1233 - Pharmaceutical Products Variation Guidelines 3-2018 - 1st Edition PDF

1 st Edition of Egyptian Variation Guidelines 3/2018
Egyptian Variation Guidelines

Variation Definition:
A variation application details a proposed change to approved documentation,
providing a formal means by which the approved licence details held by the
Competent Authorities for a given medicinal product can be updated.
Types of variation:
Variation Variation Technical
department committee committee
Types Notification (N)
approval approval (VCA) approval
(VDA) (TCA)
Definition These are variations, They need They need prior They need to
which don't require prior approval approval by the be approved by
approval before by the variation variation the the
implementation; department committee technical
however they require (VDA) before (VCA) before committee
to be notification "N" implementation implementation (TCA) before
to be submitted by implementation
Applicant
Requirements to be fulfilled according to the type of change in the guidelines:

A) NODCAR
1. Notification (N)
2. Analysis inspection Department (AI)
3. Analysis registration Department (AR)
B) Stability
1. None
2. Ongoing
3. Accelerated (6M)
4. 6M + long term stability (discussed with committee)
C) Dissolution
1. None (DN)
2. Comparative In-Vitro dissolution in most suitable medium (D1)
3. Comparative In-Vitro Dissolution at 3 different PH media (1.2/4.5/6.8) and most
suitable medium (D3/4).
4. Bioequivalence study (BE).
5. Comparative In-Vitro Release in most suitable medium (R)
۱
Composition: For Non- Sterile Products

Immediate Release Oral Solid
Requirements
Dosage Forms & Modified release Reporting
oral solid dosage forms – non- Dissolution/ Category
release controlling excipient: NODCAR Stability
Bioequivalence
Deletion or partial deletion of an
ingredient intended to affect the
colour, taste or fragrance of the
1 N None DN N
product or change in the ingredient of
the printing ink to another approved
ingredient.
Addition or replacement of an
ingredient intended to affect the
2 N Ongoing DN VDA
colour, taste or fragrance of the
product.
A-Change in weight of capsule shells
by NMT 5%.
B-The total additive effect of all
excipient changes doesn't exceed
5%, with individual changes within
the limits specified.
DN
Percent excipients (w/w) out of total target Except For ODT
3 dosage form weight: N Ongoing (D1) only if VCA
Filler ±5 change in
Disintegrant: Starch ±3 / Other ±1 Disintegrant
Binder ±0.5
Lubricant:(Ca)or(Mg)Stearate
±0.25/Other±1
Glidant: Talc ±1 / Other ±0.1
Film Coat ±1
The total additive effect of all

excipient changes is more than 5 but
less than 10% with individual
Changes within the limits specified.
Percent excipients(w/w)out of total target
dosage form weight:
4 Filler ±10 AI 6M D1 VCA
Disintegrant: Starch ±6 / Other ±2
Binder ±1
Lubricant: Ca or Mg Stearate
±0.5/Other ±2
Glidant: Talc ±2 /Other ±0.2
Film Coat ±2
۲
Change in weight of capsule shell

beyond 5% or change in coating
5 weight more than 2% AI 6M D1 VDA
( where the coating is not a critical
factor for release mechanism)
Replacement of an excipient with a
comparable excipient. (e.g. AR
6 6M D1 VCA
Magnesium Stearate and Calcium
Stearate).
Any change in excipient percent
7 beyond 10% with individual changes AR 6M D3/4 VCA
are more than the limits specified in 4.
Addition, deletion or changing
8 excipient to a non-comparable AR 6M D3/4 VCA
excipient.
Any qualitative or quantitative change
in Excipient beyond 5% to a narrow
9 AR 6M BE+ D3/4 VCA
therapeutic drug and low
solubility/low permeability drugs.
Change in coating formulation
excipient (composition) if the change
10 AR 6M D1 VCA
does not alter release of the drug,
specification, or stability
Elimination or reduction of an
overage from the drug product
11 manufacturing batch formula that N Ongoing DN VDA
was previously used to
compensate for manufacturing losses
Addition of overage to the drug
product manufacturing batch formula
12 to compensate manufacturing losses AR Ongoing DN VCA
(for active ingredients or
preservatives only )
Administrative documents:
Common Administrative documents
In addition to
Commitment that the change does not affect stability (For 1)
Capsule shell composition on supplier paper (For 3, 4, 5)
Composition of coating blends e.g. Opadry on supplier paper (For 5, 10)
Scientific justification (For 11, 12)
۳
Formulation changes : Modified Requirements

