PHA6123LAB.3GPH - PHARMACY INFORMATICS LABORATORY 2022
INVESTIGATIONAL NEW DRUG
Mr. Marlon C. Mallillin, RPh MPhil
University of Santo Tomas
2022
pOUTLINE o CBER – Center for Biologics Evaluation and
I. Learning Objectives Research
II. Background o CDER – Center for Drug Evaluation and
III. Definition of Terms and Acronyms Research
IV. History of Drug Development o NDA – new drug application
A. Evolution of FDA’s Drug Approval Process o NME – new molecular entity
B. Transparency and Harmonization of Drug Development o GCP – good clinical practice
C. Protection of Human Subjects o IRB/IEC – investigational review board/institutional
V. Drug Approval Process ethics committee
A. Investigational New Drug (IND) Application o CFR – Code of Federal Regulations
B. Amendment of IND o FDA – Food and Drug Administration
VI. Phases of Clinical Trials
A. Phase I
B. Phase II • Definition of Terms
C. Phase III Terms Definition
D. New Drug Application (NDA) Clinical Any experiment in which a drug is administered
a. Expanded Access to Investigational Drugs for Treatment Investigation or dispensed to one or more human subjects.
Use Investigational A drug, antibiotic, or biologic that is used in a
b. Cost of Using Investigation Drugs New Drug (IND) clinical investigation. The label of an
c. Expedited Review of New Drugs investigational drug must bear the statement:
E. Phase IV “Caution: New Drug—Limited by Federal (or
F. Risk Evaluation and Mitigation Strategies (REMS) U.S.) law to investigational use.”
VII. Orphan Drug Act IND application A submission to the FDA containing chemical
VIII. IRB/IEC Committee information, preclinical data, and a detailed
A. Review of a Clinical Research Protocol
description of the planned clinical trials.
B. Responsibilities of IRB Committees
IX. Role of Healthcare Professional Commercial IND An IND for which the sponsor is usually either a
A. Getting Involved in Clinical Research corporate entity or one of the institutes of the
X. Role of Pharmacist National Institutes of Health (NIH).
A. Clinical Research Associate (CRA) Investigator The individual responsible for initiating the
a. Managing Drug Cost clinical trial at the study site. This individual
b. Disseminating Research Information must treat the patients, assure that the protocol
c. Securing Drug Supplies for Research is followed, evaluate responses and adverse
d. Maintaining Drug Accountability Records reactions, assure proper conduct of the study,
e. Randomizing and Blinding of Interventions and solve problems as they arise.
f. Seeking Reimbursement for Services Subject An individual who participates in a clinical
XI. DOH-PCHRD “Tuklas Lunas Research Fellowship Program” investigation (either as the recipient of the
XII. Conclusion investigational drug or as a member of the
control group).
I. Learning Objectives Good Clinical A standard for the design, conduct, monitoring,
• List the steps in the drug approval process Practice (GCP) analyses, and reporting of clinical trials that
• List the components of an investigational new drug (IND) provides assurance that the results are credible
application and accurate, and that the rights of study
• Identify the task of an Institutional Review Board (IRB) subjects are protected.
• Identify the areas where the pharmacist is involved in the IND Institutional A committee of reviewers that is responsible for
application and monitoring process Review Board ensuring the protection of the rights, safety, and
• Learn about the Investigational New Drug in the Philippine (IRB)/Institutional well-being of human subjects involved in a
setting Ethics clinical investigation
Committee (IEC)
II. Background
• Approximately 2.6 billion dollars is spent to get a new drug IV. History of Drug Development in the USA
product to market in the USA. • There was a time when drug products were not regulated.
o Substandard, addictive, toxic and even lethal drugs
• The Food and Drug Administration (FDA) is the federal agency o No licensed physicians and nearly anyone can
that decides which drugs, biologics, and medical devices are practice medicine.
