New Drug Development

Question 1

What is a drug product?

Answer 1

Drug (components)

Drug products: systems of mixtures: API and Excipients

(Basic) Dosage Forms

(Advanced) Drug Delivery Systems

Question 2

What are Basic Dosage Forms?

Answer 2

Liquid Dosage Forms:

Solutions

Collodial Dispersions

Coarse Dispersions (Suspensions and emulsions)

Semisolids

Question 3

What is the definition of a drug?

Answer 3

A drug: articles intended for use in the diagnosis, cure, mitigation, treatment or prevention of disease in man or other animals (CFR)

Question 4

What is “new” drug?

Answer 4

A new drug is not recognized among qualified experts

A new drug can be a

• New chemical entitiy (NCE)
• New Formulation
• New combination
• New proposed used for an established drug

Question 5

FDA Drug Classification System

Answer 5

Type 1: New molecular entity; not marketed in US

Type 2: New ester, salt, or other derivatives of an approved active moiety

Type 3: New Formulation of a drug marketed in US

Type 4: New combination of two or more compounds

Type 5: New Manufacturer of drug marketed in US

Type 6: New therapeutic indication for an approved

Question 6

How is a new drug named?

Answer 6

• Empirical formula and systematic chemical name
• Code name by the inventor
• Nonproprietary (generic) name: Aspirin
• Proprietary name

Question 7

What is the roadmap of NDDDA?

Answer 7

1. Drug Discovery (& design)
2. Drug Development
   
   1. Preclinical studies: preformulation & formulation, animal testing, process development
3. Investigational New Drug Application (IND)
   
   1. Phase 1
   2. Phase II (a,b)
   3. Phase III
4. New Drug Application (NDA)

Question 8

What are the preformulation studies?

Answer 8

Preformulation studies

• Chemical characterization structure MW
• Physical characterization
  
  • pKa, pH and ionic properties
  • Drug solubility
  • Partition coefficient
  • Rheology and/or powder properties (micrometrics)
  • Physical form -polymorphism
• Stability (chemically, physical and biological)

Question 9

IND application Submission

Answer 9

• Application for the first human clinical trial
• General Content of the
  
  • Contact information
  • Investigation plan
  • Chemistry Manufacture and Control (CMC) information
  • Pharmacology and toxicology information
  • Clinical protocol
  • Institutional review board (IRB) approval
  • Investigator brochure
• The FDA must reply in 30 days

Question 10

What are the three phases of clinical investigations?

Answer 10

Phase I

• 20~100
• First in man
• Safety
• tolerability
• ADME (pharmacokinetics, PK)

Phase II

• ~hundreds
• Controlled
• Effectiveness: proof of concept
• Dose ranging and determination
• Safety
• Additional PK

Phase III

• Hundreds to thousands
• Usually controlled
• Usually replicated
• Primary data to support marketing approval in FDA

Question 11

What is the clinical trial design?

Answer 11

• Controlled Trial - investigational drug is compared to another agent
  
  • Placebo controlled
  • Positive controlled - investigational drug is compared to another active drug or comparative agent (comparator)
• Blinded studies - identities of IND and placebo/other agent are not revealed to certain participants
  
  • Main advantage = decreases bias
  • Single blind study - patient unaware of administered agent
  • Double blind - both patient and clinician are unaware of administered agent
• Parallel and crossover

Question 12

What is involved in New Drug application (NDA)

Answer 12

• General Content of the NDA submission
  
  • Product information: name, DF, strength
  • Statement and summary
  • CMC
  • Non-clincal pharmacology and toxicology
  • Human Pharmacokinetics and bioavailability
  • Clinical data
  • IRB compliance
  • Common Technical Document Format
• Drug Product Labeling
• FDA review And Action letters

Question 13

What is the formulation development during the process

Answer 13

• Preformulation study: Physical and chemical characterization
• Initial formulation with the considerations of: preformuation data, proper dose, proper dosage form and route of administration
• Formulation during the clinical trial
  
  • Phase 1: simple formulations with multiple strength (e.g. sapsule)
  • Phase 2: developed formulations for finalizing
  • Phase 3: final formulation is determined and used
• Control materials: placebo and comparator products
• cGMP (current good manufacture practice) quality
• Formulation design

Question 14

What is the drug product labeling?

Answer 14

• Description
• Clinical pharmacology
• Indication and usage
• Contra-indications
• Warnings
• Precautions
• Adverse reactions
• Drug abuse and dependences
• Over-dosage
• Dosage administration
• How supplied
• For packaging label, container label, package inserts and others (company literature, promotion materials)

Question 15

What are the other ND application routes?

Answer 15

• Supplement New Drug Application (SNDA)
  
  • The sponsor want to make a change on an approved NDA
• Abbreviated New Drug Application (ANDA)
  
  • Generic copies
• Biologics license application (BLA)
  
  • biological products
• New Animal Drug Appliaction (NADA)
• Medical Device

Question 16

What are the “Phase 4” studies and Post marketing surveillance?

Answer 16

“Phase 4” - controlled clinical investigations which help contribute to the understanding of a drugs mechanism/scope of action

Help indicate:

• New therapeutic uses
• Need for additional strengths, dosage forms, ROA’s
• Additional side effects, serious reactions, and drug interactions

Question 17

What is regulatory Science?

Answer 17

An emerging field & new FDA initiative

It is the science of the assemessment and evaluation of safety, effectiveness, potency, quality and performance of a product

To develop new mehtods, assays, standards and models that will help development, review and approval of medical products