NMRA

Regulatory overview

Definition

“Borderline products” are products having combined characteristics of medicines along with foods, medical devices or cosmetics. The following criteria shall be taken into consideration when evaluating borderline products for registration

• The intended use of the product (or its primary function) and its mode of action
• The therapeutic claims made by the manufacturer regarding the product in terms of its ability to treat or prevent diseases
• Pharmacologically active substance(s), if any, used in the product.
• The concentration of the active substances
• The level of efficacy of the active substance of the product
• The ingredients used and the concentrations at which they are used.

According to the National Medicines Regulatory Authority Act No. 05 of 2015 the National Medicines Regulatory Authority shall be responsible for the regulation and control of registration, licensing, manufacturing, importation and all other aspects pertaining to borderline products; The Borderline Products Evaluation Committee (BPEC) will carry out the technical evaluation of products submitted for registration and assist the Authority to regulate and control all aspects pertaining to borderline products.

Scope and Responsibilities of the NMRA in the approval of borderline products

The National Medicines Regulatory Authority (NMRA) is responsible to build a healthier nation by ensuring the availability of quality and safe borderline products in Sri Lanka. As such all products which may come under Borderline Product category should be registered with the Authority.
All foreign borderline products manufactures should submit application for registration through a Marketing Authorization Holder (local agent) in Sri Lanka who shall be responsible for the registration, licensing, importation, sale and distribution, handing of quality failures and all aspects pertaining to the particular borderline product in Sri Lanka.

Scheduling criteria of Borderline products depending on the level of risk

Borderline products have been classified to three schedules by the BPR division in the registration process depending on the level of risk and to make sure the awareness of the general public regarding the level of risk of such products.

How to register your product

The product registration process is in two steps:

I. Preliminary Evaluation (Product Classification) –Valid period (only 1 year)

II. Product Registration- Valid period (1 year, 2 year or 5 years)

Local Agent Profile Creation / Local Manufacturing Profile Creation and obtaining a Preliminary Evaluation Report (Product Classification Report) are mandatory requirements to initiate the product registration process and application submission should be done through eNMRA facility. Before the preliminary evaluation, local agent / local manufacturing profile creation is a main requirement. (via eNMRA platform). Except Preliminary Evaluation (Product Classification) and profile creation all the other applications should be submitted manually.

Currently this process (Local Agent Profile Creation / Local Manufacturing Profile Creation) has been hold temporally due to online system failure and all the submissions should be done manually.

Steps in Borderline product registration:

1. Preliminary evaluation (product classification)

2. Obtaining formulation approval (applicable only for local manufacturers) or sample import license (applicable only for foreign manufacturers)

3. Product registration (Local / Foreign)

Process of registration.

1.0 Required documents for “Preliminary evaluation (Product Classification)” under Borderline Product Category
1. Covering letter including contact details of the local agent (e-mail address, contact numbers, address/s)
2. Copy of Letter of Authorization from the manufacturer which addressed to Director General / CEO , NMRA ((If more than one local agent present for a manufacturer, the list of local agents appointed by the manufacturer and approved product list - for local agents only)
3. Formulation * (Batch manufacturing formula)
4. Valid copy of Free Sale Certificate (FSC) /Certificate of Pharmaceutical product (COPP) / or a certificate to prove the registration status in country of origin (Not applicable for locally manufactured products)
5. Copy of Certificate of Analysis for Finish Product
6. Specimen colored label, Packaging materials (art work acceptable)
7. Legible product information leaflet
8. Patient information leaflet, Promotional materials (If applicable only)
* All applicants who submit applications under Borderline products should submit the composition of unit dose along with the batch manufacturing formula.

Vitamins and minerals should be provided according to the “Guideline on Product categorization Reference details of Vitamins & Elements” publish in the NMRA website under borderline product category. (Units and form of vitamin & minerals)
Examples:
• Elemental –Sodium (Sodium should be given as “Na” but not as “NaCl”)
• Vitamins-Vitamin A (Vitamin A should be given as “ vitamin A” but not as “ retinol’)
• Units- Vitamin D in μg/day, Zn in mg/day)
Refer the Borderline Product Guideline - “Guidance Document on definitions and information for applications submitted under Borderline Product category”
For further Information click here

All noncompliant applications will be rejected with effect from 13th of July 2020.
After the classification process, Classification Report will be issued. Validity period of Preliminary Evaluation Report (Classification Report) is one year and product registration process should be initiated within the validity period of the Classification Report.

