Alternative Routes of Administration for Therapeutic Antibodies—State of the Art

Abstract

Background: For the past two decades, there has been a huge expansion in the development of therapeutic antibodies, with 6 to 10 novel entities approved each year. Around 70% of these Abs are delivered through IV injection, a mode of administration allowing rapid and systemic delivery of the drug. However, according to the evidence presented in the literature, beyond the reduction of invasiveness, a better efficacy can be achieved with local delivery. Consequently, efforts have been made toward the development of innovative methods of administration, and in the formulation and engineering of novel Abs to improve their therapeutic index. Objective: This review presents an overview of the routes of administration used to deliver Abs, different from the IV route, whether approved or in the clinical evaluation stage. We provide a description of the physical and biological fundamentals for each route of administration, highlighting their relevance with examples of clinically-relevant Abs, and discussing their strengths and limitations. Methods: We reviewed and analyzed the current literature, published as of the 1 April 2022 using MEDLINE and EMBASE databases, as well as the FDA and EMA websites. Ongoing trials were identified using clinicaltrials.gov. Publications and data were identified using a list of general keywords. Conclusions: Apart from the most commonly used IV route, topical delivery of Abs has shown clinical successes, improving drug bioavailability and efficacy while reducing side-effects. However, additional research is necessary to understand the consequences of biological barriers associated with local delivery for Ab partitioning, in order to optimize delivery methods and devices, and to adapt Ab formulation to local delivery. Novel modes of administration for Abs might in fine allow a better support to patients, especially in the context of chronic diseases, as well as a reduction of the treatment cost.

Uses and Challenges of Antiviral Polyclonal and Monoclonal Antibody Therapies

“…The recombinant human hyaluronidase degrades hyaluronic acid in the extracellular matrix, facilitating rapid delivery of large volume subcutaneous injections and bioavailability of the product. This has already been accomplished with several mAbs for oncology, including the combination of rituximab, trastuzumab, daratumumab or trastuzumab and pertuzumab with recombinant human hyaluronidase 235 . This approach is being studied with an anti-HIV mAb (clinicaltrials.gov #NCT03538626).…”

Predicting Colloidal Stability of High-Concentration Monoclonal Antibody Formulations in Common Pharmaceutical Buffers Using Improved Polyethylene Glycol Induced Protein Precipitation Assay

“…The slope of the linear regression, a, in eq 4 was determined for the 144 conditions and evaluated as a function of C mid in Figure 4B. (6) where, v 1 = 0.73 mL/g is the average partial specific volume of proteins 49 to make the parameter a dimensionless. When fitted with an exponential function, the exponents of the (a, C mid ) plot and the (Δv, C mid ) plot are −0.389 and −1.35, respectively (Figure 4).…”

Transportation of mAb Dosing Solution in Intravenous Bag: Impact of Manual, Vehicle, and Pneumatic Tube System Transportation Methods on Product Quality

“…The success in treating diseases with therapeutic mAbs can be attributed to their higher level of specificity and affinity to the target antigen and desired safety and pharmacokinetic profile. 6,7,9 The majority of therapeutic mAbs are administered to patients via IV infusion. 6−9 Preparation of dosing solution for IV infusion typically involves diluting mAb drug product in a compatible infusion solution/diluent [commonly used diluents are 0.9% sodium chloride (normal saline) and 5% dextrose solution (D5W)] contained in an IV infusion bag.…”

“…Therapeutic monoclonal antibody products have become increasingly prevalent for treating various diseases and conditions. − Every year, 6–12 new monoclonal antibodies (mAbs) are approved by the United States Food and Drug Administration and/or the European Medicines Agency. − Several new mAbs are entering clinical trials every month. The success in treating diseases with therapeutic mAbs can be attributed to their higher level of specificity and affinity to the target antigen and desired safety and pharmacokinetic profile. ,, The majority of therapeutic mAbs are administered to patients via IV infusion. − Preparation of dosing solution for IV infusion typically involves diluting mAb drug product in a compatible infusion solution/diluent [commonly used diluents are 0.9% sodium chloride (normal saline) and 5% dextrose solution (D5W)] contained in an IV infusion bag …”