Protein Pharmaceuticals and Sterility Principles

Most protein pharmaceuticals are administered parenterally, meaning they are injected into the body. This direct entry into the bloodstream makes sterility essential to prevent infections and ensure patient safety.

Protein pharmaceuticals are sensitive to high temperatures and radiation, which can denature or degrade the protein structure and compromise its activity.

Filtration techniques use microporous membranes with pore sizes typically 0.2 or 0.22 µm to physically trap and remove bacteria and other microorganisms.

<p>Aseptic processing involves maintaining a sterile environment throughout the manufacturing process to prevent contamination from microorganisms that could compromise the sterility of the final product.</p> Signup and view all the answers

<p>Viral contamination can be a serious risk, especially when using microorganisms for production. Decontamination methods must effectively remove viruses without damaging the protein's activity or introducing other contaminants.</p> Signup and view all the answers

<p>Viral decontamination methods can be harsh and denature proteins if not carefully controlled. Finding effective methods that eliminate viruses while preserving the protein's structure and activity is crucial.</p> Signup and view all the answers

<p>Viral decontamination techniques need to be efficient and effective at both small-scale research and large-scale manufacturing levels to meet global demand for protein pharmaceuticals.</p> Signup and view all the answers

<p>Testing for viral contaminants is essential to ensure the safety and efficacy of protein pharmaceuticals. Viral contamination can lead to serious adverse effects in patients.</p> Signup and view all the answers

<p>Two approaches include selecting the appropriate pH and ionic strength conditions, as well as adding amino acids such as lysine or arginine.</p> Signup and view all the answers

<p>Anti-adsorption agents reduce the protein's tendency to adhere to surfaces like containers, air interfaces, and administration materials.</p> Signup and view all the answers

<p>Insulin aggregation can occur when it interacts with hydrophobic surfaces, leading to reversible self-association and irreversible aggregation of adsorbed protein.</p> Signup and view all the answers

<p>Albumin, due to its strong adsorption properties, competes with therapeutic proteins for surface binding, preventing their adsorption.</p> Signup and view all the answers

<p>Surfactants, with their hydrophilic and hydrophobic parts, adsorb to hydrophobic interfaces, rendering them hydrophilic and reducing protein adsorption.</p> Signup and view all the answers

<p>Buffer choice influences the pH of the formulation, which significantly affects the protein's solubility, physical stability, and chemical stability.</p> Signup and view all the answers

<p>Lysine is an example of an amino acid used to enhance the solubility of proteins in parenteral formulations.</p> Signup and view all the answers

<p>Lyoprotectants in parenteral formulations protect the therapeutic protein from damage during freeze-drying, minimizing the risk of aggregation and denaturation.</p> Signup and view all the answers

<p>To prevent fever and potential adverse reactions, including inflammation, shock, organ failure, and death, in patients receiving the drug.</p> Signup and view all the answers

<p>Pyrogens are primarily lipopolysaccharides (LPS), which are components of the outer membrane of Gram-negative bacteria.</p> Signup and view all the answers

<p>Two common methods are ion exchange chromatography, which utilizes the negative charge of endotoxins to separate them from the protein, and activated charcoal, which binds to endotoxins via hydrophobic interactions.</p> Signup and view all the answers

<p>Ion exchange chromatography separates molecules based on their charge. Endotoxins, with their negative charge, bind to positively charged resins while proteins with different charge properties flow through.</p> Signup and view all the answers

<p>Activated charcoal has a large surface area with hydrophobic binding sites that attract and bind to the hydrophobic lipid A portion of the endotoxin, removing it from the solution.</p> Signup and view all the answers

<p>Polymyxin B, a peptide antibiotic, binds very tightly to the lipid A component of endotoxins, effectively rendering them inactive or removing them from the solution.</p> Signup and view all the answers

<p>The protein's stability, its intended route of administration (multiple injections), and the need for specific excipients, along with manufacturing techniques like freeze-drying or aseptic preparation, all contribute to the complexity of parenteral protein formulations.</p> Signup and view all the answers

<p>Sterilization, typically achieved by heat treatment above 160°C for extended periods, is crucial to eliminate or reduce pyrogen levels in equipment and containers used in parenteral formulations.</p> Signup and view all the answers

<p>Phosphate, citrate, and acetate.</p> Signup and view all the answers

<p>Proteins rich in amino acids like methionine, cysteine, tryptophan, tyrosine, and histidine are susceptible to oxidation, which can lead to loss of activity and stability.</p> Signup and view all the answers

<ol> <li>Replacing oxygen with inert gases in vials. 2. Adding antioxidants such as ascorbic acid or acetylcysteine.</li> </ol> Signup and view all the answers

<p>To prevent microbial contamination after the first dose is administered.</p> Signup and view all the answers

<p>Oral delivery is preferable due to its patient-friendly nature, eliminating the need for healthcare professional intervention.</p> Signup and view all the answers

<p>Saline and mono- or disaccharide solutions, such as glucose or sucrose.</p> Signup and view all the answers

<p>Water structure promoters, such as sugars or polyhydric alcohols, interact with the solvent and are excluded from the protein surface layer, leading to preferential hydration of the protein.</p> Signup and view all the answers

<p>The primary reasons are protein degradation within the gastrointestinal tract and the poor permeability of the GI tract wall.</p> Signup and view all the answers

<p>Oral vaccines only require a small fraction of the antigen to reach its target site, which are lymphocytes and antigen-presenting cells in Peyer's patches, to elicit an immune response.</p> Signup and view all the answers

<p>It can increase the tendency of proteins to self-associate, which can lead to aggregation and loss of activity.</p> Signup and view all the answers

