Final Flashcards
Diagnostics
Diagnostic is a test used to identify a disease or medical condition, or to monitor
the effect of treatment
role of target identification and target validation
Approval process
clinical research
4 pharmacautical quality characteristics
- Process performance and product quality
monitoring system - Corrective action and preventive action
(CAPA) system - Change management system
- Management review of process
performance and product qualtiy
Dendritic cells (DC), what are they and how they work?
DC take up and process antigens and migrate to regional lymph node
Process and present antigens for the immune system to recognize
DC vaccines, Form of personalized medicine
Generic Drugs
Generic drugs are copying that one company makes of a brand-name
drug that was developed by another company
Toehold switchs
- Toehold switches are synthetic RNAs that mimic messenger RNAs
- They contain a recognition sequence (toehold) for a specific stimulus in form of a specific “input” RNA, and a recognition sequence that the protein-synthesizing machinery (ribosome) needs to bind to initiate the translation of a fused protein-coding sequence into its encoded protein product.
- In the absence of the “input” RNA, the toehold switch is kept in its OFF state by forming a hairpin structure that uses part of the “input” recognition sequence and the ribosome recognition sequence, which is kept inaccessible.
- The toehold switch is turned on when a stimulating “input” RNA binds to the toehold and induces the hairpin structure to open up, giving the ribosome access to its recognition sequence to start the synthesis of the encoded protein downstream.
industrializations of biotherapeutic production
approval process
importance of cell culture
Licensing of a biologic
BLA (biologics licensing application)
growth of antibody-producing cell lines
Viral inactivation
Virus inactivation by manipulation of the chemical (e.g. use of solvent and detergent) and environmental (e.g. low pH) conditions of the process materials
what are some assays/tests and how do they work
RNA therapies in human cells (Toehold switches)
- RNA based control switch (Harvard and MIT)
- Turn on gene expression in target cells
- Eliminate the danger effects of transgene on non targeted cells
- Reading only specific RNA sequence inside the targeted cell
- Create new therapies to destroy tumors by designing their system to
identify cancer cells and produce a toxic protein just inside those
cells, killing them in the process
Two reasons for rejection of patents
Lack of Novelty Rejection- the invention must be considered to be new and novel, if the prior products are not exactly the same then its considered novel
Obviousness Rejection- would the new invention have been obvious to a person having ordinary skill in the type of technology
Cell culture challenges
Relatively low yield of desired protein
* Variability in culture (Not well understood)
* Laborious and extensive clones screening process (several months)
* Each new therapeutic needs experience team of scientists
* Development, characterization and optimization
* The cells may not behave the same in large scale such as bioreactors
know the difference between CD4 T cells and CD8 T cells, and what DCs do and why we use them in drug therapies
Criteria for cell line selection
Stability
Product biological activity
Product expression: level, duration, and inducibility
Growth and productivity in large scale culture
ease of selection of high producers
adaptation to protein-free suspension culture
apoptosis; proliferation rate; max cell number
Safety issues
Cell culture improvements
Enhancing cell viability (limiting lactate production)
* Understand cell cycle mechanisms (apoptosis and cell death)
* Study the effect of large scale protein on host cell machinery
* Membrane biogenesis (high turnover rate in protein
secretion cells)
* Engineering of glycosylation enzymes to enhance product
quality
* Genomic and proteomics studies (gene and protein
expression)
What is GMP, examples
Good manufacturing Processes
steps in each phase of clinical research
cell line development
Pros of Gene Therapy
Process of Obtaining
File a provisional patent application
Establishes a filing date
Within 12 months of provisional filing date, file a utility patent application
Patent prosecution is the process of negotiating with the patent examiner to identify allowable subject matter
Utility patent application and provisional priority documents
Biologics
Biologics are made from living organisms, with complex manufacturing processes. Differences and improvements between manufactured lots are target for potential IPs interest from industry
Types of Cells in Cell culture
- Epithelial like-attached to a substrate and appears flattened and polygonal in shape
- Lymphoblast like - cells do not attach remain in suspension with a spherical shape
- Fibroblast like - cells attached to a substrate appears elongated and bipolar
BioBetters
Biobetters considered a new and improved version of a biologic, biobetters are evaluated like a new drug
Understand biologics and protein functionality (these basics are important for
understanding medical applications of biotechnology)
Approval Process for Diagnostics
Understand the role of target identification and target validation
Industrializations of biotherapeutic production
CHO cell advantages
bioethics in the analytical phase
What are some human factors
human factors/usability engineering
focuses on the interactions between people and medical devices. Demonstrates that the device can be used by the intended users,
under expected use conditions, without serious use errors or
problems
Applications of Stem Cells
Tissue Repair, Cancers, Autoimmune Disease
What is quality risk managment (QRM)
a process that is structured and aligns strategy, processes, people, technology and knowledge in order to evaluate and manage uncertainties.
