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Post-approval changes/variations is defined as changes in of any aspect of a pharmaceutical product after approval which includes but is not limited to manufacture process changes, packaging changes, labelling changes, finished product changes, API changes, excipient changes, etc. Among all these variations, this study is focusing on the impact on source change of API and its regulatory requirements in different regions/countries like Europe & Emerging markets (ASEAN, GCC, African). While changing API source, alternate Supplier selection plays a major role which includes quality assessment, audits, evaluation of the API, and compliance to regulations. Each country defined some conditions and document requirements for approval of variations which varies from country to country. The study focuses on similarities and differences for post-approval change in API source. Some similarities include classification of the type of variation, submission of the application process, the update of the dossier, etc. Differences highlighted across the type of application form, timelines, and fees for approval of the variation. A comparison table for all the countries/regions for documentation requirements is included in this study. This study aims to understand how the variations implemented in each country and how it differs from country to country.
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STUDY ON REQUIREMENTS OF CHANGE IN SOURCE OF API
ACROSS EUROPEAN UNION AND EMERGING MARKETS
Sita Priya Darsini Yallabandi1*, Ravi Kumar Reddy Juturi1 and Basava Raju D.2
1Department of Pharmaceutical Drug Regulatory Affairs, Shri Vishnu College of Pharmacy,
Bimavaram, 534202.
2Department of Pharmaceutical Sciences, Shri Vishnu College of Pharmacy,
Bimavaram, 534202.
ABSTRACT
Post-approval changes/variations is defined as changes in of any aspect
of a pharmaceutical product after approval which includes but is not
limited to manufacture process changes, packaging changes, labelling
changes, finished product changes, API changes, excipient changes, etc.
Among all these variations, this study is focusing on the impact on
source change of API and its regulatory requirements in different
regions/countries like Europe & Emerging markets (ASEAN, GCC,
African). While changing API source, alternate Supplier selection
plays a major role which includes quality assessment, audits,
evaluation of the API, and compliance to regulations. Each country
defined some conditions and document requirements for approval of
variations which varies from country to country. The study focuses on
similarities and differences for post-approval change in API source.
Some similarities include classification of the type of variation, submission of the application
process, the update of the dossier, etc. Differences highlighted across the type of application
form, timelines, and fees for approval of the variation. A comparison table for all the
countries/regions for documentation requirements is included in this study. This study aims to
understand how the variations implemented in each country and how it differs from country
to country.
KEYWORDS: Variation. API, Regulations, Countries.
WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES
SJIF Impact Factor 7.632
Volume 9, Issue 11, 1528-1548 Research Article ISSN 2278 4357
*Corresponding Author
Sita Priya Darsini
Yallabandi
Department of
Pharmaceutical Drug
Regulatory Affairs, Shri
Vishnu College of
Pharmacy, Bimavaram,
534202.
Article Received on
27 August 2020,
Revised on 17 Sept. 2020,
Accepted on 07 October 2020
DOI: 10.20959/wjpps202011-17582
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INTRODUCTION
Components of pharmaceutical formulation consist of Active pharmaceutical ingredient (API)
and Inactive ingredient (excipient). API is the central element of the formulation that causes
'Pharmacological activity or other direct effects in the diagnosis, cure, mitigation, treatment
or prevention of disease or to affect the structure and function of the human body. The
excipient is an inactive substance that serves as the vehicle for the delivery of API.
APIs are generally manufactured through a variety of processes that include:
Chemical synthesis
Fermentation processes
Recombinant DNA
Isolation and recovery from natural sources
A combination of these processes
Based on the requirements and delivery of active substance at the target site. To market any
drug product, the manufacturer must take approval from a regulatory authority. Once a drug
product is released into the market now the focus of the company changes to maintain
consistency in quality, safety, and efficacy of the product and as a drug product lifecycle
management an applicant may propose post-approval changes on product registration dossier.
