Sahithya K S et al /J. Pharm. Sci. & Res. Vol.

12(9), 2020, 1150-1161

Regulatory Pathway for Registration and Approval of Indian

Drug Products in Overseas Market.
Sahithya K S1, Kumar D S 2, Madhavi B L R3, Divakar Goli4, Shanthakumar G S5.
1
Sahithya K S, M.Pharmacy- Drug Regulatory Affairs, Acharya and B M Reddy College of Pharmacy, Soladevanahalli, Bengaluru,
Karnataka, India. Pin code: 560107
E-mail ID: sahithyausha23@gmail.com
2
Kumar D S- Chief Operating Officer- Clear Labs. #377, 16th Cross Kirloskar layout Opp Sapthagiri College Bangalore-560073.
3
Madhavi B L R- Assistant Professor- Department of Pharmaceutics, Acharya & BM Reddy College of Pharmacy, Bengaluru.
4
Divakar Goli- Professor and Consultant, Bengaluru
5
Shanthakumar G S- Professor, HOD- Regulatory Affairs and Dean- Industry Relations, Acharya & BM Reddy College of Pharmacy,
Bengaluru.

Abstract:
Pharmaceutical products in India are being regulated under Drugs and cosmetics act, 1940 and rules 1945. India, mainly a
generic hub and leading supplier of generic drugs worldwide, contributes to 70% of the market. Indian pharmaceutical
exports include Intermediates, Drug formulations, API, Bulk drugs, Herbals, Biologics and Surgical. Registration of
Pharmaceutical product or a drug is a process or a system where it subjects to evaluation of certain documents and need to
conform to standards for approval thereby getting authority to sell in the particular market. This article covers the processes
involved and requirements like import export code, technical documentation, filing and reviewing process of drug master
file, certificate of pharmaceutical product, common technical document (CTD), eCTD and ACTD, for the registration and
approval of Indian drug products in overseas market.
Key Words: Import Export Code, DMF, LOA, CTD, eCTD, Electronic Submission Gateway.
ABBREVIATIONS:
1. R & D- Research and Development.
2. API- Active Pharmaceutical Ingredient.
3. ICH- International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use.
4. WHO- World Health Organization.
5. IEC- Import Export Code.
6. DGFT- Directorate General of Foreign Trade.
7. GMP- Good Manufacturing Practices.
8. CTD- Common Technical Document.
9. eCTD - Electronic Common Technical Document.
10. ACTD- ASEAN Common Technical Dossier.
11. COA- Certificate of Analysis.
12. DCGI- Drug Controller General of India.
13. ADC- Assistant Drug Controller.
14. COPP- Certificate of Pharmaceutical Product.
15. DMF- Drug Master File.
16. MFR- Master Formula Record.
17. BMR- Batch Manufacturing Record.
18. BA/BE- Bioavailability/ Bioequivalence.
19. NDA- New Drug Application.
20. ANDA- Abbreviated New Drug Application.
21. LOA- Letter of authorization.
22. OTC- Over the counter drugs.
23. ESG- Electronic Submission Gateway.

INTRODUCTION: 3. Low cost of production and increasing expenses on R

India comes under Asian market. India, mainly a generic & D [2].
hub is the leading supplier of generic drugs worldwide (20 Indian pharmaceutical exports like Intermediates, Drug
to 22 per cent of global volume). Indian pharma sector is formulations, API, Bulk drugs, Herbals, Biologics and
the third largest by means of volume and thirteen largest Surgical. Registration of Pharmaceutical product or a drug
by means of value. India is the leading country in global is a process or a system where it subjects to evaluation of
manufacturing and research hub for generic medicines certain documents and need to conform with standards for
which contribute 70% of the market [1]. approval thereby getting authority to sale in that particular
Advantages for Indian Pharmaceutical Industry, market or area [3].
1. E government policies like Government of India’s Not only Indian drugs, each and every pharmaceutical
pharma vision 2020, which is having prior objective products needs to be registered and approved by the
to make India a global leader in complete drug regulatory authority. Before the products needs to be
manufacturing. registered, the manufacturing company needs to be
2. Increasing investment by private sector for R & D. registered and licensed for the same.

