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Questions and Answers
What is a correct practice during the transport of drug products?
What is a correct practice during the transport of drug products?
It is acceptable to store drug products in any temperature and humidity level as long as they are covered from light.
It is acceptable to store drug products in any temperature and humidity level as long as they are covered from light.
False
Name one critical mistake to avoid during drug preparations.
Name one critical mistake to avoid during drug preparations.
Preparing the wrong drug
Mixing biologics requires avoiding __________, which can lead to aggregates.
Mixing biologics requires avoiding __________, which can lead to aggregates.
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Match the following safety procedures with their purpose:
Match the following safety procedures with their purpose:
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Which of the following is a goal of biologics formulation?
Which of the following is a goal of biologics formulation?
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Neutralizing antibodies lead to a faster clearance of the therapeutic protein.
Neutralizing antibodies lead to a faster clearance of the therapeutic protein.
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Name one risk associated with injections.
Name one risk associated with injections.
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ADA stands for ______________.
ADA stands for ______________.
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Match the formulation types with their primary characteristics:
Match the formulation types with their primary characteristics:
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Which mechanism is NOT a key degradation mechanism for biologics?
Which mechanism is NOT a key degradation mechanism for biologics?
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Dilution always leads to stable formulations.
Dilution always leads to stable formulations.
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What is a common use for excipients in biologics?
What is a common use for excipients in biologics?
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The primary packing material in contact with a pharmaceutical formulation must be ____________.
The primary packing material in contact with a pharmaceutical formulation must be ____________.
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Which of the following is a potential effect of temperature on biologics?
Which of the following is a potential effect of temperature on biologics?
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All excipients used in biologics must be proven safe.
All excipients used in biologics must be proven safe.
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What type of excipients is necessary for injection formulations?
What type of excipients is necessary for injection formulations?
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Key degradation mechanisms are affected by temperature, pH, and the presence of _____________ from production.
Key degradation mechanisms are affected by temperature, pH, and the presence of _____________ from production.
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Match the following types of antibodies with their effects:
Match the following types of antibodies with their effects:
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Which of the following is a concern related to drug delivery systems?
Which of the following is a concern related to drug delivery systems?
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Biodegradable particles are often made from non-degradable polymers.
Biodegradable particles are often made from non-degradable polymers.
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What are typical targeting molecules used in enhanced drug uptake?
What are typical targeting molecules used in enhanced drug uptake?
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The most common biodegradable particles are made from __________.
The most common biodegradable particles are made from __________.
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Match the type of system with its characteristic:
Match the type of system with its characteristic:
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What could trigger insitu gelling systems?
What could trigger insitu gelling systems?
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Chemical stability is crucial for the function of drug delivery systems.
Chemical stability is crucial for the function of drug delivery systems.
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Name one strategy to improve the uptake of polynucleotides.
Name one strategy to improve the uptake of polynucleotides.
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The delivery of __________ has been associated with severe side effects, including cancer and immunological responses.
The delivery of __________ has been associated with severe side effects, including cancer and immunological responses.
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Match the type of virus with its example usage in gene therapy:
Match the type of virus with its example usage in gene therapy:
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Which of the following is a method to enhance drug transport across epithelial barriers?
Which of the following is a method to enhance drug transport across epithelial barriers?
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Encapsulation is a technique used to prolong the half-life of drugs in the body.
Encapsulation is a technique used to prolong the half-life of drugs in the body.
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What are non-viral vectors typically used for?
What are non-viral vectors typically used for?
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_______ and _______ are examples of polymers used in drug delivery systems.
_______ and _______ are examples of polymers used in drug delivery systems.
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Match the delivery method with its description:
Match the delivery method with its description:
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Study Notes
Formulation of Biologics
- Biologics require careful formulation to ensure safety and efficacy.
- Key goals of formulation include correct dosage, safety and stability of the pharmaceutical, correct pharmacokinetics, patient convenience, and compliance.