These post-approval changes also known as Variations. Categories of variations differ from
country to country. Based on the variation type, each country has set conditions and
documents to grant permission for it. Regulatory requirements for post-approval changes vary
from country-to-country.
Active pharmaceutical ingredients
Active pharmaceutical ingredients are commonly manufactured by the company other than
the manufacturer of the finished product. The pharmaceutical industry has to maintain
documentation as evidence of maintaining the quality of drug substance. European
pharmacopoeia commission deals with unique procedures for the drug substance with some
quality specifications. The drug substance active substance information is generally
submitted for getting a certification of suitability to the monograph of the European
Pharmacopoeia (CEP) and Drug master file (DMF).
API’s registration
There are two ways by which sponsors can provide information on drug substances.
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Drug master file (DMF)
1) CEP issued by the European Directorate for the Quality of Medicines and Healthcare.
A CEP may be submitted instead of DMF.
For a request to make a variation to include an additional site of drug substance
manufacturer.
When a drug substance manufacturer ceases operation of a DMF and refers to a CEP
instead.
1. DMF
Drug master files (DMF) are submission to FDA used to provide confidential, detailed
information about facilities, processes, or articles used in the manufacturing, processing,
packaging, and storing of human drug products. They are:
They are 2 types of DMF
1) Open part: Applicants part of a DMF. It normally includes a brief outline of the
manufacturing process, information on potential impurities, etc.
2) Closed part/restricted part of DMF: It includes a detailed description of step-by-step
manufacturing process, critical steps, validations, and qualities control test. Such
information is provided to authorities only.
2. CEP
Certificate of Suitability of European Pharmacopoeia (CEP) is to certify the compliance of a
material with the requirements laid down in the relevant monograph of the European
Pharmacopoeia. Active pharmaceutical ingredients for which a Certificate of Suitability has
been granted are suitable for use in medicinal products.
CEP is generally applicable for
a) Manufactured or extracted organic, or inorganic substances (active or excipients)
Substance which are metabolites of microorganisms produced by fermentation as indirect
gene products.
b) The CEP applicant is responsible to confirm that the substance is manufactured as per
Good manufacturing practices (GMP) requirements.
c) EDQM issue CEP upon the compliance of GMP for the respective drug substance. It will
not provide a GMP certificate nor is a GMP certificate equal to CEP.[1]
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Figure 1: Advantages in CEP.
Types of changes in the organization
Change within an organization: It means if the source is changed from one plant of an
organization to another plant of an organization where the organization has more than one
manufacturing site. In that case, the route of synthesis, specification of the API remains
the same. The only site of manufacturing and equipment to synthesize the API changes.
Change outside the organization: It means a change in the manufacturer of the API. API
remains the same but the route of synthesis may differ. In most cases, the impurity profile
remains the same.
If a drug product manufacturer wants to change the API source within the organization,
then the specification and route of synthesis of the API remain the same which means the
variation is minor because there is no effect on end product specification. But if the
change is outside the organization, then it is considered as major change because as the
specification of the API is already changed, there is a need to assure if the API gives the
desired end product with the required specifications.
Also, to consider if the source change of API is within the organization, there is a need to
identify if the previous and new source has CEP or DMF.
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While changing the API source, four parameters to consider: CEP, DMF, change within
the organization, and change outside the organization. These four parameters to decide
the extent of variation and depending on that conditions to be followed and documents to
be submitted to the regulatory authority for approval of source change.
MATERIALS AND METHODS
The study was conducted to chalk out the regulatory requirements and several variations in
different countries. Among all these variations, this study is focusing on the impact of source
change of API and its regulatory requirements in different regions/countries like Europe &
Emerging markets (ASEAN, GCC, African).
API source change
Changes to the API source is proposed and implemented after product approval. It is
necessary to ensure the impurity profile, chemical, and physical properties, and other
specifications to remain the same as they may affect the quality of the drug product. This is
ensured by using appropriate methods like NMR, X-ray powder diffraction, assay, etc.