Reporting
release oral solid dosage forms –
Dissolution Category
release controlling excipient NODCAR Stability
/Bioequivalence
Changes in the release controlling
excipient(s), expressed as percentage
(w/w) of total release controlling
1 excipient(s) in the formulation less than AI Ongoing D1 VCA
or equal to 5% w/w of total release
controlling excipient content in the
modified release solid oral dosage form.
Changes in the release controlling Non-narrow
excipient(s), expressed as percentage therapeutic
(w/w) of total release controlling range drugs
excipient(s) in the formulation, is more D1
2 AI 6M narrow VCA
than 5% but less than 10% w/w of total
release therapeutic
Controlling excipient content in the range drugs
modified release solid oral dosage form. BE
a- Addition or deletion of release Non-narrow
controlling excipient(s) (e.g., therapeutic
release controlling range drugs
polymer/plasticizer).
b. Changes in the release controlling
excipient(s), expressed as percentage D3/4
(w/w) of total release controlling
excipient(s) in the formulation, greater narrow
3 AR 6M VCA
than those listed above for point 2 therapeutic
change (i.e., greater than 10% w/w of range drugs
total release controlling excipient
content in the modified release solid
oral dosage form).
Total weight of the dosage form may be BE
within or outside the original approved
application range.
In addition to
Capsule shell composition on supplier paper
"In case of change or addition of capsule shell components in hard gelatin capsules"
Composition of coating blends e.g. Opadry on supplier paper
C.O.A &/or Composition of pellets/Premix on all supplier papers
Calculations of pellets/Premix on company paper
٤
eporti
Formulation changes: Non-Sterile ng
Requirements
Semisolid Dosage forms (Eg. Creams, Categ
Gels, lotions & ointments) intended for ory
topical routes of administration Dissolution
NODCAR Stability
/Bioequivalence
Deletion or partial deletion of color.
1 N None DN N
Fragrance or flavor.
Up to 5% change in approved amount of an
excipient with the total additive effect of all
excipient changes ≤ 5%. A change in
2 diluent (q.s. excipient) due to component N Ongoing DN VCA
and composition changes in excipient may
be made and is excluded from the 5%
change limit.
Change of > 5% and ≤ 10% of approved
amount of an excipient with the total
additive effect of all excipient changes ≤
10% or Change in particle size
distribution of the drug substance, if the
3 AI 6M DN VCA
drug is in suspension. Changes in diluent
(q.s. excipient) due to component and
composition changes in excipients are
acceptable and are excluded from the
10% change limit.
Any qualitative and quantitative changes in
an excipient beyond the ranges noted in
4 point 3 change or Change in crystalline AR 6M DN VCA
form of the drug substance, if the drug is in
suspension
Elimination or reduction of an overage from
the drug product manufacturing batch
5 N Ongoing DN VDA
formula that was previously used to
compensate for manufacturing losses
Addition of overage to the drug product
manufacturing batch formula to
6 AR Ongoing DN VCA
compensate manufacturing losses (for
active ingredients or preservatives only)
In addition to
Commitment that the change does not affect stability (For 1)
C.O.A &/or Composition of supplier for active ingredient or premixes
٥
Requirements
Formulation Changes : Liquid Reporting
dosage form ( Solution) NODCA Dissolution Category
Stability
R /Bioequivalence
Reduction or deletion of one or more
1 components of the coloring / flavoring N None DN N
systems
Increase ,addition or replacement of one
2 or more components of the coloring / AI Ongoing DN VDA
flavoring systems
a. Replacement of an excipient with a
AR 6M DN VCA
comparable excipient
b. Changing in percentage of the used
3 AR 6M DN VCA
excipients.
c. Addition, deletion of excipient to a
AR 6M DN VCA
non – comparable excipient
Elimination or reduction of an overage
from the drug product manufacturing
4 N Ongoing DN VDA
batch formula that was previously used
to compensate for manufacturing losses
5 AR Ongoing DN VCA
active ingredients or preservatives only )
In addition to
٦
Requirements
Formulation Changes : Liquid Reporting
dosage form ( Suspension) Dissolution/ Category
NODCAR Stability
Bioequivalence
Reduction or deletion of one or more
1 components of the coloring / flavoring N None DN N
systems
Increase ,addition or replacement of one
2 or more components of the coloring / AI Ongoing DN VDA
flavoring systems
a. Replacement of an excipient with a
AR 6M DN VCA
comparable excipient
Non release
controlling
excipient
b. Changing in percentage of the used DN
AR 6M VCA
excipients release
controlling
excipient
3 D1
Non release
controlling
excipient
c. Addition, deletion of excipient to a DN
AR 6M VCA
non – comparable excipient release
controlling
excipient
D1
D3/4 or D1
Any change in the crystalline form of according to
4 AR 6M VCA
the drug substance the committee
decision
Elimination or reduction of an overage
from the drug product manufacturing
5 N Ongoing DN VDA
batch formula that was previously used
to compensate for manufacturing losses
6 AR Ongoing DN VCA
active ingredients or preservatives only )
In addition to
۷
Calculations of Premix on company paper
Composition: Sterile
Requirements
Reporting
Sterile dosage forms Dissolution/
NODCAR Stability Category
Bioequivalence
comparable* excipient. (Same
1 AR Ongoing DN VCA
functional characteristics of the
excipient.)
2 AR 6M DN VCA
non-comparable* excipient.
Increase or Decrease of quantity of
3 AR 6M DN VCA
any excipient
Elimination or reduction of an
overage from the drug product
manufacturing batch formula that
4 N Ongoing DN VCA
was previously used to
compensate for manufacturing
losses
Addition of overage to the drug
product manufacturing batch
5 formula to compensate AR Ongoing DN VCA
manufacturing losses (for active
ingredients or preservatives only )
In addition to
Calculations of pellets/Premix on company paper
۸
Change in Finished Product Specification:

Requirements
Reporting
Variation Item Dissolution/
Bioequivalence
1 Tightening of specification limits N None DN VCA
Addition of a new test parameter to the
2 N None DN VCA
specification
None or
Widening of specification limits or stability
deletion of a test parameter from the 6M
3 specification provided that the change N accordin DN VCA
is not the result of unexpected events g to the
arising during manufacture added
test )
Updating specifications to comply with
4 an update of the relevant monograph of N None DN VCA
the Pharmacopoeia.
In addition to
Validation Process is needed (For 2, 3)
Old & New Certificate of Analysis "on Company Paper" (2 Copies)
Old & New Finished Product Specification "on Company Paper"(2 Copies)
Pharmacopeia Monograph
۹
Change in Physical Character of Finished Product:
Requirements
Reporting
Variation Item
Dissolution/ Category
NODCAR Stability
Bioequivalence
Change or addition of imprints,
embossing or other markings (except
scoring/break lines) on tablets or
printing on capsules, including
1 N None DN VDA
replacement, or addition of inks used
for product marking (provided that the
change in finished product
specification is only in appearance)
Change or addition of scoring/break
2 lines on tablets ( is not applicable when Subdivision
test
None DN VDA
the coat is intended to control release
or mask taste )
Deletion of scoring/break lines on
3 N None DN VDA
tablets :
Addition of Scoring / break lines as a
4 N None DN VDA
mark and not intended for breakage.
Addition limit range of color without None or
DN*
5. any qualitative or quantitative change N stability VCA
If Needed
in excipients or active ingredients 6M
Change in shape of dosage form or
6. capsule size without change in total N None D1 VCA
weight of dosage form
In addition to
Old & New Certificate of Analysis "on Company Paper" (2 Copies)
Old & New Finished Product Specification "on Company Paper"(2 Copies) (For 1, 2, 3, 4)
Safety data Sheet for Ink (For 1)
Reference for scoring (For 2)
Commitment to be written in pamphlet or pack (For 4)
Pharmacopeia Monograph (For 5)
Certificate of analysis of supplier of active ingredient or pellets or premixes (For 5)
۱۰
Changing / Clarifying Active Ingredient Specification:

Requirements Reporting
Variation Item Dissolution/
Bioequivalence
Change from One Pharmacopeia to
1 N None DN VDA
another Pharmacopeial Specification.
Change From Pharmacopeial
Specification to In-house
2 AR None D1 VCA
Specification. ( if change is within
pharmacopeial limits
Change From In-house Specification to
3 N None DN VDA
Pharmacopeial Specification.
Clarifying Specification ( For Both
4 N None DN VDA
Active and Inactive Ingredients )
In addition to
Pharmacopeia Monograph
Certificate of analysis of supplier of active ingredient or pellets or premixes
Previous importation approvals
۱۱
Common Administrative Documents:
Covering Letter from the applicant Describing the reasons for the required change in details
" on company paper signed and
stamped"
Payment receipt. 1000 LE
Valid registration license In case the registration license is not valid please submit
an approval for renewal and in case of tentative
registration license an extension for the license
Variation Notification form According to template attached

NODCAR composition Recent edition with maximum two years ago
NODCAR certificate of analysis

Calculations & scientific reference In case of change or correcting or clarification of salt
for molecular weight equivalence
stamped"
Previous importation approvals In case of clarification of salt equivalence / Premix

For composition change only :
Old composition ( 3 copies ) Identical to NODCAR composition
New composition ( 3 copies) According to attached template
Comparison table between old and According to attached template

new composition
stamped"
Copy of CPP ( and see original one )
In case of imported / bulk / under license
Declaration letter from the license holder

clarifying type of the change needed
" Signed and stamped"
Declaration Letter According to template attached
stamped"
۱۲
Pack: Non Sterile
Requirements
Reporting
Type of change and Examples Condition
Category
NODCAR Stability Pricing
1 Changes - Adding or • The Change

that Have changing child is not in Direct
minimal resistant features Contact with
potential to of the closure. the product.
have - Change from a
adverse metal to plastic
effects on screw cap or
the product plastic to metal
screw cap Or
Change of Seal
while the inner
Liner remains
unchanged. N None N VDA
- Change in or
addition of any
accessory that is
not in direct
contact with the
drug (eg. Spoon,
measuring cup,
Dropper .etc).
- Addition of a
desiccant.
-Addition of
Aluminum Pouch
*Administrative documents:
Common Pack Administrative documents
In addition to
Certificate of Analysis of new accessory or Cap Liner from supplier
Sample For the Old & New Pack
۱۳
2 Changes 1-Change in the -Liquid or semi

That have size of container Solid dosage
moderate for non-sterile form.
potential to drug product. -Same or less
have an head/space or
adverse contact area
effect on the ratio.
product. -Same primary
packaging N None N VDA
material
In addition to
Declaration Letter on Company paper states the old and New Capacity of the Bottle
2-Change in size -Liquid or semi

and/or shape of a Solid dosage
container for non- form.
sterile drug - Increase in
product. the
head/space or N 6M N VDA
Contact area
ratio.
- Same primary
packaging
material
In addition to
Scientific Reference
Declaration Letter on Company paper states the old and New Capacity of the
Bottle
۱٤
3. Deletion of a - Solid dosage

desiccant OR an form N 6M N VDA
Aluminum Pouch
4-Change to a new -The new

container closure container
system within closure system
Same Category of provide same None/
Packaging or 6M
N N VCA
(eg. Change from better If
AL/PVC To protective needed
AL/AL). properties than
the approved
system
In addition to
3 Changes 1. A change to a new -The new
that have a container closure container
substantial system within same closure system
potential to Category of does not None/
have an Packaging. provide the 6M
N N VCA
adverse same or better If
effect on the protective needed
product properties than
the approved
system.
2. Change to a new
container closure
system within
different AR 6M N VCA
Categories of
Packaging.
In addition to
۱٥
4 Adding / 1. For solid dosage -Same primary

Deletion of a forms : added or packaging
pack size of Change in the material.
the container number of units -The new pack
of finished (ex: tab, cap) size should be
product. consistent with
the dosage
regimen &
treatment N None P VDA
duration as
approved in any
Scientific
Reference
(exception:
Tender &
Export Packs).
2. For liquid or -Same primary

semisolid: addition packaging
of a new pack size material
(ex: 30 gm , 50gm -The new pack
cream). size should be
consistent with
the dosage
regimen &
N None P VDA
treatment
duration as
approved in any
Scientific
Reference
(exception:
Tender &
Export Packs).
In addition to
Pricing certificate (original to be seen)
Declaration Letter on Company paper states the old and New Capacity of the
Bottle
۱٦
Pack: Sterile
Requirements
Change in Container / Reporting
Condition
Closure System Category
NODCAR Stability Pricing
Change in any part of the • Not affecting

Primary packaging delivery، use، safety of
1 Material in Direct drug product AR 6M N VCA
Contact with the finished • No change in drug
Product formulation. product specification
In addition to
Change in any part of the
Primary packaging
The change does not
material NOT in Direct
concern a fundamental
Contact with the finished
part of the packaging
2 product formulation (such N None N VDA
material, which affects
as color of the flip-off
the delivery, use, safety
caps, change of needle-
of the finished product.
shield/ different plastic
used)
*No change in the
quantitative or
qualitative
Change in Primary
composition of the
Container/Closure shape
container.
in case there is a change
3 *The change does not N 6M N VCA
in the headspace or
concern a fundamental
change in the surface/
part of the packaging
volume ratio.
material, which affects
the delivery, use, safety
of the finished product
۱۷
In addition to
Declaration Letter on Company paper states the old and New Capacity of the Bottle
*New pack size should

be consistent with the
posology and treatment
duration as approved in
the summary of
Adding/ Deletion of pack product characteristics
4 size (number of the (exception: Tender & N None P VDA
unites) Export Packs).
*The primary
packaging material
remains the same.
*Except in Single Unit
Dose Dosage Forms.
In addition to
Pricing certificate (original to be seen)
۱۸
Common Pack Administrative Documents:
Covering Letter from the applicant Describing the reasons for the required change in details
stamped"
Payment receipt. 1000 LE
Valid registration license In case the registration license is not valid please submit
an approval for renewal and in case of tentative
registration license an extension for the license
Variation Notification form According to template attached