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Overseas markets means the foreign countries, these TABLE 1- Total export of medicinal and
countries we call in regulatory affairs as markets. They are pharmaceutical products in India.
classified as, Year Export (Rupees in crore)
i. Regulated markets (For example: USA, Canada, 2013-14 90,356.00
Europe, Australia, Japan) 2014-15 94,350.00
ii. Semi regulated markets (For example: Asian, 2015-16 1,10,522.77
ASEAN, Gulf countries, African countries etc.) 2016-17 1,12,915.48
The registration requirements will differ from country to
country. Regulated markets have stringent regulations PROCEDURE FOR EXPORT OF
which is harmonized by ICH. But the semi regulated PHARMACEUTICAL PRODUCTS
countries does not have stringent regulation but asks for Indian products needs to be registered and approved prior
general requirements related to drug product and drug to export. Export means selling of the drugs and
substance. But the regulated markets have their own pharmaceuticals to other countries without trade barrier
checklist for drug substance, drug product etc. [3]. and crossing the geographical frontier.
While filing an application for regulated market, one has Rules and acts responsible [6]
for import and export of
to read and comply with the guidelines as per the country pharmaceutical products :
requirements related to documents required, language, 1. Drugs and Cosmetics act, 1940 and Rules, 1945.
packaging and labelling instructions etc. 2. The Drugs (Prices Control) order, 1995.
So that the company should carefully prepare the 3. Medicinal and Toilet Preparation act, 1956.
documents and files while registering in each country. For 4. Pharmacy act, 1948
all these preparation, regulatory affairs team plays an 5. Narcotic and Psychotropic Substances act, 1985.
important and significant role and acts as link or 6. Drugs and Magic Remedies act, 1954.
connection between pharma industry and the regulatory Documents required for export of drugs from India:
bodies. Registration of the drug does not require more 1. Covering letter.
documents and time, it is immediate process it takes 2. Import export code Number (IEC) given by
maximum 6 months, minimum 1 month. Whereas DGFT.
approval takes more than 6 months and even a year also 3. Purchase order.
depending upon the country, dossier review process and 4. Manufacturing license.
queries. 5. Performa invoice.
So we can say registration is easy and approval process is 6. Indent.
difficult because registering a drug product is nothing but 7. Custom clearance certificate.
recoding the name of the product in official list just to 8. Registration certificate.
identify that drug product. Whereas approval is nothing 9. Certificate of Analysis (COA).
but saying that the drug product is safe and effective for 10. GST
intended disease and acceptable for human use in terms of 11. Consignment sample.
quality, safety and effectiveness. 12. Pre-shipment sample.
As mentioned above, regulated and semi regulated 13. Department of Economic Affairs [7].
markets are there. Here in some countries like south East Flow chart for export of pharmaceutical products from
Asian countries, applicant can sale the drug product once India: The figure below explains about the steps involved
the product is registered. But in western countries, in export of pharmaceutical products from India.
applicant needs to get approval (Marketing authorization) Apply for IEC number
prior to sale the drug product. For this they might come for
GMP inspection/ audit etc.
Regulated countries have clear cut guidelines and one
Register your product
should comply with that. To approve the drug in overseas
market people think only the 5 modules of CTD are
important but some legal formalities are there which the
proprietor will consider as important for export purpose. In Get the approval for export from DCGI
general people knows only about the CTD module but
beyond that things which we don’t know which is
mandatory to know by the proprietor.
India is one of the highest number of USFDA approved Finalize the shipping method
plants. Indian drugs are exporting to more than 200
countries [4]. For the Registration, approval and Export of
drugs from India to overseas market one has to understand
and comply with the Drugs and Cosmetics Act 1940 and Receive the purchase order and prepare for commercial invoice
Rules 1945.
Total export of medicinal and Pharmaceutical
products in India [5]: The below table demonstrates the
FIGURE 1. Flow chart for export of pharmaceutical
total export of products in rupees year wise.
products from India

