Clinical grade, EU-licensed therapeutic monoclonal antibodies

.. and how are they different from the non-clincial recombinant mAbs?

Clinical-grade antibody versus non-clinical: what is the difference?

Antibodies are glycoproteins that can bind specifically to a wide variety of molecules with high affinity. This unique property finds wide-scale applications in medicine and biomedical research, making antibodies an indispensable tool in molecular biology, clinical diagnosis and even clinical therapy.

The revolutionary hybridoma technology made large scale manufacturing of monoclonal antibodies (mAbs) possible. However, the translation of mAbs for clinical therapy is an odyssey in itself. The first generation of therapeutic mAbs was encountered with numerous roadblocks such as immunogenecity, low biological efficacy and product purification.

But advancements in antibody engineering technologies over the last few decades, led to the emergence of new generation mAb formats that are now being successfully used for targeted therapy of complex diseases. Currently, several clinical grade mAbs are approved for therapy in oncology, auto-immune diseases and inflammation, with many other therapeutic areas gaining momentum.

Evidentic provides aliquots of clinical grade, EU-licensed monoclonal antibodies that have been approved for clinical use. These aliquots are intended research consumables and can be used as reference drugs for research and development of new mAb drugs and biosimilars.

What distinguishes therapeutic mAbs from non-clinical mAbs?

Therapeutic mAbs

Non-clinical grade mAbs

Application

Designed and approved for use in the humans, with proven clinical safety and efficacy

Used in in-vitro or in-vivo assays for biological research or medical diagnosis

Biological target

The biology of the therapeutic target protein is well-studied and characterized

Used in quantitative or qualitative assays to detect a target protein (in-vitro diagnosis) or study the biology of a target

Technology

Recombinant Ab technology is used to produce chimeric, humanized or fully human mAbs

Recombinant Ab technology or hybridoma technology is used to produce human or non-human mAb clones (mouse/rabbit/goat).

Antibody format

Whole immunoglobulins or fragments with single or multiple valencies.
Toxin-conjugated therapeutic mAbs are used to directly target and eliminate unwanted cells in the body.

Can be polyclonal or monoclonal. Monoclonal Abs can be whole immunoglobulins or fragments.
Depending on the application they can be tagged with radioelements, florescent proteins or enzymes.

Quality Characterization

Extensive structural and functional characterization is necessary.

  • Structural characterization includes detailed molecular, biochemical and bio-physical analysis to evaluate structure-function relationships.
  • Functional characterization involves ligand binding and effector functions to determine in-vivo mode of action.
  • In-vivo PK/PD studies and clinical studies are necessary to evaluate safety and efficacy

Mainly antigen binding specificity and sensitivity is validated for in-vitro use.

Scale up

Require internal reference standards and high quality-control measures in a GMP set-up to ensure minimal heterogeneity and batch variability

Require internal reference standards and high quality-control measures in a GMP set-up to ensure minimal heterogeneity and batch variability

Purification

Extensive purification steps under GMP conditions.
Endotoxin levels should be within acceptable range set as per the mode of drug administration (e.g., intravenous, subcutaneous, combination therapies, etc.)

Endotoxin profile is often unknown

Formulation buffer and stability

The formulation must ensure product stability and integrity under freeze-thaw conditions, agitation and pH variations. The excipients used (i.e., fillers, extenders, diluents, solvents, preservatives, absorption enhancers and sustained release matrices) must be approved by the regulatory authorities.

No regulatory approval required. Most mAbs are formulated in PBS buffer.

Purchase restrictions

Require license to purchase medicinal product. Drug substance (DS) in most cases not available for purchase.

No license required – usually available as research consumable.

Patent

Patent protected drug substance.

Usually not patent protected.

Download the list of therapeutic antibodies approved in the EMA (European Union's FDA)