REGULATORY APPROVAL
PROCESS OF NDA

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For the new drug approval process following steps are followed :

1. Clinical Trials of New Drugs :

1. Phase I: Involves a small number of healthy subjects to test the toxicity,
absorption, distribution and metabolism of the drug.

2. Phase II: Involves trials with a larger set of individuals suffering from the
condition for which the drug was developed, to test efficacy and safety.

3. Phase III: Involves a greater number of people also with the condition in
question, to test the drug’s performance in relation to a placebo and/or standard
therapy.

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4. Phase IV: Involves all studies conducted after a drug has received approval that were
not considered necessary for approval but are often important for optimizing the drug’s
use, also referred to as post-market or post-approval studies.

These trials are subject to the clinical trial regulations under part C, division 5 of be Food
and Drug Regulations (the Regulations) which seek to ensure: The safety the participants;
the integrity of the study; the validity of the data; and strict controls over the use of an
unapproved drug. Authorization to conduct phase I, II, or III clinical trials must be
obtained from Health Canada before starting the investigation. Phase IV clinical trials do
not require authorization.

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2. Regulatory process
for drugs approvals in
Canada :

Flow chart image

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New drug approval process involved the below mentioned steps:

(a) Pre-submission meeting: Once the developer and/or manufacturer of a new
investigational drug is confident that it has produced a compound that can successfully
gain Health Canada’s approval, a pre-submission meeting is encouraged by TPD, but is not
essential. This meeting can be beneficial to the drug sponsor as well as Health Canada as it
alerts the regulator to upcoming submissions and allows the sponsor an opportunity to
optimize their submission package.

(b) Submission filing: This is the first step in the drug approval process. Submission
filing involves submitting to TPD a new drug submission, or NDS. The NDS must contain
information that: describes the drug; asserts its quality; summarizes the investigational
studies and clinical trials pertaining to the drug including adverse reactions observed
during clinical trials; and finally, includes raw data from preclinical studies

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(c) Screening: When IPD receives an NDS, it first screens the package to ensure that the
submission is complete and in the proper format. Health Canada aims to meet a target of
45 calendar days for screening NDSS. Upon a successful screening, the submission
proceeds to the technical review. If, however, deficiencies are identified in the submission
filing, the sponsor is sent a screening deficiency notice to which it has 45 calendar days to
respond and address the noted deficiencies. Unsuccessful candidates are sent a screening
rejection letter.

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(d) Technical review: Upon successful completion of the screening process, the
submission passes to the technical review component. TPD has established a target of
300 days for this phase of the drug approval process. Evaluation of the submission
involves a detailed review of all the material submitted in the filing in order to produce
a comprehensive analysis of the quality, safety and efficacy of the candidate drug and
ensures that the risks associated with taking the drug do not outweigh the benefits.
Clinical trial data is central to determine the safety/efficacy profile for a candidate
drug. At any point during the review TPD can request clarification, re-evaluation or
expansion of the submitted material.

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Possible outcomes of the technical review are:

i. A notice of deficiency if the submission is incomplete, at which point the review process
stops but can resume if the deficiencies are addressed;

ii. A notice of deficiency-withdrawal letter if the applicant does not satisfactorily address
deficiencies;

iii. A notice of non-compliance if TPD finds that the submission is incomplete or deficient
which lists all deficient or incomplete aspects of the submission, to which the applicant can
respond;

iv. A notice of non-compliance-withdrawal letter if the applicant does not respond or if the
response is unacceptable at which time the submission will be considered withdrawn;

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v. A notice of compliance (NOC) which certifies that the drug complies with all
requirements of the Act and its regulations. At this time a drug identification number
(DIN), an eight digit number, is also issued which authorizes the drug to be marketed in
Canada;

vi. A notice of decision and a summary basis of decision for each approved drug
outlining its risk-benefit analysis which are posted on Health Canada’s website.

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Drug Regulatory Approval Process in the USA :

▪ In 1820, the new era of the USA drug regulation was started with the establishment of the
US Pharmacopoeia.

▪ In 1906, Congress passed the original Food and Drugs Act, which require that drugs must
meet official standards of strength and purity.

▪ However, in 1937, due to sulphanilamide tragedy, the Federal Food, Drug and Cosmetic
Act (of 1938) was enacted and added new provisions that new drugs must be shown safe
before marketing.

▪ Further, in 1962, the Kefauver-Harris Amendment Act was passed which require that
manufacturers must prove that drug is safe and effective (for the claims made in labeling).

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The Food and Drug Administration (FDA) is responsible for protecting and promoting public

health.

Like general drug approval process, FDA’s new drug approval process is also accomplished

in two phases:

▪ Clinical trials (CT) and new drug application (NDA) approval.

▪ FDA approval process begins only after submission of investigational new drug (IND)

application.

▪ The IND application should provide high quality preclinical data to justify the testing of

the drug in humans.

▪ Almost 85% of drugs are subjected to clinical trials, for which IND applications are filed.

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▪ The next step is phase I clinical trials (1-3 years) on human subjects (~100). The drug’s
safety profile and pharmacokinetics of drug are focused in this phase.

▪ Phase II trials (2 years) are performed if the drug successfully passes phase I. To
evaluate dosage, broad efficacy and additional safety in people (-300) are the main
objective of the phase II.

▪ If evidence of effectiveness is shown in phase II, phase III studies (3-4 years) begins.
These phase III concerns more about safety and effectiveness of drug from data of
different populations, dosages and its combination with other drugs in several hundred
to about 3,000 peoples.

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Drug Regulatory
Approval Process in
the USA :

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▪ A new drug application (NDA) can be filed only when the drug successfully passes all
three phases of clinical trials and includes all animal and human data, data analyses,
pharmacokinetics of drug and its manufacturing and proposed labeling.

▪ The preclinical, clinical reports and risk-benefit analysis (product’s beneficial effects
outweigh its possible harmful effects) are reviewed at the center for drug evaluation and
research by a team of scientists.

▪ Generally approval of an NDA is granted within two years (on an average), however, this
process can be completed from two months to several years.

▪ The innovating company is allowed to market the drug after the approval of an NDA and
is considered to be in phase IV trials.

▪ In this phase, new areas, uses or new populations, long-term effects, and how
participants respond to different dosages are explored.

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THANK YOU

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