BP804ET (PHARMACEUTICAL REGULATORY SCIENCE) Dr.

Shaheen Sultana

Unit: 2

Definition of an Investigational New Drug

The Code of Federal Regulations (CFR) defines an investigational new drug as: “A new drug or
biological drug that is used in a clinical investigation.”

Investigational New Drug Application

An Investigational New Drug Application (IND) is a request for authorization from the Food and
Drug Administration (FDA) to administer an investigational drug or biological product to
humans.
An investigational new drug is a new drug or biological drug that is used in a clinical
investigation. This term also includes biological products used in vitro for diagnostic purposes.
Upon completion of preclinical study and collection of data, the sponsor (the person who takes
responsibility for and initiates a clinical investigation) must submit an application to FDA to
notify FDA it is conducting a clinical study on human subjects. This application is called an
Investigational New Drug Application (INDA or IND).
Investigational new drug application abbreviated as INDA is a mandatory requirement filed with
the FDA in order to seek permission for administering a new drug under investigation to Human
subjects after completion of the preclinical studies on it.

Regulatory Approval Process

Content of Investigational New Drug Application
1. Cover sheet
A cover sheet for the application containing the following information:
a) The name, the contact details (e.g. address and telephone number) of the sponsor, the date of
the application, and the name of the investigational new drug.
b) Identification of the phase or phases of the clinical investigation to be conducted.
c) A commitment not to begin clinical investigations until the IND application is approved by
FDA.
d) A commitment that an Institutional Review Board (IRB) will be responsible for the initial and
continuing review and approval of each of the studies in the proposed clinical investigation and
that the investigator will report to the IRB proposed changes in the research.
e) A commitment to conduct the investigation in accordance with all other applicable regulatory
requirements.
f) The name and title of the person responsible for monitoring the conduct and progress of the
clinical investigations.
g) The name(s) and title(s) of the person(s) responsible for review and evaluation of information
relevant to the safety of the drug.
h) If a sponsor has transferred any obligations for the conduct of any clinical study to a contract
research organization (CRO), a statement containing the name and address of the CRO,
identification of the clinical study, and a listing of the obligations transferred.
i) The signature of the sponsor or the sponsor’s authorized representative.

Galgotias College of Pharmacy B. Pharm (VIII Sem)

BP804ET (PHARMACEUTICAL REGULATORY SCIENCE) Dr. Shaheen Sultana

2. A table of contents
All sections under the table of contents should be paginated.

3 &4. Introductory statement and general investigational plan

a) A brief introductory statement giving the name of the drug and all active ingredients, the
drug’s pharmacological class, the structural formula of the drug (if known), the formulation of
the dosage form(s) to be used, the route of administration, and the broad objectives and planned
duration of the proposed clinical investigation(s).
b) A brief summary of previous human experience with the drug, with reference to other IND’s
if pertinent, and to investigational or marketing experience in other
c) If the drug has been withdrawn from investigation or marketing in any country for any reason
related to safety or effectiveness, identification of the country(ies) where the drug was withdrawn
and the reasons for the withdrawal.
d) A brief description of the overall plan for investigating the drug product. The plan should
include the following:
i. The rationale for the drug or the research study.
ii. The indication(s) to be studied.
iii. The general approach to be followed in evaluating the drug.
iv. The kinds of clinical trials to be conducted in the first year following the submission (if plans
are not developed for the entire year, the sponsor should so indicate).
v. The estimated number of patients to be given the drug in those studies.
vi. Any risks of particular severity or seriousness anticipated on the basis of the toxicological
data in animals or prior studies in humans with the drug or related drugs.

5. Investigator’s brochure
A copy of the investigator’s brochure, containing the following information:
a) A brief description of the drug substance and the formulation, including the structural formula,
if known.
b) A summary of the pharmacological and toxicological effects of the drug in animals and, to the
extent known, in humans.
c) A summary of the pharmacokinetics and biological disposition of the drug in animals and, if
known, in humans.

Galgotias College of Pharmacy B. Pharm (VIII Sem)

BP804ET (PHARMACEUTICAL REGULATORY SCIENCE) Dr. Shaheen Sultana

d) A summary of information relating to safety and effectiveness in humans obtained from prior
clinical studies.
e) A description of possible risks and side effects to be anticipated on the basis of prior
experience with the drug under investigation or with related drugs, and of precautions or special
monitoring to be done as part of the investigational use of the drug.

6. Protocols
i. A statement of the objectives and purpose of the study.
ii. The name and address and a statement of the qualifications (curriculum vitae or other
statement of qualifications) of each investigator, and the name of each sub-investigator, and the
name and address of each reviewing Institutional Review Board (IRB).
iii. The criteria for patient selection and for exclusion of patients and an estimate of the number
of patients to be studied.
iv. A description of the design of the study, including the kind of control group to be used, if any,
and a description of methods to be used to minimize bias on the part of subjects, investigators,
and analysts.
v. The method for determining the dose(s) to be administered, the planned maximum dosage, and
the duration of individual patient exposure to the drug.
vi. A description of the observations and measurements to be made to fulfill the objectives of the
study.
vii. A description of clinical procedures, laboratory tests, or other measures to be taken to
monitor the effects of the drug in human subjects and to minimize risk.

7. Chemistry, manufacturing, and control (CMC) information

a. A description of the drug substance, including its physical, chemical, or biological
characteristics.
b. The name and address of its manufacturer
c. The general method of preparation of the drug substance
d. The acceptable limits and analytical methods used to assure the identity, strength, quality, and
purity of the drug substance
e. A brief description of the stability study and the test methods used to monitor the stability of
the drug substance should be submitted.

8. Pharmacology and toxicology information

a. A description of the pharmacological effects and mechanism(s) of action(s) of the drug in
animals.
b. Information on the absorption, distribution, metabolism, and excretions of the drug.
c. A summary of the toxicological effects of the drug in animals and in vitro.

9. Previous human experience with the investigational drug

A summary of previous human experience known to the applicant, if any, with the
investigational drug

After submission of IND to the FDA, it is assigned to the FDA for its review and evaluation. The
FDA has 30days from the receipt of IND to decide whether the proposed clinical trial should
proceed or not. If the sponsor is not contacted within 30days, the trial may proceed. Meanwhile

Galgotias College of Pharmacy B. Pharm (VIII Sem)

BP804ET (PHARMACEUTICAL REGULATORY SCIENCE) Dr. Shaheen Sultana

reviewers at FDA may put a “Clinical Hold” on the proposed Clinical trials at any time. This
prevents human testing of drug. It may be due to the following reasons
i. If there is any unreasoned threat to the safety of the trial subjects i.e. if the subjects face any
illness or injury due to treatment.
ii. Insufficient data to assess patient risks.
iii. If the investigators involved in the study do not meet the necessary requirements with respect
their qualification.
iv. Misleading or incomplete investigators brochure.
In case if all the requirements for FDA approval are satisfied an IND is granted. Once an IND is
in effect, all the proposed changes to the original IND thereafter, must be submitted as
amendments for approval.

