Give the more clear picture about Notified IVD Products regulation in India..!!!

1. CONFIDENTIAL. INTERNAL USE ONLY.
Procedure for Getting the Manufacturing License
of Notified IVDs Products in India
Mayank Saini

2. CONFIDENTIAL. INTERNAL USE ONLY.
Agenda
1
Purpose & Scope
Responsibility
Definitions
Procedure of Getting Mfg. License (Notified IVDs)
Brief Flow Chart of getting the Notified IVD’s Mfg. License
Validity of Manufacturing License
1
2
3
4
5
7
66
Basic difference between Notified and Non notified IVD’s
Manufacturing License.

3. CONFIDENTIAL. INTERNAL USE ONLY.
Purpose & Scope
2
Purpose
This procedure shall
provide the guidelines
and steps to be followed
for the issuance of
Manufacturing License
(Notified & Non- Notified
Products) from the SLA-
FDA
Scope
This document/procedure
shall be applicable for
getting the Manufacturing
License for (Notified &
Non- Notified Products)
of In vitro Diagnostic Kits

4. CONFIDENTIAL. INTERNAL USE ONLY.
Responsibility
3

5. CONFIDENTIAL. INTERNAL USE ONLY.
Responsibility
4
Regulatory Affairs Department shall be responsible for creating or
writing of documents/SOPs as per guidelines described in the Drugs
& Cosmetics Act, 1940 and Rules.
Regulatory Affairs Department and Authorized Signatory of Alere
Medical (Plant) shall be responsible for review of RA related
SOPs to ensure compliance with the Drugs & Cosmetics Act,
1940 & Rules 1945
The Quality Operations Head shall be responsible for approval and
release of SOPs

6. CONFIDENTIAL. INTERNAL USE ONLY.
Definitions
5

7. CONFIDENTIAL. INTERNAL USE ONLY.
Definitions
6
CDSCO: The Central Drugs Standard Control Organization is the national
regulatory body responsible for laying down the standards of drugs, cosmetics,
diagnostics and devices and enforcing the rules of Good Manufacturing Practice
(GMP) in India for manufacturers of Finished Pharmaceuticals Products (FPP) and
Active Pharmaceutical Ingredients (API).
Drug: According to Drugs & Cosmetics Act 1940, a drug can be defined as all
medicines for internal or external use of human beings or animals and all
substances intended to be used for or in the diagnosis, treatment, mitigation or
prevention of any disease or disorder in human beings or animals.
Manufacturing License: Manufacturing License of any drug is the authorization in
writing given by SLA-FDA, to manufacture the same to any drug manufacturing
organization (the licensee) under certain terms and conditions.
In Vitro Diagnostics: In-Vitro Diagnostic Products are those substances that are
intended to be used for or in the use in diagnosis of disease or disorders in human
being or animals. IVDs are considered as “Drugs” as defined under sub-clause (i) of
clause (b) of Section 3 of Drugs and Cosmetic Act 1940.

8. CONFIDENTIAL. INTERNAL USE ONLY.
Definitions
7
Medical Device: According to World Health Organization, ‘Medical device’ mea
ns any instrument, apparatus, implement, machine, appliance, implant, reagent
for in vitro use, software, material or other similar or related article, intended by
the manufacturer to be used, alone or in combination, for human
beings, for one or more of the specific medical purpose(s) of:
• diagnosis, prevention, monitoring, treatment or alleviation of disease,
• diagnosis, monitoring, treatment, alleviation of or compensation for an injury,
• investigation, replacement, modification, or support of the anatomy or of a ph
ysiological process,
• supporting or sustaining life,
• control of conception,
• providing information by means of in vitro examination of specimens derived
from the human body;
& does not achieve its primary intended action by pharmacological, immunologi
cal or metabolic means, in or on the human body, but which may be assisted in
its intended function by such means.