safe and efficacious
o Monitors the manufacture, import, transport, Article
storage and sale of 25% of all goods purchased in Import Drug Act provided for the inspection, detention and
the USA annually. of 1848 destruction or reexport of imported drug
shipments that failed to meet standards
Pure Food and drugs not to be mislabeled or adulterated and
III. Definition of Terms and Acronyms
Drugs Act must meet recognized standards for strength and
• Acronyms
(1906) purity
o PI – primary investigator
Food, Drug and safety of drugs, and be proven through testing
o IND – investigational new drug
Cosmetic Act of before they can be marketed
o QCT – qualifying clinical trial
1938
o DMF – drug master file
Submission of NDA to the FDA was described
1
, Durham and- creation of OTC and Rx drugs
Humphrey • The IND is the application by the study sponsor (e.g.,
Amendment pharmaceutical company, individual investigator as sponsor-
Kefauver-Harris manufacturer had to demonstrate efficacy, and investigator) to the FDA to begin clinical trials in humans.
Drug safety of drug prior to marketing (because of
Amendment phocomelia secondary to Thalidomide) • An IND is not required if the drug is marketed in the USA and
all following requirements are met:
CGMP o Study is not reported to the FDA in support of a new
indication
o Study does not involve a different dose, route,
A. EVOLUTION OF FDA’S DRUG APPROVAL PROCESS patient population that increase risk to patients
• FDA o IRB approval and informed consent are secured
- decides which drugs, biologics, and medical devices o Study will not be used to promote drug’s
are safe and efficacious and therefore can be marketed. effectiveness for a new indication
o Goal:
▪ provide consumers with safe and effective
drugs, biologics, and devices
▪ Review priority drugs in six (6) months and
standard drugs within ten (10) months
B. TRANSPARENCY AND HARMONIZATION OF DRUG
DEVELOPMENT
• National Institute of Health (NIH) developed a web-based
system that offers information about ongoing clinical trials for a
wide range of diseases and conditions.
o Search for studies for particular diseases and identify
treatment centers that offer enrollment into these
studies.
o http://clinicaltrials.gov
• International Conference on Harmonization (ICH) – for the
regulatory requirements for drug approval • Contents of IND
o Goal: Content Information
▪ provide methods to ensure simultaneous 1. Cover Sheet Form 1571
submission and rapid regulatory 2. Table of Contents
approval in the world’s largest markets 3. Introductory • Name
▪ Minimize duplication of effort, improve statement • Structure
efficiency, increase quality and efficiency • Pharmacologic class
of medical treatments worldwide • Dosage form
• Active ingredients
C. PROTECTION OF HUMAN SUBJECTS 4. General give FDA a general overview of the plan
• Research protocols are reviewed for ethical appropriateness investigational plan to study the drug
by IRBs.
• Rationale
• Indications
Nuremberg judge the human experimentation conducted by • General approach for
Code the Nazis in the middle of the twentieth century evaluation of the drug
• Projected number of patients
“voluntary consent of the human subjects is to be treated
absolutely essential”
• Potential safety concerns
Declaration of re-emphasized protection of human subjects
5. Investigator’s information packet containing all
Helsinki (1964)
brochure available information on the drug
Belmont Report basic ethical principles underlying medical
(1978) research on human subjects should be current and comprehensive,
Code of Federal designed to make the protection of human amended as necessary
Regulations subjects in all federal agencies uniform
(CFR) • Formula
• Pharmacology
V. DRUG APPROVAL PROCESS • Toxicology
• The drug approval process in the United States is standardized • Pharmacokinetics
by FDA review. 6. Clinical protocol IRB approval for protocol
o Preclinical testing - testing conducted either in vitro
or in animals. • Objectives of the trial
o Phase I to Phase IV
• Investigator data
• Patient selection
• Before filing an IND, the sponsor must have developed a
• Study design
pharmacologic profile of the drug, determined its acute and
subacute toxicity, and had sufficient information regarding • Dose determination
chronic toxicity to support the drug's use in humans. • Observations
• Laboratory tests and clinical
procedure to be done
A. INVESTIGATIONAL NEW DRUG (IND) APPLICATION
• Done after pre-clinical testing
2
INVESTIGATIONAL NEW DRUG
Mr. Marlon C. Mallillin, RPh MPhil
University of Santo Tomas
2022
pOUTLINE o CBER – Center for Biologics Evaluation and
I. Learning Objectives Research
II. Background o CDER – Center for Drug Evaluation and
III. Definition of Terms and Acronyms Research
IV. History of Drug Development o NDA – new drug application
A. Evolution of FDA’s Drug Approval Process o NME – new molecular entity
B. Transparency and Harmonization of Drug Development o GCP – good clinical practice
C. Protection of Human Subjects o IRB/IEC – investigational review board/institutional
V. Drug Approval Process ethics committee
A. Investigational New Drug (IND) Application o CFR – Code of Federal Regulations
B. Amendment of IND o FDA – Food and Drug Administration
VI. Phases of Clinical Trials
A. Phase I
B. Phase II • Definition of Terms
C. Phase III Terms Definition
D. New Drug Application (NDA) Clinical Any experiment in which a drug is administered
a. Expanded Access to Investigational Drugs for Treatment Investigation or dispensed to one or more human subjects.
