Reviewer in Manuf Lec

What is a pharmaceutical manufacturing firm?

Pharmaceutical: Relating to drugs - involved in or related to
the manufacture, preparation, dispensing, or sale of drugs used
in medicine
Drug (RA 3720)
1) articles recognized in the current edition of the USP-NF
official homeopathic pharmacopoeia of the US, official national
Drug formulary, or any supplement to any of them,
2) articles intended for use in the diagnosis, cure, mitigation,
treatment, or prevention of disease in man or animals;
3) articles (other than food) intended to affect the structure or
any function of the body of man or animals
4) articles intended for use as a component in any articles
specified in 1,2 or 3 but do not include devices or their
components, parts or accessories.
Drug (RA 9711)
(1) articles recognized in official pharmacopeias and formularies,
including official homeopathic pharmacopeias, or any documentary
supplement to any of them, which are recognized and adopted by
the FDA
(2) articles intended for use in the diagnosis, cure, mitigation,
treatment, or prevention of disease in man or other animals
(3) articles (other than food) intended to affect the structure of any
function of the body of humans or animals
(4)
articles intended for useas a component of any articles
specified in clauses (I), (2), or (3) but do not include devices or their
components, parts or accessories
RA No. 3720 as amended by Executive Order Nos. 851, 119,
and 175
AN ACT TO ENSURE THE SAFETY AND PURITY OF FOODS AND
COSMETICS, AND THE PURITY, SAFETY , EFFICACY AND QUALITY
OF DRUGS AND DEVICES BEING MADE AVAILABLE TO THE
PUBLIC, VESTING THE BUREAU OF FOOD AND DRUGS WITH
AUTHORITY TO ADMINISTER AND ADMINISTER THE LAWS
PERTAINING THERETO, AND FOR OTHER PURPOSES (as
amended by Executive order No. 175 dated May 22, 1987)
RA No. 9711 Food and Drug Administration (FDA) Act of
2009
AN ACT STRENGTHENING AND RATIONALIZING THE BUREAU OF
FOOD AND DRUGS (BFAD) BY ESTABLISHING ADEQUATE
TESTING LABORATORIES AND FIELD OFFICES, UPGRADING ITS
FQUIPMENT,
AUGMENTING
ITS
HUMAN
RESOURCE
COMPLEMENT, GIVING AUTHORITY TO RETAIN ITS INCOME,
RENAMING IT THE FOOD AND DRUG ADMINISTRATION (FDA),

AMENDING CERTAIN SECTIONS OF REPUBLIC ACT NO. 3720, AS

AMENDED, AND APPROPRIATING FUNDS THEREOF

President
President

Administratio
Administratio
nn

Finance
Finance

Manufacturing
Manufacturing

Research
Research
&& Devt.
Devt.
Quality
Quality
Affairs
Affairs

Medical
Medical
Affairs
Affairs

Distribution
Distribution

Regulatory
Regulatory
Affairs
Affairs

Marketing
Marketing

Procurement
Procurement
&& Logistics
Logistics

Sales
Sales

Organization of a Typical Pharmaceutical

Manufacturing/Marketing Company

Administration
Determines the overall direction of the company and takes care of
the day-to-day operations of the company
Executive Offices
Human Resource Department
Organizational Development
Legal Department
Finance
Takes care of the financial processes necessary to for the
continuous operation of the company
Budget
Accounting
Auditing
Product Planning (Business Development)
Conducts feasibility studies to determine the products that a
company should manufacture and market including the

