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    Bioteknologi Farmasetika: Definition and Examples of Biologics

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    Putri Nur Azizah
    Biotechnology uses living organisms such as microorganisms to produce or modify products. Recombinant DNA technology was used to produce therapeutic proteins, but biotechnology now also uses tissue culture and cells. Biologics are complex medicinal products containing proteins, nucleic acids, sugars, or intact cells. They include vaccines, antibodies, hormones, and enzymes. Compared to small molecules, biologics have a larger molecular size and more complex structure, making them less stable and more susceptible to degradation. Their production is also more complex and costly than traditional small molecule drugs.

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    Bioteknologi Farmasetika: Definition and Examples of Biologics

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    Putri Nur Azizah
    72 views3 pages
    Biotechnology uses living organisms such as microorganisms to produce or modify products. Recombinant DNA technology was used to produce therapeutic proteins, but biotechnology now also uses tissue culture and cells. Biologics are complex medicinal products containing proteins, nucleic acids, sugars, or intact cells. They include vaccines, antibodies, hormones, and enzymes. Compared to small molecules, biologics have a larger molecular size and more complex structure, making them less stable and more susceptible to degradation. Their production is also more complex and costly than traditional small molecule drugs.

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    BIOTEKNOLOGI FARMASETIKA_PRIN

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    Biotechnology uses living organisms such as microorganisms to produce or modify products. Recombinant DNA technology was used to produce therapeutic proteins, but biotechnology now also uses tissue culture and cells. Biologics are complex medicinal products containing proteins, nucleic acids, sugars, or intact cells. They include vaccines, antibodies, hormones, and enzymes. Compared to small molecules, biologics have a larger molecular size and more complex structure, making them less stable and more susceptible to degradation. Their production is also more complex and costly than traditional small molecule drugs.

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    72 views3 pages

    Bioteknologi Farmasetika: Definition and Examples of Biologics

    Uploaded by

    Putri Nur Azizah
    Biotechnology uses living organisms such as microorganisms to produce or modify products. Recombinant DNA technology was used to produce therapeutic proteins, but biotechnology now also uses tissue culture and cells. Biologics are complex medicinal products containing proteins, nucleic acids, sugars, or intact cells. They include vaccines, antibodies, hormones, and enzymes. Compared to small molecules, biologics have a larger molecular size and more complex structure, making them less stable and more susceptible to degradation. Their production is also more complex and costly than traditional small molecule drugs.

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    of 3

    The term biotechnology encompasses any technique which

    uses living organisms (e.g., microorganisms) in the production


    or modification of products.
    The classic example of biotechnologic drugs was proteins
    obtained from recombinant DNA (rDNA) technology.
    However, biotechnology now encompasses the use of tissue
    culture, living cells, or cell enzymes to make a defined
    product.
    BIOTEKNOLOGI rDNA and monoclonal antibody (MAb) technologies have
    provided exciting opportunities for development of more
    FARMASETIKA pharmaceuticals and approaches to the diagnosis,
    treatment, and prevention of disease.
    Mia Fitriana, M.Si., Apt.

    FDA-Approved Biologic Products of Various Types


    Definition and Examples of Biologics Available for Treating or Preventing Various Conditions

    Class of Medicinal Products that Contains Active Substance (s)

    Proteins, Nucleic Acids, Sugars, Intact Cells


    Vaccines (Prevnor - Pneumonia, Gardasil - HPV)
    Antibodies (Avastin, Humira, Remicade, Herceptin)
    Fc Fusion Proteins (Enbrel, Orencia)
    Hormones (Elonva- long acting FSH, Growth Hormone)
    Enzymes (Pulmozyme rHu-DNAase- )
    Proteins (Clotting factors, Interleukins, Albumin)
    Gene Therapy and RNAi (Still in development)
    Cell Therapy (Provenge Prostate cancer vaccine)
    Antibody Drug conjugates - Adcetris (Brentuximab vedotin for HL)

    Complexity of Biologics by Molecular Size


    (Small Molecule vs. Peptide vs. Protein) Conformational Complexity of Biologics
    Routes of Biologics Drug Delivery Distinct Attributes of Biologics
    Biochemical and Biophysical
    Relatively unstable in solution
    High Mw, complex structural organization and delicate
    conformation
    Sensitive to environment (temperature, pH, oxidation, non-
    polar solvents etc)
    Prone to enzymatic degradation (proteolysis)
    Susceptible to adsorption , unfolding, aggregation and
    inactivation
    Prone to microbial contamination
    Increased viscosity and low solubility at high concentrations
    Needs special care during fill-finish, storage and shipping

    Physiological Short half life (In-vivo)


    Conc.
    .
    Limited adsorption / Low Mucosal PermeabilityLow BA
    Immunogenic

    Cost of Goods, Manufacture, Transportation and Storage


    Very Expensive
    **API (Drug Substance) Cell Culture & Complex Purification Steps
    Low Production Yields
    Sterile Suites for cell culture (USP), Purification (DSP) and Fill-Finish
    Cold Chain

    Oxidation of Proteins Protein Aggregation


    During Aerosolization proteins are prone to Oxidation and Protein aggregation is a common issue encountered during
    Aggregation manufacture, storage and transportation of therapeutic proteins.
    Metal and peroxide contaminants present in excipients and delivery Aggregates of proteins may arise from several mechanisms and
    devices catalyze oxidation. various stress conditions
    Amino Acids prone to OxidationMet, Cys, Trp,Tyr High temperature and mechanical agitation
    Oxidized proteins are often functionally inactive and their unfolding Types of aggregates: soluble / insoluble, covalent / non-covalent,
    is associated with enhanced susceptibility to proteolytic reversible / irreversible, and native / denatured.
    degradation. For protein therapeutics, the presence of aggregates of any type is
    Oxidation is known to affect the structure, activity, and rate of typically considered to be undesirable because aggregates may
    degradation of proteins, and is believed to contribute to a variety lead to an immunogenic reaction (small aggregates)
    of pathological conditions or may cause adverse reactions on administration (particulates).
    Oxidation affects stability, purity and safety of therapeutic proteins.
    Aggregation occurs due to exposure of protein to air-water inter-
    phase
    Special Formulation Considerations
    Immunogenicity
    for Biologics
    Permeability enhancers (to improve BA) : Surfactants, fatty acids, saccharides,
    Complex Immunological Phenomenon chelating agents

    Influenced by various factors Adjuvants (to enhance absorption) : Glycocholate, Surfactin, Span 85, Nafamostat
    Protein aggregates in biological drugs have the
    Fatty acids and PEG (to prolong residence time) : Lauric acid : Increases dissolution
    potential to trigger an immune response in the half-time

    patient, which, at the very least, can decrease the Most important issue Protein Stability
    drug's effectiveness Stresses during Fill-Finish, Storage, Transportation and Delivery : Aggregation,
    Oxidation
    at worst could cause potentially harmful side effects
    Any Structural modification Increased Immunogenicity
    Immunogenicity is a safety issue

    Liquid or Lyophilized

    Liquid formulations are generally the


    preferred presentation although
    lyophilized formulations are more stable.
    The decision has to be strategic and
    based on the intrinsic stability of the
    protein, as not all proteins are stable
    enough for liquid formulation.
    Development of lyophilized formulation
    requires additional effort for the extra
    process.
    Different excipients are generally used for
    liquid and lyophilized formulation
    candidates.

    15

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