2.1 Required documents for obtaining the formulation approval (Only for Local Manufacturers)
1. Preliminary evaluation report (Classification Report)
2. Covering letter
3. Formulation (Master formula & Batch manufacturing formula)

2.2 Required documents for obtaining the Sample Import License (for imported products)
1. Preliminary Evaluation Report (Classification Report) issued by NMRA
2. Application for a License to import a limited quantity of any borderline product(s) for testing, examination, distribution, sample analysis or clinical trial
3. Copy of Business Registration Certificate.
4. Copy of Letter of Authorization from the manufacturer which addressed to Director General / CEO, NMRA (If more than one local agent present for a manufacturer, the list of local agents appointed by the manufacturer and approved product list).
5. Catalogue (If applicable only)
6. Valid Copy of Free Sale Certificate (FSC) /Copy of Certificate of Pharmaceutical Product (COPP)
7. Specimen colored label and packaging materials

3.0 Required documents for product registration
3.1 Local Manufactured products
1. Acknowledgment form – 02 copies
2. Declaration letter
3. Borderline Classification Report issued by NMRA
4. Formulation approval letter – for new registration
5. Previous Registration certificate – for re registration
6. Maximum retail price
7. Business registration certificate
8. Wholesale License (If available).
9. GMP report or GMP certificate for manufacturing site
10. ISO certificate ( If GMP certificate is not available)
11. Manufacturing license
12. Registration certificates of other countries ( If available)
13. Finish product test specifications
14. Certificate of analysis for finished Product ( Original)
15. Certificate of Analysis of Active Pharmaceutical Ingredient (API)
16. API GMP compliance certificates (If applicable)
17. Certificate of Analysis of excipients
18. Manufacturing formula with batch size and master formula with function of each ingredient
19. Manufacturing process with process flow diagram clearly
20. Manufacturing process validation report for three consecutive commercial batches (If applicable only)
21. Analytical validation report (if applicable only)
22. Stability data for 3 commercial batches (Real time and accelerated data) – Original documents ( If applicable only)
23. Specifications & Certificates of Analysis of Packaging materials
24. Product Information Leaflet
25. Patient Information Leaflet (If applicable only)
26. Efficacy data ( If applicable only)
27. Packaging materials- Specimen colored label & six side displayed secondary package (If applicable only)
28. Promotional Material (If applicable only)
29. Two samples
30. Post marketing data (If applicable only)
31. Published Clinical trial data for finish product (If applicable only)
32. Catalogue (If applicable only)

3.2 For Imported Products
1. Acknowledgment form – 02 copies
2. Declaration letter
3. Letter of Authorization from the manufacturer which addressed to Director General / CEO, NMRA (If more than one local agent present for a manufacturer, the list of local agents appointed by the manufacturer and approved product list)
4. Borderline Classification Report issued by NMRA
5. Sample Import License – for new registration
6. Previous Registration certificate – for re registration
7. Maximum retail price
8. Business registration certificate
9. Wholesale License (If available)
10. Valid original of Free Sale Certificate (FSC) /Certificate of Pharmaceutical product (COPP) / or a certificate to prove the registration status in country of origin
11. GMP report or GMP certificate for manufacturing site
12. ISO certificate ( If GMP certificate is not available)
13. Manufacturing license
14. Registration certificates of other countries ( If available only)
15. Finish product test specifications
16. Certificate of analysis for finished Product (Original)
17. Finish product test specifications (If applicable only)
18. Certificate of Analysis of API
19. API GMP compliance certificates (If applicable only)
20. Certificate of Analysis of excipients
21. Manufacturing formula with batch size and master formula with function of each ingredient
22. Manufacturing process with process flow diagram clearly
23. Manufacturing process validation report for three consecutive commercial batches (If applicable only)
24. Analytical validation report (if applicable only)
25. Stability data for 3 commercial batches (Real time and accelerated data) – Original documents – (If applicable only)
26. Specifications & Certificates of Analysis of Packaging materials
27. Product Information Leaflet
28. Patient Information Leaflet (If applicable only)
29. Efficacy data ( If applicable only)
30. Packaging materials- Specimen colored label & six side displayed secondary package (If applicable only)
31. Promotional Material (If applicable only)
32. Two samples
33. Post marketing data (If applicable only)
34. Published Clinical trial data for finish product (If applicable only)
35. Catalogue (If applicable only)

Refer –
• Borderline Product Guideline – “Guidance Document on definitions and information for applications submitted under Borderline Product category”

• F-BPR-01 Assessment form Registration Application
For further Information click here

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Classification

Required documents for “Preliminary evaluation (Product Classification)” under Borderline Category National Medicines Regulatory Authority

1.Covering letter including contact details of the local agent (e-mail address, phone numbers,
address)
2. Copy of Letter of Authorization from the manufacturer which addressed to Director General,
NMRA
3. Formulation (for a device-not applicable)
4. Copy of Free Sale Certificate /COPP/ or a certificate to prove the registration status in
country of origin (Not applicable for local manufacturer)
5. Copy of Certificate of Analysis for Finish Product
6. Specimen colored label, Packaging materials (art work acceptable)
7. Clinical evidences for claims
8. Legible product information leaflet
9. Patient information leaflet, Promotional materials (If applicable)

All applicants who submit applications under Borderline products should submit the composition of unit dose along with the batch manufacturing formula.