product combinations that would best fit the objectives of the

company
Research and Development
Develops products to be marketed by the company
Basic research (development of active
pharmaceutical ingredients)
Pharmaceutical dosage form development
Preformulation studies
Laboratory trials
Packaging Development
Analytical methods development
Stability studies
Scale-up studies
Bioavailability studies
Validation
Medical Affairs
Takes care of the medical aspects of the products that will be
marketed by the company
Clinical studies
Post-Marketing Surveillance
Product labelling
Regulatory Affairs
Liaises with the regulatory bodies on the registration of the
company and its products
Bureau of Food and Drugs
Philippines Drug Enforcement Agency
A pharmaceutical manufacturing company is required to
have a company pharmacist registered with BFAD and PDEA
(if regulated drugs are involved)
Company pharmacists are required for different activities of
a pharmaceutical company
Drug manufacturer
Drug trader
Drug importer
Drug distributor
Procurement and Logistics
Purchases and stores the materials and products including
services that will be used by the company in the smooth
performance of its operations
Purchasing Department
Materials Planning
Warehousing Department
Raw Materials

Packaging Materials
Finished Products
Manufacturing
Converts raw and packaging materials into finished products
for distribution and sale
Dispensing
Processing
Packaging
Production Planning and Inventory Control
Engineering
Quality Assurance
Ensures that the materials, products and processes in the
manufacture of the products are in accordance with the
predetermined quality characteristics
Incoming materials QA
In-process QA
Finished products QA
Analytical testing
Documentation
Stability testing
CGMP audit
Distribution
Makes products physically available to the trade (customers)
Marketing
Creates the demand for the products
Develops promotional strategies
Provides product information to customers
Doctors
Pharmacists (Drugstore, Hospital)
Retail outlets
Government entities
Advertising
Sales
Fulfills the demand of the customers for the products
Gets purchase orders from customers

 includes those components that may undergo chemical

change in the manufacture of the drug product and be
present in the drug product in a modified form intended to
furnish the specified activity and effect

President

Marketing
Marketing

Procurement
Procurement

Sales

Medical
Affairs

Administration
Administration

Distribution
Distribution

&& Logistics
Logistics

Finance
Finance

Regulatory
Regulatory
Affairs
Affairs

Make arrangements for the delivery of stocks

Coordinates payments of customer purchases
Organization of a Typical Pharmaceutical Marketing
Company

Unit 2 Drug Product Development

Definitions of a Drug
Article intended for and having as their main use the
diagnosis, cure, mitigation, treatment or prevention of disease
in man and other animals
Article recognized by monograph in the compendia
Article (other than food) used to affect the structure or any
function of the body of man and other animals
Article used as a component of any of the previously
mentioned articles
Active Ingredient
any component that is intended to furnish pharmacological
activity or other direct effect in the diagnosis, cure,
mitigation, treatment or prevention of disease or to affect
the structure or function of the body of man or other
animals

The Pharmaceutical Product Development Process

Research activities directed to the creation of new drugs for
new products
New drugs may be intentionally or accidentally produced
from natural sources or by chemical synthesis
Sequence of Events in Pharmaceutical Product Development
Lead Compound Selection
(Identifying a promising compound)

Discovery Testing
(Compound design and testing)

Pre-Clinical Research
and
Manufacture Research
(Safety testing in lab animals)
(Technical development)

Investigational New Drug (IND) Application

(Assessing safety of testing in humans)

Clinical Trials: Phase I, Phase II, Phase III

(Safety and efficacy testing)

New Drug Application (NDA)

(Assessing safety and efficacy for marketing)

Post-Marketing Surveillance
(Safety and efficacy in general population)
Pharmaceutical Product Development
Drug Discovery
Determine target disease.
Develop hypothesis for a mechanism of treatment.
Evaluate hypothesis.
Determine feasibility of producing and evaluating the
selected compound.
Screening
Combination Chemistry
Make many possible compounds at one time.