Approval processes and time-lines involved in Investigational New Drug (IND)

 During a new drug’s early preclinical development, the sponsor’s primary goal is to
determine if the product is reasonably safe for initial use in humans, and if the compound
exhibits pharmacological activity that justifies commercial development.
 When a product is identified as a viable candidate for further development, the sponsor
then focuses on collecting the data and information necessary to establish that the product
will not expose humans to unreasonable risks when used in limited, early-stage clinical
studies.
 FDA’s role in the development of a new drug begins when the drug’s sponsor (usually
the manufacturer or potential marketer), having screened the new molecule for
pharmacological activity and acute toxicity potential in animals, wants to test its
diagnostic or therapeutic potential in humans.

IND categories
Commercial: These are applications that are submitted primarily by the companies to obtain
marketing approval for a new product.
Research (non-commercial): These INDs are filed for noncommercial research. These are three
types:
a. Investigator IND: It is submitted by a physician who both initiates and conducts an
investigation, and under whose immediate direction the investigational drug is
administered or dispensed. A physician might submit a research IND to propose studying
an unapproved drug, or an approved product for a new indication or in a new patient
population.
b. Emergency Use IND: It allows the FDA to authorize use of an experimental drug in an
emergency situation that does not allow time for submission of an IND in accordance
with 21CFR, Sec. 312.23 or Sec. 312.20. It is also used for patients who do not meet the
criteria of an existing study protocol, or if an approved study protocol does not exist.
c. Treatment IND: It is submitted for experimental drugs showing promise in clinical
testing for serious or immediately life-threatening conditions while the final clinical work
is conducted and the FDA review takes place.

The IND application must contain information in three broad areas:

1. Animal Pharmacology and Toxicology Studies

Galgotias College of Pharmacy B. Pharm (VIII Sem)

BP804ET (PHARMACEUTICAL REGULATORY SCIENCE) Dr. Shaheen Sultana

Preclinical data to provide information that the product is reasonably safe for initial testing in
humans. Also included are any previous experience with the drug in humans (often foreign use).
2. 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.
3. Clinical Protocols and Investigator Information
Detailed protocols for proposed clinical studies to assess whether the initial-phase trials will
expose subjects to unnecessary risks.
4. 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. Finally,
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.

Investigational New Drugs Responsibilities

1. Responsibilities of Sponsors
a. Selecting qualified investigators
b. Providing investigators with the information they need to conduct the investigation
c. Ensuring proper monitoring of the trial
d. Ensuring the trial is conducted according to the plan and protocols contained in the IND,
Informing the FDA and all investigators of significant new adverse effects or risks that
are reasonably likely to be caused by the investigational new drug.
e. Maintaining proper records, disposing of unused supplies of the investigational new drug.
f. Unless the sponsor is a sponsor investigator, the sponsor does not actually conduct the
investigation.
g. Ensuring that the Investigational Product is manufactured in accordance with Good
Manufacturing Practices.
h. Ensuring that Investigational Product is packaged in a way that prevents contamination
and unacceptable deterioration during transport and storage.
i. Supplying investigators/institutions with the Investigational Product.
j. Having written procedures that include instructions on the handling and storage of
Investigational product that sites should follow.
k. Maintaining sufficient quantities of the Investigational Product used in the trial

2. Responsibilities of Investigators
a. Conducting the trial in accordance with the signed investigator statement, protocol, and
applicable regulations.
b. Protecting the rights, safety, and welfare of trial participants.
c. Obtaining informed consent from all trial participants.
d. Maintaining proper records.
e. Furnishing all required progress reports, safety reports, financial disclosure reports, and a
final report.
f. Complying with Institutional Review Board review and Ensuring the proper handling of
controlled substances.

Galgotias College of Pharmacy B. Pharm (VIII Sem)

BP804ET (PHARMACEUTICAL REGULATORY SCIENCE) Dr. Shaheen Sultana

g. Maintaining records of the Investigational Product (from delivery at the site to dispensing
to the participant as well as use by the participant, return by the participant, and
reconciling all product prior to destruction).
h. Ensuring that the Investigational Product is used in accordance with the approved
protocol. Explaining the correct use of the Investigational Product to each participant and
checking at intervals that each participant is following instructions properly.

New Drug Application (NDA)

NDA is an application submitted to the FDA for permission to market a new drug.
To obtain this permission a sponsor submits preclinical and clinical test data to NDA for
analyzing the drug information, description of manufacturing procedures.

The goals of the NDA are to provide enough information to permit 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.

NDA is an application submitted to the FDA for permission to market a new drug. To obtain
this permission a sponsor submits preclinical and clinical test data to NDA for analyzing the drug

Galgotias College of Pharmacy B. Pharm (VIII Sem)

BP804ET (PHARMACEUTICAL REGULATORY SCIENCE) Dr. Shaheen Sultana

information, description of manufacturing procedures.

After NDA received by the agency, it undergoes a technical screening. This evaluation ensures
that sufficient data and information have been submitted in each area to justify “filing” the
application that is FDA formal review. At the conclusion of FDA review of an NDA, there are 3
possible actions that can send to sponsor:
a. Not approvable- in this letter list of deficiencies and explain the reason.
b. Approvable - it means that the drug can be approved but minor deficiencies that can be
corrected like-labeling changes and possible request commitment to do post-approval
studies.
c. Approval- it states that the drug isapproved. If the action taken is either an approvable or
a not approvable, then FDA provides applicant with an opportunity to meet with agency
and discuss the deficiencies.

NDA Requirements
1. Application format
The NDA regulations require the submission of Archival copy, Review copy, field copy.
i. Archival copy :
This is a complete copy of an application submission and is intended to serve as a reference
source for FDA reviewers. This contains information which not contained in the review copy.
ii. Review copy:
It is divided into five (or six) sections containing technical and scientific information required by
FDA reviewers.
iii. Field copy: This is required by FDA inspectors during pre-approval facilities inspection.

NDA has 12 sections:

Galgotias College of Pharmacy B. Pharm (VIII Sem)

BP804ET (PHARMACEUTICAL REGULATORY SCIENCE) Dr. Shaheen Sultana

Section I: Index
Section II: labeling: it include draft labeling intended to use on container

Galgotias College of Pharmacy B. Pharm (VIII Sem)

BP804ET (PHARMACEUTICAL REGULATORY SCIENCE) Dr. Shaheen Sultana

Section III (Application Summary): It is an abbreviated version entire application which give
clear idea about drug and its application to the reviewer.

