EXTRACTABLES AND LEACHABLES
human serum albumin with polysorbate 80 in a parenteral drug led to a new leachable that resulted in a high incidence of antibody positive pure cell aplasia.3
This leachable
compound was a small-molecule, aromatic compound originating from uncoated rubber syringe stoppers. This example from a final container/closure system serves as an effective illustration of the potential for leachables to be a major safety concern. Additionally, some leachable compounds can affect the efficacy and stability of a product.3
In a 2013 article in the Journal of Pharmaceutical Science and Technology, the authors looked at the effects of leachable compounds from single-use bioprocess containers on cell viability.9
The study found
that a common leachable compound found in many bioprocess containers could inhibit cell growth. The compound from the study was a breakdown product of the common anti-oxidant Irgafos 168® (CAS # 31570-04- 4). The authors of the paper found that the degradation product of Irgafos 168® inhibited cell growth of a number of Chinese Hamster Ovary (CHO) cell lines, which are commonly used in biomanufacturing. The issue of leachables inhibiting cell growth could cause variability in batch-to-batch yields, loss of expensive cell lines, and low yields in the manufacturing process. The experiments conducted in this paper highlight the need to understand the impact of the extractables not only from a patient safety standpoint but also from a biomanufacturing standpoint.
product under manufacture. Assessing the risk posed by any given leachable can be challenging, be it from a container closure system or the biomanufacturing process. Single-use components are often constructed of numerous functional components such as bioprocess bags, tubing, and filters, each potentially made from different types of plastic and/or rubber. Additionally, sterilization, the addition of wetting agents, and other pretreatments of such assemblies can create leachables that are unrelated to the material making up the assemblies.7
The evaluation of extractables and leachables to reduce patient safety risks should not be underestimated.3
A study published in
the PDA Journal of Pharmaceutical Science and Technology8
illustrates how substituting 2 American Pharmaceutical Review | Biopharmaceutical Supplement 2014
Bag ID Bag 1
Water
Total extractables from the three bag types. IPA
ε-Caprolactam Bis(2,4-di-tert-Butylphenyl)Phosphate
3,5-di-tert-Butyl-4-Hydroxybenzaldehyde Bis(2,4-di-tert-Butylphenyl)Phosphate Palmitamide Steamide Erucamide Ethylene Bis Palmitamide Ethylene Bis Heptadecanamide Ethylene Bis Stearamide Irgafos 168 Phosphate
Bag 2
ε-Caprolactam Bis(2,4-di-tert-Butylphenyl)Phosphate
Bag 3 Bis(2,4-di-tert-Butylphenyl)Phosphate
3,5-di-tert-Butyl-4-Hydroxybenzaldehyde Bis(2,4-di-tert-Butylphenyl)Phosphate Ethylene Bis Heptadecanamide Irgafos 168 Phosphate
3,5-di-tert-Butyl-4-Hydroxybenzaldehyde Bis(2,4-di-tert-Butylphenyl)Phosphate Palmitamide Ethylene Bis Palmitamide Ethylene Bis Heptadecanamide Irgafos 168 Phosphate
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