 Focus on quantity of possible compounds, not purity

of each.
High Throughput Screening
Test hundreds at a time for activity.
Process requires serious technology.
1 in 10,000 makes it to the market.
Two Main Stages of Drug Development
Pre-clinical Stage
Clinical Stage
Preclinical Stage
Preclinical Research
involves synthesis and purification testing in the lab and
animal testing
thousands of compounds are tested in preclinical research
before a handful are chosen to enter the second stage,
which requires filing of an IND
Pre-Clinical Testing
o Evaluate acute and short term toxicity in animals
(one rodent, one non-rodent).
Dose at increasingly high levels to induce
toxicity.
Determine lethal dose.
Dose at normal levels for short and long term.
o Assess how drug is absorbed, distributed,
metabolized, and excreted in animals.
Primary goals of early preclinical development
- to determine if the product is reasonably safe for initial use in
humans
- to determine if the compound exhibits pharmacological activity
that justifies commercial development.
to determine recommended dose for initial use in humans
to establish the physicochemical properties of the drug: its
chemical makeup, stability, solubility
Objective 1: Safety
Toxicity Studies
- done on experimental animals
murine (rats or mice)
canine (dogs)
primate (monkeys)
porcine (pigs)
Dose at increasingly high levels to induce toxicity
Determine lethal dose

Dose at normal levels for short and long term

Objective 2: Pharmacologic activity
Pharmacodynamics what the drug does to the body
Pharmacokinetics what the body does to the drug
ADME absorption, distribution, metabolism excretion
Objective 3: Recommended Dose

Safe starting dose for clinical trials

Objective 4: Physicochemical properties
Structural characterization
Impurity identification
Solubility assessment
Stability
Output Raw Material Specifications

Pharmaceutical Manufacturing Research

The aim of pharmaceutical manufacturing development is to
design a quality product and its manufacturing process to
consistently deliver the intended performance of the product.
The information and knowledge gained from pharmaceutical
manufacturing development studies and manufacturing
experience provide scientific understanding to support the
establishment of the design space*, specifications, and
manufacturing controls.
quality should be built-in by design
Components of the Drug Product
Drug substance
Excipients
Container closure systems
Manufacturing processes
Drug Substance
Physicochemical and biological properties of the drug
substance
Raw material specifications
Compatibility with excipients
Influence of characteristics to manufacturing process
Excipients
Physicochemical and biological properties of excipients
Influence on drug performance (stability,
bioavailability), manufacturability
Compatibility with other excipients
Ability to provide intended functionality

Ex. Processing aids, preservatives, antioxidants,

penetration enhancers, disintegrants, release
controlling agents
Formulation Development
experimental designs
the properties of the drug substance, excipients,
container closure system, any relevant dosing
device
excipient ranges
formulations used in clinical safety and efficacy
special design features of the drug product (e.g., tablet
score line, overfill, anticounterfeiting measure as it
affects the drug product)
overages
Overages
to compensate for manufacturing losses or degradation
during a products shelf life, or to extend shelf life
Justification concerning safety and efficacy of product
1) amount of overage,
2) reason for the overage (e.g., to compensate for
expected and documented manufacturing and
stability losses)
3) justification for the amount of overage

Analytical methods development

Stability Indicating
Validated
Stability studies
According to regulatory requirements
Establish formula, packaging system, storage
conditions, shelf-life
BA/BE
According to regulatory requirements
Manufacturing Process Development
consider critical formulation attributes
appropriateness of equipment
address microbiological and chemical attributes
drug product specifications
identify any critical process parameters that should be
monitored or controlled (in-process specifications)
method of sterilization for the drug product and primary
packaging material
Manufacturing Process Development

Identify batches used for

Pivotal clinical trials (safety, efficacy,
bioavailability, bioequivalence
Stability studies
The information should include
(1) the identity (e.g., batch number) and use of the batches
produced (e.g., bioequivalence study batch number)
(2) the manufacturing site
(3) the batch size
(4) any significant equipment differences (e.g., different
design, operating principle, size).
Container Closure System
intended use of the drug product and the suitability
of the container closure system for storage and
transportation (shipping), including the storage and
shipping container for bulk drug product, where
appropriate
choice of materials for primary packaging is justified
(stability)

The choice of primary packaging materials should

consider
choice of materials
protection from moisture and light,
compatibility of the materials of construction
with the dosage form (including sorption to
container and leaching), and
safety of materials of construction

