; not easily reclosed | Screw caps and droppers; easy reclosure |
Liquid or lyophilised: practical considerations
Lyophilised calibrators and controls
Dry materials are sensitive to moisture and oxygen rather than to evaporation. The tight barrier of glass, combined with a suitable stopper and crimp seal, protects the low residual moisture and the inert headspace. Reconstitution requires accurate addition of diluent, usually by volumetric pipette after removing the stopper, and the vial geometry should allow complete dissolution without foaming.
Liquid calibrators and controls
For ready-to-use liquids, water loss is the critical mechanism: even slight evaporation over months shifts the concentration, which directly affects a calibrator's assigned value. Both glass vials and well-sealed plastic containers can work, provided the closure is tight and the material's moisture barrier suits the shelf life. Multi-use controls add open-vial stability to the picture, and easy, repeatable reclosure is an advantage of screw caps.
Light, oxygen and sensitive analytes
Bilirubin is known to degrade under light, so amber glass, amber or opaque plastic, or light-tight secondary packaging is common. Enzymes may lose activity through oxidation, surface denaturation or freeze-thaw stress. Hormones and other analytes present at low concentrations are more exposed to adsorption losses, because a small bound amount represents a large fraction of the total. Matrix proteins such as albumin often reduce these effects but do not eliminate them.
Transport and freezing
Glass needs dividers or moulded trays and is still at risk when dropped. Plastic tolerates impact better, and HDPE in particular stays tough when frozen. If a liquid product is shipped or stored frozen, leave enough headspace for expansion in either material.
Choosing by product format
The following recommendations are typical starting points, not rules. Each one must be confirmed with the actual formulation.
| Product format | Typical recommendation | Verify in particular |
|---|---|---|
| Lyophilised control or calibrator | Type I glass vial, clear or amber, with lyophilisation stopper and aluminium crimp or flip-off cap | Residual moisture, moisture transfer from the stopper, closure integrity |
| Liquid calibrator (ready to use) | Glass vial or tightly sealed plastic vial; amber if light-sensitive | Evaporation over shelf life, value drift, analyte sorption |
| Liquid control, multi-use | PP, HDPE or PET bottle with screw cap or dropper | Open-vial stability, evaporation after opening |
| Small-volume aliquot | Small glass or PP vial with minimal headspace | Higher surface-to-volume ratio increases adsorption losses |
| Bulk diluent or buffer | HDPE or PP bottle | Extractables, particles, preservative compatibility |
Documentation and next steps
For IVD products, the primary container is part of the device design. Stability of IVD reagents is commonly evaluated following EN ISO 23640, and under the EU IVDR a change of container material or closure usually has to be justified with new or bridging stability data. Ask your packaging supplier for material declarations, lot traceability, certificates of conformity and, where applicable, compliance statements for the glass type or plastic resin.
Linden Grup supplies both formats for calibrator and control projects. Our glass vials include clear and amber vials with rubber stoppers, aluminium crimp and flip-off caps, such as the 3 mL clear glass vial with flip-off cap for small lyophilised controls. Our plastic bottles in HDPE and PET, including dropper bottles, suit liquid controls and diluents. For assay-specific packaging topics, see our immunoassay page.
If you are comparing containers for a new calibrator or control, contact us to request samples for your own compatibility and stability testing.