Experimental Manufacturability Optimization Assays

Assays are integral to successful and cost-effective drug discovery, but optimizing them is not easy. Creative Biolabs now has the ability to provide a series of in vitro and in vivo experiments for drug-manufacturability modification and optimization, escorting the success of biopharmaceuticals.

Manufacturability Optimization for Biotherapeutic Drugs

Increased attrition of treatment candidates during pre-clinical and clinical development can affect productivity and lead to increased costs, which negatively affects the development of new therapies. For biopharmaceuticals, product design, lead selection, and manufacturing process development constitute important risk areas, because they have a decisive impact on product quality, biological activity and safety, as well as commodity costs. Risk management and manufacturability optimization introduced in the early stages of development can help to address potential attrition and tear causes in the pre-clinical and clinical stages associated with product manufacturing, safety, delivery and efficacy issues. The use of a series of in vitro experimental measurements as part of the optimization of the comprehensive development of new biotherapeutic drugs has had a significant impact on simplifying drug development, providing better and safer therapeutic candidate drugs, and reducing risks and development costs.

So far, there is no single detection method that can provide all the necessary information about whether a biotherapeutic drug possesses the characteristics of manufacturability. Therefore, a well-designed biological analysis strategy is needed.

A simple strategy for the detection of antibodies in patients receiving biotherapeutic products. Fig.1 A simple strategy for the detection of antibodies in patients receiving biotherapeutic products. (Wadhwa, 2015)

Experimental Manufacturability Optimization Assays in Creative Biolabs

Creative Biolabs offers a number of solutions for manufacturability optimization:

Protein aggregation is a major problem in the development of biopharmaceuticals, which affects the production process of biotherapeutic drugs, targeted products, delivery routes, and patient safety. From a regulatory point of view, the presence of aggregates is a worrying issue, as it may lead to immunogenicity and side effects associated with the use of biopharmaceuticals. Therefore, optimizing the possible aggregation is very important to improve the manufacturability of drugs.

We provide germline humanization (CDR-grafting) services, and the complementarity-determining region (CDR) of the initial antibody is grafted onto a more precisely matched human antibody reproductive system receptor framework. The program is accompanied by a set of in silico manufacturability assessment tools to examine the function of humanized antibodies and to provide reliability judgments for antibody optimization.

To reduce the immunogenicity of protein therapy, protein engineers have adopted several strategies to hide proteins from the immune system. An increasingly popular method is to identify and eliminate T cell epitopes.

In studies of non-human proteins with useful therapeutic properties, it has been found that such proteins may be very useful if their immunogenicity can be significantly reduced, allowing for many treatment cycles. At present, some studies have successfully removed B-cell epitopes and demonstrated that they can reduce the immunogenicity of proteins.

Affinity is a measure of the degree of drug-receptor binding. It has been reported that Fv molecules derived from CDR domain of IgG have lower binding affinity than IgG counterparts with the same CDR sequence. At this time, it is necessary to combine affinity optimization to improve the biological activity of Fv molecules.

Affinity maturation is a process in which antibodies acquire higher affinity, affinity and antipathogenic activity. It is the result of somatic hypermutation (SHM) of B cell immunoglobulin gene and the selection of antigen binding. It can increase the activity of antibodies through multiple somatic cell hypermutations and selection of germinal centers.

Antibody charge variants have attracted extensive attention in biotechnology industry due to their potential impact on stability and biological activity.

Suggested developability assessment workflow. Fig.2 Suggested developability assessment workflow. (Zurdo, 2013)

Creative Biolabs works hand in hand with researchers to help solve difficult problems in biopharmaceutical analysis and development. If you have any need for drug-manufacturability, please contact us for more details.


  1. Wadhwa, M.; et al. Immunogenicity assessment of biotherapeutic products: an overview of assays and their utility. Biologicals. 2015, 43(5): 298-306.
  2. Zurdo, J. Developability assessment as an early de-risking tool for biopharmaceutical development. Pharmaceutical Bioprocessing. 2013, 1(1): 29-50.

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