Container Closure System

intended use of the drug product and the suitability of the
container closure system for storage and transportation
(shipping), including the storage and shipping container for
bulk drug product, where appropriate
choice of materials for primary packaging should be
justified
The choice of primary packaging materials should consider
choice of materials
protection from moisture and light
compatibility of the materials of construction with
the dosage form (including sorption to container
and leaching)
safety of materials of construction

For dosing devices (e.g., dropper pipette, pen injection

device, dry powder inhaler), need reproducible and
accurate dose of the product is delivered under testing
conditions
Microbiological Attributes
The rationale for performing or not performing microbial
limits testing for non sterile drug products
Selection and effectiveness of preservative systems in
products containing antimicrobial preservative or the
antimicrobial effectiveness of products that are inherently
antimicrobial
For sterile products, the integrity of the container closure
system as it relates to preventing microbial contamination
Compatibility
Compatibility of the drug product with reconstitution
diluents (e.g., precipitation, stability)
Recommended in-use shelf life, at the recommended
storage temperature and at the likely extremes of
concentration
Admixture or dilution of products prior to administration
(e.g., product added to large volume infusion containers)
might need to be addressed
Investigational New Drug (IND)
IND Application: Application filed by a sponsor to get FDA
approval to conduct clinical studies of an IND on human
subjects.
Investigational New Drug (IND): means a new drug or
biological drug that is used in a clinical investigation. The
terms investigational drug and investigational new
drug are deemed to be synonymous for this purpose.
Clinical investigation (or trial) means any experiment in
which a drug is administered or dispensed to, or used
involving, one or more human subjects.
Sponsor means a person who takes responsibility for and
initiates a clinical investigation.
Contract research organization means a person that
assumes, as an independent contractor with the sponsor,
one or more of the obligations of a sponsor, e.g., design of a
protocol, selection or monitoring of investigations,
evaluation of reports, and preparation of materials to be
submitted to the Food and Drug Administration.
Investigator means an individual who actually conducts a
clinical investigation (i.e., under whose immediate direction
the drug is administered or dispensed to a subject).

Sponsor-Investigator means an individual who both

initiates and conducts an investigation, and under whose
immediate direction the investigational drug is administered
or dispensed.
Subject means a human who participates in an
investigation, either as a recipient of the investigational new
drug or as a control.
CONTENTS OF IND APPLICATION
Animal Pharmacology and Toxicology Studies
Manufacturing Information
Clinical Protocols and Investigator Information
Animal Pharmacology and Toxicology Studies - Preclinical data
to permit an assessment as to whether the product is reasonably
safe for initial testing in humans. Also included are any previous
experience with the drug in humans (often foreign use).
Manufacturing Information - Information pertaining to the
composition, manufacturer, stability, and controls used for
manufacturing the drug substance and the drug product. This
information is assessed to ensure that the company can adequately
produce and supply consistent batches of the drug.
Clinical Protocols and Investigator Information Detailed
protocols for proposed clinical studies to assess whether the initialphase trials will expose subjects to unnecessary risks. Information
on the qualifications of clinical investigators--professionals
(generally physicians) who oversee the administration of the
experimental compound--to assess whether they are qualified to
fulfill their clinical trial duties. Commitments to obtain informed
consent from the research subjects, to obtain review of the study
by an institutional review board (IRB), and to adhere to the
investigational new drug regulations.
Institutional Review Board (IRB)
Reviews, approves, and monitors research involving human
subjects in order to evaluate the ethical acceptability and the
scientific validity of any such studies.
An IRB is formally designated by an institution in which
research takes places, such as a hospital or university.
Research cannot begin until the IRB approves.
Composed of at least five members including
- at least one scientific member
- at least one nonscientific member
- at least one person not affiliated with the research
institution
- no members with conflicts of interests
- both genders if at all possible

Investigational New Drug (IND)

