Lecture 7
Introduction→ if CRO is doing a trial for the sponsor, inspection finds both CRO and
sponsor are responsible.
The regulated world of clinical trials→ world is highly regulated on different levels:
Global regulations → Guidelines: need to be put in law to have legally binding effect
Regional regulations → EU Directives
National regulations → Local law
Aim of drug development process→ obtain MAA (marketing authorization application):
Results in a license to market an IP in a particular country or region
Defines quality, permitted uses and restrictions
Restricts also promotional claims.
Defines packaging and labeling
Steps in acquiring an MAA
1. Preparation (takes significant amount of time)
2. Submission
3. Review by authorities (might take up to 2 years)
4. Inspections
5. Questions and answer (sponsor asks questions)
There are 3 ways (procedure) to get MAA in EU
1. Mutual recognition → submitted to one member state, others will mutually recognize
that decision when receiving a submission at a later time. So the review process is
performed 1 time only.
2. Centralized submission in the entire EU → submit centrally for EU authorization, in all
Member states at the same time, the EMA reviews it. Contains a difference:
Mutual recognition only gives approval for the country you submitted.
Company decides mutual recognition when it cannot export enough product
to the entire EU (after EMA approval, you need to be able to produce as
many product as needed.
EMA gives approval to use in the entire EU.
3. National fillings only available for local products or some line extensions.
Code of federal regulations (CFR), FDA tasks
New product review (food, drugs & cosmetics).
Post-marketing surveillance.
Setting standards and writing regulations (CFR) → manufacturing, distribution,
labeling, proving safety and efficacy.
Scientific research
Regulatory enforcement and corrective action (black list). For drug research and
cosmetics, the FDA puts the guidelines into regulations within the US.
FDA-CFR→ data from outside the USA are not required by CFR in order to obtain
approval. However, advantages of international trials are:
Higher number of potential subjects (shortens time, statistical consideration).
Higher marketing advantages→ region where you want to submit, you use their
population.
1
, FDA types of applications
They first work with: investigational new drug (IND) application → gives approval to
do research with that product in the US, product is not yet on market.
o Normal track
o Fast track (for pandemic or ethical reasons like cancer therapy). Only a
couple of years instead of average 12. Product may pass to phase 2 with only
1 trial
New drug application (NDA): US version of MAA,
o Also normal or fast track procedure.
o Abbreviation New Drug Application (ANDA) → using for generics,
bioequivalents, but you don't need to go to the same process so it's quicker
for marketing approval.
The IND triangle lies at the end of preclinical study, prior to clinical study every trial
needs to be approved. In the US you need an IND in place, you keep IND valid by
resubmitting CDP once something changes. Different in EU: need to get approval for
each trial.
FDA – NDA contains FDA – IND application contains
All known information about the compound All known information about the compound
Preclinical results Preclinical results
Clinical results Clinical results
Relevant marketing data Description of CDP
Manufacturing details Investigator's brochure (IB)
ANDA for generics & bioequivalents Qualifications of participating investigators
FDA needs 6 months to review FDA needs 30 days to review
2
Introduction→ if CRO is doing a trial for the sponsor, inspection finds both CRO and
sponsor are responsible.
The regulated world of clinical trials→ world is highly regulated on different levels:
Global regulations → Guidelines: need to be put in law to have legally binding effect
Regional regulations → EU Directives
National regulations → Local law
Aim of drug development process→ obtain MAA (marketing authorization application):
Results in a license to market an IP in a particular country or region
Defines quality, permitted uses and restrictions
Restricts also promotional claims.
Defines packaging and labeling
Steps in acquiring an MAA
1. Preparation (takes significant amount of time)
2. Submission
3. Review by authorities (might take up to 2 years)
4. Inspections
5. Questions and answer (sponsor asks questions)
There are 3 ways (procedure) to get MAA in EU
1. Mutual recognition → submitted to one member state, others will mutually recognize
that decision when receiving a submission at a later time. So the review process is
performed 1 time only.
2. Centralized submission in the entire EU → submit centrally for EU authorization, in all
Member states at the same time, the EMA reviews it. Contains a difference:
Mutual recognition only gives approval for the country you submitted.
Company decides mutual recognition when it cannot export enough product
to the entire EU (after EMA approval, you need to be able to produce as
many product as needed.
EMA gives approval to use in the entire EU.
3. National fillings only available for local products or some line extensions.
Code of federal regulations (CFR), FDA tasks
New product review (food, drugs & cosmetics).
Post-marketing surveillance.
Setting standards and writing regulations (CFR) → manufacturing, distribution,
labeling, proving safety and efficacy.
Scientific research
Regulatory enforcement and corrective action (black list). For drug research and
cosmetics, the FDA puts the guidelines into regulations within the US.
FDA-CFR→ data from outside the USA are not required by CFR in order to obtain
approval. However, advantages of international trials are:
Higher number of potential subjects (shortens time, statistical consideration).
Higher marketing advantages→ region where you want to submit, you use their
population.
1
, FDA types of applications
They first work with: investigational new drug (IND) application → gives approval to
do research with that product in the US, product is not yet on market.
o Normal track
o Fast track (for pandemic or ethical reasons like cancer therapy). Only a
couple of years instead of average 12. Product may pass to phase 2 with only
1 trial
New drug application (NDA): US version of MAA,
o Also normal or fast track procedure.
o Abbreviation New Drug Application (ANDA) → using for generics,
bioequivalents, but you don't need to go to the same process so it's quicker
for marketing approval.
The IND triangle lies at the end of preclinical study, prior to clinical study every trial
needs to be approved. In the US you need an IND in place, you keep IND valid by
resubmitting CDP once something changes. Different in EU: need to get approval for
each trial.
FDA – NDA contains FDA – IND application contains
All known information about the compound All known information about the compound
Preclinical results Preclinical results
Clinical results Clinical results
Relevant marketing data Description of CDP
Manufacturing details Investigator's brochure (IB)
ANDA for generics & bioequivalents Qualifications of participating investigators
FDA needs 6 months to review FDA needs 30 days to review
2