Any change which has an impact on the physical properties of API or impurity profile of the
API is evaluated from the stability perspective and its potential effect on the finished product.
Typically, a change from one drug substance source to another involves more than simply a
site change.
Classification of change[2]
1. Minor change: A change having a minimal effect on safety, quality, purity of the drug
product., E.g. Change in the address of the manufacturer of a drug product.
2. Moderate change: Change that moderate effect on the safety, quality, and purity of the
drug product., E.g. Manufacturing site of drug product changes to the new location.
3. Major change: change that has a significant effect on the quality, safety, and purity of
the drug product.
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Categories of variation
Need for changing API source[2]
1. To improve the quality of the drug producer.
2. To find a source (vendor) having bettered regulatory compliance.
3. To ensure timely material availability with minimum lead times.
Documents required for API source change
1. Variation application form
2. A document describing, discussing, and justifying the change.
3. Replacement of a relevant section of the dossier (DMF/APIMF/CEP)
4. Batch analysis data
5. Stability data.
Table 1: Countries selected for the study of post-approval API source change are as
below.
Countries/regions.
European Union
Jordan
china
Kazakhstan
GCC (Saudi Arabia, UAE)
Brazil
ASEAN‟s countries
Ukraine
African countries
API supplier selection[3,4]
Manufacture of the Active pharmaceutical ingredients are subjected to the strict Good
Manufacturing Practices regulations that are designed to ensure the quality, safety, and purity
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of API. GMP is the major criterion while a selection of API source. Before selecting the
supplier there is a need for quality system evaluation. By considering criteria like quality,
safety, and purity manufacturer will do vendor qualification. For that, the following
information from the supplier is requested.
Specifications
Manufacturing/packaging/labeling details
Materials Safety Data Sheets
Logistic information (lead time to produce, delivery time, etc)
Certificates regarding the Quality system, residual solvents.
BSE/TSE evaluation
Quality assessment
Quality assessment of the API includes
1. TSE/BSE assessment: The supplier must be able to certify that all raw materials/ source
materials used at any stage of the production process of API comply with “Note for
guidance on minimising the risk of Transmitting An animal Spongiform Encephalopathy
Agents via Medicinal Products.”
2. Manufacturer/Supplier questionnaire: Each manufacturer questionnaire should be
tailored to the API being purchased. The format of the questionnaire can mimic that of a
pre-audit questionnaire.
3. Manufacturer audit (GMP compliance, third party certification, sample analysis):
ICH Q7 will be the preferred standard for auditing. The sample analysis is done during
the audit to check. Whether it meets all the specifications or not. Once the audit gets
completed audit report being prepared. The report should state whether predetermined
acceptance criteria have been met and if not, what points require remediation. Once the
audit gets completed GMP certificate is provided.
4. Quality agreement: It is forwarded to the supplier when the rest of the quality
assessment is a ongoing. The Quality agreement must be approved and signed by both
these parties before any manufacturing takes place. The quality assessment should
address the need for:
1. Notification of any potential changes that may impact the quality of the product and
2. No changes can be made without prior approval.
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DISCUSSION
API source change in various countries
Table 2: Categories of variation.
ASEAN
Malaysia
Minor variation Notification (MiV-N)
“Do & Tell”
No need for prior approval
Minor variation-Prior Approval
(MiV-PA)
Minimal/no significant
impact on aspects of efficacy, quality &
safety
Major variation (MAV)
May affect significantly and/or directly
aspects of quality, safety, and efficacy
2) the Philippines
Minor variation (MiV)
Minimal/no significant impact on the
aspects of efficacy, quality, and safety
MiV-N
MiV-PA
Major variation (MAV)
Significantly affects quality,
Safety, and efficacy
3) Singapore
Minor variation (MiV)
1)MiV-1: Requires prior approval before
the changes can be implemented.