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Steps involved in export of Pharmaceutical products: Documentation is the Essential and crucial part in any of
1. Apply for IEC number. the company. In pharma we can say “If it is not
2. Get the customers means contact the countries documented, it has not done”. Documentation is an
interested in importing the drug. evidence to show or to prove that the things have done
3. Register the drug product in the country where accordingly. Quality assurance documents are the heart of
you are going to export. the company.
4. Get the DCGI approval for exporting. Technical documents are
5. Finalize the shipping method.
6. Receive the purchase order from the country  Master Formula Record (MFR).
which is importing and send invoice with  Batch Manufacturing Record (BMR).

complete product details.
7. Sign the contract with the agency of the Batch Packaging Record (BPR).
importing country.
8. Pre-shipment inspection.
 Certificate of Analysis (COA).
9. Export of the product.  Certificate of Pharmaceutical Product (COPP).
Requirements to apply for IEC:
• Current bank account
 Product specifications.
While registering the Indian product in overseas
• Pan card market RA team should be carefully check, verify all
• IEC Application fee receipt (Rs.250) the documents for the genuinity, quality and
 IEC number given to an applicant will be remain uniformity from batch to batch and to avoid delay in
same for all the branches/ division. the approval process.
 When exporting to Overseas markets one should be
carefully manufacture the products and comply with Documentation flow chart:
all the standards of the importing country without fail
in production, packaging, labelling instructions as Formulation and development
approved by the importing country.
 Inspection is done at various stages of the
manufacturing. The exporter should register his/ her Technology transfer
facility/ unit as “Export worthy”.
 Inspection will be done the approved and notified Master Formula Record
export inspection agency time to time and Inspection
reports should be maintained carefully.
Once the applicant get order copy and confirmed invoice
the product is ready to export but before that an important
stage has to pass that is Quality control pre-shipment
inspection. Once the product is ready for dispatch it has to Scale up batch
be inspected by the Assistant Drug Controller (ADC) and
should get ADC clearance certificate. ADC will verify all
commercial documents such as,
 Copy of commercial invoice.
 Copy of letter of credit. Batch Manufacturing Record
 Details of packaging specifications.
 Copy of contract order. FIGURE 2. Documentation Process-Flowchart.

 License. Master Formula Record (MFR):

 Certificate of Pharmaceutical Product (COPP) MFR is a master document which contains detailed
information about the product, process etc. MFR is
 Certificate of Analysis (COA). prepared by the Formulation and Development team which
 Pre-shipment sample.
is called technology transfer. By this master document
BMR and BPR prepared.
On the time of export, ADC will verify all the necessary
Contents of MFR:
documents and check the Samples given. Usually the ADC
1. Product details:
sample will be 5. If he gets ant doubt he may asks for
 Name, address, logo of the manufacturing
consignment sample and he will check and reseal it and
company.
issue ADC clearance certificate and customs clearance
 Product name.
certificate. Thereby ready for export.
 Dosage form.
Technical Documentation  Brand name.
 Generic name.

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 Product code.  Product details like Type of the product,