Use Investigational A drug, antibiotic, or biologic that is used in a
b. Cost of Using Investigation Drugs New Drug (IND) clinical investigation. The label of an
c. Expedited Review of New Drugs investigational drug must bear the statement:
E. Phase IV “Caution: New Drug—Limited by Federal (or
F. Risk Evaluation and Mitigation Strategies (REMS) U.S.) law to investigational use.”
VII. Orphan Drug Act IND application A submission to the FDA containing chemical
VIII. IRB/IEC Committee information, preclinical data, and a detailed
A. Review of a Clinical Research Protocol
description of the planned clinical trials.
B. Responsibilities of IRB Committees
IX. Role of Healthcare Professional Commercial IND An IND for which the sponsor is usually either a
A. Getting Involved in Clinical Research corporate entity or one of the institutes of the
X. Role of Pharmacist National Institutes of Health (NIH).
A. Clinical Research Associate (CRA) Investigator The individual responsible for initiating the
a. Managing Drug Cost clinical trial at the study site. This individual
b. Disseminating Research Information must treat the patients, assure that the protocol
c. Securing Drug Supplies for Research is followed, evaluate responses and adverse
d. Maintaining Drug Accountability Records reactions, assure proper conduct of the study,
e. Randomizing and Blinding of Interventions and solve problems as they arise.
f. Seeking Reimbursement for Services Subject An individual who participates in a clinical
XI. DOH-PCHRD “Tuklas Lunas Research Fellowship Program” investigation (either as the recipient of the
XII. Conclusion investigational drug or as a member of the
control group).
I. Learning Objectives Good Clinical A standard for the design, conduct, monitoring,
• List the steps in the drug approval process Practice (GCP) analyses, and reporting of clinical trials that
• List the components of an investigational new drug (IND) provides assurance that the results are credible
application and accurate, and that the rights of study
• Identify the task of an Institutional Review Board (IRB) subjects are protected.
• Identify the areas where the pharmacist is involved in the IND Institutional A committee of reviewers that is responsible for
application and monitoring process Review Board ensuring the protection of the rights, safety, and
• Learn about the Investigational New Drug in the Philippine (IRB)/Institutional well-being of human subjects involved in a
setting Ethics clinical investigation
Committee (IEC)
II. Background
• Approximately 2.6 billion dollars is spent to get a new drug IV. History of Drug Development in the USA
product to market in the USA. • There was a time when drug products were not regulated.
o Substandard, addictive, toxic and even lethal drugs
• The Food and Drug Administration (FDA) is the federal agency o No licensed physicians and nearly anyone can
that decides which drugs, biologics, and medical devices are practice medicine.