2)MiV-2:
a)MiV-2 (Notification):
Implemented within 40 days Upon
application submission if there are no
objections raised by HSA.
b)MiV-2 (Do and Tell):
No prior approval
Change notifies within 6 months Of
implementation
Major variation (MAV)
Requires prior approval from HAS before
implementation.
1.MAV-1: Any variation to the approved
indication, dosing regimen, patient group
2.MAV-2: A change in the current
approved forensic classification also
called reclassification.
GCC
1)Saudi Arabia
I. Type IA:
“Do and Tell” procedure
Notification submitted by the marketing
authorization holder (MAH) within 60
working days after implementation.
II. Type IB:
“Tell, Wait and Do‟ procedure
Notification before implementation, but
not require prior approval
Wait period:120 days to ensure that the
application is deemed acceptable by the
SFDA before implementing the change
Significant impact on the quality, safety or efficacy of a medicinal product Require
prior approval before Implementation.
UAE
Type IA: notification to the drug
registration department
Tell & Do
No variation certificate is issued
Stamped receipt of submission is
considered as an approval document.
Type IB:
This type of variation is to be submitted
Type IIA:
This type of variation
is to be submitted directly to the QCL
department official.
Tell, Wait & Do (90 days)
No notification of disposition Of request
for variances will be issued for the type
of variation
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directly to the drug registration
department official
Tell, Wait & Do a variation
Waiting period:10 days
Stamped receipt of
submission is considered the approval
document after the waiting time
Type IIB:
This type of variation is to be submitted
directly to the QCL stability department
official
Tell, Wait & Do
Waiting period:60, days
No Notification of disposition of a
request for variances will be issued for
this type of variation
Stamped receipt of submission is
considered the approval document after
the waiting time
china
Type I
No impact on product quality, safety,
and effectiveness
Type II (moderate)
Corresponding research work is required
to prove changes does not affect product
Type III
Significant impact on quality, safety &
efficacy
Ethiopia
a. Notification: need to be notified to the
authority but can be implemented if the
authority has no objection immediately
after proper categorisation confirmed by
EFMHACA experts and official
submission to the authority.
b) Prior approval: need prior approval
before implementation
Prior approval from EFMHACA before
the implementation of variation.
Uganda
Minimal/no adverse effects on overall
Safety, efficacy, and quality of FPP.
M1
Changes to be submitted to NDA within
12 months of implementation
Documents not required
M2
Notification application for change is
required along with documents
M3
Variation application is required along
with documents
Major effects on overall Safety,
efficacy & quality of FPP
Prior acceptance by
National Drug Authority is required
before changes can be implemented.
1) A letter of acceptance will be issued
for all major variations
2) when a variation is considered
acceptable
These variations will be
handled within 6 months from the date of
acknowledgment of receipt.
Tanzania
1. Minor variation
i)Notification „N‟
Evaluation of application done by TFDA
Period of evaluation:3 months
ii) Prior approval:
Waiting period:3 months
2. Major variation
3. Changes that make new
application/extension application
4. stability requirements for variation and
changes to register FPPs.
Kazakhstan
Type I alteration: Minor change
Not require a new registration
Type II alteration:
Significant changes in
product characteristics
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Ukraine
Type IA:
No prior approval
„Do & Tell‟
Notification within 12 months from the
amendment of variation
Type IB:
Notified before the implementation of
variation
„Tell, wait & Do‟
Waiting period:30 days
Type II:
Significant impact on
quality, safety or efficacy of a medicinal
product Require prior approval before
implementation
Kenya
Minor effects on the overall safety
efficacy and quality of FPP.
Such variations only are implemented on
receipt of a letter of acceptance from PPB
Notification (N):
Minimal or no adverse effects on overall
safety, efficacy, and quality of FPP.
Major effects on overall safety, efficacy,
and quality of FPP.
Table 3: Timelines and fees for approval of variations in different countries.