Amount of all active ingredients per unit dose should be given in the form of vitamin or mineral and units according to the "Guideline on Product categorization Reference details Vitamins &
Elements & quot;

Examples:
o Minerals in elemental level (Na but not as Sodium chloride)
o Vitamins (Vitamin A but not as retinol, beta-carotene, etc)
o Units (Vitamin D in μg/day, Zn in mg/day)

All noncompliant applications with above will be rejected with effect from 13th of July 2020.

Validity period of Preliminary Evaluation Report (Classification report) is one year and product registration dossiers should be submitted within the validity period of the Classification report.

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Approval of Manufacturig sites

‍Approval of Foreign Manufacturing Facilities

Introduction & Scope:

The process applies for overseas manufacturing sites who intended to get marketing authorization for their products in Sri Lanka. The procedure includes a desk review of essential documents including the site master file. A GMP inspection of the site may be necessary before approval of the site.

A foreign manufacturer who wants to register products in Sri Lanka needs to appoint a Sri Lankan business entity as its local authorized agent. The local agent will furnish applications on behalf of its principal company, the foreign manufacturer. A separate application needs to be submitted to each manufacturing site from which the manufacturer plans to export products to Sri Lanka.

Application has to be submitted online via NMRA’s web portal eNMRA which requires uploading of essential information and documents to enable a desk review. If all documents indicate fulfilment of NMRA requirements, the next step would be to carry out a GMP inspection of the facility. The NMRA Act, No. 5 of 2015 (section 51) & regulations 2 to 10 of part I of medicines regulations pronounce the legal requirements. The NMRA would exempt onsite GMP inspection if the particular site had been inspected by a stringent NRA or WHO, in terms of regulation 24 of the medicines regulations. After these procedures, an approved foreign manufacturer can submit an application for marketing authorization of its products through the local agent.

Flow Chart- Foreign Manufacturing Site Approval

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Licensing of Local Manufacturing facilities

The process applies for local manufacturing sites who intended to get marketing authorization for their products in Sri Lanka. The procedure includes a desk review of essential documents including the site master file and several GMP Inspections.

A local manufacturer who wants to register products in Sri Lanka needs to furnish applications regarding his manufacturing facilities. A separate application needs to be submitted to each manufacturing site.

Application has to be submitted online via NMRA’s web portal eNMRA which requires uploading of essential information and documents to enable a desk review and GMP Inspections.

The NMRA Act, No. 5 of 2015 (section 51) & regulations 26 to 30 of part II of medicines regulations pronounce the legal requirements.

After these procedures, an approved Local manufacturer can submit application for formulation approvals.

After obtaining the formulation approval and GMP approval for commercial manufacturing of the facility, local manufacturer can apply for the product registration. After that, local manufacturer can apply for the manufacturing license.

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Stages for beginners;

Local manufacturer’s profile creation
Approval of the proposed layout of the manufacturing plant
Initial land inspection (optional)
Approval for the formulations
Initial building inspection -during the construction (Optional)
Inspection of the plant before installing the manufacturing equipment and machineries after completion of construction of the building
Application to request inspection of the plant after completion of the installment of manufacturing equipment and machineries including necessary qualifications (Complete SMF)
Approval of the manufacturing facility (Licensing of manufacturing site)
Inspection of the plant to get approval for commercial batch manufacturing (GMP Inspection)
Application for GMP certificate (Optional)
Application for product registration
Application to get manufacturing licenses for individual products
Application to get COPP/FSC (Optional)

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Site Master Files

Site Master Files are submissions to NMRA used to provide confidential, detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of Medicines, Medical Devices, Borderline products and cosmetics.

Guidance for Site master Files

References:

WHO guideline for drafting a site master file, Annex 14, WHO TRS No. 961, 2011
Explanatory notes for pharmaceutical manufacturers on the preparation of a site master file; PE 008 – 4, 1 January 2011, Pharmaceutical Inspection Co-operation Scheme (PIC/S)

Good Manufacturing Practices (GMP)

Good manufacturing practice (GMP) is that part of quality assurance which ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by the marketing authorization.

