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TPN, syringe drivers, Lab Results > Biopharmaceuticals > Flashcards

Biopharmaceuticals Flashcards

1
Q

Biopharmaceutical definition

A

drug product manufactured from biological sources

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2
Q

small molecule to mAB increasing in?

A

increasing complexity

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3
Q 
Biopharmaceutical characteristic:
MW
impurities
dosing route
dose
toxicity
specificity
immunogenicity
A 
high MW
unfamiliar impurities
IV dosing
optimal biologic dose
uncertain chronic toxicity
species specific
immunogenic
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4
Q

Recombinant DNA technology

A

Gene of interest extracted from HUMAN cell
Sticky ends used to insert into bacterial chromosome.
Chromosome is inserted into bacterial cell producing protein of interest

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5
Q

Process of manufacture

A
  1. Cell line - insertion to mammalian/bacterial cell
  2. Culture - transfer to large vessels
  3. Fermentation - transfer to bioreactors and nutrients added
  4. Purification - Biologic separated from biomass leading to pure solution
  5. Conjugation - with small molecule then further purification
  6. Formulation - into stable form then packed into vials
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6
Q 
Biopharmaceutical pharmacokinetics:
Tissue penetration
Binding 
Degradation
Renal clearance
Unbound concentration
Pharmacokinetics
A 
Poor
binding implies clearance
Proteolytic degradation
Renal clearance uncommon
unbound concentration can exert effect and immunogenicity
PK nonlinear, dependent on PD
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7
Q

Elimination pathways

A

Refer to table on sticky note

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8
Q

CQAs

A

Critical Quality Attributes
structural (chemical, physical, biological) and microbiological characteristics which relate to structural characteristics of the protein or peptide that defines the biopharmaceutical.
major biophysical structural changes:
loss of drug material from solution and
formation of soluble and insoluble (precipitates) aggregates).

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9
Q

Tiers of biopharmaceutical characterisation. Not representative of higher order structures etc

A

4- NMR
3- MS, SAXS (small angle X-ray scattering)
2- DSC, AUC
1- UV fluorescence, particle analysis

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10
Q

Affecting downstream processing

A

Resolution of properties of purification processes

detection and quantification capabilities

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11
Q

Regulation of biologics

A

EU directive
ICH Q5E
analytical testing,
biological assays, and, in some cases, nonclinical and clinical data.
stability, critical points in the manufacturing process, biological assays to evaluate the maintenance of the compound’s effects.
UV
Peptide maps

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12
Q

Primary through to quaternary plus their methods of analysis

A

Primary - peptide map
2ary - FT-IR (fourier transfer- infrared spectroscopy)
3ary - near UV CD (circular dichroism)
4ary - NMR

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13
Q

Steps in process - QA of final product

A

Impurities removal
Batch analyses,
Process validation/evaluation
Characterisation and stability

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14
Q

Comparable

Bio-similar definitions

A 
comparable = highly similar quality attributes before and after manufacturing process changes
bio-similar = biological medicine highly similar to another already approved medicine
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15
Q

What are higher order structures and their significance in biosimilar medicine

A

2ary to 4ary protein structures.

These must be analysed and if found to be significantly changed - the medicine is no longer a biosimilar

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16
Q

Reproduce antibody structure (found in folder)

A

…

17
Q

Different classifications of antibodies (Ig?) based on their constant regions

A 
A
D
E
G
M
18
Q

mAb production

A
  1. Mouse challenged with antigen
  2. spleen cells produced from mouse fused with myeloma cells
  3. hybridomas produced and cultured in HAT medium
  4. positive cells selected and mAbs harvested
19
Q

3 common methods of mAb isolation

EXPLANATION OF METHODS ON SLIDE 8 of lecture 11

A
  1. Phage display
  2. B cell immortilisation
  3. single-cell expression cloning
20
Q

% mouse of chimeric and humanised

A 
chimeric = 25%
humanised = 10%
21
Q

slide 10

A

mab naming

22
Q

Evaluation of mAb stability (3 types)

A
  1. Chromatographic methods (.g., routine batch analyses, in-process control, process validation/evaluation data, characterisation and stability) - POLARITY/CHARGE changes
  2. Electrophoretic methods
    Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS PAGE)
    Isoelectric focusing (IEF)
    Capillary electrophoresis (CE)
    Membrane-confined electrophoresis(MCE)
    CHARGE changes
  3. Spectroscopic methods
    Ultraviolet (UV)
    Circular dichroism (CD)
    Fluorescence spectroscopy (FS )
    Fourier-transform infrared spectroscopy (FTIR)
    MOLECULES or GROUPS WITH EM RADIATION
23
Q

additional stability tests for mAbs

A 
Mass spectrometry (MS)
Surface plasmon resonance (SPR)
Analytical ultracentrifugation (AUC)
Dynamic light scattering (DLS)
Differential scanning calorimetry (DSC)
Field flow fractionation (FFF)
24
Q

Rituximab - accepted and hypothesised

A

anti-CD20 chimeric antibody
direct lysis
complement-mediated cytotoxicity (C3-C3b-MAC)
FC1R/RC-mediated opsonic phagocytosis or ADCC
Hypothesis - supress disease injury through promotion elimination of circulating and possibly lymphoid-tissue-associated B cells

25
Q

Rituximab care in follicular lymphoma

A
  1. Asymptomatic - ritux. monotherapy
  2. Mild -Ritux. + radio-immunotherapy
  3. High tumour burden - immunotherapy, RCHOP, R-CVP +/- ritux.
26
Q

CQAs -Analytical methods. Proof of similarity

A
  1. STRUCTURE - higher order (NMR, CD, FTIR)
  2. STABILITY/Post-translational modifications (expansion on this in notes - related to glycans)
  3. BIOLOGICAL ACTIVITY - Binding, ADCC and CDC assays
  4. IMPURITIES - CEX - acid/base variants
    - peptide mapping deamidation
    - oxidation, mutation, glycation
    - SEC/FFF/AUC aggregation
27
Q

For biosimilar approval (3)

A
  1. high analytical similarity - amino acid sequence, comparable glycan variants, aggregates, deamidation, stability, purity
  2. Biosimilarity (PK/PD/Preclinical) - therapeutic effect the same
  3. Extrapolation of indications - must be functionally the same for 1-2 indications and these scientifically evaluated

TPN, syringe drivers, Lab Results (13 decks)

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