- Formulation also aims to minimize intrusion in daily life, improve healthcare system convenience, and enhance safe handling at hospitals.
- Shelf life and the ability for self-medication are also crucial.
Risks Related to Injections
- Potential risks include infection, adverse reactions (allergy, endotoxins, particles), and potentially damage to nerves or blood vessels from injections.
- Bleeding and bruising are also possible complications.
- Intravascular injections pose a risk of causing adverse effects.
Anti-Drug Antibody (ADA)
- ADA is an unwanted immune response of the host against a therapeutic protein.
- Two types of ADA exist: non-neutralizing and neutralizing.
- ADA can lead to a loss of activity and changes in pharmacokinetics (faster clearance).
- Immunological reactions to infusions and immunity against endogenous proteins are also potential consequences.
Chemical Stability
- Key degradation mechanisms include deamidation and isomerization, oxidation, hydrolytic fragmentation, racemization and β-elimination, and Maillard reactions.
- General issues affecting degradation include temperature, protein structure (primary, secondary, tertiary, and quaternary), pH, choice of buffer and ionic strength, presence of contaminants (excipients and metals), reactive oxygen species (ROS), and light and air exposure.
Heat and Cold
- Proteins can denature at both high and low temperatures.
- Ice formation can alter the composition of a drug product.
- Dropping a product can cause cavitation, leading to localized high temperatures.
- Proteins can adsorb to ice crystals.
Interfaces, Shake, and Flow
- Aggregation can be induced by contact with interfaces, such as air bubbles and silicon oil.
- Extensional flow aggregation is also a concern.
Dilution
- Formulation composition changes, such as pH, ionic strength and surfactant concentration, are key considerations during dilution.
- Example: Trastuzumab can be diluted in 0.9% NaCl but not in 5% dextrose.
How to Evaluate Structural Stability
- Methods for evaluating structural stability include UV spectra, fluorimetry, circular dichroism, size analysis, rheology, light scatter, dynamic light scattering (DLS), AUC, size-exclusion chromatography (SEC), and fast protein liquid chromatography (FPLC).
- Immunological tests, affinity binding assays, differential scanning calorimetry (DSC), and differential scanning fluorimetry (DSF), and nuclear magnetic resonance (NMR) can also be used assess stability.
Key Things to Know When Formulating a Biological Drug
- Understanding the desired pharmacokinetic profile for the active substance is critical.
- Stability and compatibility of the active substance are essential considerations during formulation.
- Potential risks to patients need to be carefully assessed.
- Route of delivery, type of formulation, choice of excipients, and choice of primary packaging are all decision points in the formulation design.
Excipients
- Excipients, other than the active substance, are added to pharmaceutical products to enhance desired properties.
- They are crucial for physical characteristics and pharmacokinetics.
- Excipients may include those that enhance uptake, enable controlled release or enhance stability.
- Excipients should only be used if necessary and must be safe or proven safe.
Primary Packing Material
- The packing material of pharmaceutical formulations needs consideration for the pharmaceutical formulation .
- Common types include vials, ampoules, pre-filled syringes, auto-injectors, IV bags, and pumps.
- Proper selection of materials is crucial to prevent contamination and degradation of the active substance.
- Care must be taken with extractables from plastics and alkali from glass.
Type of Formulation
- Different formulation types for biologics include solutions, lyophilized powders, and controlled release/targeted delivery preparations.
Solutions
- Advantages of solutions include ease of production and fast onset of action.
- Disadvantages may include potential stability issues and patient compliance concerns.
- Excipients may include tonicity agents, buffers, stabilizing agents, surfactants, preservatives and rheology modifiers.
Lyophilized Product
- Lyophilization offers stability gains and mild drying technology with ease of reconstitution.
- Disadvantages include higher production costs and handling needs, and slightly decreased patient compliance.
- Similar excipients compared to solutions are used.
Controlled Release Formulations
- Biocompatibility of materials is critical for controlled release formulations, as it prevents interactions with the immune or clotting systems.