Section IV: CMC

This summary must provide overview of the drug substances and the drug product.
1. Drug substance: It includes description about of drug substance, physical and chemical
characteristics and stability of the drug substance.
2. Drug product: It includes information about:
a. Composition and dosage form
b. Name and address of manufacturer
c. Container and closure system
d. Stability
e. Specifications for drug product and test methods to assure the specifications

Section V: (Non clinical Pharmacology and Toxicology)

It includes information about:
3. Pharmacology studies
4. Acute toxicity studies
5. Multi dose toxicity studies
6. Carcinogenicity studies
7. Special toxicity studies
8. Reproduction studies
9. Mutagenicity studies
10. ADME studies

Section VI: Human Pharmacokinetics and bio-availability Summary

It includes brief description about bio-availability study of drug, pharmacokinetic characteristic
of active ingredient and dissolution profile of drug.

Section VII: Microbiology Summary

Galgotias College of Pharmacy B. Pharm (VIII Sem)

BP804ET (PHARMACEUTICAL REGULATORY SCIENCE) Dr. Shaheen Sultana

It provides summary of results of the microbiologic studies conducted with anti-infective

and antiviral drug. This includes mechanism of action, antimicrobial spectrum of action and
mechanism of resistance to the drug.

Section VIII: Clinical Data Summary

It is the basis of efficacy and safety that will determine an NDA approval. It includes
• Clinical pharmacology studies including animal study and toxicology.
• Controlled clinical studies including the protocol and description of the statistical analysis used
to evaluate the studies.
• Uncontrolled clinical studies, including all necessary details of the studies.
• Any other data/information relevant to an evaluation of safety and effectiveness obtained from
any source, foreign or domestic (U.S.).

Section IX: Safety update reports: Safety update reports are submitted 120 days after the initial
application, following the receipt of an approval letter. New data related to safety is updated in
this report.

Section X: statistics: Statistics section should include:

 A statistical evaluation of the clinical data
 A copy of the data given in the description and analysis of each controlled clinical study,
along with the statistical analysis.
 A copy of the data included in the integrated summary of all available information about
the safety of the drug.

Section XI: Case reports for taulations: It include complete tabulation for each patient from
phase I to Phase III study.

Section XII: Case reports forms: It is mandatory to submit the case report form for each patient
who either hve died during the study or dropped from the study due to adverse event regardless
of whether patient was receiving drug or placebo.

Galgotias College of Pharmacy B. Pharm (VIII Sem)

BP804ET (PHARMACEUTICAL REGULATORY SCIENCE) Dr. Shaheen Sultana

Review Time Frames (21 CFR 314.100):

This time frames includes:
• Within 180 days of receipt of an application, the FDA will review and issue an approval,
approvable, or not approvable letter. This 180-day period is called the “review-clock”
• During the review period an applicant may withdraw an application (21 CFR 314-65) and
later resubmit it.
• The time period may be extended by mutual agreement between the FDA and the
applicant or as the result of submission of a major amendment (21 CFR 314.60)
Filing Time Frames (21 CFR 314.101):
• Within 60 days after the FDA receives an application, a determination will be made
whether the application may be filed.
• This will determine whether sufficient information is provided to proceed with an in-
depth review of application.
• If FDA files the application, the applicant will be notified in written. The date of filing
will be the date 60 days after the FDA received the application.
• The date of filing begins the 180-days period of the review. If FDA refuses to file the
application, the sponsor will be given the opportunity to meet with FDA to discuss the
reasons why the application is not file able.

Galgotias College of Pharmacy B. Pharm (VIII Sem)

BP804ET (PHARMACEUTICAL REGULATORY SCIENCE) Dr. Shaheen Sultana

Abbreviated new drug application

 An abbreviated new drug application (ANDA) contains data which is submitted to FDA
for the review and potential approval of a generic drug product.
 Once approved, an applicant may manufacture and market the generic drug product to
provide a safe, effective, lower cost alternative to the brand-drugs.
 The sponsor is not required to reproduce the clinical studies that were done for the
original, brand name product.
 Instead, generic drug manufacturers must demonstrate that their product is the same as,
and bioequivalent to, a previously approved brand name product
 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 must scientifically demonstrate that their
product is bioequivalent (i.e., performs in the same manner as the innovator drug).
 One of the ways that scientists use to demonstrate bioequivalence is to measure the time
taken by the generic drug to reach the bloodstream in 24 to 36 healthy volunteers. This
will 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.

Requirement for filing ANDA

At the time of filing an ANDA application, the applicant seeking approval of a particular drug
(innovate drug or patent expired drug) make one of four certifications:
 The required patent application has not been filed
 That the patent as expired
 That the patent has not expired, but will expire on a particular date
 That the patent is unenforceable, invalid or will not be infringed by the drug for which
ANDA applicant seeks approval (paragraph IV)

If more than one ANDA has been filed on a particular drug, first filed ANDA may be given 180
days exclusivity following approval against later filed ANDAs. Therefore first generic company
will acquire a larger market share. Therefore market benefit is provided to the first ANDA
applicant in terms of 180 days market exclusivity.

Galgotias College of Pharmacy B. Pharm (VIII Sem)

BP804ET (PHARMACEUTICAL REGULATORY SCIENCE) Dr. Shaheen Sultana

Types of ANDA filing

While filing ANDA, the egenric company hs to choose one of the following options:
Para I: The drug has not been patented
Para II: The patent for the drug has already expired
Para III: The patent for the product exists but the generic company enters the market after the
date of patent expire passes
Para IV: Patent in not infringed upon or is invalid
In case of Para I and Para II, once the application is complete, it is simply processed for
approval. In case of para III, the application is processed for approval, however its approval is
depends upon the products patent expiry. Para IV are the most tedious, time consuming and
costly.

Galgotias College of Pharmacy B. Pharm (VIII Sem)

BP804ET (PHARMACEUTICAL REGULATORY SCIENCE) Dr. Shaheen Sultana

FORMAT AND CONTENT OF ANDA

• 3 copies of the Abbreviated application are required to be submitted; an archival copy, a review
copy and a field copy. An Archival copy shall contain the following:
• Application form
• Table of Contents
• Basis for ANDA submission
• Conditions of use
• Active Ingredients
• Route of Administration
• Dosage form and Strength

FILING OF ANDA:
• In order to file ANDA all required items should be in proper order (organization). Detail
information is available under Regulation 21 CFR 314.50, 21 CFR 314.94 and 21 CFR
314.440
• Office of Generic Drug (OGD) strongly encourages submission of the bioequivalence,
chemistry and labeling portions of an application in electronic format.

MANUFACTURING AND CONTROL REQUIREMENTS OF THE ANDA:

• One of the most critical portions of an ANDA

Galgotias College of Pharmacy B. Pharm (VIII Sem)

BP804ET (PHARMACEUTICAL REGULATORY SCIENCE) Dr. Shaheen Sultana

• From 1977-1992, 105 Non approval letter issued by FDA due to chemistry &
manufacturing deficiencies.

• According to this guidelines information that applicant provide should prove that the
proposed product is the same as listed product with respect to its indications for use,
active ingredients(s), route of administration, dosage form, strength, bioavailability, and
labeling.