9. CONFIDENTIAL. INTERNAL USE ONLY.
Definitions
8
Test License: Test License is a license issued by SLA-FDA, to a manufacturing firm
stating the authority to manufacture products for evaluation with a purpose of
statement of “Not for sale or Commercial Use”.
Cover Letter: Cover Letter is a letter of introduction which clearly specifies the
purpose for submission of an application to the SLA- FDA, from the company
seeking the issuance of Manufacturing License in this case.
Verification Letter: Verification Letter is a letter sent by inspecting authority to the
SLA-FDA stating the non-conformities present in the inspected firm for further
ensuring the follow up with the same.
Recommendation Letter: Recommendation Letter is a document in which the
inspecting authority assesses the qualities, characteristics, and capabilities of the
firm being recommended in terms of that firm’s ability to perform a particular task or
function here in this case which is the carrying out of manufacturing activities in
compliance with Drugs & Cosmetics Act 1940 & Rules 1945.

10. CONFIDENTIAL. INTERNAL USE ONLY.
India
The Regulatory Process of IVDs approval.
Prior to 2005, no medical device or IVD's regulations existed in
India. However, today there are registration procedures for certain
types and classes of medical devices regulated under the
provisions of the Drugs and Cosmetics Act & Rules.
The Drugs Controller General (India) of Central Drugs Standard
Control Organization (CDSCO) is the Regulatory Authority that
Governs the Import and Manufacturing of IVD Kits/Reagents in
India to ensure the products which are Approved, Manufactured
and Imported are of acceptable Quality, Safety and Efficacy.
9

11. CONFIDENTIAL. INTERNAL USE ONLY.
Classification of IVDs in India
In India CDSCO has classified the IVD kits in the following manner.
10
Classification of IVDs
Notified IVD Devices
Non-Notified IVD
Devices
Non-
Critical
Semi
Critical

12. CONFIDENTIAL. INTERNAL USE ONLY.
Further Classification of Notified & Non-Notified
IVDs
11
Notified
IVDs
1.IVD kits of HIV
2.IVD kits of HCV
3.IVD kits of HBsAg
Non-Notified
IVDs
Semi-critical
1.Cancer Markers
2.Dengue
3.Chikungunya
4.Malaria
5.Typhoid
6.Tuberculosis
Non-Critical
All In-vitro diagnostic Kits
and Reagents that are not
listed under
Notified/Critical IVDs and
Semi- Critical IVDs

13. CONFIDENTIAL. INTERNAL USE ONLY.
“ Medical Devices & IVD’s have been notified as
Drugs and their Notification No. ”
12

14. CONFIDENTIAL. INTERNAL USE ONLY.
Procedure of Getting Manufacturing
License (Notified IVDs)
13

15. CONFIDENTIAL. INTERNAL USE ONLY.
Procedure for Notified IVDs
14
Application on Form 27 of Schedule A of D & C Act 1940 along with a cover letter addressed to SLA-FDA with a copy
to concerned CDSCO Zonal/Sub-Zonal Office & CDSCO (HQ) with certain details.
SLA-FDA, concerned CDSCO Zonal/Sub-Zonal Office & the Drugs Controller General of India CDSCO (HQ) shall
screen the documents.
If (a) query/ queries as per checklist issued by CDSCO shall be generated during the screening process, it will be
apprised in writing to the firm seeking the license.
Once all the queries if any, will be answered by us, the SLA-FDA Haryana will issue a letter to CSDCO (NZ) for their a
vailability for joint inspection at the site of our manufacturing firm
Corresponding communication shall be done between CSDCO (NZ) and SDC-FDA resulting in the fixation of a date
for joint inspection.
Joint inspection shall be conducted by SLA & CDSCO (NZ) under CLAA scheme at the manufacturing site.

16. CONFIDENTIAL. INTERNAL USE ONLY.
Procedure for Notified IVDs
15
After the inspection, the SDCO will generate 4 copies of spot memo out of which one with verification letter will be
sent to the SDC-FDA, one copy would be given to us, the other will be kept by the SDCO & the fourth one shall be
sent to CDSCO (NZ).
SLA-FDA may issue a letter to the us regarding the deficiencies if found during inspection
After the correction of deficiencies, the firm shall apprise the same with documentary proof to SLA-FDA, & they may
issue a verification letter to the SDCO for carrying out another inspection at the site of firm with a copy to CDSCO
(NZ) & DCGI (CDSCO), if required.
SDCO will again pay a visit at the manufacturing site for inspecting the correctness of defects and shall again
generate 4 copies of spot memo, out of which one along with a recommendation letter which is in accordance with
the provision of Rule 79 of D & C Act 1940, shall be sent to the SLA-FDA.
Firm will also be applying a test license for Critical Products on Form 30 to SLA-FDA parallel to Mfg. Lic.
After getting the test license on Form 29, RA shall be intimating in writing all the concerned departments of the firm
about the issuance of the same.