Countries
Type of variation
Timeline
Fees
European Union
Type IAIN
30 Days
3000EURO
Type IB
1-2 months
7000EURO
Type II
5-7 months
8300EURO
Malaysia
MiV-N
20 working days
No fee
MiV-PAS
3 months
150 RM
MaV
6 months
300 RM
Philippines
MiV
3 months
5000-10000
MaV
6 months
10000-30000
Singapore
MiV
120 days
$550
MaV
180 days
$2500
GCC
a) Saudi Arabia
MiV
120 days
MaV
145 days
b)UAE
MiV (Type I)
Within 1 Month
1000 AED
MaV (Type II)
3 Months
1000 AED
China
MiV
-
-
MaV
6 months
2,83,600 Yuan
Ethiopia
MiV
3 months
USD 100 (approx.)
MaV
6 months
USD100-200 (approx.)
Mexico
MiV
-
-
MaV
3-5 months
$59,735
Uganda
MiV
3 months
USD 400
MaV
6 months
USD 700
Tanzania
MiV
MaV
Jordan
MiV
1 month
-
MaV
3 months
-
Kazakhstan
MiV
6 month
200-250 USD
MaV
6 months
500-600USD
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Ukraine
MiV
6 month
200 USD
MaV
6-9 months
350 USD
Kenya
MiV
3 month
200USD
MaV
6-9 month
200 USD
Brazil
MiV
-
-
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Table 4: Comparison table for classification of Variation.[6,7,8,9,10,11]
Classification of variation in different regions
Type
EU
ASE
AN
GCC
Malay
Asia
Uganda
Philip
pines
Tanza
nia
Singa
pore
Kenya
china
china
Minor
Type-IA
MiV-N
Type-IA
MiV-N
MI &M2
MiV-N
N
MiV-I
N
I-Type
Moderate
Type-IB
MiV-
PA
Type-IB
MiV-PA
M3
MiV-PA
Prior
approval
MIV-2
Mn
II-Type
Major
Type-II
MaV
Type-II
MaV
Vmaj
MaV
Major
variation
MAV-1
MAV-2
Mj
III-type
Classification of variation in different regions
Type
Brazil
Ukraine
Jordan
UAE
Kazakhstan
Mexico
Minor
Immediate
Implementation
Type-IA
N
Type-IA
Type-IA
-
Moderate
Immediate
Implementation
But require
Individual protocol
Type-IB
RA
Type-IB,
Type-
IIA&
Type-IIB
-
-
Major
Requires prior
approval
Type-II
TCA
-
Type-II
Major
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Table 5: Comparison table for API source change.
Types of variation and documents required for change
a. Non-CEP to Non-CEP
Type of
variation
Malay
Asia
PH
iliP
in es
SinGa
Po
re
UK
Ra
ine
Ke
n
ya
Ta
Nz
An ia
Et
Hio
pia
Uk
Ra
ine
Ka Zak
Hst
an
Jor
dan
Mex
ico
Brazil
Ch
ina
EU
AS
EA
N
GC
C
Change within
The
organization
Ma
V
Ma
V
Mi
V-1
M
2
M
n
N
Ma
j
or
I
AI
N
Ty
Pe I
RA
Maj
or
Immed
iate
Imple
Menta
tion
II-
ty
pe
I
AI
N
Ma
V
IB
Change outside
the
organization
Ma
V
Ma
V
Mi
V-1
Vm
aj
Mj
P
A
Ma
j
or
II
Typ
E I
RA
Maj
or
Wait
For ap
proval
II-
typ
e
LI
Ma
V
II
Documents
DMF/ACTD
CTD section
-
-
-
-
-
-
-
-
-
Amendment of
relevant action
of
dossier
-
-
-
-
-
-
-
-
-
-
-
Variation
Applic
Ation form
-
-
-
-
-
-
-
-
-
-
-
-
-
QP
declaration:
GMP
compliance
-
-
-
-
-
-
-
-
-
-
-
-
GMP
certificate
-
-
-
-
-
-
-
-
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ASMF/MAH
Holder
declaration
-
-
-
-
-
-
-
Batch analysis
data
-
-
-
-
-
-
COA
-
-
-
-
-
-
-
-
-
-
Comparison Of
current
&Propos
ed substance
-
-
-
-
-
-
-
-
-
Stability report
-
-
-
-
-
-
-
-
-
Accelerated
Stability study
& stability of
long term
sample
data retention
-
-
-
-
-
-
-
-
-
-
-
-
-
Validation
report
lab report &
stability study
report
-
-
-
-
-
-
-
-
-
-
-
-
Note: If a variation is outside the organization, these countries have to submit a complete DMF document for approval of the variation.