Requirements for Drug substances sources:

• It is important to obtain a copy of potential supplier’s most recent establishment
inspection report describing FDA’s findings. This document should be reviewed by the
applicant to check acceptability of that manufacturer by FDA.
• In addition, the supplier should have a DMF available at FDA for reference purposes.
This will describes the facilities, personnel, equipment, and manufacturing & controls
procedure used at the site (s) where the bulk drug substance is made.

Specifications for drug substances:-

• There must be properly developed assay method for drug
• Carefully evaluate impurity peaks observed in a supplier’s bulk substance and compare
them with those observed in the marketed product.
• The extent that the peaks differ may determine the need to obtain further information,
including toxicity.
• If samples of impurities, degradation products are available from the supplier or are
identified in published literature then the assay methods should be appropriately validated
by the ANDA sponsor for their sensitivities and specifications with respect to them.
• Sponsor of an ANDA set up and maintain a stability program for the bulk drug substance.

Drug product requirements:-

• Similar to NDA.
• The extent of stability data submitted is much less than that usually available for an
NDA.
• Adequate validation studies should be carried out to verify the accuracy, precision,
specificity, recovery and sensitivity of the analytical method(s)
• Data comparing the dissolution characteristics and performance of the sponsors and the
brand name tablet or capsule products at several different time points

Galgotias College of Pharmacy B. Pharm (VIII Sem)

BP804ET (PHARMACEUTICAL REGULATORY SCIENCE) Dr. Shaheen Sultana

Changes to an approved NDA / ANDA

 A postapproval change is any change in a drug product after it has been approved for
marketing by the FDA.
 Since safety and efficacy are established using clinical batches, the same level of quality
must be ensured in the finished drug product released to the public. A change to a
marketed drug product can be initiated for a number of reasons, including a revised
market forecast, change in an API source, change in excipients, optimization of the
manufacturing process, and upgrade of the packaging system.
 A change within a given parameter can have varied effect depending on the type of
product.
 For example, a change in the container closure/system of a solid oral dosage form may
have little impact on an oral tablet dosage form unless the primary packaging component
is critical to the shelf life of the finished product
 If a pharmaceutical manufacturer makes any change in the drug formulation, scales up
the formulation to a larger batch size, or changes the process, equipment, or
manufacturing site, the manufacturer should consider whether any of these changes will
affect the identity, strength, purity, quality, safety, and efficacy of the approved drug
product.
 Moreover, any changes in the raw material (ie, active pharmaceutical ingredient),
excipients (including a change in grade or supplier), or packaging (including container
closure system) should also be shown not to affect the quality of the drug product.

Galgotias College of Pharmacy B. Pharm (VIII Sem)

BP804ET (PHARMACEUTICAL REGULATORY SCIENCE) Dr. Shaheen Sultana

 The manufacturer should assess the effect of the change on the identity, strength (eg,
assay, content uniformity), quality (eg, physical, chemical, and biological properties),
purity (eg, impurities and degradation products), or potency (eg, biological activity,
bioavailability, bioequivalence) of a product as they may relate to the safety or
effectiveness of the product.
 The FDA has published several SUPAC guidances, including Changes to an Approved
NDA or ANDA for the pharmaceutical industry.
 These guidances address the following issues:
1. Components and composition
2. Manufacturing sites
3. Manufacturing process
4. Specifications
5. Container closure system, and
6. Labeling, as well as
7. Miscellaneous changes and
8. Multiple related changes.
 These documents describe
(1) the level of change,
(2) recommended CMC tests for each level of change,
(3) in vitro dissolution tests and/or bioequivalence tests for each level of change, and
(4) documentation that should support the change.

General requirement for the Changes:

a. Components & Composition Changes: Any changes in the quantitative or qualitative
formulation, including inactive ingredients that were approved in the application, are
considered to be major changes and thus require the submission of a prior approval
supplement.
b. Manufacturing Sites Changes: If a drug maker changes to a manufacturing site other
than those specified in the approved application, CDER must be notified. In addition,
FDA states that construction activities that are occurring at a manufacturing site or
moving production operations within or between buildings, but within the same
manufacturing site do not have to be reported to the Agency
c. Manufacturing Process Changes: Changes in the manufacturing process that has
adverse effects on the identity, strength, quality, purity, or potency of a drug product must
be submitted to the FDA in a prior approval submission.
d. Specification Changes: The Agency states that all changes in specifications from those
in the approved application must be submitted in a prior approval supplement unless
otherwise exempted by regulation or guidance.
e. Labeling Changes: All labeling changes for ANDA drug products must be consistent
with section 505(j) of the Act.
f. Multiple Related Changes for an Approved NDA or ANDA: Multiple related changes
involve various combinations of individual changes. If an applicant has multiple related
changes that fall into different recommended reporting categories, "CDER recommends
that the submission be in accordance with the reporting category for the individual
changes.

Galgotias College of Pharmacy B. Pharm (VIII Sem)

BP804ET (PHARMACEUTICAL REGULATORY SCIENCE) Dr. Shaheen Sultana

g. Container Closure System Changes: Reporting category for the packaging change
needs to be considered

The levels of change as described by the FDA are listed

To assess the effect of the change on the identity, strength (e.g., assay, content uniformity),
Quality (e.g., physical, chemical, and biological properties), Purity (e.g., impurities and
degradation products), or Potency (e.g., biological activity, bio-availability, bioequivalence) of a
drug product as these factors may relate to the safety or effectiveness of the drug product, CDER
has published guidance, including the SUPAC (scale-up and post approval changes) guidance,
that provide recommendations on reporting categories. Reporting categories:

A. Major change
Major change is a change that has a substantial potential to have an adverse effect on the identity,
strength, quality, purity, or potency of a drug product as these factors may relate to the safety or
effectiveness of the drug product. Examples:
1. Changes that may affect the controlled (or modified) release,
2. Changes that may affect drug product sterility assurance (eg change in sterilization method)
3. Manufacturing process or technology (eg. Dry to wet granulation)

A major change requires the submission of a supplement and approval by FDA prior to
distribution of the drug product made using the change.