17. CONFIDENTIAL. INTERNAL USE ONLY.
Procedure for Notified IVDs
16
After the manufacturing of the concerned products, RA shall get Quality Certification from QC & QA and on the
basis of the same shall intimate the warehouse Dep't. in writing to dispatch the required number of kits for evaluati
on at authorized government laboratories.
c
Once the evaluation report containing desired results will be generated by concerned authorized laboratories,
application will be sent to SLA-FDA for issuance of manufacturing license
On the basis of the recommendation letter by the SDCO & test report of applied products, NOC issued by CDSCO
the SLA-FDA may issue the Manufacturing License to the applying firm.
c
The whole exercise generally takes 6-9 months depending upon the number of queries, availability of drug officials
and postage issues.
After issuance of the license the conditions of Rule 78 of Drugs & Cosmetics Act 1940 & Rules 1945 should be
fulfilled.
c
After the manufacturing of the concerned products, the same shall undergo stability testing as per Procedure of
QA/042

18. CONFIDENTIAL. INTERNAL USE ONLY. 17
Submit
Application
• Details of Manufacturing
Facility
• Product Dossiers , etc.
Joint Inspection under
CLLA by State &
Central Drug Authority
Approved
NO
Approved Product Evaluation Make 3 Test
Batches
NIB Noida or
NICD, Noida
NO
Apply for Mfg.
License
Audit by Drug Officials Approved
Verification Inspection Lets Have Party..!!!
Brief Flow Chart of getting the Notified IVD’s Mfg. License
NO (Re-Audit)

19. CONFIDENTIAL. INTERNAL USE ONLY.
Validity of Manufacturing License and Fee
18

20. CONFIDENTIAL. INTERNAL USE ONLY.
Validity of Manufacturing License
19
• According to Rule 77 of Drugs & Cosmetics Act 1940, the Manufacturing
License will be valid for 5 years from the date of issuance.
• According to Rule 83 AA of Drugs & Cosmetics Act 1940, if the application
for the renewal of a license is made before its expiry, or within six
months of its expiry, after payment of the additional fee, the license
shall continue to be in force until orders are passed on the application and
the license shall be deemed to have expired if the application for its
renewal is not made within six months of its expiry.

21. CONFIDENTIAL. INTERNAL USE ONLY.
Fees of License & other Cash Deposits
20
Sr. No. Form and Fee Description
1
Category of drugs Drugs specified in Schedule C&C(1) excluding those specified in Sch. X (i) O
wn unit
2 Application Form 27 up to 10 items for each category R: 75(1)
3 License Form of Mfg. Lic 28 (R: 76)
4
Fees for Grant/Renewal
Lic. fee of Rs. 6000 + Insp. fee of Rs1500 for every inspection or for renewal
of license R: 75(1)
5
Penalty after expiry but within
6 months
Rs.6000+Rs.1000 p.m.or part thereof in addition to insp. fee of Rs.1500
R: 75A(1)
6
Fee for addl. item for more th
an 10 item for each category
Rs. 300 per item R: 75(5)
7
Application & License Form
of Test. Lic
Form 30 up to 10 items and issued on Form 29
R: 90 (1-2)

22. CONFIDENTIAL. INTERNAL USE ONLY.
The Regulatory control over notified medical devices is imposed
thorough by this scheme.
Not
Required
Joint
Inspection
Generally joint inspection consist of Following members .
1. Representative from CDSCO
2. Expert From NIB
3. One Drug Officer From Concern State- FDA Office
4. Area Senior Drug Controller Officer
Only Point
3 & 4
Applicable
Stability
Testing
Generally Getting the Notified IVD’s Mfg. License takes of 6-9
Months
30-45 Days
Notified IVD’s Non Notified IVD’s
As per Procedure the Notified IVD products are kept at Accelerated
Stability Study for 60 days.
Time Line
Less then
6 month
Basic difference between Notified and Non notified
IVD’s Manufacturing License.
CLLA
Scheme

23. CONFIDENTIAL. INTERNAL USE ONLY. 22