BOC Sciences possesses GMP and ISO-certified contract manufacturing facilities, and we provide custom GMP-grade antibody-drug conjugates (ADC) manufacturing services to meet clinical and commercial development needs. Our strong expertise in process development, characterization, optimization, and scale-up can support successful GMP manufacturing and productive long-term cooperative relationships with pharmaceutical companies, institutions, and universities.
Antibody-drug conjugates (ADCs) are formed by conjugating monoclonal antibodies (mAb) and small-molecule drugs through linkers. The specificity of mAb to tumor cells allows small-molecule drugs to target tumor tissues, effectively reducing the high toxicity of traditional small-molecule drugs and improving overall treatment efficiency. Most ADCs follow similar action mechanisms, including antibody-mediated receptor binding, ADC internalization, the release of payload cytotoxicity, and bystander effects. The success of ADC depends on several key factors: target antigens, antibody types, payload types, linker types, conjugation methods, and target indications.
Fig 1. GMP capability for payloads and linkers.
The advent of ADCs provides a promising treatment for many types of cancer. As increasing numbers of ADC drugs enter clinical trials, the industry is shifting gradually from traditional technologies to novel and powerful techniques to afford ADCs. These techniques include exploring new tumor antigens, new antibody structures, new payloads, new linkers, and advanced conjugation methods that improve the therapeutic window of ADC. BOC Sciences offers a complete and flexible range of ADC manufacturing services, from process development & analytical support to GMP production. Our services include biopharmaceutical contract research and development, process development, cGMP manufacturing, QA and QC solutions for scientific research, preclinical, clinical, and commercial supply.
The therapeutic effect of ADC drugs is affected by various factors; thus, rational design and selection of antibodies, small molecule drugs, linkers in the initial stage of ADC drug development are critical for the entire development process. BOC Sciences provides the most advanced and comprehensive ADC biopharmaceutical contract research and development services according to project research needs and supports our customers in discovering the most suitable ADC drugs.
Based on our extensive experience with organic synthetic chemistry and R&D in GMP environments, BOC Sciences supports GMP-scale route design as well as optimization for payloads and payload linkers, including the use of HPAPI products.
The conjugation method between antibody, linker, and cytotoxin will affect the drug antibody coupling ratio (DAR) and the uniformity of ADC drugs, thereby affecting the biological activity, tolerance, and drug stability. Generally, the ideal DAR is 2-4. To match your ideal DAR, BOC Sciences provides ADC drug conjugation methods, including random conjugation and site-specific conjugation.
Impurities related to the ADCs specific process include unbound payloads, free linkers, or other chemicals used in the manufacturing process. For product-related impurities, such as polymers, fragments, charge variants and other PTMs on antibodies, BOC Sciences can adapt SEC, analytical ultracentrifugation, CE, capillary isoelectric focusing, ion-exchange chromatography and peptide maps for evaluation. Nevertheless, BOC Sciences uses advanced filtration equipment, such as ultrafiltration and tangential flow filtration (TFF) systems to remove therapeutic impurities and achieve optimum purification.
After verifying the small-scale conjugation scheme, complete ADC conjugation can be achieved in a GMP-certified reactor. ADC products are purified using a disposable chromatography system and filled into sterile vials through a GMP aseptic filling pipeline.
|AD Systems and Equipment||QC Lab Systems and Equipment|
|HPLC 2DHPLC||Instrument Group||HCP|
|Bio-LC||SEC-HPLC||Residual Host Cell DNA|
|cIEF (iCE3)||cIEF||Residual Protein A|
|CE (PA800)||Peptide Mapping (UPLC)||Protein Concentration by UV|
|Q-TOF ( Agilent 6530B)||IEX-HPLC (Ion-Exchange)||EM/Microbiology Group|
|UPLC ( Agilent 1290 Infinity)||CE-SDS (reduced and non-reduced)||Bioburden|
|CE (Agilent)||Biochem/Chem Group||Endotoxin|
|Flow Cytometry||Cell-based Bioassay||Sterility|
|GC||ELISA / Western Blot||Water Testing|
|qPCR instruments||Trypsin Inhibitory Activity||Environmental Monitoring|
|2DHPLC||SDS-PAGE (reduced and non-reduced)||Particulate Matter|
BOC Sciences' cGMP manufacturing can prepare ADCs for scale-up and commercialization. We have strict cGMP manufacturing standards, including scientific isolation controls, rigorous cleaning and sterilization processes, and FDA-compliant production and purification facilities.