Monoclonal Antibodies (mABs)
Monoclonal antibodies (mAbs) are immunoglobulins derived from a monoclonal cell line and which have a defined specificity. Their immunological activities are based on binding to a specific ligand or antigen and may also depend on other effector functions. Encompassing a wide range of clinical indications, mAbs represent a large class of therapeutic biological products that continue to transform modern medicine. In recent years, mAb products have dominated the biotherapeutics market, with hundreds of novel mAbs and mAb-like proteins now in clinical development for the treatment of diseases in areas such as haematology, immunology, oncology and infectious diseases. The success of therapeutic mAbs can largely be attributed to their specificity and the technological advances that have driven their development.
Classically, mAbs are immunoglobulin G (IgG) molecules, although it is possible to generate mAbs of other immunoglobulin classes. Advances in recombinant biotechnology and protein chemistry, combined with a greater understanding of mAb structure and function, have led to growing interest in recombinant varieties of mAbs such as chimeric mAbs, mAb fragments, single domain mAbs and multispecific mAbs. These mAb variants may offer significant production, formulation and clinical advantages, including improved production yields, greater stability, the potential for alternative routes of administration, multiple antigen targeting, prolonged half-lives, increased bioavailability, enhanced functional activity and/or altered tissue penetration characteristics. An understanding of these different mAbs and mAb-related products is important in order to ensure their quality, safety and efficacy.
Monoclonal Antibody standardization
Written Standards
The first WHO guideline for assuring the quality of mAb products for use in humans was adopted in 1991. Since then there have been extensive technological advances in mAb production which have rendered such early guidance obsolete. Most notably is the use of recombinant DNA and cloning technologies which has allowed for the expression of mAbs in various mammalian cell lines, as well as in bacteria, yeasts, protozoa, plants and transgenic animals. In 2022, the Expert Committee on Biological Standardization adopted a new guideline on the production and quality control of mAbs and related mAb products. This guideline is applicable to mAbs regardless of the expression system in which they are produced, whether they are classic mAb proteins or mAb-related products or biosimilars, their intended route of administration, or their clinical indication.
The use of convalescent plasma therapy for the prevention and treatment of infectious diseases has a long history. Although mAbs have not replaced these blood-derived antibodies, their use provides several advantages including the reduced risk of transmitting blood-borne pathogens and a more consistent source of the product. The development of mAbs to SARS-CoV-2 virus highlighted the potential importance of these products in public health emergencies and for the prevention and/or treatment of other infectious diseases. The evaluation of the safety and efficacy of mAbs directed to the non-endogenous antigens of infecting agents poses unique challenges which may not be encountered with mAbs to noncommunicable diseases. To address this, the Expert Committee on Biological Standardization endorsed a project to draft a guideline on the nonclinical and clinical evaluation of mAbs and related products intended for the prevention and treatment of infectious diseases. This guideline was adopted by the Committee in March 2023. This guideline is general and applicable regardless of the mAb type or infecting organism.
Disease-specific addenda to the guideline have been developed to provide additional regulatory considerations relevant to the nonclinical and clinical evaluation of mAb products specific to the infecting agents.
Meeting reports