A sponsor shall not begin a clinical investigation until the
investigation is subject to an IND which is in effect in
accordance with corresponding regulations.
Promotion of an investigational new drug. A sponsor or
investigator, or any person acting on behalf of a sponsor or
investigator, shall not represent in a promotional context that
an investigational new drug is safe or effective for the purposes
for which it is under investigation or otherwise promote the
drug.
Before testing a new drug on human subjects, the company
must file an IND.
Prior to filing an IND, the sponsor develops information on the
chemistry of the drug so that it can be produced in batches of
known strength and purity.
The sponsor must conduct a number of animal studies to
produce information on the pharmacology and toxicology of the
drug. Information, for example, must be produced on the
absorption, distribution, metabolism, and excretion properties of
the drug.
Detailed protocols for testing on human subjects must be
submitted.
The FDA has required that all proposed clinical studies be
reviewed by an institutional review board.
Technically, unless otherwise notified, the sponsor can begin
clinical studies within thirty days (if the IRB approves).
The FDA can, however, terminate an IND at any time; thus in
practice the FDA must approve the IND proposal.
Clinical Studies
Sequence of Events in Pharmaceutical Product Development
Lead Compound Selection
(Identifying a promising compound)

Discovery Testing
(Compound design and testing)

Pre-Clinical Research
and
Manufacture Research
(Safety testing in lab animals)
(Technical development)

Investigational New Drug (IND) Application

(Assessing safety of testing in humans)

Clinical Trials: Phase I, Phase II, Phase III

(Safety and efficacy testing)

New Drug Application (NDA)

(Assessing safety and efficacy for marketing)

Post-Marketing Surveillance
(Safety and efficacy in general population)
Clinical trials are research studies done to evaluate whether
a drug or treatment is both safe and effective for
people.
Prior to being used in clinical trials, drugs or procedures are
first evaluated extensively in the lab and/or in animal
studies.
Participating in a clinical trial can provide
researchers with valuable information on new
treatments; in some cases, it may also offer the
chance for a cure or improvement in a patient's
quality of life that's not provided by standard
therapy.
Participation in clinical trials is voluntary, and individuals are
allowed to discontinue the treatment at any time .
Clinical trials are research studies that are conducted on
human subjects.
The purpose of clinical trials is to decide if a new medication
or treatment is safe and effective.
They may also be done to find
information on new treatments with fewer side
effects,
treatments that are easier for patients to tolerate
the chance for a cure or improvement in a patient's
quality of life that's not provided by standard therapy
Participation in clinical trials is voluntary, and
individuals are allowed to discontinue the treatment
at any time
Phases
Phase 0 :
Exploratory, to establish if agent will
work as desired
Phase I :
Determine basic pharmacological and
toxicological
information in humans especially on safety
Phase II :
Conducted on a larger number of
patients to further
evaluate the safety of the treatment and to
determine
how well it works

 Phase III
risks and
Phase IV
works over
what it

Involves a large number of patients to asses

benefits
Post marketing study to determine if drug
time and if it works for purposes other than

was intended for

Phase 0
A recent designation for exploratory, first-in-human trials
conducted in accordance with the US FDAs 2006 Guidance on
Exploratory IND Studies.
They are exploratory studies that often use only a few small
doses of a new drug in a few patients
Also known as human microdosing studies
Designed to speed up the development of promising drugs by
establishing very early on whether the drug behaves in human
subjects as was expected from preclinical studies.
Involves the administration of single subtherapeutic doses of
the study drug to a small number of subjects (10 to 15) to
gather preliminary data on the agent's pharmacokinetics (what
the body does to the drugs).
Help researchers find out whether the drugs do what they are
expected to do.
May help avoid the delay and expense of finding out years later
in phase II or even phase III clinical trials that the drug doesnt
act as expected to based on lab studies
If there are problems with the way the drug is absorbed or acts
in the body, this should become clear very quickly in a phase 0
clinical trial.
Not yet being used widely, and there are some drugs for which
they wouldnt be helpful.
Studies are very small, often with fewer than 15 people, and the
drug is given only for a short time.
Theyre not a required part of testing a new drug.
Phase I
This phase consists of short-term clinical tests of the drug on 20
to 80 healthy volunteers to determine basic pharmacological
and toxicological information in humans especially as regards
safety.
The FDA can stop clinical testing if they deem the drug unsafe.
Studies that are usually conducted with healthy volunteers
and that emphasize safety.

