Drug Discovery and Development for Cell and Gene Therapy

Vocabulary flashcards focusing on key terms, preclinical models, manufacturing processes, and regulatory frameworks in cell and gene therapy development.

Target Identification

The essential process of directing drug development toward biologically relevant molecules to address specific disease mechanisms and improve patient outcomes.

Multi-Omics Approaches

Integrated biological analytical methods—comprising Genomics, Transcriptomics, Proteomics, and Metabolomics—used to obtain a comprehensive view of disease biology for precise target selection.

CFTR Gene Mutation

The specific genetic alteration that causes Cystic Fibrosis, serving as an example of genetic linkage in disease-relevant target selection.

Biological Feasibility

An assessment in target selection evaluating disease eradication potential based on host range and treatment availability, such as Measles being eradicable because it exclusively infects humans and has an effective vaccine.

CRISPR-Cas9

An advanced genomic editing innovation enabling precise modifications of target genes to investigate functional consequences in disease models.

Proteomic Profiling Methods

Quantitative analytical techniques such as mass spectrometry and protein arrays used to evaluate protein expression and modifications in disease pathways.

In-Vitro Models

Controlled experimental setups that isolate specific variables to study cellular responses, investigate mechanisms of action, and detect early dosage toxicity without confounding factors.

In-Vivo Models

Preclinical animal studies that evaluate systemic biological interactions, physiological impacts, chronic durability, and predictive translational relevance for human trials.

Quantitative Polymerase Chain Reaction (qPCR)

A laboratory technique used in preclinical AAV studies to quantify and analyze the distribution of vector genomes in harvested tissue and organ samples.

Shedding Assay

A preclinical evaluation method that samples urine, saliva, and feces to track the excretion and presence of AAV viral vectors.

AAV Neutralizing Antibodies

Immune proteins produced against viral vectors that can significantly diminish treatment effectiveness in gene therapy.

Off-Target Effects

Unintended genetic modifications resulting from imperfect binding of guide RNAs during gene editing, posing health risks such as oncogenesis.

AAV Production Standard Procedure

A bioprocess consisting of upstream HEK293 cell culture with triple transfection and downstream lysis, depth filtration, ultrafiltration/diafiltration, affinity and ion exchange chromatography, and formulation.

30-Day Review Clock

The statutory timeframe utilized during the FDA's IND Review Phase to evaluate participant safety and clinical trial protocols before trials can proceed.

Cell and Gene Therapy Regulatory Meeting Timeline

The structured progression of regulatory interactions spanning Pre-IND (INTERACT, Pre-IND), IND Review, Clinical Trials (End of Ph 1, End of Ph 2, Pre-BLA), BLA Review (Post BLA), and Post-Marketing (Safety Meetings).

Kymriah and Yescarta

The first two CAR-T therapies approved by the FDA in 2017 and subsequently approved by the EMA in 2018.

Regulatory Requirements for Cell-Based Therapies

Regulatory pathways focusing on donor variability in autologous products, raw material safety, and communicable disease prevention, requiring either an IND application or a BLA depending on the therapy.

Regulatory Requirements for Gene-Based Therapies

Regulatory pathways enforcing strict regulations on delivery vectors and target cells with long-term safety follow-up, requiring both an IND application and a BLA.

FDA vs. EMA Review Framework

A comparison where the FDA offers a flexible framework with adaptive trial designs and faster 30-day IND reviews, whereas the EMA uses a centralized, structured approach with longer authorization timelines.

Chemistry, Manufacturing, and Controls (CMC)

A required component of an Investigational New Drug (IND) application detailing product quality, stability, and manufacturing controls for cell and gene therapies.