 Product description. dosage, shape of the drug.
 Label claim of all ingredients used.  Batch size and Total number of tablets or
 Batch size. capsules.
 Pack size.  Pack size and packaging Instructions.
 Shelf life.  Storage instructions.
 Storage conditions.  Production batch record issuance.
 MFR number and date.  Reference documents i.e., SOP’s such as
 Supersede number of MFR and date. Dispensing of the product, temperature and
 Effective batch number. humidity monitoring, material weighing,
 Checked, verified and authorized by cleaning procedure, use, operation and cleaning
production and QA head [8]. of the equipment.
2. Flow chart:  List of raw material along with quantity
 Steps involved in the manufacturing process required.
and flow chart representing the material  Equipment description, calibration certificate
movement from dispensing to the finished etc.
product to packaging and to the store.  Area clearance- step by step cleaning of the
3. Equipment: equipment and area.
 List of equipment required for the  Production procedure- Instruction for each step
manufacture of the product with the capacity of the production from dispensing to dispatch.
4. Special instructions:  Calculation of yield.
 Warnings and precautions related to Yield= Weight of tablets × 100
Weight of raw materials
manufacturing process should be clearly
Finished product yield
mentioned. =No. of goods produced in process+Rejects+Samples+Returned × 100
 Quantity to be added should be mentioned. No. of goods received at the start of procedure
 Time interval and overages to be added to be
mentioned clearly.  Post production review- Complete batch has
 Name of the ingredient with tests and been reviewed for the completeness and
specification limit as per IP, BP and USP. accuracy in the entries for Good
5. Calculations: Documentation Practices.
 Quantity to be added to get 100% final  Product release- the product should comply
product. with the finished goods specifications and
 It can be done by using water content or released to market [10].
LOD to get 100% potency.
6. Manufacturing process: Certificate of Analysis (COA):
 It should include all the steps involved the COA will be issued to prove the purity of the product. The
manufacturing process like sifting, milling, Laboratory where the testing will be done should be
granulation, mixing, blending, lubricating, approved by the WHO and should comply with the Good
compression, coating, filling, if necessary Laboratory Practices. COA will be issued to each batch to
filtration with environmental conditions such show that the product is uniform from batch to batch. Here
as temperature, humidity, storage to be the received products will be tested or analyzed for the
maintained with time. presence of impurities.
7. Packaging process:
 Details of packaging materials used. Contents of COA:
 Line clearance, batch reconciliation of the  Name and address of the laboratory where the
packing material. analysis will be carried out.
8. Yield:  Registration number of COA.
 It includes theoretical yield, Practical yield  Name and description of the product (quantity
and acceptance limit of the batch [9]. received, grade, batch number etc.)
 Batch for which certificate is issued-
Batch Manufacturing Record (BMR): Once the Master manufacturing date and expiry date.
formula is prepared, pilot batch will be started to  Name of the tests performed and the acceptance
validation and BA/BE studies, upon getting the report limit.
from the pilot batch BMR will be prepared which will be  Results of tests performed.
used for commercial batch manufacturing.  Date on which certificate issued.
 Signature of the person or authorized person.
Contents of BMR:
 Name of the product, Batch number, revision
number, effective date.

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Model COA [11]:

Certificate of Analysis for API, Drug product, Excipients.

Registration number of sample or certificate:

Name and address of laboratory testing the sample:

Sample information

Name of product (INN, brand name(s), etc.):

Dosage form (if applicable):

Marketing authorization number (if applicable):

Description (appearance of container and contents):

Batch number(s):

Required storage conditions:

Date received:

Date of manufacture:

Expiry date (for medicinal products) or retest date (for starting materials or excipients):

Name and address of original manufacturer:

Telephone: Fax:

Name and address of repacker and/or trader (if applicable):

Telephone: Fax:

Test procedure (reference Result (numerical Acceptance criteria to test procedure) result) (limits) (if applicable) (if applicable)

A. Tests performed on samples from batch for which certificate is issued

B. Tests performed as part of periodic statistically based testing program

Conclusions: Compliance with acceptance criteria: yes No

Date of test performed/finalized:

Name and address of head of laboratory/authorized person:

Telephone: Fax: Signature:

Explanatory notes:

1. Statement of expected conditions of shipping, packaging, storage and distribution, deviation from which could render the
certificate invalid.
2. Indicate if the results were obtained from periodic statistically based testing.

References:
Important note: The product is highly costly and effective but when it is not certified for its purity, it is valueless [12].

FIGURE 3. Model COA.

Certificate of pharmaceutical Product (COPP): When the proprietor wishes to commercialize his/ her
COPP is a certificate issued in the format of WHO by the product in overseas markets, he/ she has to apply for
National Health Authorities. COPP will be issued by the COPP. Upon requisition the National Health Authority of
Exporting country upon request from the applicant. that country will come and inspect the facility according to
It will be issued for each product for each country. Same the WHO norms there by issue COPP [13].
COPP cannot be used for all the markets.

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Model COPP:

FIGURE 4. Model COPP.