B. Moderate change
Moderate change is a change that has a moderate potential to have an adverse effect on the
identity, strength, quality, purity, or potency of the drug product as these factors may relate to the
safety or effectiveness of the drug product. There are two types of moderate change:
Supplement - Changes Being Affected in 30 Days: requires the submission of a supplement to
FDA at least 30 days before the distribution of the drug product made using the change. These
changes:
a. A change in the container closure system that does not affect the quality of the drug
product
b. An increase or decrease in production scale that involves different equipment

Galgotias College of Pharmacy B. Pharm (VIII Sem)

BP804ET (PHARMACEUTICAL REGULATORY SCIENCE) Dr. Shaheen Sultana

c. Replacement of equipment with that of a different design that does not affect the process
methodology
The applicant must not distribute the drug product made using the change if within 30 days, FDA
informs the applicant that either:
(i) The change requires approval prior to distribution of the drug product
(ii) Any of the required is missing; the applicant must not distribute the drug product made using
the change until the supplement has been amended to provide the missing information

Supplement - Changes Being Affected: FDA may identify certain moderate changes for which
distribution can occur when FDA receives the supplement. Example of such changes involved:
a. Addition to a specification or changes in the methods or controls to provide increased
assurance that the drug substance or drug product will have the characteristics of identity,
strength, quality, purity, or potency that it purports or is represented to possess;
b. A change in the size and/or shape of a container for a nonsterile drug product, except for
solid dosage forms,
c. Changes in the labeling to reflect newly acquired information
d. To add or strengthen a contraindication, warning, precaution, or adverse reaction
e. To add or strengthen an instruction about dosage and administration that is intended to
increase the safe use of the drug product;
f. To delete false, misleading, or unsupported indications for use or claims for effectiveness

C. Minor change
Minimal potential to have an adverse effect on the identity, strength, quality, purity, or potency
of the drug product as these factors may relate to the safety or effectiveness of the drug product.
Examples of changes:
a. The deletion or reduction of an ingredient intended to affect only the color of the drug product
b. Editorial changes: in previously submitted information (e.g., correction of spelling or
typographical errors, reformatting of batch records).
c. Replacement of equipment with that of the same design and operating principles

The applicant (for minor changes) is required to submit in the annual report:
(i) A statement by the holder of the approved NDA that the effects of the change have been
assessed;
(ii) A full description of the manufacturing and controls changes, including the manufacturing
site(s) or area(s) involved;
(iii) The date each change was implemented;
(iv) Data from studies and tests performed to assess the effects of the change

Assessment of the Effects of the Change

Evaluation of any changes in the chemical, physical, microbiological, biological, bioavailability,
or stability profiles must be checked. For example:
a. Evaluation of changes in the impurity: Toxicology tests to qualify a new impurity.
b. Evaluation of the hardness or friability: Effect of change on hardness or friability must be
assessed.
c. Adverse Effect: Some manufacturing changes have an adverse effect on the identity, strength,
quality, purity, or potency of the drug product must be prior approved.

Galgotias College of Pharmacy B. Pharm (VIII Sem)

BP804ET (PHARMACEUTICAL REGULATORY SCIENCE) Dr. Shaheen Sultana

d. Changes in the qualitative or quantitative formulation: including inactive ingredients, as

provided in the approved application, are considered major changes requiring a prior approval
supplement, unless exempted by regulation or guidance.
e. The deletion or reduction of an ingredient: Intended to affect only the color of the drug
product may be reported in an annual report.

Regulatory authorities and agencies

World Health Organization (WHO), Pan American Health Organization (PAHO), World Trade
Organization (WTO), International Conference on Harmonization (ICH), World Intellectual
Property Organization (WIPO) are some of the international regulatory agencies and
organizations which also play essential role inall aspects of pharmaceutical regulations related to
drug product registration, manufacturing, distribution, price control, marketing, research and
development, and intellectual property protection.
Drug regulation means to promote various activities to ensure the efficacy and safety, quality of
drug. Pharmaceutical drugs are available from a large number of sources. People and
Governments willing to spend money on drugs for many reasons so, it must be safe, effective
and good quality and used appropriately. Therefore, effective drug regulation is required to
ensure the safety, efficacy and quality of drugs as well as accuracy and appropriateness of the
drug information available to the public.Every country has its own regulatory authority, which is
responsible to enforce the rules and regulations and issue guidelines for drug development,
licensing, registration, manufacturing, marketing and labelling of pharmaceutical products.

Effective regulation of drug requires a variety of functions:

- Guaranteeing the safety, efficacy and quality of drugs.
- Licensing of premises, persons and practices.
- Inspection of manufacturing facilities and distribution channels.
- Product assessment and registration.
- Adverse drug reaction monitoring.
- Quality control.
- Control of drug promotion and advertising.
Most importantly, the process of drug regulation.

The drug regulation consists of:

1. Drug Laws
2. Drug Regulatory Agencies

Galgotias College of Pharmacy B. Pharm (VIII Sem)

BP804ET (PHARMACEUTICAL REGULATORY SCIENCE) Dr. Shaheen Sultana

3. Drug Regulatory Boards

4. Quality Control
5. Drug Information Centres.

DRUG REGULATORY AGENCIES IN INDIA:

India has emerged as one of the leading markets for pharmaceutical products. Increase in the
private healthcare infrastructure, widening rural markets, and inclusion of newer technologies
have placed healthcare as an independent sector in India. With privatization of healthcare, the
medical devices sector is growing too.
In order to regulate the import, manufacture, distribution and sale of drugs and cosmetics, the
Drugs and Cosmetics Act, 1940 (“D&C, Act”) was introduced in India in 1940. However, no
separate regulation has been enacted for regulating the import, manufacture, distribution or sale
of medical devices in India till date by the Government of India.
Drugs and Health is in concurrent list of Indian Constitution. It is governed by both Centre and
State Governments under the Drugs & Cosmetics Act, 1940.

Indian Council of Medical

Research (ICMR) Indian
Pharmaceutical Association (IPA) Drug Technical Advisory Board (DTAB)
Central Drug Testing Laboratory (CDTL) Indian Pharmacopoeia Commission (IPC)
National Pharmaceutical Pricing Authority (NPPA)

MAIN BODIES:-
Central Drug Standard Control Organization (CDSCO)
Ministry of Health & Family Welfare (MHFW)
Indian Council of Medical Research (ICMR)
Indian Pharmaceutical Association (IPA)
Drug Technical Advisory Board (DTAB)
Central Drug Testing Laboratory (CDTL)
Indian Pharmacopoeia Commission (IPC)

Galgotias College of Pharmacy B. Pharm (VIII Sem)

BP804ET (PHARMACEUTICAL REGULATORY SCIENCE) Dr. Shaheen Sultana

National Pharmaceutical Pricing Authority (NPPA)

Functions undertaken by Central Government:

 Laying down standards of drugs, cosmetics, diagnostics and devices.
 Laying down regulatory measures
 Amendments to Acts and Rules.
 To regulate market authorization of new drugs.
 To regulate clinical research in India to approve licenses to manufacture certain
categories of drugs as Central Licence
 Approving Authority i.e. for Blood Banks, Large Volume Parenteral and Vaccines &
Sera.
 To regulate the standards of imported drugs.
 Work relating to the Drugs Technical Advisory Board (DTAB) and Drugs
Consultative Committee (DCC).
 Testing of drugs by Central Drugs Labs.
 Publication of Indian Pharmacopoeia.