- Burst effects are often possible, and proper stability of the active substance is key throughout the release period.
Implants and Biodegradable Particles
- Implants can be removed, often composed of non-degradable polymers like polyethylene vinyl acetate.
- Common biodegradable particle polymers include PLGA (poly lactic glyco acid).
In-situ Gelling Systems
- Liquid injectables transform to solid tissues triggered by a variety of factors, including heat, ions, or pH changes in the target environment.
- The systems include polymers such as chitosan and PEG, or lipids.
- Peptides are also included within these systems.
Improve Uptake
- Protein modification and excipients can enhance uptake.
- Excipients in formulations may inhibit or protect proteins, enhance transport barriers (epithelial, intestinal), and increase the residence time within the intestine.
- Formulations such as nanoparticles and microparticles, and excipients such as chitosan, can improve uptake efficiency.
Targeting and Enhanced Uptake
- High specificity and targeted uptake into cells can be achieved by targeting molecules such as antibodies, proteins like lectins and transferrin, peptides and/or carbohydrates (e.g., galactose).
Lipid Nano-Formulations for Drug Delivery
- Lipid nanoformulations employ various structures (conventional, theranostic, PEGylated, ligand-targeted) to encapsulate drugs for targeted delivery and enhanced stability.
Delivery of Polynucleotides as Active Substance
- Polynucleotides, such as siRNA and miRNA, have very short half-lives, hence needing chemical modification for enhanced stability and encapsulation.
- Vector-based and naked DNA delivery approaches are crucial for transporting them into cells.
Viral Vectors
- Viral vectors, such as adenoviruses, adeno-associated viruses (AAVs), and retroviruses, can be used for delivering polynucleotides.
- Viral vectors have a trigger immune response potential.
- Potential uses of viral vectors are in cancer treatments.
- Safety limitations include potential immunological responses and limited DNA quantities potentially available.
Stability Is Key for Function
- Drug formulations must be physically and chemically stable for proper function.
Risks Related to Handling of Protein Biological Drugs in Real Life
- Issues arising from the handling, transport, and storage of proteins in biological drug products.
Transport with Care
- Ensure proper handling and temperature control during transport, preventing shaking, vibrations, or drops.
- Use suitable delivery systems.
Store Safely
- Store biological drugs at the appropriate temperature and humidity, protected from light.
- Safely isolate from potentially damaging materials and products to prevent mix ups.
Evaluate Transport Effects on Product
- Pharmaceutical companies should validate transport procedures thorough design.
- Qualification, continuous monitoring, drop, shock and vibration, photostability, temperature and humidity tests are necessary.
Critical Mistakes to Avoid During Preparations
- Avoid mix-ups (wrong drug preparation or concentration), appropriate mixing methods and compatible materials.
- Safe procedures are crucial.
Mixing Biologics
- Incorrect mixing techniques (shaking, flicking, dropping) may lead to aggregate formation.
Material and Devices Used for Preparation
- Proteins are sensitive to certain materials that may cause aggregate formation and/or substance loss.
- Use suitable materials, such as specific syringes, tubing, IV bags, and spikes/CSTDs for proper mixing, delivering and administrating biologics.
Closed Systems Transfer Devices (CSTDs)
- Closed systems transfer devices (CSTDs) are beneficial in protecting healthcare workers and reducing patient risks due to improved aseptic handling, reduced aggregates and/or particulate formation, and reduced loss of substance (reduction of the administered dose and decreased protein adsorption).
...and Uses Biological Drugs
- Biological drugs are used in various medical practices.
Infusion
- Biologicals can be incompatible with some diluents or with other drugs.
- Avoid mixing incompatible drugs within an infusion line.
- Direct sunlight and inline filters should be avoided when possible.
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Description
Explore the critical aspects of formulating biologics to ensure their safety and efficacy. This quiz covers key formulation goals, risks related to injections, and the implications of anti-drug antibodies. Test your knowledge on how these factors impact patient care and medication stability.
