This is part 2 of a series of articles discussing the importance of E&L assessments in the production of cell and gene therapies (C&GTs). These articles come ahead of a Q&A session which you can watch on demand here. For part 1 of the blog series, click here.

Cell and Gene Therapies vs mAb

In many ways, the extractable and leachable assessment of C&GTs is similar to biopharmaceuticals, such as mAbs.  However, there are some key differences which can affect the extractable and leachable strategy for C&GTs.

Table 1 compares some of the key C&GT and mAb product attributes.

Attribute C&GT mAb
Product Type Live human cells Antibody grown from mammalian cells
Batch Size Small scale (tens of mLs) Larger scale (thousands of litres)
Dosing Regimen Acute Acute/chronic
DP Storage Frozen Refrigerated
Manufacturing equipment Single use Multi use and/or single use
DP Storage Time Short Long
Manufacturing Temperature 37°C Room temperature
Product Administration Specific treatment centres Varies
Cost of product Very, very expensive! Expansive

The biggest challenge for the assessment of C&GTs is the small batch sizes, making it difficult to perform leachable studies.

This means that there is a greater reliance on extractable data and data which simulates in-use conditions.

The first case study in this series of blogs looks at extractable data generated from various solvents on a gamma-irradiated polyethylene bag which was extracted for 16 weeks at 40°C.

The following chart represents the number of extractables detected from each solvent.

The Ethanol extract contained the largest number of extractables with 49 being detected.

DMSO was included in the study as it is a common solvent used in the manufacture of C&GT products. The following 6 extractables were detected from the 10% DMSO solution:

  • C7 carboxylic acid
  • Hexanoic acid
  • 7,9-di-tert-butyl-1-oxaspiro(4,5)deca-6,9-diene-2,8-dione
  • Caprolactam
  • Di-(2-ethylhexyl) phthalate
  • 2,4-Di-tert-butyl-phenol

Question – Can extractable data from other solvents systems help us understand the risk of a material in contact with DMSO?

  Water (10x conc.) Ethanol 1% PS 80 1 M HCl 1 M NaOH 4 M NaCl
Carboxylic acid x x
2,4 Di-tert-butyl-phenol x x
Di-(2-ethylhexyl) phthalate x x x x x x
Caprolactam x x
Dione x
Hexanoic acid x

All 6 of the compounds were only detected in the water extraction when the water extract was concentrated 10 times. Suggesting that whilst the same compounds were observed the levels extracted were different.

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