1. CDSCO In India, the Central Drugs Standard Control Organization (‘CDSCO’) is the main
regulatory body currently regulating import, sale and manufacture of medical devices which
have been notified as drugs by virtue of Section 3(b) (IV) of the D&C Act. The CDSCO lays

Galgotias College of Pharmacy B. Pharm (VIII Sem)

BP804ET (PHARMACEUTICAL REGULATORY SCIENCE) Dr. Shaheen Sultana

down standards of drugs, cosmetics, diagnostics and devices and issues licenses to drug
manufacturers and importers. It also lays down regulatory measures, amendments to Acts and
Rules and regulates market authorization of new drugs, clinical research in India and standards
of imported drugs etc. Headquartered in New Delhi, the CDSCO is India's main regulatory body
for pharmaceuticals and medical devices and Within the CDSCO, the Drug Controller General of
India (DCGI) is responsible for the regulation of pharmaceuticals and medical devices. The
DCGI is advised by the Drug Technical Advisory Board (DTAB) and the Drug Consultative
Committee (DCC). Licensing and classification of medical devices are handled by the Central
Licensing Approval Authority (CLAA). The CLAA is also responsible for setting and enforcing
safety standards, appointing notified bodies to oversee conformity assessment, conducting
postmarket surveillance and issuing warnings and recalls for adverse events.
The CDSCO establishes safety, efficacy, and quality standards for pharmaceuticals and medical
devices. It publishes and updates the Indian Pharmacopeia, a list of regulated pharmaceuticals
and devices. For all drug and device applications, the CDSCO appoints notified bodies to
perform conformity assessment procedures, including testing, in order to ensure compliance with
their standards. The CDSCO is also divided into several zonal offices which do pre-licensing and
post-licensing inspections, post-market surveillance, and recalls when necessary.
In addition to its regulatory functions, the CDSCO offers technical guidance, trains regulatory
officials and analysts, and monitors adverse events. The CDSCO works with the World Health
Organization to promote Good Manufacturing Practice (GMP) and international regulatory
harmony.
2. National Institute of Health and Family Welfare (NIHFW)-NIHFW is an Apex Technical
Institute, funded by Ministry of Health and Family Welfare, for promotion of health and family
welfare programmers in the country through education, training, research, evaluation,
consultancy and specialized services. The NIHFW was established on March 9, 1977 by a
merger of the National Institute of Health Administration and Education (NIHAE) with the
National Institute of Family Planning (NIFP).
List of Governing Body Members of NIHFW
18 members
1 Chairman (ex-officio)
1 Vice Chairman (ex-officio)
9 Member (ex-officio)
6 Member
1 Member Secretary (ex-officio)
ACTIVITIES AND RESPONSIBILITIES:
 Measuring weight of children to assess the nutritional status.
 Assessment of diseases like level of anaemia.
 Testing of food material like cooking salt for level iodine.
 To release fund on the advice of the Ministry.
 It is responsible for all governmental programs relating to family planning in India.

3. DRUG TECHNICAL ADVISORY BOARD (DTAB):

The Central Government constitute a Board (to be called the Drugs Technical Advisory Board)
to advise the Central Government and the State Governments on technical matters arising out of
the administration of D&C, Act 1940.
List of Governing Body Members of NIHFW:

Galgotias College of Pharmacy B. Pharm (VIII Sem)

BP804ET (PHARMACEUTICAL REGULATORY SCIENCE) Dr. Shaheen Sultana

18 Members
10 ex-officio Members
5 Nominated Members
5 Elected Members

ACTIVITIES AND RESPONSIBILITIES:

It advices matter related to Drugs. The nominated and elected members of the Board shall hold
office for three years, but shall be eligible for re-nomination and re-election. The Board may,
subject to the previous approval of the Central Government, make bye-laws fixing a quorum and
regulating its own procedure.

4. CENTRAL DRUG TESTING LABORATORY (CDTL): The central drug laboratory, Kolkata
is national statutory laboratory of the government of India for quality control of drug and
cosmetic and established under the D&C act, 1940. Oldest quality control laboratory of the drug
control authorities in India. Function under the director general of Health Services in the
Ministry of Health and Family Welfare.

COMPOSITION: Indian Pharmacopoeia Commission (IPC)

General Body 19 Members
Governing Body 10 Members
Scientific Body 23 Experts

ACTIVITIES AND RESPONSIBILITIES:

 Development of comprehensive monographs.
 Accord priority to monographs of drugs included in the national Essential Drug List and
their dosage forms.
 Preparation of monograph for products that have normally been in the market for not less
than 2 years.
 Collaborate with pharmacopoeias like the BP, USP, JP and International Pharmacopoeia
with a view to harmonizing with global standards.

DRUG REGULATORY AGENCIES IN USA:

USFDA
The Food and Drug Administration (FDA) is an agency within the U.S. Department of Health
and Human Services. It consists of six product centres, one research centre, and two offices.
FDA’s responsibilities extend to the 50 United States, the District of Columbia, Puerto Rico,
Guam, the Virgin Islands, American Samoa, and other U.S. territories and possessions.

The Food and Drug Modernization Act states that the FDA has 4 roles:
*To promote health by reviewing research and approving new products.
*To ensure foods and drugs are safe and properly labelled.
*To work with other nations to “reduce the burden of regulation”.
*To cooperate with scientific experts and consumers to effectively carry out these obligations

The FDA is led by the Commissioner of Food and Drugs, who is appointed by the President
and confirmed by the Senate.

Galgotias College of Pharmacy B. Pharm (VIII Sem)

BP804ET (PHARMACEUTICAL REGULATORY SCIENCE) Dr. Shaheen Sultana

FDA is responsible for

 Protecting the public health by assuring that foods are safe, wholesome, sanitary and
properly labelled;
 Assuring human and veterinary drugs, and vaccines and other biological products and
medical devices intended for human use are safe and effective,
 Protecting the public from electronic product radiation
 Assuring cosmetics and dietary supplements are safe and properly labelled
 Regulating tobacco products
 Advancing the public health by helping to speed product innovations
 Helping the public get the accurate science-based information they need to use
medicines, devices, and foods to improve their health
 Initiation of a Recall.

 Type of Applications:
 Investigational New Drug Application (IND): Application submitted to FDA to seek
permission to test a new drug or a biologic in human. New Drug Application (NDA):
When the sponsor of the new drug believes that enough Evidence on the drugs safety and
effectiveness has been obtained to meet FDA’s requirements for marketing approval, the
sponsor submits to FDA a New Drug Application.
 Abbreviated New Drug Application (ANDA): An Abbreviated New Drug Application
(ANDA) contains data that, when submitted to FDA's Centre for Drug Evaluation and
Research, Office of Generic Drugs, provides for the review and ultimate approval of a
generic drug product. Generic drug applications are called "abbreviated” because they are
generally, not required to include preclinical (animal) and clinical (human) data to
establish safety and effectiveness
 Biologic License Application (BLA): A biologics license application is a submission
that contains specific information on the manufacturing processes, chemistry
pharmacology, clinical pharmacology and the medical effects of the biologic product.

Galgotias College of Pharmacy B. Pharm (VIII Sem)

BP804ET (PHARMACEUTICAL REGULATORY SCIENCE) Dr. Shaheen Sultana

DRUG REGULATORY AGENCIES IN EUROPE:

European Medicines Agency (EMA)
• EMA is a European agency for the evaluation of medicinal product.
• EMA was setup in 1995.
• From 1995 to 2004, EMA was known as European agency for the evaluation of
medicinal product.
• The European Medicines Agency (EMA) is a decentralized body of the European Union,
located in London
• EMA protects public and animal health by ensuring that all medicines available on the
EU market are safe, effective and of high quality.