<p>Pulmonary inhalation provides a faster uptake of insulin, with peak levels reached in 5-60 minutes compared to 60-180 minutes for subcutaneous injections.</p> Signup and view all the answers

<ol> <li>Aqueous solutions 2) Freeze-dried form 3) Dried in a compacted state (tablet).</li> </ol> Signup and view all the answers

<p>The route of administration significantly impacts the absorption rate of insulin, with different routes such as subcutaneous, intravenous, inhalation, oral, and transdermal resulting in varying rates of absorption.</p> Signup and view all the answers

<p>The absorption rate varies depending on the injection site, with the abdomen showing faster absorption compared to the arms, thighs, and buttocks.</p> Signup and view all the answers

<p>Other factors include the specific insulin formulation, individual patient characteristics (e.g., age, body weight, metabolism), and even environmental factors.</p> Signup and view all the answers

<p>New routes of administration can provide safer, more efficient, and patient-friendly options for delivering protein drugs, leading to improved therapeutic outcomes.</p> Signup and view all the answers

<p>Increased blood flow, often caused by exercise or heat, enhances the absorption rate of a subcutaneous injection. The increased blood flow carries the injected substance away from the injection site more rapidly, leading to quicker absorption into the bloodstream.</p> Signup and view all the answers

<p>The nasal route of administration can bypass the first-pass effect in the liver, leading to a higher bioavailability of the drug. This means more of the drug reaches the intended target tissues and exerts its therapeutic effect.</p> Signup and view all the answers

<p>The pulmonary route of administration allows for faster absorption of insulin compared to subcutaneous injections because the lungs have a large surface area for drug absorption and a rich blood supply.</p> Signup and view all the answers

<p>A major disadvantage of the rectal route is the low bioavailability for proteins. This means that a significant proportion of the administered drug may not be absorbed into the bloodstream, limiting its effectiveness.</p> Signup and view all the answers

<p>Two advantages of the transdermal route are: 1. It avoids the hepatic first-pass effect, resulting in a higher bioavailability of the drug. 2. It allows for sustained and controlled release of the drug, providing a more consistent therapeutic effect over time.</p> Signup and view all the answers

<p>Warmer temperatures can increase blood flow to the injection site, which in turn enhances the absorption rate of the injected substance. This is because greater blood flow carries the medication away from the injection site and into the bloodstream more rapidly.</p> Signup and view all the answers

<p>Lipohypertrophy, a buildup of fat tissue at the injection site, can hinder the absorption rate of a subcutaneous injection. The thicker fat layer can impede the diffusion of the medication into the bloodstream, leading to a slower absorption process.</p> Signup and view all the answers

<p>Two patient-specific factors are: 1. Circulatory health: Individuals with poor circulation may experience slower absorption of medication due to reduced blood flow at the injection site. 2. Metabolic rate: People with a higher metabolic rate may absorb medications more quickly due to increased overall metabolism.</p> Signup and view all the answers

The condition in which products are free from all living microorganisms.

Controlled environment preventing contamination during product assembly.

Methods used to remove microbial contaminants from liquid products.

Processes to eliminate viral contamination in biopharmaceuticals.

Issues faced during viral removal like preserving protein function.

Viruses lacking a protective lipid layer, often more resistant.

High-efficiency particulate air filters used in clean environments.

Unwanted microorganisms that can spoil biopharmaceuticals.

Substances that induce fever, often from microorganisms.

LPS derived from the outer membrane of bacteria, can induce fever.

Process to reduce pyrogens by heating equipment above 160°C.

Technique to reduce endotoxins by exchanging ions in solution.

Material with high surface area to bind and remove endotoxins.

Antibiotic with high binding affinity for lipid A of endotoxins.

Process to remove endotoxins using compounds like peroxide.

Substances added to parenteral formulations to enhance stability.

The primary substance in a formulation that provides the intended therapeutic effect.

Substances used to increase the solubility of the active ingredient in formulations.

Agents added to prevent active proteins from adhering to surfaces during formulation.

Chemicals used to maintain a stable pH in a formulation, crucial for protein stability.

Compounds that lower surface tension and can help solubilize proteins by changing interface properties.

Substances that help regulate osmotic pressure in parenteral formulations.

Compounds that protect biological materials during freeze-drying processes.

Substances used to prevent the clumping of proteins in formulations, enhancing stability.

The method of drug delivery through the mouth.

The limited amount of a drug that reaches systemic circulation when taken orally.

The breakdown of protein drugs in the digestive system.

The ability of substances to pass through the gastrointestinal wall.

Vaccines that can be administered through the mouth for immune response.

Lymphoid tissues in the intestine that help initiate immune responses.

Insulin delivery via inhalation for faster glucose control.

Different body locations affect drug absorption rates.

Increased blood flow enhances absorption, while decreased flow slows it.

Insulins can be rapid-, intermediate-, or long-acting with different absorption rates.

Higher doses and concentrations can slow the absorption process.

Thickness of fat, lipohypertrophy, and scar tissue reduce absorption efficiency.

Circulatory health, metabolism, and hydration affect drug absorption.

Warmer temperatures and physical activity near the injection site boost absorption.

Fast uptake, avoids first-pass effect, lower proteolytic activity than GI tract.

Easily accessible, avoids first-pass metabolism and allows controlled release.

Compounds that help maintain pH in biotech formulations, like phosphate, citrate, and acetate.

Damage to proteins caused by oxidation, often due to amino acids like methionine and cysteine.

Substances like ascorbic acid that prevent oxidation in protein formulations.

Compounds added to prevent microbial growth in multi-dose protein containers.

Substances that inhibit bacterial growth without killing them, unlike bactericidal agents.

A phenomenon where additives enhance protein hydration by being excluded from the protein surface.

Proteins can be stored as solutions, freeze-dried, or compacted tablets.