NODCAR certificate of analysis In case of Appeals if you need to prove a pack that is not
mentioned in Registration License
Copy of CPP ( and see original one )
Declaration letter from the license holder

clarifying type of the change needed In case of imported / bulk / under license
" Signed and stamped"
Declaration Letter According to template attached
stamped"
۱۹
Manufacturer of Active Ingredient(s)
Requirements
Reporting
Variation Item Category
Dissolution
NODCAR Stability
/Bioequivalence
Change / addition of
Manufacturer of the Active AI* 6M* D1* VDA
Ingredient(s)
Change in Name of Manufacturer N None N VDA
of Active Ingredient(s)
Final Approval for change /
addition of Manufacturer of N None N VDA
Active Ingredient(s)
* Requirements (where AI and D1 are Conditions of release) are done on first

production batch from new manufacturer of API at:
• 2 years from date of manufacturing of the first production For Final License.
• Within the period of license validity For Tentative License.
N.B:
In case of tentative license, the requirements of tentative license should be
fulfilled on Pre-determined main supplier within the period of license validity.
۲۰
Others:
Requirements*
Reporting
Variation Item
Category
Process
NODCAR Stability
validation
Change in Applicant N None N VDA
Change in Name/Address of N None N VDA

Product License Holder
Change in Name of Manufacturer N None N VDA

of Finished Products
Changing of product license
holder/Market Authorization N None N VDA
Holder
Change in the site for total process
(bulk manufacturer + packaging + AI** 6M*** upon request VDA
batch control + testing)
Change in Primary Packaging AI** 6M*** upon request VDA
Site
Change in Secondary Packaging N None N VDA
Site
Change or addition manufacturer
supplies the solvent for the N None N VDA
product
* Requirements (where AI is Condition of release) are done on first three

consecutive production batches from new Manufacturer of Finished Product/
Primary Packaging Site.
** Analysis registration (AR) must be done on the first production batch if

finished product was not analyzed at NODCAR registration department
before.
*** Accelerated Stability Study (6M) must be submitted at:

• 30 months from date of Approval on change /addition new Manufacturer of
Finished Product/ Primary Packaging Site
• Within the period of license validity For Tentative License.

After which Production is stopped until all requirements are fulfilled.
۲۱
Attachments
• Appendix I: Declaration Letter.
• Appendix II: Variation Notification form.
• Appendix III: Composition Form
• Appendix IV: Comparison Composition Form
• Appendix V: Dosage Form List
• Appendix VI: Narrow Therapeutic Range Drugs.
• Appendix VII: Reference List.
• Appendix VIII: Abbreviations.
۲۲
‫‪1 st Edition of Egyptian Variation Guidelines 3/2018‬‬
‫‪• Appendix I: Declaration Letter.‬‬
‫اﻟﺴﯿﺪ اﻟﺪﻛﺘﻮر ‪ /‬رﺋﯿﺲ اﻹدارة اﻟﻤﺮﻛﺰﯾﺔ ﻟﻠﺸﺌﻮن اﻟﺼﯿﺪﻟﯿﺔ‪.‬‬

‫ﺗﺤﯿﺔ طﯿﺒﺔ وﺑﻌﺪ‪،،،،،‬‬
‫ﺑﺨﺼﻮص اﻟﻤﺴﺘﺤﻀﺮ اﻻﺗﻲ‪:‬‬
‫‪Trade Name:‬‬
‫‪Generic Name:‬‬
‫‪Strength:‬‬
‫‪Dosage Form:‬‬
‫‪Applicant Company :‬‬
‫‪License Holder :‬‬
‫‪Manufacturer:‬‬
‫‪Reg. No.:‬‬
‫‪-۱‬ﻧﻔﯿﺪ ﺳﯿﺎدﺗﻜﻢ ﻋﻠﻤﺎ ً ﺑﺄن اﻟﺴﯿﺪ اﻟﺪﻛﺘﻮر‪ ................................/‬وﺑﯿﺎﻧﺎﺗﮫ ﻛﺎﻵﺗﻲ‪:‬‬
‫رﻗﻢ إﺛﺒﺎت اﻟﺸﺨﺼﯿﺔ‪:‬‬
‫ﺑﺮﯾﺪه اﻹﻟﻜﺘﺮوﻧﻲ‪:‬‬
‫ﻓﺎﻛﺲ‪:‬‬
‫رﻗﻢ ﻣﻮﺑﯿﻞ‪:‬‬
‫ھﻮ اﻟﻤﻔﻮض ﻣﻦ ﻗﺒﻞ اﻟﺸﺮﻛﺔ ﻟﺘﻘﺪﯾﻢ‪ ،‬ﻣﺘﺎﺑﻌﺔ وإﻧﮭﺎء طﻠﺒﺎت اﻟﻤﺘﻐﯿﺮات اﻟﺨﺎﺻﺔ‪.‬‬
‫‪-۲‬ﻧﺘﻌﮭﺪ ﻧﺤﻦ ﺷﺮﻛﺔ ‪ ................‬ﺑﺄن‪:‬‬
‫• اﻹﺧﻄﺎر اﻟﻤﻘﺪم ھﻮ أﺧﺮ إﺧﻄﺎر ﺻﺎدر ﻟﻠﻤﺴﺘﺤﻀﺮ وھﺬا ﺗﻌﮭﺪ ﻣﻨﺎ ﺑﺬﻟﻚ‪.‬‬
‫• ﺟﻤﯿﻊ اﻟﻤﺴ��ﺘﻨﺪات اﻟﻤﻘﺪﻣﺔ ﺑﺎﻟﻤﻠﻒ ﺻ��ﺤﯿﺤﺔ وﻋﻠﻰ ﻣﺴ��ﺌﻮﻟﯿﺔ اﻟﺸ��ﺮﻛﺔ وأﻧﮫ ﻣﺮﻓﻖ ﺟﻤﯿﻊ ﻣﻮاﻓﻘﺎت اﻟﻤﺘﻐﯿﺮات اﻟﺴ��ﺎﺑﻘﺔ‬
‫اﻟﺨﺎﺻﺔ ﺑﮫ وھﺬا ﺗﻌﮭﺪ ﻣﻨﺎ ﺑﺬﻟﻚ‪.‬‬
‫ﻣﺮﻓﻖ‪:‬‬
‫‪-۱‬‬
‫‪-۲‬‬
‫• ﻟﻢ ﯾﺘﻢ إﻧﺘﺎج‪/‬اﺳﺘﯿﺮاد أو ﺗﺪاول اﻟﻤﺴﺘﺤﻀﺮ ﺑﺎﻟﺴﻮق اﻟﻤﺤﻠﻲ‬
‫* ﺗﻢ إﻧﺘﺎج‪ /‬اﺳﺘﯿﺮاد اﻟﻤﺴﺘﺤﻀﺮ وﻣﺮﻓﻖ ﺟﻤﯿﻊ اﻟﺪراﺳﺎت اﻟﺘﻲ ﺗﻢ إﺟﺮاءھﺎ‪.‬‬
‫ﻣﺮﻓﻖ اﻟﺪراﺳﺎت )ﻓﻲ ﺣﺎﻟﺔ أن ﺗﻢ إﻧﺘﺎﺟﮫ(‪:‬‬
‫‪-۱‬‬
‫‪-۲‬‬
‫وﺗﻔﻀﻠﻮا ﺑﻘﺒﻮل ﻓﺎﺋﻖ اﻟﺘﺤﯿﺔ واﻟﺘﻘﺪﯾﺮ‪.‬‬
‫ﺧﺘﻢ اﻟﺸﺮﻛﺔ‬ ‫رﺋﯿﺲ ﻣﺠﻠﺲ ادارة اﻟﺸﺮﻛﺔ‬
‫‪۲۳‬‬
• Appendix II: Variation Notification form.
Trade Name:
Generic Name/ strength :
Dosage Form:
Applicant:
License Holder :
Manufacturer:
Reg. No.
Current Situation
Proposed Change
 Category of the change:

Notification Approval (N)
Details of the change
Variation Department Approval (VDA)

Variation Committee Approval (VCA)

 I declare that there are no other changes except mentioned above.
‫ﺧﺘﻢ اﻟﺸﺮﻛﺔ‬ ‫رﺋﯿﺲ ﻣﺠﻠﺲ ادارة اﻟﺸﺮﻛﺔ‬
۲٤
Appendix III: Composition Form
1. Submit composition certificate on the company letter head signed and stamped
2. Check spelling of trade name and active ingredient(s) according to Registration license, It's
(their) hydrate(s) and salt form(s) with its (their) quantity (ies) per unit dose is (are) specified.
3. Separate active and inactive ingredients in composition
4. Arrange the item of composition as the following
Ingredients Quantity Specifications Function
Total Weight Must be Mentioned

5. Unify the units of the ingredient's amount in the composition.
6. Specify the adjusted PH in case of presence of alkalinizer or any other PH adjuster.
7. Write the ingredients without abbreviations.
8. Write the coloring index of any coloring ingredient and determine the grade of the
following ingredients :
- Povidone
- Powdered Cellulose
- Hydroxy propyl methyl cellulose (HPMC)(Hypromellose)
- Methacrylic acid
- Methy cellulose
- Hydroxy ethyl cellulose
- Microcrystalline cellulose (MCC)
- Polyethylene glycol
- Poly vinyl pyrrolidine (PVP)
- Lactose (monohydrate – anhydrous)
- Colloidal silicon dioxide
9. In Case of Coated tablets: write the core and coat separated, mention the weight of tablet.
10. Hard gelatin capsules: *write the body and cap. Separated, mention the color and size of capsule.
*Composition of the capsule shell on the supplier head letter.
* In case of pellets- granules or premix, composition on supplier letterhead should be
Attached & attach the calculation of pellets weight /capsule on company letterhead
۲٥
11. N.B: * Please write the Composition Per:
1gm 1ml 5ml Dosage Form