ACTIVITIES OF EMA
THE ROLE OF EMA
• EMA is responsible for the scientific evaluation, primarily of innovative and high-
technology medicines developed by pharmaceutical companies for use in the EU.
• EMA was established in 1995 to ensure the best use of scientific resources across Europe
for the evaluation, supervision and pharmacovigilance of medicines.
• Experts participate in the work of EMA as members of its scientific committees, working
parties, scientific advisory groups or as members of the national assessment teams that
evaluate medicines. The experts are chosen on the basis of their scientific expertise and
many of them are made available to EMA by the NCAs in Member States.
• Increasingly, patients and healthcare professionals are involved in the work of the
Agency including in the evaluation of medicines.

Functions of EMA
1. GUIDELINES AND SCIENTIFIC ADVICE
 EMA prepares scientific guidelines in cooperation with experts from its scientific
committees and working groups.
 These guidelines reflect the latest thinking on developments in biomedical science.
 They are available to guide the development programmes of all medicine developers who
wish to submit an application for a marketing authorisation in the EU, and to ensure that
medicines are developed consistently and to the highest quality.
 EMA also gives product-specific scientific advice to companies for the development of
medicines.

2. AUTHORIZATION AND SUPERVISION OF MANUFACTURERS

 Manufacturers, importers and distributors of medicines in the EU must be licensed before
they can carry out those activities.
 The regulatory authorities of each Member State are responsible for granting liscences for
such activities taking place within their respective territories.
 All manufacturing and importing licenses are entered into EudraGMDP, the publicly-
available European database operated by EMA.

Galgotias College of Pharmacy B. Pharm (VIII Sem)

BP804ET (PHARMACEUTICAL REGULATORY SCIENCE) Dr. Shaheen Sultana

3. SAFETY MONITORING OF MEDICINES

• The European regulatory system for medicines monitors the safety of all medicines that
are available on the European market throughout their life span.
• All suspected side effects that are reported by patients and healthcare professionals must
be entered into EudraVigilance, the EU web-based information system operated by EMA
that collects, manages and analyses reports of suspected side effects of medicines.
• These data are continuously monitored by EMA and the Member States in order to
identify any new safety information. The committee provides advice and
recommendations to the European medicines regulatory network on risk management
planning and benefit-risk assessment for medicines after marketing.

4. CLINICAL TRIALS
• The authorisation and oversight of a clinical trial is the responsibility of the Member
State in which the trial is taking place.
• The European Clinical Trials Database (EudraCT) tracks which clinical trials have been
authorised in the EU. It is used by NCAs and clinical-trial sponsors to enter information
protocols and results of clinical trials.
• A subset of this information is made publicly available by EMA via the EU clinical trials
register.

5. Evaluate applications for marketing authorisation: EMA evaluates marketing-authorisation

applications submitted through the centralised procedure that provide authorisation of
medicines in Europe.

Galgotias College of Pharmacy B. Pharm (VIII Sem)

BP804ET (PHARMACEUTICAL REGULATORY SCIENCE) Dr. Shaheen Sultana

Types of application in the EU

1. Full (Stand-alone) application
For full applications the results of pharmaceutical tests (physico-chemical, biological or
microbiological), pre-clinical tests (pharmacological and toxicological), and clinical trials need
to be submitted.
2. Generic application
The applicant for an MA is not required to provide the results of non-clinical tests and clinical
trials if the applicant can demonstrate that the medicine is a generic medicine of a
reference medicine which is or has been authorised for not less than 8 years in a Member
State or in the Union.
3. Hybrid application
A hybrid application is submitted where results of non-clinical tests or clinical trials are required.
This is necessary in three cases:
a. where the strict definition of ‘generic medicine’ is not met.
b. where the bioavailability studies cannot be used to demonstrate bioequivalence.
c. where there are changes in the active substance(s), therapeutic indications, strength,
pharmaceutical form or route of administration of the generic product compared to the
reference medicine
4. Biosimilars application
A biosimilar is a biological medicine highly similar to another biological medicine already
approved in the EU, the reference medicine.
5. Well-established use application
Results of non-clinical tests and/or clinical trials are not required if the applicant can demonstrate
that the active substances of the medicine have been in well-established medicinal use for at least
ten years in the EU, with accepted efficacy and an acceptable level of safety.
6. Informed consent application
The marketing authorisation application for a product is called an ‘informed
consent application’, if it possesses the same qualitative and quantitative composition in terms
of active substance(s) and the same pharmaceutical form as a reference product already
authorised, using that dossier. For such application it is a prerequisite that consent has been
obtained from the marketing authorisation holder of the reference product for all three modules
containing the pharmaceutical, pre-clinical and clinical data (modules 3, 4 and 5).
7. Fixed combination application
The combination of active substances within a single pharmaceutical form of administration
according to the legal basis is a so-called 'fixed combination'.

DRUG REGULATORY AGENCIES IN JAPAN:

MHLW: The Ministry of Health, Labour, and Welfare (MHLW) was established by a merger of
the Ministry of Health and Welfare (MHW) and the Ministry of Labour, on January 6, 2001.
The MHLW, which was originally established in 1938, has been in charge of the improvement
and promotion of social welfare, social security and public health, and the new organization has
the same tasks.
It consists of the ministry proper, affiliated institutions, councils, local branches, and an external
organization.

Galgotias College of Pharmacy B. Pharm (VIII Sem)

BP804ET (PHARMACEUTICAL REGULATORY SCIENCE) Dr. Shaheen Sultana

FUNCTION OF MHLW:
a. Health Policy: The MHLW is responsible for formulating and implementing policies related
to healthcare, medical services, and public health in Japan. This includes regulating
pharmaceuticals, medical devices, and food safety, as well as promoting health promotion and
disease prevention.
b. Labour Policy: The MHLW is responsible for overseeing policies related to labour and
employment in Japan. This includes regulating working conditions, minimum wage, and social
security programs.
C. Social Welfare Policy: The MHLW is responsible for formulating and implementing policies
related to social welfare, including support for the elderly, people with disabilities, and children.
d. Disaster Management: The MHLW plays a crucial role in disaster management in Japan,
including responding to natural disasters and pandemics, and providing emergency medical care
and assistance.

