Date: 2020-03-04Category: Not ApplicableState: Union GovernmentCountry: India
Circular regarding disposal of the application of WC for active substances exported to the Eu for medicinal products for Human use in accordance with Acrticle 42(2)
**Executive Summary:**
This circular from the Central Drugs Standard Control Organization (CDSCO) outlines updated procedures for issuing Written Confirmations (WC) for active pharmaceutical ingredients (APIs) exported to the EU. It aims to streamline the process through uniform inspection and document review, emphasizing quality compliance. The circular details application procedures, required documentation (Annexures A & B), and timelines for processing applications.
**Key Points / Main Content:**
* **Application Submission:**
* Applicants must submit applications with supporting documents as per Annexure A (initial WC) or Annexure B (additional product).
* Refer to SOP no. EPINS001 for guidance.
* **Documentation Requirements (Annexure A - Initial WC):**
* Application from Manufacturer
* Site Master File (WHO TRS 961, Annexure 14)
* Original Authorization Letter
* GMP certificate (e.g., WHO, USFDA, EDQM) if any
* Copy of Manufacturing License
* Lists of approved and applied APIs
* List of SOPs and STPs
* Stability studies (3 batches, minimum 6 months)
* Equipment and Instruments list
* Technical Staff list
* Organogram
* Manufacturing Layout Plan
* Validation Master Plan
* Process Validation (3 batches per product)
* Annual Product Review (last 3 years)
* Export data (last 3 years)
* Good Distribution Practices
* Analytical Method Validation
* Market Complaint Review
* Impurity profiling data
* NSQ reports (if any)
* Legal undertaking.
* **Documentation Requirements (Annexure B - Additional Product):**
* Application from Manufacturer for additional product
* Original Authorization Letter
* Name of applied API
* List of approved APIs
* Stability studies (3 batches, minimum 6 months)
* Process Validation (3 batches per product)
* Analytical Method Validation
* Annual product review (last 3 years)
* Export data (last 3 years)
* Market Complaint Review
* Impurity profiling data
* NSQ reports (if any)
* **Processing Timelines:**
* CDSCO Zonal/Sub-Zonal offices forward recommendations to CDSCO HQ within:
* 7 days of complete application if no inspection is required.
* 15 days of complete application if inspection is required.
* CDSCO HQ issues WC within 5 working days of receiving the recommendation.
* **Inspection Requirements:**
* No inspection for first-time applicants holding valid Pharmaceutical Product Certificates (WHO, US FDA, EDQM, TGA) issued within the last 24 months.
* Otherwise, inspection is required as per SOP no. EPINS005.
* Inspections follow Directives 2001/83EC, WHO GMP, or ICH guidelines; report as per SOP no. EPINS004.
* WC issued upon compliance with deficiencies.
* **Additional Product Applications:**
* For firms inspected within two years and compliant with Article 462b of Directives No. 2001/83EC, WC is issued based on Annexure B data.
* **Dynamic Document:** The circular is subject to updates based on developments in the area.
**Impact Analysis:**
* **API Manufacturers/Exporters:**
* *Impact:* Must adhere to the updated application procedures and documentation requirements for obtaining Written Confirmations for API export to the EU.
* *Action Required:* Review and implement the updated procedures, ensure compliance with documentation checklists (Annexures A & B), and meet inspection requirements.
* **CDSCO Zonal/Sub-Zonal Offices:**
* *Impact:* Responsible for processing WC applications, conducting inspections (if required), and forwarding recommendations to CDSCO HQ within specified timelines.
* *Action Required:* Implement the updated procedures for application review and inspection, adhere to processing timelines, and ensure consistent application of standards.
* **CDSCO HQ:**
* *Impact:* Responsible for issuing WC certificates based on recommendations from Zonal/Sub-Zonal offices.
* *Action Required:* Issue WC certificates within 5 working days of receiving recommendations from Zonal/Sub-Zonal offices.
Key Entities Referenced
Central Drugs Standard Control Organization: A national regulatory body in India responsible for the regulation of pharmaceuticals and medical devices.
European Union: A political and economic union of member states located primarily in Europe, a key export market referenced in the context of active pharmaceutical ingredients.
Article 462 b of Directives no. 2001/83/EC: A specific article within a European Union directive concerning medicinal products for human use, outlining requirements for written confirmation of active substance manufacturing.
Active Pharmaceutical Ingredients: The active ingredients used in pharmaceuticals, subject to quality compliance procedures as outlined in the circular.
Written Confirmation: A certificate issued by CDSCO for active substances exported to the EU, confirming compliance with GMP standards.
WHO Good Manufacturing Practices: A set of quality assurance guidelines established by the World Health Organization (WHO) for the production and control of pharmaceuticals.
USFDA: United States Food and Drug Administration.
Dr. V. G. Somani: The Drugs Controller General of India, as indicated by the signature at the end of the circular.
F. No:7-5/2019/Misc/101
Government of India
Directorate General of Health Services
Central Drugs Standard Control Organization
(International Cell)
FDA Bhawan, Kotla Road,
New Delhi - 110002
Dated:- /:\2}nme
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.
In order to streamline the process of issuance of Written Confirmation (WC)
Certificate through a 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 applicant 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 .
g) List of APIs applied for issuance of WC.
h) List of SOPs and STPs
Page 1 of 3Stability 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
/) List of Technical Staff, their Qualification, Experience and approval status&
Organogram.
k) List of Equipment and Instruments
!) Manufacturing Layout Plan.
m) Validation Master Plan.
Process Validation for 3 batches of each Product.
Annual Product Review for last 3 years
Export data for last 3 years
Good Distribution Practices followed by the firm.
Analytical Method Validation
Market Complaint Review.
Data of impurity profiling.
NSQ reports, if any.
Legal undertaking
Checklist for additional Product:(Annexure-B)
Application from Manufacturer for additional product
An Authorization letter in original issued by the Director/Secretary/Partner of
the firm
Name of the applied API
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.
Process Validation for 3 batches of Product
Analytical Method Validation.
Annual product review for last 3 years.
Export data for last 3 years
Market Complaint Review.
Data of impurity profiling.
NSQ reports, if any.
subnitD ii es dp o ts o a Cl D o Sf C a Op p Zl oi nc aa lt i oo rn : S u- b -F zr oo nam l t oh fe f icd ea ste receipt of complete application
ERecommendation 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 3a. When no inspection is required — 07 days of receipt of complete
application
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.
iii. Application for additional product to the 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.
This circular/documentt is to be treated as dynamic for updation as per development in
this area.
Your faithfully,
ao
(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
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