Drug Master File (DMF) 1. Open part (Applicant’s part): Contains all the
DMF is a confidential document for API (Active required information related to method of
Pharmaceutical Ingredient) submitted to the regulatory manufacture and brief outline of method of
body for the approval process. In fact there is no manufacture, potential impurities, manufacturing
regulations to file a DMF. It is not reviewed on receipt as system etc.
like dossier and DMF’s are neither approved nor 2. Closed Part (Restricted part): Contains
disapproved. Confidential information on the manufacture of
It has divided into 2 parts API like Extraction, validation, process, solvents

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•
used, reactions, temperature, conditions, critical
steps in manufacture etc. [14]. Composition of the packing material.

•
Apart from this DMF is divided into 5 types
1. Type I: Plant information (No more a part of Name of the suppliers.
DMF)
2. Type II: Drug substance, drug products, • Specifications.
intermediates
manufacturing.
and materials used in
• Toxicological data on the packing material.
3. Type III: Packaging materials.
4. Type IV: Excipients or additives.  Type IV DMF:
5. Type V: FDA accepted reference information
[15]
. • Excipients used in the manufacture of the
product.
 Type I DMF: It contains information about the plant
information like • Compendia excipients usually not reviewed
so DMF is not required.
• Manufacturing site.
Differences between the Application (Dossier) and
• Equipment capabilities. DMF [16]:

• Operational layout. TABLE 2- Differences between Dossier and DMF.

•
SL.NO Application (Dossier) DMF
Corporate headquarters. Must be filed by Not mandatory to
01
•
applicant file DMF
Site Address. Comes under regulatory
02 No such regulations
status
 Type II DMF: It includes information about all the Each applications and
significant steps in manufacturing and control of drug DMF’s are entered
their supplements are
substance and intermediates. 03 in separate database
entered in common
as per the type
• Manufacturing sections.
04
database
Submitted to intended Submitted to
review division Regulatory body
• Quality control
05
Review procedure is
different than that of
Reviewed only when
referenced with
NDA/ ANDA
DMF
applications
Approval timeline is
06 No approval timeline
there
Finished drug substance
Inputs DMF Filing System:
Intermediates and In-process

Applicant files DMF

Packing materials
Raw materials

Submitted to Regulatory Body

• Validations.

• Stability data. Information in DMF is checked (Not reviewed) and

• Impurities.
entered into DMF database

• Packaging and labelling.

DMF number will be assigned and acknowledgement letter
 Type III DMF: It contains detailed information will be sent to DMF Holder along with reminder of
of the packaging material used. i.e., obligations

• Intended use of the packing material. FIGURE 5. DMF Filing Process.

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DMF Reviewing System: • Should notify regulatory body of change in

agent or representative.
Applicant files NDA or • Issue LOA to each applicant who intends to
ANDA use that API.

• Should submit annual report to regulatory

body on the anniversary date of DMF filing.
 Symbols used in finding the status of DMF

• “A”- Active, (DMF is acceptable and up to

Submits Dossier and quotes DMF number as date)
supportive document for Drug substance
• “I”- Inactive

• “N”- Not assigned DMF number

• “P”- Pending filing review

 DMF for OTC drugs and compendia excipients
are never reviewed.
Applicant will send Letter of  DMF cannot be registered or approved, it just
authorization (LOA) entered in DMF database.
 Letter of Authorization (LOA) shall be send by
DMF holder to regulatory body (2 copies) and
NDA/ANDA applicant (1 copy).
 DMF number will be assigned only when the
regulatory body receives 2 copies of DMF along
with the cover letter.
Upon receiving LOA DMF will be taken  If any deficiencies found in DMF it shall be
for review communicated with the holder and the applicant
will be just notified.
 DMF shall be registered immediately but not
FIGURE 6. DMF Reviewing Process. reviewed.
 Regulatory body will issue termination letter to
Important points to be noted in DMF DMF holder when there is no communication for
 Holder: The person who submits a DMF. 3 consecutive years (i.e., no annual report)
 Agent: The person or company who represents regarding the DMF.
the DMF holder.  If annual report is not send, it causes delay in the
 Applicant: The person or company who use the review process of the filed NDA and ANDA.
DMF for referencing in the NDA or ANDA  Regulatory body shall send a reminder letter
submission. called overdue notice letter (ONL) to DMF
 Agent will be appointed by the DMF holder to holder, if there is no response from the holder
file DMF and to communicate with the regulatory within 90 days, one copy will be send to federal
body. center and the other will be destroyed [17].
 Major contents of DMF are, Transmittal letter,  Now a days DMF filing also become electronic
Administrative information of DMF holder, submission and can convert existing Paper MF’s
Technical information of the product. to eCTD [18].
 Reason to file DMF: DMF filed for API’s which
acts as supportive document while submitting COMMON TECHNICAL DOCUMENT (CTD).
NDA or ANDA. Common Technical Document is an essential document to
be submitted to regulatory body as a supportive list of
 Obligations of DMF Holder: leaflets attached with the registration applications for
• Should submit any changes as amendments.
pharmaceuticals to get market authorization. Mainly CTD
tells about the format for the data.
• Should notify regulatory body of change in
holder name or address.