Organization:
Three main parts of the MHLW are:
1) Health Policy Bureau
2) Pharmaceutical and Food Safety Bureau (PFSB)
3) Pharmaceutical and Medical Device Agency (PMDA)
Health Policy Bureau: The Health policy bureau handles promotion of R&D, production,
distribution policies and drug pricing and other functions related to the pharmaceutical firms.
PFSB: The Pharmaceutical and Food Safety Bureau (PFSB) strives to protect people's life and
health through comprehensive efforts, covering clinical experiments, technical examinations for
registration and after-sales follow-ups, to secure the safety, efficacy, etc. of pharmaceuticals.
PMDA: The Pharmaceuticals and Medical Devices Agency (PMDA) was established and came
into service on April 1, 2004, under the Act on the Pharmaceuticals and Medical Devices
Agency, which consolidated the services of the Pharmaceuticals and Medical Devices Evaluation
Center of the National Institute of Health Sciences (PMDEC), the Organization for
Pharmaceutical Safety and Research (OPSR), and part of the Japan Association for the
Advancement of Medical Equipment (JAAME).

Galgotias College of Pharmacy B. Pharm (VIII Sem)

BP804ET (PHARMACEUTICAL REGULATORY SCIENCE) Dr. Shaheen Sultana

The three (03) main types of drug applications that you can submit to the PMDA are as follows:
a. Investigational New Drug (IND): You need to submit this application before conducting
clinical trials in Japan.
b. New Drug Application (NDA): You need to submit this application to get approval for
marketing a new drug in Japan.
c. Abbreviated New Drug Application (ANDA): You must submit this application to get
approval for marketing a generic drug in Japan.

Australia
Therapeutics Goods Administration is the regulatory body for therapeutic goods in Australia.
TGA is responsible for conducting assessment and monitoring activities to ensure that
therapeutic goods available in Australia are of an acceptable standard.
The objectives of Therapeutic Goods Act 1989, which came into effect on 15 Feb, 1991 is to
1) provide a national framework for the regulation of therapeutic goods in Australia to
ensure quality, safety and efficacy of the medicines and ensure quality, safety and
performance of medical devices
2) Essentially therapeutic goods must be entered on the Australian Register of Therapeutic
Goods (ARTG) before they can be supplied in Australia.

Galgotias College of Pharmacy B. Pharm (VIII Sem)

BP804ET (PHARMACEUTICAL REGULATORY SCIENCE) Dr. Shaheen Sultana

Role of TGA
The TGA carries out an overall control through five main processes:
1. Pre-market evaluation and approval of registered products intended for supply in
Australia;
2. Development, maintenance and monitoring of the systems for listing of medicines;
3. Licensing of manufacturers in accordance with international standards of GMPs
4. Post-market monitoring, through sampling, adverseevent reporting, surveillance
activities, and response to public inquiries;
5. The assessment of medicines for export.

Application category:
a. Generic product
b. New medicine requiring proof of efficacy of the product.
c. A variation to an existing approved assessed listed medicine, where the medicine
contains one of the following:
1. different active ingredient(s)
2. different strength (i.e. quantity of active ingredient(s))
3. different indication(s) (other than removing an indication)
4. different dosage form; or
5. different excipients.

Elements to Regulate
• Licensing and Audit of Manufactures Act requires each Australian manufacturer of
medicinal products for human use to hold a manufacturing license. License holders are
required to comply with the manufacturing principles of the Act, including compliance
with GMP.

Galgotias College of Pharmacy B. Pharm (VIII Sem)

BP804ET (PHARMACEUTICAL REGULATORY SCIENCE) Dr. Shaheen Sultana

• Pre-Market Assessment: This includes study of toxicity and dosage form of medicines.
The product risk is determine by side effects, inappropriate self medication, adverse
effect for prolonged use

Post-Market Regulatory Authority

The essential elements of this systematic rick-based approach include:
1. Monitoring of adverse reactions to medicines.
2. Targeted and random surveillance in the market place.
3. An effective, responsive and timely recalls procedure.
4. Audit of GMP.
5. Effective controls for the advertising of therapeutic goods.

TGA regulates therapeutic goods before the products reach the market (pre-market) and
afterwards, when they are in general use (post-market).
At the pre-market stage, TGA acquires the information necessary for a decision about whether or
not to register, list or include therapeutic goods on the ARTG. They do this through accepting
certification, actively evaluating information supplied by sponsors or manufacturers, or by direct
inspection.
Medicines containing low-risk ingredients, including most complementary medicines, receive a
lesser degree of checking than higher risk products, and are listed (AUST L) on the ARTG. The
listing process is based on the certification of claims by sponsors. For products containing low-
risk ingredients, regulation centers on the safety of the product and the consistency of the
manufacturing process; less emphasis is placed on assessing the evidence for the claims being
made.
Products carrying a higher risk, which include all prescription medicines, receive a higher degree
of scrutiny and, if found to comply, are registered (AUST R) on the ARTG. Registration
involves the evaluation of data related to safety, manufacturing and efficacy. Thus, when taking
a therapeutic good that is registered on the ARTG, Australians can be confident that the product
does not only meet safety and quality criteria, but that it has been demonstrated to have the
claimed effect.

Canada
Canada is the second largest pharmaceutical market in North America. The Health Canada is the
federal Regulatory body which is responsible to ensure the safe and effective use of drugs and
health products in Canada. Strict Regulatory regime of different bodies for Food and Veterinary,
Pharma and Biological drugs, makes it challenging for foreign manufacturers to enter the region.
Those Regulatory bodies include:
• Health Canada’s Health Products and Food Branch (HPFB) – for Food, Health and
Veterinary
• Therapeutic Product Directorate (TPD) – for Pharmaceuticals and Medical Devices
• Biologics and Genetic Therapies Directorate (BGTD) – for Biological and
Radiopharmaceutical drugs
• Health Canada's Health product and food branch (HPFB) is the national authority that
regulated, evaluates and monitor the safety, efficacy and quality of therapeutic and
diagnostic products available to Canadians

Galgotias College of Pharmacy B. Pharm (VIII Sem)

BP804ET (PHARMACEUTICAL REGULATORY SCIENCE) Dr. Shaheen Sultana

• Health products-drugs, biologics, genetic therapies, medical devices, natural health

products are all reviewed and authorized by the HPFB through either the Therapeutic
products directorate (TPD) or the biologic and genetic Therapeutic Direcyate (BGTD)
• Applications to conduct clinical trias are also managed by HPFB
• The marketed health products directorate is responsible for surveillance, benefits-risk
assessment and information sharing for approved health products.

Types of Applications
1. SANDS (Supplement to Abbreviated New Drug Submission)
2. SNDS (Supplement to a New Drug Submission) are types of submission towards Health
Canada which stand as important resources to ANDS (Abbreviated New Drug
Submission) and NDS (New Drug Submission).

Galgotias College of Pharmacy B. Pharm (VIII Sem)

BP804ET (PHARMACEUTICAL REGULATORY SCIENCE) Dr. Shaheen Sultana

3. ANDS (Abbreviated New Drug Submission)

4. NDS (New Drug submission)
Abbreviated New Drug Submission (ANDS): ANDS is an application to Health Canada to obtain
marketing approval of a generic product. It provides necessary information for the government
agency to evaluate how safe a drug is in comparison to its brand name.

Galgotias College of Pharmacy B. Pharm (VIII Sem)