REGULATORY REQUIREMENTS FOR APPROVAL OF API

1. REGULATORY REQUIREMENTS FOR
APPROVAL OF API
PRESENTED BY
NIVEDITHA G
1st sem Mpharm
(Pharmaceutics)

2. API
◦API(active pharmaceutical ingredient)means the active ingredient
which contained medicine
◦Active ingredient only posses the therapeutic efficacy or
pharmacological action for treatment of diseases.
For ex; active ingredient(aspirin) have therapeutic action to relief the
body pain.

3. REGULATORY REQUIREMENTS FOR
API
Introduction
◦ Active Pharmaceutical Ingredient (API) (or Drug Substance): Any substance or
mixture of substances intended to be used in the manufacture of a drug
(medicinal) product and that, when used in the production of a drug, becomes an
active ingredient of the drug product.
◦ This substances are intended to furnish pharmacological activity or other direct
effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to
affect the structure and function of the body.
◦ API materials that are the active for new drugs are covered by NDA
documentation.

4. ◦ API materials that are the active for new drugs are covered by
NDA documentation.
◦Innovator companies would use their IND or NDA filings to
provide the expected details covering an API, while all others
would establish and submit a DMF with the FDA or other
appropriate country authority, such as EMA in Europe.

5. CONTENTS FOR APPROVAL OF API
1. NDA
2. DMF
3. TYPES OF DMF
4. FILING OF DMF
5. ORGANIZATION OF e-CTD
6. DMF FEE

6. NDA
◦ When the drug successfully passes the clinical trials and include all animal and
human data, data analysis, pharmacokinetics of drug and proposed labelling then
the NDA can be filed.
◦ The manufacturer files a NDA, actual request to manufacture and sell in US after
the clinical trials confirms the new drug or API is safety and efficacy.
◦ Approval of NDA is granted within 2 years.
◦ Once the application is submitted ,the FDA has 60 days to conduct preliminary
review which asses the NDA is sufficiently complete to permit the substantive
review
◦ But FDA finds any insufficiently complete then the FDA rejects the application
form.

7. ◦ This rejection of application form is called refuse letter.

9. DMF(DRUG MASTER FILE)
◦Drug master files is a confidential,detailed document submitted by API
manufactures to the US FDA
◦Recently USFDA has issued completeness assessment for type 2 API
DMF under generic drug user fee amendment (GDUFA).
◦It is also called active substance master file(ASMF).
◦Type 2 DMF include the drug substance ,drug substance
intermediate,and materials used in the preparation and drug product.

10. TYPES OF DMF
◦Type 1 DMF manufacturing site, facilities,operating
procedures,and personnel.
◦ Type 2 DMF include the drug substance ,drug substance
intermediate,and materials used in the preparation and drug
product.
◦Type 3 DMF include packaging material
◦Type 4 DMF include excipient,colorant,essence
◦Type 5 DMF include FDA accepted reference information.

11. ◦ According to type 2 DMF is limited to single drug intermediate, drug
substance, drug product, or type of material in drug preparation.
◦ Significant steps in the manufacturing and control of the drug intermediate
or substance,the guidance on what should be included in a type 2 DMF for
drug intermediates
◦ That guidance are
1. Guideline for submitting supporting documenting in drug applications for
the manufacture of drug substances.
2. Guidelines for the format and content of the chemistry,manufacturing and
control section of an application.

12. FILING OF DMF
◦Recent update regarding the USFDA DMF is now we can
submit e-CTD through an ESG(electronic submission
gateway)
◦The deadline for the conversion of the paper format to e-
CTD is beginning may 5,2017, all submission types
NDA,ANDA,BLA,and master files must be submitted in e-
CTD.

13. ORGANIZATION OF e-CTD
◦MODULE 1
a. Cover letter
b. Regulatory description of the submission, including appropriate
regulatory information and any desired hyper links to submitted
information.
c. Technical description of the submission, including the approximate
size of the submission upto 2GB
d. Certifying statement hat the submission is virus free, with a
description of the software ( name, version , and company) that was
used to check the for viruses.

14. ◦A regulatory and technical point of contact for the submission,
including email address should be mentioned.
ANNUAL REPORT
◦Sponsors and applicants should include a bookmark for each
study
◦The reporting period covered by the annual report should be
included in the e-CTD leaf title

15. LETTERS OF AUTHORIZATION
◦Submission by the owner of information giving authorization for the
information to be used by another.
STATEMENT OF RIGHT OF REFERENCE
◦Submission by recipient of a letter of authorization with a copy of the
LOA and statement of right of reference
◦Submitted in a DMF only when another DMF is referenced.

16. DMF FEE
◦DMF for new API : $ 51,140
◦DMF (domestic) : $ 44234
◦DMF (foreign) : $ 59234

17. THANK YOU