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Some of the overseas countries with their regulatory It is common that RA expert knows the documents to be
bodies are as follows: [19, 20] submitted while getting approval for any drug product. But
CTD mainly tells about the organization of the
TABLE 3- List of Countries with Regulatory Bodies. information in order. CTD documents should be clear,
Sl. Country Regulatory Body unambiguous and transparent. Accordingly it is having 5
No Name modules.
01 India Central Drug Standard Control 1. Module 1: Administrative and prescribing
Organization (CDSCO) information
02 USA Food and Drug Administration 2. Module 2: Common Technical Document
(USFDA) Summaries (Quality Overall summary)
03 European European Medicines Agency (EMA) 3. Module 3: Quality Data
Union 4. Module 4: Non- Clinical study reports
04 Canada Health Canada 5. Module 5: Clinical Study reports
05 Australia Therapeutic Goods Administration
(TGA)  Module 2 is Question based summary- This
06 Japan Pharmaceutical and Medical Device should not exceed 40 pages if it is biotech
Agency (PMDA) product or product containing more complex
07 China National Medical Products process information can be longer but should not
Administration (NMPA) exceed 80 pages of text excluding tables and
08 South South African Health Products figures.
Africa Regulatory Authority (SAHPRA)  Module 3 documents should be as described in
M4Q.
09 Singapore Health Science Authority (HAS)
 Module 4 documents should be as described in
10 Malaysia National Pharmaceutical Regulatory
M4S.
Agency (NPRA)
 Module 5 documents should be as described in
11 Brazil Agencia National De Vigilancia
M4E.
Sanitoria (ANVISA)
12 Nigeria National Agency for Food and Drug The Format should be clear in such a way that it should be
Administration and Control
clearly readable and understandable
(NAFDAC)
13 Thailand Thai FDA  Font size: 12.
14 Russia Ministry of Health (MOH)
15 Cambodia Department of Drugs and Food
 Font: Times New Roman.
16 South Ministry of Food and Drug Safety  Page layout: For EU and Japan – A4 paper
Korea (MFDS) For U.S.A – 8.5 × 11
17 Philippines Food and Drug Administration (FDA)
18 Indonesia National Agency of Drug and Food
 The left hand margin should be large enough so
that the information should not be hidden or
Control (NADFC)
unclear after binding.
19 Saudi Saudi Food and Drug Authority
Arabia (SFDA)  Acronyms and abbreviations should be defined at
20 Myanmar Food and Drug Administration (FDA) the first time they used in each module [22].
Note:
CTD Triangle [21]:  CTD dossier should be detailed and easily
acceptable by the regulatory authority.
 The documents should be arranged in such a way
that it can be easily reviewed by the reviewer.
 Documents submitted should be signed and
dated.
 Labelling should be clearly mentioned as per the
country regulatory guidelines.
 Required documents should be submitted
according to the checklist to avoid rejection of
the application or queries which in turn speed up
the review process and approval.
 The justification for certain tests should be
clearly mentioned and supportive documents
should be attached.
 Once dossier is prepared before sending it has to
FIGURE 7. CTD Triangle checked and verified for any mistakes.