A. Cream A. Drops A. Syrup A. Tablet
B. Ointment B. Vial (if multiple dose) B. Suspension B. Capsule
C. Powder for C. Ampoule (if multiple (After Re- C. Patch
external use dose) constitution) D. Sachet4
D. Gel C. Emulsion E. Suppository
E. Paste D. Elixir F. Vial contains
powder5(if single
dose)
G. Ampoule(if single
dose)
H. Prefilled Syringe
I. Cartridge
J. Lotion
K. Topical Solution
12. In case of powder for reconstitution write the amount of water used to reconstitute the
powder & the final volume reached.
13. In case that the composition contains any type of parabens, please calculate it
according to the technical committee decision in 18/2/2016:
‫ ﺒﺤﯿث ﻻ ﺘﺘﺨطﻰ اﻟﺠرﻋﺔ‬%٠,٢ ‫ اﻟﻰ‬%٠,٠١٥ ‫ ﯿﺘم اﺴﺘﺨداﻤﻬﺎ ﺒﺘرﻛﯿز ﯿﺘراوح ﻤن‬: Methylparaben ‫ ﺒﺎﻟﻨﺴﺒﺔ ﻟﻤﺎدة اﻟـ‬-١
.‫ﯿوم( ﻓﻰ اﻟﻤﺴﺘﺤﻀرات اﻟﺘﻲ ﺘﻌطﻰ ﻋن طرﯿق اﻟﻔم دون اﻟﺘﻘﯿد ﺒﻔﺌﺔ ﻋﻤرﯿﺔ ﻤﺤددة‬/‫ﻛﺠم‬/‫ ﻤﺠم‬١٠) ‫اﻟﯿوﻤﯿﺔ‬
‫ ﻓﻰ اﻟﻤﺴﺘﺤﻀرات اﻟﺘﻲ ﺘﻌطﻰ‬%٠,٠٦ ‫ اﻟﻰ‬%٠,٠٢ ‫ ﯿﺘم اﺴﺘﺨداﻤﻬﺎ ﺒﺘرﻛﯿز ﻤن‬: Propylparaben ‫ ﺒﺎﻟﻨﺴﺒﺔ ﻟﻤﺎدة اﻟـ‬-٢
.‫ﯿوم( وذﻟك ﻟﻸطﻔﺎل واﻟﻛﺒﺎر ﻋﻠﻰ ﺤد ﺴواء‬/‫ﻛﺠم‬/‫ ﻤﺠم‬٢) ‫ﻋن طرﯿق اﻟﻔم ﺒﺤﯿث ﻻ ﺘﺘﺨطﻰ اﻟﺠرﻋﺔ اﻟﯿوﻤﯿﺔ‬
‫ ﯿﺠب اﻻ ﺘزﯿد اﻟﺠرﻋﺔ ﻤن ﻫذﻩ اﻟﻤواد ﻤﺠﺘﻤﻌﺔ ﻋن‬Combination of Methyl & Propyl parabens ‫ ﺒﺎﻟﻨﺴﺒﺔ ﻟﻠـ‬-٣
.‫ﯿوم ﻤﻊ اﻻﻟﺘزام ﺒﺄﻻ ﯿﺘم ﺘﺠﺎوز اﻟﺠرﻋﺔ اﻟﯿوﻤﯿﺔ اﻟﻤﺴﻤوح ﺒﻬﺎ ﻟﻛل ﻤﻨﻬﻤﺎ ﻋﻠﻰ ﺤدة‬/‫ﻛﺠم‬/‫ﻤﺠم‬١٠
۲٦
First Edition of Egyptian Variation Guidelines 5/1/2018
• Appendix IV: Comparison Composition Form
Trade Name:
Generic Name/Strength:
Dosage Form:
Ingredients Old formula New formula Function [%change]* %change

allowance**
Total
* % change should be in absolute value.

* *From Guidelines
۲۷
• Appendix V: Dosage Form List
* Please write the product's dosage form as mentioned in the below table
Oral Dosage Forms
Tablet ‫أﻗﺮاص‬
Film coated tablet ‫أﻗﺮاص ﻣﻐﻠﻔﺔ‬
Sugar coated tablet ‫أﻗﺮاص ذات ﻛﺴﻮة ﺳﻜﺮﯾﺔ‬
Enteric coated tablet ‫أﻗﺮاص ذات ﻛﺴﻮة ﻣﻌﻮﯾﺔ‬
Extended release tablet ‫أﻗﺮاص ﻣﻤﺘﺪة اﻟﻤﻔﻌﻮل‬
Effervescent tablet ‫أﻗﺮاص ﻓﻮارة‬
Dispersible tablet ‫أﻗﺮاص ﻗﺎﺑﻠﺔ ﻟﻺﻧﺘﺸﺎر‬
Orodispersible tablet ‫أﻗﺮاص ﻗﺎﺑﻠﺔ ﻟﻠﺬوﺑﺎن ﺑﺎﻟﻔﻢ‬
Orally Disintegrating Tablet ‫أﻗﺮاص ﻟﻠﺬوﺑﺎن ﺑﺎﻟﻔﻢ‬
Hard gelatin capsule ‫ﻛﺒﺴﻮﻻت ﺻﻠﺒﮫ‬
Hard gelatin capsules containing enteric coated
‫ﻛﺒﺴﻮﻻت ﺗﺤﺘﻮى ﻋﻠﻰ ﺣﺒﯿﺒﺎت ذات ﻛﺴﻮة ﻣﻌﻮﯾﺔ‬
pellets
‫ﻛﺒﺴﻮﻻت ﺗﺤﺘﻮى ﻋﻠﻰ ﺣﺒﯿﺒﺎت ذات ﻛﺴﻮة ﻣﻌﻮﯾﺔ‬
granules
‫ﻛﺒﺴﻮﻻت ﺗﺤﺘﻮى ﻋﻠﻰ أﻗﺮاص ذات ﻛﺴﻮة ﻣﻌﻮﯾﺔ‬
minitablets
Soft gelatin capsule ‫ﻛﺒﺴﻮﻻت ﺟﯿﻼﺗﻨﯿﺔ رﺧﻮة‬
Enteric coated soft gelatin capsule ‫ﻛﺒﺴﻮﻻت ﺟﯿﻼﺗﻨﯿﺔ رﺧﻮة ذات ﻛﺴﻮة ﻣﻌﻮﯾﺔ‬
Powder in sachets for oral solution ‫ﺑﻮدرة ﻓﻰ أﻛﯿﺎس ﻟﻌﻤﻞ ﻣﺤﻠﻮل ﻟﻠﺘﻨﺎول ﺑﺎﻟﻔﻢ‬
Powder in sachets for oral suspension ‫ﺑﻮدرة ﻓﻰ أﻛﯿﺎس ﻟﻌﻤﻞ ﻣﻌﻠﻖ ﻟﻠﺸﺮب‬
Powder for oral suspension ‫ﺑﻮدرة ﻟﻌﻤﻞ ﻣﻌﻠﻖ ﻟﻠﺸﺮب‬
Oral suspension (‫ﻣﻌﻠﻖ ﻟﻠﺸﺮب )ﻋﻦ طﺮﯾﻖ اﻟﻔﻢ‬
Syrup ‫ﺷﺮاب‬
Oral liquid (‫ﻣﺤﻠﻮل ﻟﻠﺸﺮب)ﻋﻦ طﺮﯾﻖ اﻟﻔﻢ‬
Oral solution (‫ﻣﺤﻠﻮل ﻟﻠﺸﺮب)ﻋﻦ طﺮﯾﻖ اﻟﻔﻢ‬
Oral Emulsion (‫ﻣﺴﺘﺤﻠﺐ ﻟﻠﺸﺮب)ﻋﻦ طﺮﯾﻖ اﻟﻔﻢ‬
۲۸
Granules in sachets ‫ﺣﺒﯿﺒﺎت ﻓﻰ أﻛﯿﺎس‬

