ANTIBODY DRUG CONJUGATES

ANTIBODY
DRUG CONJUGATES
ANTIBODY DRUG CONJUGATES
Walk-in Hood fitted with a
mobile reactor. ADC Clean
Room (Class C area)
Antibody Drug Conjugates (ADCs) are the
combination of a monoclonal antibody
(mAb) with a cell-killing cytotoxic drug.
The antibody acts as a delivery system and
selectively targets the tumour cells, due
to its high binding specificity for tumourspecific antigens.
Once the antibody has reached the tumour,
it enters the cancer cell by endocytosis and
releases its cytotoxic payload by chemical or
enzymatic processes, eventually leading to the
death of the targeted cell. The drug conjugate
can also act as vascular-targeting agent and
selectively attack the blood vessels of the
cancer leading to the tumour’s necrosis after
the rapid shutdown of its blood supply. The
recent approvals of Adcetris® for Hodgkin’s
lymphoma and Kadcyla® for Her2-positive
breast cancer have provided further evidence
of the potential of ADCs in the treatment
of cancer. In addition, there are roughly
30 ADCs in clinical and 160 in preclinical
development, so there is a need for high
quality manufacturing to bring new products
into the clinic and ultimately to the public.
Autoclave and Hot Air Sterilizer
in the ADC Clean Room
(Class D area)
The Three Main Components of an ADC:
1 The antibody, responsible for the pharmacokinetic and
pharmacodynamics properties of the ADC.
2 The warhead accountable for the cell-killing potency.
Typical warheads are cytotoxic payloads such highly potent
tubulin inhibitors, DNA-alkylating agents or cross-linkers, as
well as topoisomerase inhibitors.
3 The warhead linker, the position and the number of
drug molecules loaded onto each antibody and the
conjugation strategy.
Warheads and Linkers Manufacture:
Cytotoxic molecules are effective at a low dosage and are
therefore classified as highly potent APIs. Because their
occupational exposure limit (OEL) is in the low nano-gram
range, they must be manufactured in dedicated engineeredbased containment facilities by highly trained personnel.
CARBOGEN AMCIS offers highly potent development
and manufacturing services since 2002. We are able to
manufacture linkers and toxins, from laboratory scale for
process research and development purposes up to large
scale manufacturing on 1’600 L. Our containment facility
has been recently qualified for OEL down to 10 ng/m3 OEL
at 8-hour time weighted average. We operate at negative
and positive pressure cascade (+30 Pa, +15 Pa, 0 Pa, -15
Pa) and in a dedicated ADC clean room with separated
Grade D and C aseptic areas.
Conjugation Strategies:
Our dedicated team of chemists, biochemists and
biologists can advise you on the best linker and
conjugation strategy. We have practical experience
with the most common conjugation.
CARBOGEN AMCIS - Your Partner
for Conjugation Projects
CARBOGEN AMCIS can handle all aspects the ADC production
with the exception of antibody manufacture.
Conjugation Activities:
Pioneers in the highly potent landscape, we successfully
managed numerous drug-linker projects. Our first ADC
project was in 2005 and since then it has been a growing
interest from our customers, both large pharmaceutical
companies and small biotech’s.
•• Manipulation of biological molecules
•• High potency services since 2002
•• Chemical modification with linkers and activators
•• First ADC project in 2005
•• Conjugation of monoclonal antibodies to small molecule
compounds up to 20 L volume (aqueous systems)
•• Committed to safety
•• OEL 10 ng/m3 8h-TWA
•• Multiple drugs on the market and undergoing validation
•• A septic environment with Grade D and C qualified areas
•• Complete service offering for:
•• cGMP Compliant
•• Warheads, linkers and conjugation
Purification & Analytics:
•• Process development
•• In-process monitoring by various means such as: UV/
Vis, HPLC, Endo-Safe, pH, capillary electrophoresis and
conductivity
•• Scale-up for drug conjugates
•• ICH stability studies
•• Full on-site analytical support for the release testing of
the product:
•• Enzyme Linked Immunosorbent Assay (ELISA)
•• SDS-PAGE (Gel Electrophoresis)
•• Outstanding track record
•• Analytics and purification
•• Fill-&-Finish capabilities
•• Regulatory and CMC support
•• Dedicated project management
•• Tailored programmes based on your
needs and budget
•• Capillary Isoelectric Focusing (cIEF)
•• Endotoxin analysis
•• RP-HPLC (SEC, HIC, PLRP)
TFF equipment in the ADC Clean
Room (Class C area)
Fill-&-Finish Capabilities
In addition to our process research and manufacturing
services for the fast supply of highly-potent APIs,
CARBOGEN AMCIS offers formulation services for
highly-potent drug products and GMP aseptic
production of parenteral drugs, including cytostatics
and cytotoxics.
•• The native cysteine conjugation that exploits the solvent
accessible inter-chain disulphide bonds of the antibody
in the cysteine.
•• Pre-clinical batches (for technical, stability or toxicology
studies)
•• The lysine conjugation technique uses the terminal amino
group –NH2 of the lysine residue as conjugation site.
•• Liquid forms, semi-solids and injectables
•• The genetic modification approach genetically modifies
the antibody sequence to display a functional group on
pre-defined positions of the antibody.
Why ADC at CARBOGEN AMCIS?
•• Clinical batches (for phases I, II and III)
GMP Lyophilisation
•• Validation of aseptic processes (media fill testing)
www.carbogen-amcis.com
Bubendorf (Headquarters)
CARBOGEN AMCIS AG
Hauptstrasse 171
CH-4416 Bubendorf Switzerland
www.carbogen-amcis.com
CARBOGEN AMCIS AG is a leading service provider, offering a portfolio of drug-development and
commercialization services to the pharmaceutical and biopharmaceutical industry at all stages
of drug development. The integrated services provide innovative chemistry solutions to support
timely and safe drug development allowing customers to make the best use of available resources.
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