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 While in clinical study report (Module 5) CRF,  Hyperlink- “Insert cross- Reference” feature in
all study reports should be attached. MS word is known as Hyperlinking
 BMR is required not MFR.  Hyperlink improves overall quality and accuracy
 Some countries asks for validation certificates of the complete file.


that should be up date.
Changes done in any batches should be notified  eCTD will be submitted in Electronic Submission
and justified. Gateway (ESG)
 Amendments, supplements should be submitted  All documents should be scanned properly which will
to regulatory body. help to recognize the file clearly.


Annual reports should be submitted.
Scanning will be done by using OCR software (Optical
ELECTRONIC COMMON TECHNICAL DOCUMENT Character Recognition).
(eCTD)
eCTD is electronic Common Technical Document, an
electronic format where the information and document is
submitted to regulatory body electronically by using a
software. Some of the eCTD software are Pharm ready,
Edios etc.
eCTD submission is for applications, amendments,
variations, supplements, reports, Master formulae etc.
Understanding the eCTD format and applying successfully
in submission is the biggest hurdle. While sponsor or the
applicant may face problem when the documents does not
fit into the format because the application or submission
shall be bounced back known as technical rejection [23].
Here the main thing to be noted is the software used
should be validated.
Requirements of eCTD:
1. Copy and paste.
2. Verifying and printing documents.
3. Document Annotation.
4. Export of information to databases.
Modular Structure of eCTD:
Overall structure of submission is defined by XML eCTD
DTD (Document Type Definition). The XML file is the
backbone for eCTD submission. The purpose of XML Screenshot of the folder structure [25]:
backbone is, FIGURE 8. eCTD Folder Structure.
1. To manage meta-data of the entire submission Advantages of eCTD:
like information about submitting and receiving A. Reduced cost in producing, checking and storage
organization, manufacturer, ID etc. and of paper documents.
documents. B. Easy to Review
2. To form Comprehensive table of contents and C. Faster process.
provide corresponding navigation aids. D. Greater search functionality
Common Formats of eCTD: E. Easy to manage dossier life cycle
1. Narrative: Portable Document Format (PDF) F. Can reuse the documents
[Calibri 12] G. Easy to do any amendments
2. Structure: Extensible Markup Language (XML) H. Reviewer friendly in comparing the dossier with
3. Graphic: Use PDF, whenever PDF is not amendments.
supporting, use Joint Photographic Experts I. Several people can read the documents at the
Group (JPEG), Portable Network Graphics same time.
(PNG), Scalable Vector Graphics (SVG) and J. More predictable format
Graphic Interchange Format (GIF). K. More convenient for exchange of information.
4. Font size 9 and 10 are suggested for tables. L. Time saving process [26].
Folder and File Naming Conventions: ASEAN Common Technical Document (ACTD)
 The maximum length of name of a single folder ASEAN (Association of South East Asian Nations)
or file is 64 characters. Common Technical Document (ACTD) is a structured
 Folder name should be written in lower case only. document for the registration of pharmaceuticals in
For example: Study Report 1 should be written as ASEAN countries.
study-report-1.pdf [24]. ASEAN countries and their regulatory bodies,
 File should not exceed more than 2 GB 1. Indonesia- National Agency of Drug and Food
Control (NADFC).

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2. Vietnam- Drug Administration of Vietnam. Section D: Tabular Listing of All Clinical