safe and efficacious
o Monitors the manufacture, import, transport, Article
storage and sale of 25% of all goods purchased in Import Drug Act provided for the inspection, detention and
the USA annually. of 1848 destruction or reexport of imported drug
shipments that failed to meet standards
Pure Food and drugs not to be mislabeled or adulterated and
III. Definition of Terms and Acronyms
Drugs Act must meet recognized standards for strength and
• Acronyms
(1906) purity
o PI – primary investigator
Food, Drug and safety of drugs, and be proven through testing
o IND – investigational new drug
Cosmetic Act of before they can be marketed
o QCT – qualifying clinical trial
1938
o DMF – drug master file
Submission of NDA to the FDA was described
1
, Durham and- creation of OTC and Rx drugs
Humphrey • The IND is the application by the study sponsor (e.g.,
Amendment pharmaceutical company, individual investigator as sponsor-
Kefauver-Harris manufacturer had to demonstrate efficacy, and investigator) to the FDA to begin clinical trials in humans.
Drug safety of drug prior to marketing (because of
Amendment phocomelia secondary to Thalidomide) • An IND is not required if the drug is marketed in the USA and
all following requirements are met:
CGMP o Study is not reported to the FDA in support of a new
indication
o Study does not involve a different dose, route,
A. EVOLUTION OF FDA’S DRUG APPROVAL PROCESS patient population that increase risk to patients
• FDA o IRB approval and informed consent are secured
- decides which drugs, biologics, and medical devices o Study will not be used to promote drug’s
are safe and efficacious and therefore can be marketed. effectiveness for a new indication
o Goal:
▪ provide consumers with safe and effective
drugs, biologics, and devices
▪ Review priority drugs in six (6) months and
standard drugs within ten (10) months
B. TRANSPARENCY AND HARMONIZATION OF DRUG
DEVELOPMENT
• National Institute of Health (NIH) developed a web-based
system that offers information about ongoing clinical trials for a
wide range of diseases and conditions.
o Search for studies for particular diseases and identify
treatment centers that offer enrollment into these
studies.
o http://clinicaltrials.gov
• International Conference on Harmonization (ICH) – for the
regulatory requirements for drug approval • Contents of IND
o Goal: Content Information
▪ provide methods to ensure simultaneous 1. Cover Sheet Form 1571
submission and rapid regulatory 2. Table of Contents
approval in the world’s largest markets 3. Introductory • Name
▪ Minimize duplication of effort, improve statement • Structure
efficiency, increase quality and efficiency • Pharmacologic class
of medical treatments worldwide • Dosage form
• Active ingredients
C. PROTECTION OF HUMAN SUBJECTS 4. General give FDA a general overview of the plan
• Research protocols are reviewed for ethical appropriateness investigational plan to study the drug
by IRBs.
• Rationale
• Indications
Nuremberg judge the human experimentation conducted by • General approach for
Code the Nazis in the middle of the twentieth century evaluation of the drug
• Projected number of patients
“voluntary consent of the human subjects is to be treated
absolutely essential”
• Potential safety concerns
Declaration of re-emphasized protection of human subjects
5. Investigator’s information packet containing all
Helsinki (1964)
brochure available information on the drug
Belmont Report basic ethical principles underlying medical
(1978) research on human subjects should be current and comprehensive,
Code of Federal designed to make the protection of human amended as necessary
Regulations subjects in all federal agencies uniform
(CFR) • Formula
• Pharmacology
V. DRUG APPROVAL PROCESS • Toxicology
• The drug approval process in the United States is standardized • Pharmacokinetics
by FDA review. 6. Clinical protocol IRB approval for protocol
o Preclinical testing - testing conducted either in vitro
or in animals. • Objectives of the trial
o Phase I to Phase IV
• Investigator data
• Patient selection
• Before filing an IND, the sponsor must have developed a
• Study design
pharmacologic profile of the drug, determined its acute and
subacute toxicity, and had sufficient information regarding • Dose determination
chronic toxicity to support the drug's use in humans. • Observations
• Laboratory tests and clinical
procedure to be done
A. INVESTIGATIONAL NEW DRUG (IND) APPLICATION
• Done after pre-clinical testing
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