The National Medicines Regulatory Authority Act No. 5 of 2015 interprets GMP guidelines as ‘good manufacturing guidelines issued by the World Health Organization’. As such, the National Medicines Regulatory Authority (NMRA) adopts the WHO GMP guidelines along with its subsequent updates for the purpose of regulation of pharmaceutical manufacture. The manufacturers are expected to adhere to the Good Manufacturing Practices throughout their activities.

Pharmaceutical manufacturers who intend to apply for marketing authorization in Sri Lanka may be subjected to one or several GMP inspections prior to their site approvals.

GMP Guidelines available on WHO website:

https://www.who.int/teams/health-product-and-policy-standards/standards-and-specifications/norms-and-standards-for-pharmaceuticals/guidelines/production

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WHO good manufacturing practices for pharmaceutical products: main principles:

https://www.who.int/medicines/areas/quality_safety/quality_assurance/TRS986annex2.pdf?ua=1

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WHO good manufacturing practices for sterile pharmaceutical products:

https://www.who.int/docs/default-source/medicines/norms-and-standards/guidelines/production/trs961-annex6-gmp-sterile-pharmaceutical-products.pdf?sfvrsn=61682f0c_0

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WHO good manufacturing practices for biological products:

https://www.who.int/publications/m/item/annex-2-WHO-gmp-for-biological-products

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Guidelines

Guideline on Approval of an Overseas Manufacturing Plant of Medicines

Guideline on Preparation of Site Master Files

Guideline for preparation and conduct of the GMP inspection

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Report Adverse Events

Healthcare professional such as doctors, dentists, pharmacists and nurses are encouraged to report suspected adverse events encountered in their day to day practice.

Using the ADR google form given by the following link here, you can report Adverse Events.

Adverse Drug events reporting

Address

Director General / CEO

National Medicines Regulatory Authority,

No: 120,

Norris Canal Road,

Colombo 10.

Telephone

+94 112 698 896, +94 112 698 897

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Fax

+94 112 689 704

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A copy of the form shall be forwarded to Adverse Drug Reaction Monitoring Unit of the Department of Pharmacology, Faculty of Medicine, University of Colombo, Kynsey Road, Colombo 08. (TP/ Fax: +94 112 697 483).

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Importance of Reporting Adverse Events

When a new chemical entity (NCE) is first marketed, it would have been tested only in a limited number of patients/volunteers. Rare adverse drug reactions/events could be identified only after the drug is marketed and used by a much larger population. Safety information in use in special groups such as children, elderly, pregnant women etc. are not often available at the time of first marketing of a new drug.

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Advertisements & Promotions

The Advertising Evaluation Sub Committee of the NMRA regulates advertisements - printed and electronic material - related to medicines, devices, borderline products to ensure such advertisements are ethical, accurate and appropriate.

Working definition & general rules

Advertisement includes any representation by any means whatsoever, for the purpose of promoting directly or indirectly the manufacture, sale or disposal of any medicine, medical device, borderline product.

Any person who wishes to advertise or promote a medicine, medical device, borderline product should get prior written approval of the Authority to do so.
Medicines, medical devices, borderline products should not be advertised or promoted to the general public for the treatment, prevention or cure of any of the prescribed diseases, disorders or abnormal physical states.

Our Scope & Responsibility

Provide standards and general requirements that must be adhered to when producing commercials, infomercials and public service announcements, which are relevant to medicines, medical devices, and borderline products.
Scrutinize each advertisement and ensure it complies with the advertisement guidelines that are published in the NMRA website before granting approval or rejecting an application.
Provide assistance to applicants regarding general interpretation of advertising guidelines related to medicines, medical devices, and borderline products prior to advertise.

Procedure for applying approval for advertisements

All the applicants who which to obtain approval for the advertisement on medicines, medical device and borderline products should be followed below procedure.

1. Submit the duly filled application (Please mention email address correctly for sending evaluation sheet) along with copy of valid registration certificate, story board of the advertisement to the accepting counter on every Friday (From 9.00 am to 3.30 pm)for obtaining the payment note for processing fee (1000USD).

2. Payment Receipt issued by account division should be submitted to NMRA after the payment along with the application with following documents to accepting pharmacist (Every Friday from 9.00 am to 3.30 pm). Application should be submitted in a file. Accepting pharmacist accepts the application and assign a reference number.

Documents Needed to be enclosed with the application :-

Duly filled and signed application
Copy of the valid registration certificates
3 sets of printed copies/story board of the advertisement (If advertisement is containing any sound/ video, story board and 2 CD s including the video clip or sound clip need to be submitted)
Supportive documents (Clinical data, test report etc.) for proving any claims

3. All the applications will be tabled to the committee (Once a month) and evaluation reports will be emailed to the applicants.

4. Approved letters can be collected from the issuing counter.in the advertisements

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Applicants should consider the following when designing an advertisement: