The drug development process through a bioanalytical lens
DRUG DISCOVERY
Identification of suitable candidate molecules that impact appropriate targets involved in disease(s).
Key stages: • Target identification • Target validation • Screening (hit identification) • Lead identification • Lead optimization • Candidate selection
PRECLINICAL
Assessment of bioactivity, effectiveness and toxicity of candidate drug molecules via: (i) In vitro tests examining drug molecule interactions in test tubes within the laboratory settings; (ii) In vivo tests examining drug molecules in animal models or living cell cultures.
Key stages: • Acute and chronic dose tox studies • Repeated dose studies • Genetic tox studies • Carcinogenicity studies • ADME, TK, PK, PD studies • In vitro DDI studies
CLINICAL TRIALS Approved
candidate drug molecule moves into clinical trials
Phase I trials are the first studies to be conducted in humans primarily focused on evaluating safety and side effects, and determining the maximum tolerated dose levels.
Patient pool: ~20–100 healthy volunteers (variable for different indications)
Phase II trials continue to focus on safety and side-effect profile, while also evaluating the candidate drug’s preliminary efficacy. Dosing schemes are adjusted to establish which dose performs optimally.
Investigational New Drug (IND) Application
Patient pool: ~100–250 patients (indication-specific populations)
Phase III trials demonstrate whether the candidate drug offers treatment benefit to a specific population by meeting a defined primary endpoint and safety.
IND
application prepared for review by US FDA (or equivalent filing in other countries)
Patient pool: ~300–3000 patients (indication-specific populations)
If drug
meets primary endpoint and demonstrates
adequate safety for intended use, it can be filed for marketing approval
Filing of the NDA currently reviewed by the US FDA’s Center for Drug Evaluation & Research (CDER)
New Drug Application (NDA) / Biologics License Application (BLA)
Filing of the BLA currently reviewed by the US FDA’s Center for Biologics Evaluation & Research (CBER) and CDER
If accepted,
a Prescription Drug User Fee Act (PDUFA) date is set (10 months on) by when the
US FDA is expected to make its decision
POST-MARKETING SURVEILLANCE
Phase IV studies (also known as Post-marketing surveillance) evaluate the long-term benefits, risks and cost–effectiveness of the drug.
Patient pool: ~1000< patients (indication-specific populations)
Bioanalytical laboratory work supports multiple stages of the drug development process. This includes appropriate characterization of molecules; optimal method development; supporting preclinical testing and clinical trials; and QC and QA for the entire development process (some examples below).
Discovery bioanalysis (non-regulated)
• Efficacy (pharmacology model) support
• Plasma protein binding (PPB) • PK/PD studies • ADME/DMPK
Preclinical bioanalysis (generally regulated and GLP, with some non-regulated, non-GLP studies)
• Method development • Method validation
• Sample analysis • CYP inhibition
Clinical bioanalysis (generally regulated and GLP/GCP studies)
• Method validation • Sample analysis • Assess PK
• Single and/or multi dose PK • Intervention effectiveness • Biomarker evaluations
• Safety/pharmacovigilance • Drug-drug interaction studies (DDIs) • Immunogenicity testing
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