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b. CEP to CEP
Type of
variation
Malysia
Phili
Ppin es
Singa
pore
Uga
nda
Ken
ya
Tanz
ania
Ukra
ine
UAE
Jor
dan
EU
ASE
AN
GCC
Change within
The organization
MiV-
PA
MiV-
PA
MiV-
I
M2
Mn
N
IA
Type
IIB
RA
IA
MiV-
PA
IA
Change outside
The organization
MiV-
PA
MIV
-PA
MiV
-I
M2
Mn
Prior
approval
IA
Type
IIB
RA
IA
MiV-
PA
IA
Documents
Updated CEP
Amendment of
relevant section
of
dossier
-
-
-
-
--
-
--
Variation
applica
Tion form
-
-
-
-
-
-
-
-
-
-
QP declaration
-
-
-
-
-
-
-
-
ASMF/MAH
holder
declaration
-
-
-
-
-
-
-
-
-
-
--
Batch analysis
data
-
-
-
-
-
-
-
-
COA
-
-
-
-
-
-
-
-
-
Comparative
current &
proposed
specifications
-
-
-
-
-
-
-
-
-
-
-
C. Non-CEP to CEP
Type of
variation
Malaysia
Philip
pines
Singa
pore
Uga
nda
Kenya
Tanza
nia
Ukr
aine
EU
ASE
AN
GCC
Change within
the
Organization
MiV-
PA
MiV-
PA
MiV-
I
M3
Mn
N
IAIN
IAIN
MiV-
PA
IA
Change
outside
The
organization
MiV-
PA
MiV-
PA
MiV-
I
M3
Mn
Prior
approval
IAIN
IAIN
MiV-
PA
IB
Documents
Updated CEP
Amendment of
Relevant
section
Of dossier
-
-
-
-
-
Variation
applica
tion form
-
-
-
-
-
-
-
-
QP
declaration:
GMP
compliance
-
-
-
-
-
-
-
ASMF/MAH
hold
er declaration
-
-
-
-
-
-
-
-
-
-
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Batch analysis
data
-
-
-
-
-
Certificate of
analysis
-
-
-
-
-
-
-
-
Comparative
Current &
proposed
specifications
-
-
-
-
-
-
-
-
-
Documents:
present &
proposed
manufacturer
-
-
-
-
-
-
-
Commitment
letter
To conduct
stability study
-
-
-
-
-
D. CEP to Non-CEP
Type of variation
Malay
sia
Philipp
ines
Singapo
re
Ugan
da
Kenya
Tanza
nia
Ukrai
ne
EU
ASEAN
GCC
Change within
The organization
MaV
MaV
MIV-I
Vmaj
Mj
Major
change
II
II
MaV
II
Change outside
The organization
MaV
MaV
MIV-I
Vmaj
Mj
Major
change
II
II
MaV
II
Documents
DMF/ACTD/CTD section
Amendment of the relevant section of dossier
-
-
-
Variation application form
-
-
-
QP declaration: GMP compliance
-
-
-
GMP compliance
-
-
ASMF/MAH holder declaration: the synthetic route,
quality control procedure and remains the same
-
-
-
-
Batch analysis data
Certificate of analysis
-
-
Comparison of current and proposed substance
-
Documents: present and proposed manufacturer
-
-
-
-
Commitment letter to conduct stability study
-
Note: Following countries/ regions have to submit complete DMF for approval of
variation (CEP to Non-CEP)
