F. No:7-5/2019/Misc/101 Government of India ; Directorate General of Health Services Central Drugs Standard Control Organization (International Cell)

==> picture [13 x 15] intentionally omitted <==

----- Start of picture text -----<br> @<br>----- End of picture text -----<br>

FDA Bhawan, Kotla Road, New Delhi - 110002 Dated:- 4:\2| nm

To All Zonal /Sub Zonal offices of CDSCO

Circular

Subject: Disposal of the applications of “Written Confirmation” for active substances exported to the EU for medicinal Products for Human use in accordance with Article 46(2) (b) of Directives no. 2001/83/EC — Reg.

for active

in order to streamline the process of issuance of Written Confirmation (WC) Certificate through @ uniform procedure of inspection and review of documents, it has been decided to adopt following updated procedures by the inspectorate in CDSCO Zonal/Sub-Zonal offices with primary focus towards quality compliance for Active Pharmaceutical ingredients (AP).

For issuance of WC for the purpose of grant/renewal or issuance of additional product:

• A. - The applican: shall submit the application along with supporting document & details given in checklist (Annexure A) & Checklist for additional Product (Annexure B), as per the guidance in the SOP no. EP-INS-001 (Procedure for issue of “Written Confirmation” for active substances exported to the EU for medicinal Products for Human use in accordance with Article 46(2) (b) of Directives no. 2001/83/EC)

Checklist (Annexure-A):

• a) Application from Manufacture

• b) Site master file (as specified under WHO TRS 961, Annexure 14)

• c) An Authorization letter in original issued by the Director/Secretary/Partner of the firm

• d) Copy of GMP certificate issued as Certificate of Pharmaceutical product issued as per WHO guidelines, USFDA, EDQM etc., if any

• e) Copy of Manufacturing license.

• f) List of Approved APIs.

==> picture [2 x 2] intentionally omitted <==

----- Start of picture text -----<br> ,<br>----- End of picture text -----<br>

• g) List of APIs applied for issuance of WC.

• h) List of SOPs and STPs

Page 1 of 3

:

• i) Stability studies of 3 batches for minimum 06 months for accelerated and @ real time studies along with stability protocol and commitment List of equipment and Instruments

• j) List of Technical Staff, their Qualification, Experience and approval status& Organogram.

• k) List of Equipment and Instruments

• 1. Manufacturing Layout Plan.

• m) Validation Master Plan.

• n) Process Validation for 3 batches of each Product.

• 0. Annual Product Review for last 3 years

• p) Export data for last 3 years

• q) Good Distribution Practices followed by the firm.

• r) Analytical Method Validation

• Ss) Market Complaint Review.

• t) Data of impurity profiling.

• u) NSQ reports, if any.

• v) Legal undertaking

Checklist for additional Product:(Annexure-B)

• a) Application from Manufacturer for additional product

• b) An Authorization letter in original issued by the Director/Secretary/Partner of the firm

• c) Name of the applied API

• d) List of API approved

• €) Stability studies of 3 batches for minimum 06 months for accelerated and real time studies along with stability protocol and commitment.

• f) Process Validation for 3 batches of Product

• g) Analytical Method Validation.

• h) Annual product review for last 3 years.

• i) Export data for last 3 years

• j) Market Complaint Review.

• k) Data of impurity profiling.

• !) NSQ reports, if any.

• B. Disposal of application: - From the date receipt of complete application submitted to CDSCO Zonal or Sub-zonal offices

• i. Recommendation for issuance/further compliance /rejection of WC by the CDSCO Zonal or Sub-zonal office shall be forwarded to CDSCO(HQ) as per the following timeline:

Page 2 of 3

• a. When no inspection is required — 07 days of receipt of complete application

==> picture [24 x 37] intentionally omitted <==

----- Start of picture text -----<br> ;<br>.<br>€<br>----- End of picture text -----<br>

b. When inspection is required — 15 days of receipt of complete application ii. Based on the recommendations of Zonal/Sub Zonal Heads, CDSCO (HQ) shall issue WC within 5 working days of the receipt of the recommendation.

Cc.

First time Applicant for WC certificate:

No inspection is required, if firm is holding valid Certificate of Pharmaceutical Product issued as per WHO guidelines or US FDA or EDQM/TGA certificates (not more than 24 months old). If the company does not have any of these, then inspection to be conducted. Inspection shall be planned by officers of Zonal or Sub-zonal as per SOP no. EP-INS-005 after review of documents submitted under Annexure A. Inspection shall be carried out as per the guidelines laid down in SOPs and checklist in accordance with Article 46(2)(b) of Directives No. 2001/83/EC: GMP requirements as per Directives 2001/83/EC or WHO Good Manufacturing Practices (GMP) for Active Pharmaceutical Ingredients or Good Manufacturing Practice for Active Pharmaceutical Ingredients as per ICH guideline and report shall be prepared as per SOP no. EP-INS-004. WC certificate shall be issued when the firm had made necessary compliance to the deficiencies observed during such inspection, (if any) as per procedures laid down in SOP no. EP-INS-005. for additional product to the WC WC Certificate: For those firms which have been previously inspected within two years by officers of CDSCO zonal or sub-zonal and found to comply with requirements of Article 46(2)(b) of Directives No. 2001/83/EC: GMP requirements as per Directives 2001/83/EC or WHO Good Manufacturing Practices (GMP) for Active Pharmaceutical Ingredients or Good Manufacturing Practice for Active Pharmaceutical Ingredients as per ICH guideline, WC certificate shall be issued on providing the complete data of products as mentioned in Annexure B.

iii. Application for additional product to the WC WC Certificate:

This circular/documentt is to be treated as dynamic for updation as per development in this area.

Your faithfully, eo (Dr. V. G. Somani) Drugs Controller General (India)

Copy for information to :

1. Stakeholders CC: Joint Secretary (R), MoHFW, Govt. of India, Nirman Bhawan, New Delhi

Page3 of 3