3. Thailand- Thai FDA. Studies.
4. Singapore- Health Science Authority (HAS). Section E: Clinical Study Reports.
5. Malaysia- National pharmaceutical Regulatory Section F: List of Key Literature References.
Agency (NPRA). The registration fee will differ from country to country.
6. Philippines- Food and Drug Administration The documents shall be submitted to the particular
(FDA). regulatory authority. The documents related to drug
7. Brunei- Ministry of Health. substance and drug products and new chemical entity will
8. Cambodia- Department of Drugs and Food. be according to the country requirements [28].
9. Myanmar- Food and Drug Administration (FDA).
10. Laos- Food and Drug Department [27]. Differences between CTD/ eCTD/ ACTD [29]:
ACTD includes 4 parts TABLE 4- Differences Between CTD, eCTD and
1. Part 1: Table of Contents, Administrative data ACTD.
and Product information. SL.NO. CTD eCTD ACTD
2. Part 2: Quality Document. Electronic ASEAN
3. Part 3: Non- clinical Document. Common
Common Common
4. Part 4: Clinical document. 01 Technical
Technical Technical
Organization of ACTD: Document
Document Document
1. Part 1: Table of Contents, Administrative data Electronic
and Product information. Paper Paper or
02 (Using
Section A: Introduction. submission Electronic
Software)
Section B: Overall ASEAN CTD Table of Tedious and
contents. Depends
Difficult Faster review
Section C: Documents like registration 03 upon the
Review process
application, product data sheet, prescribing country
process
information and labelling.
2. Part 2: Quality Document Bulk and XML files
Section A: Table of Contents. Large
04 Large storage will be
Section B: Quality Overall summary. documents
documents in GB
Section C: Body of Data.
3. Part 3: Non- clinical Document Includes 5 Includes 4
Section A: Table of Contents. 05 5 modules
modules parts
Section B: Non- clinical Overview.
Section C: Non-clinical written and tabulated Cross Cross Cross
summaries. references references references
 Table of Contents.
06 include CTD
section
include
hyperlink and
include CTD
section
 Pharmacology. number book mark number

 Pharmacokinetics. CTD eCTD CTD

 Toxicology. 07
navigation
through TOC
navigation by
XML
navigation
through TOC
Section D: Non- clinical Study Reports,
and Volumes backbone and Volumes
 Table of Contents.
 Pharmacology.
08
Paper
Layout shall
be A4 or US
Paper
 Pharmacokinetics.
volume- A4
letter size
volume- A4

 Toxicology.
Submitted in
Submitted on
Submitted in
4. Part 4: Clinical document. CD or DVD or
09 Binders or Binders or
Section A: Table of Contents e-mail or
boxes boxes
Section B: Clinical Overview Portal.
Section C: Clinical Summary Compiled
1. Summary of Bio pharmaceutics and Compiled
electronically
Associated Analytical Methods. electronically Compiled
with
2. Summary of Clinical Pharmacology with volumes, electronically
volumes,
Studies. 10 tabs and slip with
tabs and slip
3. Summary of Clinical Efficacy. sheets and documents in
sheets and
4. Summary of Clinical Safety. then printed folders
then printed
5. Synopses of Individual Studies. to paper.
to paper.

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CONCLUSION: 14 Pooja et al. Dmf filing in us, Europe and Canada. IJDRA.2015;
volume 3(issue 4).
Registration and approval phase is very crucial part in
15 FDA, Types of drug master files. Available from:
commercialization of the pharmaceutical products. As per https://www.fda.gov/drugs/drug-master-files-dmfs/types-drug-
the regulatory point of view, one has to prepare and master-files-dmfs Accessed on 28 Feb 2020
compile the documents as per CTD module. But other 16 Yamini kanti S P et al, Filing of DMF in US, Canada and Europe.
PDRAJ, Volume 2; issue (1). Available from:
requiremets like import export code, Drug master file,
https://medwinpublishers.com/PDRAJ/PDRAJ16000108.pdf
technical documentation are the supportive documents to 17 Inside story for review of DMF and Dossiers by regulatory
be submitted to the regulatory body for review and authorities. Available from:
approval. In this article we have covered all the http://www.perfectdossier.com/pdf/Inside%20Story%20for%20Rev
iew%20of%20DMF%20&%20Dossiers%20by%20Regulatory%20
certification process suach as COA and COPP also actual
Authorities.pdf. Accessed on 20 March 2020
process like DMF filing and revieing system, arangements 18 US FDA, New requirements for the electronic submissions of MFs
of floders in eCTD structure and differences between the Available from: https://www.fda.gov/media/98898/download.
CTD, eCTD and ACTD module for better understanding Accessed on 25 Feb 2020
19 https://www.pharmatutor.org/articles/pharmaceutical-regulatory-
in regulatory point of view.
agencies-and-organizations-around-world-scope-challenges-in-
drug-development
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