The goal is to find out what the drug's most frequent and
serious adverse events are and, often, how the drug is
metabolized and excreted.
The aims of this initial trial include:
Determining that the drug is safe for humans
Gaining information about proper dosage amounts
Assessing side effects at different dosage amounts
Determining how the drug is metabolized by the human
body
Assessing the effect of the drug on target symptoms
Phase I typically takes about one year, which is much
shorter than other phases of the trial period.
The short time period is because a Phase 1 trial is not used
to see if the drug is effective, only that it is mainly safe for
humans to use.
Some of the questions researchers may be looking to answer
about a drug with a Phase 1 trial include:
Does it cause any serious side effects?
Are patients able to tolerate the drug?
What's the safest route of administration (such as pill,
injection, infusion)?
How is it metabolized by the body?
What's the highest dose that is tolerable to patients?
Phase II
Conducted on a larger group of people to further evaluate the
safety of the treatment and to determine how well it works.
Typically the drug is tested in 100 to 300 patients.
Dosage levels are experimented with to find optimal dosage
levels, and further information on safety is collected
The main purpose of a Phase II clinical trial is to begin to
assess whether a drug is effective while exposing as few
people as possible to any unwanted side effects.
All study participants will have been diagnosed with the
condition that the new medication has been designed to treat.
Phase III
Designed to provide proof of the drug's effectiveness in
treating the target health problem and to assess the risk vs.
benefits of using the drug
Drug is given to large groups of people often numbering in the
thousands (1,000 to 3,000)
Data is gathered regarding side effects and optimal dosage
amounts in order to provide labeling and physician
prescription information

 Trials are tightly controlled and can take several months to

several years to complete
Done to determine if the new treatment is more effective, or
has less side effects, than the standard (currently approved)
method.
This phase answers the question "does it work better than the
standard treatment?"
Controlled clinical trial is a type of treatment research study in
which a treatment is compared to a control group.
This control group may be either
another active treatment (e.g., another medication),
a non-active treatment (e.g., a placebo), or
some other type of control group.
In some forms of research, a control group is used to provide a
basis of comparison to the group of individuals who are being
studied in support of the research theory.
A placebo is a substance given to a study participant that has
no known treatment value.
Placebos are made as similar to the actual treatment as
possible. If the new medication being studied is in the form of
an injection, the placebo will be an injection. The idea is that
the study participant and the researchers do not know who is
getting the real treatment and who is getting a placebo.
Trials are typically conducted in a "double-blind" manner,
where neither the researchers nor the participants know who
received the placebo and who received the medication.
In this study, half of the participants usually receive a placebo
and the other half get the actual medication of interest.
Double-blind studies are conducted to prevent bias on the part
of the researchers and the participants.
Any effects seen as a result of taking the placebo are usually
attributed to the expectations of the patient is known as the
"placebo effect."

New Drug Application (NDA)

The NDA application is the vehicle through which drug sponsors
formally propose that the FDA approve a new pharmaceutical
product for sale and marketing.
The data gathered during the animal studies (preclinical) and
human clinical trials of an Investigational New Drug become
part of the NDA.
The goals of the NDA are to provide enough information to
permit the FDA reviewer to reach the following key decisions:

Whether the drug is safe and effective in its proposed

use(s), and whether the benefits of the drug outweigh the
risks.
Whether the drug's proposed labeling (package insert) is
appropriate, and what it should contain.
Whether the methods used in manufacturing the drug and
the controls used to maintain the drug's quality are
adequate to preserve the drug's identity, strength, quality,
and purity.
The documentation required in an NDA is supposed to tell the
drug's whole story, including
what happened during the clinical tests,
what the ingredients of the drug are,
the results of the animal studies,
how the drug behaves in the body, how it is
manufactured, processed and packaged.
Abbreviated New Drug Application
Contains data which when submitted to the provides for the
review and ultimate approval of a generic drug product.
Once approved, an applicant may manufacture and market
the generic drug product to provide a safe, effective, low
cost alternative to the public.
Generic Drug Product
Product that is comparable to an innovator drug product in
dosage form, strength, route of administration, quality,
performance characteristics and intended use.
Generic drug applications are termed "abbreviated" because
they are generally not required to include preclinical
(animal) and clinical (human) data to establish safety and
effectiveness.
Instead, generic applicants are required to scientifically
demonstrate that their product is bioequivalent (i.e.,
performs in the same manner as the innovator drug).
Generic applicants are required to scientifically demonstrate
that their product is bioequivalent (i.e., performs in the
same manner as the innovator drug).
One way scientists demonstrate bioequivalence is to
measure the time it takes the generic drug to reach the
bloodstream in 24 to 36 healthy, volunteers.
This gives them the rate of absorption, or bioavailability,
of the generic drug, which they can then compare to that of
the innovator drug.
The generic version must deliver the same amount of active
ingredients into a patient's bloodstream in the same amount
of time as the innovator drug. - bioequivalence

Local Product Registration (ACTD/ACTR)

ACTD
ASEAN Common Technical Dossier the part of
the marketing authorization application that is
common to all ASEAN countries
Part I
Table of Contents, Administrative Data
and Product Information
Part II
Quality Document
Part III
Non-Clinical Document
Part IV
Clinical Document
Part I Table of Contents, Administrative Data
and Product Information
1. Application Form
2. Letter of Authorisation (where applicable)
3. Certifications
4. Labelling
5. Product Information
Part II Quality Document
A. Drug Substance
General Information
Manufacture
Characterization
Control of Drug Substance
Reference Standards or Materials
Container Closure System
Stability
B. Drug Product
Description and Composition
Pharmaceutical Development
Manufacture
Control of Excipients
Control of Finished Product
Reference Standards or Materials
Container Closure System
Stability
Product Interchangeability or Equivalence
Evidence

Part III Non-clinical (Safety)

Pharmacology
Pharmacokinetics
Toxicology
Part IV Clinical Document (Efficacy)
Biopharmaceutics
Clinical Pharmacology
Efficacy

Safety
Benefits and Risks
ACTR
ASEAN Common Technical Requirements a set of
written materials to guide applicants to prepare
application dossiers in a way that is consistent
with the expectations of all ASEAN Drug
Regulatory Authorities
ASEAN Guidelines on Stability Study of Drug
Product
ASEAN Guidelines for Submission of
Manufacturing Process Validation Data for Drug
Registration
ASEAN Guidelines for Validation of Analytical
Procedures

 ASEAN Guidelines for the Conduct of

Bioavailability and Bioequivalency Studies
ASEAN Guidelines on Nonclinical (Safety)
Document
ASEAN Guidelines on Clinical (Efficacy) Document
ASEAN Variation Guidelines for Pharmaceutical
Products
Product is registered
MARKETING AUTHORIZATION (MA)
CERTIFICATE OF PRODUCT REGISTRATION (CPR)
Routine Commercial Production New Product
Launching Marketing
Clinical Studies : Phase IV
Phase IV
Done in the post-marketing stages - after the Food
and Drug Administration (FDA) has approved the
product for general use
Studies are conducted on hundreds to thousands
of people
Study answers the question "does it work over
time and for purposes other than what it was
initially meant for?"
done to continue monitoring the risks and benefits
of the drug

may look at the drug's effect on different

subgroups of individuals (such as different
genders or ages) or to gather information about
the long-term effects of drug usage
may be conducted in order to get FDA approval for
the drug to be used for a different purpose than
the target symptoms it was originally approved for