Viral Removal
Virus removal by using chromatographic steps that provide rigorous washing of the process material, or by using filters (e.g. nanofilter) that can selectively remove viruses but with minimum impact on the yield of the product of interest at an acceptable level of product quality
What is the manufacturing process?
Approach for cell line engineering
Identification of genes/proteins that are specifically up-regulated in bioprocessing conditions (-omics approach)
Engineering of cells and selection of a new cell line
Engineering of cells to over-express the gene(s) of interest (historical approach)
Examine the effect and select a new cell line
Further understanding of genes/pathways directly regulated by the gene of interest
Biosimilars
Biosimilars typically are the same gene in the same cell type with slight difference in glycosylation, biosimilar is a biological product that is highly similar to and has no clinically meaningful
Device development process
Design controls- part of the QMS
Design and development
Verification and validation
Human factors
Manufacturing transfer
bioethics in the post-analytical phase
Ethical guidelines
What are some Assays/tests and how do they work?
Elisas
requirements for IP
eligible subject matter, non-obviousness, novelty, and usefulness
Difference between small molecules and biologics
small molecules are chemicals, stable, and not made from living things,
Upstream Processes
The upstream process in biopharmaceutical production refers to the
process of manufacturing the products of interest using biological
entities, such as bacterial or animal cells
What is intellectual Property
The term used to describe the branch of law which protects the application of thoughts, ideas, and information which are of commercial value
bioethics in the pre-analytical phase
reasons for rejection and process of obtaining approval
What is quality risk management (QRM)?
A systematic process for the assessment, control, communication, and review of risks to the quality of the drug product across the product lifecycle
Understand drug development
Key genes in proliferation and apoptosis
bcl-2 suppresses cell death
p21 arrests the cell proliferation and enhance specific productivity
c-myc enhances proliferation rate, reduces serum dependency, and induces anchorage independence
hTERT reduces apoptosis, enhances proliferation, and increases attachment tendency in the absence of serum
what are common cell lines
Growth of antibody-producing cell lines
Delivery systems for Gene Therapy
RNAi or viral vectors
Bioprocessing of Recombinant Proteins
- Development of Stable Lines
- Cell Banking
- Upstream Processing
- Harvest
- Downstream Processing
- Finish/Fill
Intellectual Property
term used to describe the branch of law that protects the application of thoughts, ideas, and information which are of commercial value
Understand clinical research and the steps involved for each phase
Biomarker
Biomarker is a characteristic that is measured and evaluated as an indicator of
normal biological processes, pathogenic processes, or pharmacologic
responses to a therapeutic intervention.
CHO (advantages)
their robustness,
genomic stability, easy transfectability
yields of recombinant protein production.
Gene Therapy
Uses genetic material, or DNA to manipulate a patient’s cells for the treatment of an inherited or acquired disease
GMP and Drug manufacturing
Ensures that products are consistently produced and controlled
according to quality standards
* Designed to minimize the risks involved in any pharmaceutical
production that cannot be eliminated through testing the final product
* Covers all aspects of production from the starting materials, premises,
and equipment to the training and personal hygiene of staff
* Must be systems to provide documented proof that correct procedures
are consistently followed at each step in the manufacturing process -
every time a product is made
how mAbs work and different components of them
Heavy chain, light chain
GMP regulations address
issues including recordkeeping, personnel
qualifications, sanitation, cleanliness, equipment verification, process
validation, and complaint handling
Types of Gene Therapy
RNAi and viral vectors
basic of cell culture
how viral vectors work
What is a combination Product
Combination produces are comprised of two or more regulated components
Cons of Gene Therapy
viral vectors raise safety concerns, high failure rate in clinical trials, ethical issues
