ADC · mAbs · Viral Vector · Cell-/Gene Therapy · OEL · OEB · Toxicity
Drugs
Advanced drugs and requirements for their processing
These days people are talking a lot about cell / gene therapy drugs, clinical trials, monoclonal antibodies and other exciting topics around small batch fill-finish solutions. This page brings a little light into some of these terms and gives you an idea of acceptable technical solutions appropriate for this specific field of drugs.
What are Antibody Drug Conjugates?
Antibody Drug Conjugates (ADCs) are monoclonal antibodies (mAbs) attached to biologically active drugs by chemical linkers with labile bonds. They are precise weapons against cancer, autoimmune and cardiovascular diseases. mAbs are immunologically active proteins produced by a cell clone.
Why ADCs / monoclonal antibodies (mAbs) are harmful?
Monoclonal antibodies are laboratory-produced molecules engineered to serve as substitute antibodies that can restore, enhance or mimic the immune system's attack on cancer cells.
What are some challenges in dealing with monoclonal antibodies (mAbs)?
- Harmful for operators if released to the environment
- Cross contamination prevention between APIs on different mAbs
- Tendency to foam because of protein base
- Sensitive against shear forces, pressure and temperature
- Fragile and tend to decompose
- Need for highly optimized fill-finish solutions
Classification of risk
- Risk management and requirement definition
- Risk reduction per design, material studies, cleaning studies and operator protection
- Drug categorization
(HP-) API / (Highly Potent-) Active Pharmaceutical Ingredients
An active pharmaceutical ingredient (API) is the biologically active ingredient in a pharmaceutical drug product. Some medication products may contain more than one active ingredient.
Viral Vector Vaccines
Use live viruses to carry DNA into human cells. The DNA contained in the virus encodes antigens that, once expressed in infected human cells, elicit an immune response.
ATMPs known as Cell-/Gene Therapy
Advanced Therapy Medicinal Product (ATMP) therapies include cells, engineered tissues, or manipulation of the patient genome.
- Cell therapy: restoration or alteration of cells outside the body before injection into the patient.
- Gene therapy: replacing, inactivating or introducing genes into cells in vivo or ex vivo.
Drivers for choosing Isolator Technology in drug manufacturing
- Enclosed processes excluding ambient conditions for safer aseptic manufacturing
- Monitoring of particles, sterility, LF conditions, humidity and pressure
- Reduction / elimination of human intervention
- Highest quality assurance by reducing contamination risks
→ Best possible protection for drugs and operators
→ EU GMP Annex 1
Key considerations — What’s the product like?
- Dosage form — liquid, solid, intravenous, oral, etc.
- Viscosity, sensitivity (temperature, oxygen, light)
- Toxicity, ADC, HP-API, harmful aerosols
- Adequate fill solution for foaming proteins and sensitive products
- Storage conditions and process monitoring
- Container form — vial, syringe, ampoule, cartridge
- Bulk or pre-sterilized (nested or tray)
Risk Evaluation
Exposure (OEB/OEL) Categorization
Biosafety Level (BSL) Categorization
