Adalimumab Development: A Review of Manufacturing Processes

This report provides a comprehensive overview of Adalimumab, a recombinant monoclonal antibody targeting TNF-α. The report details the drug's molecular structure, including its IgG composition and molecular weights. It further elaborates on the developmental genetics, encompassing the isolation and maturation processes, and the use of expression vectors. The report delves into upstream processes, such as cell line and media optimization, and downstream processes, including cell debris removal and cell culture classification. It emphasizes the significance of chromatography in the separation and purification of Adalimumab, specifically highlighting affinity chromatography, protein A chromatography, and the use of cation, ion exchange, and other chromatography techniques for achieving a pure product. The document concludes with a list of references.

Adalimumab development
Adalimumab entails a recombinant monoclonal antibody as the active substances which are
directed to TNF- -α. The product composed of IgG antibody which is detailed by two kappa light
chains with molecular weights weighing 24kDa and presence of two IgGI and heavy chains
comprising of molecules weights weighing approximately 49kDa. The overall molecular weight is
148 kDa.1
The developmental genetics of the drug entails drug isolation and maturation process of the
sequences on the overall construction and verification of the vector expression. Expression vector
used entails variable regions obtained for the phage library display methodology and the human
IgG constants sequences. The final expression is undertaken by the final expression of the vector
through the confirmation of DNA sequencing.2
The upstream process has been utilized over the years, it entails the upstream titters of the
biological limits such as cell line and media optimization. The key common downstream process
entails the removal of the cell debris and cells yielded from broth culture and the overall
classification of cell culture and the supernatant.3
Chromatography process is essential in the separation and purification process due to its high-
resolution process. Various chromatography steps are undertaken with regards to Adalimumab.
Affinity chromatography is used for the separation of protein based on protein and specific ligand.
High protein affinity of the A protein in the Fc region of IgG antibodies forms the purification
process of IgG fragments, IgG and subclasses.4 In protein, A chromatography leads to the formation
of a pure product and requires a smaller proportion of the process and related impurities. Further 1
or 2 steps of chromatography are employed in the polishing steps thus incorporating cation and ion
exchange chromatography. Other types such as hydrophobic interaction, hydroxyapatite or mixed
mode chromatography can be utilized. 5

References
1. McCafferty J. The long and winding road to antibody therapeutics. Inmabs 2010 Sep 1 (Vol. 2,
No. 5, pp. 459-460). Taylor & Francis.
2. Tebbey PW, Varga A, Naill M, Clewell J, Venema J. Consistency of quality attributes for the
glycosylated monoclonal antibody Humira®(adalimumab). InMAbs 2015 Sep 3 (Vol. 7, No. 5,
pp. 805-811). Taylor & Francis.
3. Gronemeyer P, Ditz R, Strube J. Trends in upstream and downstream process development for
antibody manufacturing. Bioengineering. 2014;1(4):188-212.
4. Liu HF, Ma J, Winter C, Bayer R. Recovery and purification process development for
monoclonal antibody production. InMAbs 2010 Sep 1 (Vol. 2, No. 5, pp. 480-499). Taylor &
Francis.
5. de Lagrán Martínez Z, Pérez-Barrio S, Díaz-Pérez JL. Adalimumab: the molecule and
manufacturing procedure. Actas dermo-sifiliograficas. 2008 Feb;99:3-9.