Granules in sachets for oral solution (‫ﺣﺒﯿﺒﺎت ﻓﻰ أﻛﯿﺎس ﻟﻌﻤﻞ ﻣﺤﻠﻮل ﻟﻠﺸﺮب )ﻋﻦ طﺮﯾﻖ اﻟﻔﻢ‬
Granules in sachets for oral suspension (‫ﺣﺒﯿﺒﺎت ﻓﻰ أﻛﯿﺎس ﻟﻌﻤﻞ ﻣﻌﻠﻖ ﻟﻠﺸﺮب)ﻋﻦ طﺮﯾﻖ اﻟﻔﻢ‬
Oral gel ‫ﺟﻞ ﻟﻠﻔﻢ‬
Lozenges ‫أﻗﺮاص ﻟﻺﺳﺘﺤﻼب‬
Elixir ‫أﻟﻜﺴﯿﺮ‬
Linctus ‫دواء ﻟﻠﻜﺤﮫ‬
Gargles ‫ﻏﺮﻏﺮة‬
Mouth Wash ‫ﻣﻀﻤﻀﺔ‬
Gums ‫ﻋﻠﻜﺔ‬
Pill ‫أﻗﺮاص‬
Pilules Microspheres ‫ﺣﺒﯿﺒﺎت‬
Sublingual tablets ‫أﻗﺮاص ﺗﺤﺖ اﻟﻠﺴﺎن‬
Caplets ‫أﻗﺮاص‬
Melt tablets ‫أﻗﺮاص ﺗﻨﺼﮭﺮ‬
Quick tablets
Flash tablets ‫أﻗﺮاص ﺳﺮﯾﻌﺔ اﻟﺬوﺑﺎن‬
Dragees ً‫أﻗﺮاص ﺳﺮﯾﻌﺔ اﻟﺬوﺑﺎن ﺟﺪا‬
Lactab ‫ﻻﻛﺘﺎب‬
Sustained release tablet ‫أﻗﺮاص ﻣﻤﺘﺪة اﻟﻤﻔﻌﻮل‬
Controlled release tablet ‫أﻗﺮاص ﻣﻤﺘﺪة اﻟﻤﻔﻌﻮل‬
Modified release tablet ‫أﻗﺮاص ﻣﻤﺘﺪة اﻟﻤﻔﻌﻮل‬
Extended release tablet ‫أﻗﺮاص ﻣﻤﺘﺪة اﻟﻤﻔﻌﻮل‬
Retard tablet ‫أﻗﺮاص ﻣﻤﺘﺪة اﻟﻤﻔﻌﻮل‬
Enteric Coated capsule ‫ﻛﺒﺴﻮﻻت ﻣﻤﺘﺪة اﻟﻤﻔﻌﻮل ذو ﻛﺴﻮه ﻣﻌﺪﯾﺔ‬
Sustained release capsule ‫ﻛﺒﺴﻮﻻت ﻣﻤﺘﺪة اﻟﻤﻔﻌﻮل‬
Controlled release capsule ‫ﻛﺒﺴﻮﻻت ﻣﻤﺘﺪة اﻟﻤﻔﻌﻮل‬
Modified release capsule ‫ﻛﺒﺴﻮﻻت ﻣﻤﺘﺪة اﻟﻤﻔﻌﻮل‬
۲۹
Extended release capsule ‫ﻛﺒﺴﻮﻻت ﻣﻤﺘﺪة اﻟﻤﻔﻌﻮل‬

Retard Capsule ‫ﻛﺒﺴﻮﻻت ﻣﻤﺘﺪة اﻟﻤﻔﻌﻮل‬
Depotabs. ‫أﻗﺮاص ذو طﺒﻘﺔ ﻣﺨﺘﺰﻧﺔ‬
Oral Pastes ‫ﻣﻌﺠﻮن ﻟﻠﻔﻢ‬
Extended Release Film Coated tablet ‫أﻗﺮاص ﻣﻐﻠﻔﺔ ﻣﻤﺘﺪة اﻟﻤﻔﻌﻮل‬
Extended Release Granule For oral Suspension ‫ﺣﺒﯿﺒﺎت ﻣﻤﺘﺪة اﻟﻤﻔﻌﻮل ﻟﻌﻤﻞ ﻣﻌﻠﻖ ﻟﻠﺸﺮب‬
Irrigant
Pastille ‫ﺑﺴﺘﻠﯿﺔ‬
Extended Release Coated Pellets ‫ﺣﺒﯿﺒﺎت ﻣﻤﺘﺪة اﻟﻤﻔﻌﻮل‬
Delayed Release ‫ﻣﺘﺄﺧﺮة اﻷﻧﻄﻼق‬
Chewable tablet ‫أﻗﺮاص ﻟﻠﻤﻀﻎ‬
Topical Dosage Forms
Topical cream ‫ﻛﺮﯾﻢ ﻣﻮﺿﻌﻲ‬
Topical ointment ‫ﻣﺮھﻢ ﻣﻮﺿﻌﻲ‬
Topical lotion ‫ﻟﻮﺳﯿﻮن ﻣﻮﺿﻌﻲ‬
Topical solution ‫ﻣﺤﻠﻮل ﻣﻮﺿﻌﻲ‬
Topical suspension ‫ﻣﻌﻠﻖ ﻣﻮﺿﻌﻲ‬
Topical spray ‫ﺳﺒﺮاي ﻣﻮﺿﻌﻲ‬
Topical powder ‫ﺑﻮدرة ﻣﻮﺿﻌﯿﺔ‬
Topical gel ‫ﺟﻞ ﻣﻮﺿﻌﻲ‬
Transdermal patchs ‫ﻻﺻﻘﺎت ﺟﻠﺪﯾﺔ ﻟﮭﺎ ﺗﺄﺛﯿﺮ ﻋﻀﻮي‬
Topical Foam ‫ﻣﺤﻠﻮل رﻏﻮي ﻣﻮﺿﻌﻲ‬
Topical Emulsion ‫ﻣﺴﺘﺤﻠﺐ ﻣﻮﺿﻌﻲ‬
Liniment ‫ﻟﺒﺨﺔ‬
Medicated dressings ‫ﺿﻤﺎدات طﺒﯿﺔ‬
Tulles ‫ﺿﻤﺎدات طﺒﯿﺔ‬
Emulgel ‫اﯾﻤﻠﺠﻞ‬
Shampoo ‫ﺷﺎﻣﺒﻮ‬
۳۰
Massage cream ‫ﻛﺮﯾﻢ ﻣﺴﺎج‬

