Procedure for getting the manufacturing license of notified IVDs Products in India

CONFIDENTIAL. INTERNAL USE ONLY.

Procedure for Getting the Manufacturing License of Notified IVDs Products in India

Mayank Saini

CONFIDENTIAL. INTERNAL USE ONLY. 2

Agenda

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

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Basic difference between Notified and Non notified IVD’s Manufacturing License.


Purpose & Scope

PurposeThis procedure shall provide the guidelines and steps to be followed for the issuance of Manufacturing License (Notified & Non- Notified Products) from the SLA-FDA

ScopeThis document/procedure shall be applicable for getting the Manufacturing License for (Notified & Non- Notified Products) of In vitro Diagnostic Kits


Responsibility


Responsibility

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


Definitions


DefinitionsCDSCO: 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..


Definitions

Medical Device: According to World Health Organization, ‘Medical device’ means any instrument, apparatus, implement, machine, appliance, implant, reagent for in vitro use, software, material or other similar or related article, in-tended 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

physiological 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, immunolog-ical or metabolic means, in or on the human body, but which may be assisted in its intended function by such means.


Definitions

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.


IndiaThe 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.

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Classification of IVDs in India In India CDSCO has classified the IVD kits in the following manner.

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Classification of IVDs

Notified IVD Devices Non-Notified IVD Devices

Non-Critical

Semi Critical


Further Classification of Notified & Non-Notified IVDs

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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


“ Medical Devices & IVD’s have been notified as Drugs and their Notification No. ”


Procedure of Getting Manufacturing License (Notified IVDs)


Procedure for Notified IVDs 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 availability 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.


Procedure for Notified IVDsAfter 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 CD-SCO (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.


Procedure for Notified IVDs

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 evalua-tion at authorized government laboratories.

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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.

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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.

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After the manufacturing of the concerned products, the same shall undergo stability testing as per Procedure of QA/042


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 orNICD, 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)


Validity of Manufacturing License and Fee


Validity of Manufacturing License

• 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.


Fees of License & other Cash Deposits

Sr. No.

Form and Fee Description

1Category of drugs Drugs specified in Schedule C&C(1) excluding those specified in Sch. X (i)

Own unit

2 Application Form 27 up to 10 items for each category R: 75(1)

3 License Form of Mfg. Lic 28 (R: 76)

4Fees for Grant/Renewal

Lic. fee of Rs. 6000 + Insp. fee of Rs1500 for every inspection or for renewal of license R: 75(1)

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Penalty after expiry but within 6 months

Rs.6000+Rs.1000 p.m.or part thereof in addition to insp. fee of Rs.1500R: 75A(1)

6Fee for addl. item for more

than 10 item for each categoryRs. 300 per item R: 75(5)

7Application & License Form

of Test. LicForm 30 up to 10 items and issued on Form 29

R: 90 (1-2)


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 CDSCO2. Expert From NIB3. 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


Healthcare

Procedure for getting the manufacturing license of notified IVDs Products in India