Ensuring packaging integrity of frozen biopharmaceutical products

A study has investigated the challenges of freezing biological drug products with vials as a primary packaging container.

In their study, Henle et al. assessed the suitability of different vial qualities in relation to the “thermally induced mechanical stresses experienced during frozen drug product preparation and storage”.

The researchers stated that in recent years, novel vial types for special applications of parenteral drug products have entered the market.

Findings from the primary packaging study

The team investigated the impact of the freeze/thaw cycle on different types of glass and polymeric vials, eg, uncoated, coated. They found variations in physicochemical properties of the surfaces of different vial types, “including wettability, free energy and roughness”. However, this “did not change upon freezing and thawing”.

Otherwise, when screening vial content for particles originating from the container, analysis found particles in coated glass vials only in rare cases. In the same analysis in uncoated glass, polymer vials and in multilayered polymer vials, no particles were reported, according to the paper.

The team noted a key observation while testing extreme stress conditions, including a drop-test in the frozen state, Henle et al. detected a low number of particles in coated polymer vials.

Separately, “no quality issues regarding the functionality were observed upon container closure integrity testing, while the oxygen permeability was slightly increased for uncoated and especially coated polymer vials”.

Permeability of polymer vials

Following measurements of oxygen pressure, the authors identified “clear differences between the permeability of different polymer vials”. Moreover, the impact of freeze/thaw stress “did slightly increase the permeability, especially in SiO₂ coated polymer vials”, they added.

Therefore, “even repeated ice formation and thawing, especially at the vial-formulation-interface, and differences in the thermal expansion behaviour, leading to shear stresses at interfaces, had no impact on the physicochemical surface properties”.

Henle et al. emphasised that the “general oxygen permeability of polymer vials and the slight impact of freezing and thawing on certain types must be considered and studies designed accordingly, eg, including all potential temperature excursions during the life cycle of the product”.

Maintaining the integrity of biopharmaceuticals

“With the right choice of primary packaging material and careful consideration of the storage conditions, it is possible to maintain the quality and efficacy of biopharmaceuticals stored in the frozen state,” the authors concluded.

This paper is a pre-proof for publication in the European Journal of Pharmaceutical Sciences.