1. Uganda 2. Kenya 3. Tanzania 4. Ukraine 5. Kazakhstan 6. UAE 7. Jordan 8. Mexico
9. Brazil 10. China 11. USA 12. EU 13. GCC.
www.wjpps.com Vol 9, Issue 11, 2020. ISO 9001:2015 Certified Journal
1546
Sita et al. World Journal of Pharmacy and Pharmaceutical Sciences
SUMMARY AND CONCLUSION
This study discusses a change in API source, the need to change the API source, regulatory
requirements in selected countries/ regions, and comparison between them. For registration of
API, a Drug master file (DMF) is used. It is used to provide confidential, detailed information
about facilities, processes, or articles used in the manufacturing, processing, packaging, and
storing of human drug products. In the US, it is called USDMF whereas, in the EU, it is
called EDMF or ASMF. When the specification of the API complies with the requirements
laid down in the relevant monograph of European Pharmacopoeia, EDQM issues a CEP
certificate to the vendor for respective API
If a drug manufacturer wants to change the API source, then depending upon whether the
source has CEP or DMF, the conditions and documents required for change vary. Change in
the API source has to consider whether the source contains a Certificate of suitability or not.
Depending upon CEP and DMF source change, the variation classification changes. The
documents required to submit for API source change depend on the type of variation which
ultimately depends on the CEP or Non-CEP source. Type of variation also differs in case of
change of source within the organization and change of source outside the organization. The
type of variation decides the condition and documents required to submit for approval of it.
Study shows that the EU, US, and ROW market similarly divided the variation depending
upon the classification of variation. Countries like the EU, USA, GCC considered "major
variation".
If the source change forms DMF to DMF outside the organization and in case of CEP to
DMF change. Whereas for changes within the organization (for both CEP to CEP change and
DMF to DMF change), it is considered as a minor change. In the case of Singapore, any type
of API source change is considered as 'minor variation" which is exceptional from other
ASEAN countries like the Philippines and Malaysia. In the case of Tanzania, the type of
variation depends not only on CEP and DMF but also if the API is sterile or non sterile.
"Prior approval" is needed in case of the Sterile API whereas "notification' is required in case
of Non-sterile API source change.
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ResearchGate has not been able to resolve any citations for this publication.
Certificate of Suitability as a Contributory Document For the Registration of Medicinal Product in the European Union and Australia
  • Devnani J Maji
  • N Choksi
Maji, Devnani J, Choksi N.Certificate of Suitability as a Contributory Document For the Registration of Medicinal Product in the European Union and Australia, New Zealand, www.wjpps.com │ Vol 9, Issue 11, 2020. │ ISO 9001:2015 Certified Journal │ 1547
  • Sita
Sita et al. World Journal of Pharmacy and Pharmaceutical Sciences South Africa, Canada (internet), 2018; 6: 2019. Available from:
Impact of API (Active Pharmaceutical Ingredient)
  • U R Mallu
  • A K Nair
  • H R Bapatu
Mallu U. R. Nair A.K. Bapatu H.R. Impact of API (Active Pharmaceutical Ingredient)
Regulatory overview of post-approval changes of therapeutics products in Singapore
  • R Mendonca
  • D R Sumanna
Mendonca R. Sumanna D.R. Regulatory overview of post-approval changes of therapeutics products in Singapore [Internet], 2019; 2019. Available from: https://file://C:/Users/introw/Downloads/article-wipps-1551403397.pdf.
  • Uganda-Guidelines For
  • Variation
  • Registered
  • Products
UGANDA-GUIDELINES FOR VARIATION OF REGISTERED MEDICINAL PRODUCTS [Internet], 2018; 2019. Available from https://www.nda.or.ug/nda/files/downloads/PAR%20GDI%20005%20Guidelines%20for