Poultices ‫ﻛﻤﺎدات ﻟﺒﺨﺔ‬
Rectal preparations
Rectal cream ‫ﻛﺮﯾﻢ ﺷﺮﺟﻲ‬
Rectal ointment ‫ﻣﺮھﻢ ﺷﺮﺟﻲ‬
Rectal suppositories ‫أﻗﻤﺎع ﺷﺮﺟﯿﺔ‬
Rectal foam ‫ﻣﺤﻠﻮل رﻏﻮي ﺷﺮﺟﻲ‬
Enema ‫ﺣﻘﻨﺔ ﺷﺮﺟﯿﺔ‬
Vaginal preparations
Vaginal suppositories ‫أﻗﻤﺎع ﻣﮭﺒﻠﯿﺔ‬
Vaginal cream ‫ﻛﺮﯾﻢ ﻣﮭﺒﻠﻲ‬
Intravaginal cream ‫ﻛﺮﯾﻢ ﻣﮭﺒﻠﻲ‬
Vaginal ovules ‫ﺑﻮﯾﻀﺎت ﻣﮭﺒﻠﯿﺔ‬
Vaginal pessaries ‫أﻗﻤﺎع ﻣﮭﺒﻠﯿﺔ‬
Vaginal tablets ‫أﻗﺮاص ﻣﮭﺒﻠﯿﺔ‬
Injections
Sterile Water for injection ‫ﻣﺎء ﻣﻌﻘﻢ ﻟﻠﺤﻘﻦ‬
Solution for intramuscular injection ‫ﻣﺤﻠﻮل ﻟﻠﺤﻘﻦ اﻟﻌﻀﻠﻲ‬
Solution for intravenous injection ‫ﻣﺤﻠﻮل ﻟﻠﺤﻘﻦ اﻟﻮرﯾﺪي‬
Solution for subcutenous injection ‫ﻣﺤﻠﻮل ﻟﻠﺤﻘﻦ ﺗﺤﺖ اﻟﺠﻠﺪ‬
Solution for intravenous infusion ‫ﻣﺤﻠﻮل ﻟﻠﺘﻨﻘﯿﻂ اﻟﻮرﯾﺪي‬
Solution for I.M./I.V. injection ‫ﻣﺤﻠﻮل ﻟﻠﺤﻘﻦ اﻟﻌﻀﻠﻲ واﻟﻮرﯾﺪي‬
Solution for I.M./I.V./S.C. injection ‫ﻣﺤﻠﻮل ﻟﻠﺤﻘﻦ اﻟﻌﻀﻠﻲ أواﻟﻮرﯾﺪي أوﺗﺤﺖ اﻟﺠﻠﺪ‬
Concentrate for intramuscular injection ‫ﻣﺤﻠﻮل ﻣﺮﻛﺰ ﻟﻠﺤﻘﻦ اﻟﻌﻀﻠﻲ‬
Concentrate for intravenous injection ‫ﻣﺤﻠﻮل ﻣﺮﻛﺰ ﻟﻠﺤﻘﻦ اﻟﻮرﯾﺪي‬
Concentrate for subcutenous injection ‫ﻣﺤﻠﻮل ﻣﺮﻛﺰ ﻟﻠﺤﻘﻦ ﺗﺤﺖ اﻟﺠﻠﺪ‬
Concentrate for intravenous infusion ‫ﻣﺤﻠﻮل ﻣﺮﻛﺰ ﻟﻠﺘﻨﻘﯿﻂ اﻟﻮرﯾﺪي‬
Concentrate for I.M./I.V. injection ‫ﻣﺤﻠﻮل ﻣﺮﻛﺰ ﻟﻠﺤﻘﻦ اﻟﻌﻀﻠﻲ واﻟﻮرﯾﺪي‬
۳۱
Concentrate for I.M./I.V./S.C. injection ‫ﻣﺤﻠﻮل ﻣﺮﻛﺰ ﻟﻠﺤﻘﻦ اﻟﻌﻀﻠﻲ أواﻟﻮرﯾﺪي أوﺗﺤﺖ اﻟﺠﻠﺪ‬
Implantable Pellet ‫أﻗﺮاص ﺗﻮﺿﻊ ﺗﺤﺖ اﻟﺠﻠﺪ‬
Inhalations
Dry powder for inhalation ‫ﺑﻮدرة ﺟﺎﻓﺔ ﻟﻺﺳﺘﻨﺸﺎق‬
Turbohaler (= dry powder inhaler)
Aerosol inhalation
Accuhaler (dry powder for inhalation)
Powder in sachets for solution for inhalation
۳۲
• Appendix VI: Narrow Therapeutic Range Drugs.
A narrow Therapeutic Index:

Is defined medically as the ratio between the average effective dose and the average
lethal dose. It is an extremely close margin between an effective concentration of a
therapeutic drug circulating in the blood and a fatal concentration.
Aminophylline Tablets, ER Tablets

Carbamazepine Tablets, Oral
Suspension Clindamycin
Hydrochloride Capsules Clonidine
Hydrochloride Tablets Clonidine
Transdermal Patches Dyphylline
Tablets
Disopyramide Phosphate Capsules, ER Capsules
Ethinyl Estradiol/Progestin Oral Contraceptive
Tablets Guanethidine Sulfate Tablets
Isoetharine Mesylate Inhalation
Aerosol Isoproterenol Sulfate Tablets
Lithium Carbonate Capsules, Tablets, ER Tablets
Metaproterenol Sulfate Tablets
Minoxidil Tablets
Oxtriphylline Tablets, DR Tablets, ER Tablets
Phenytoin, Sodium Capsules (Prompt or Extended), Oral Suspension
Prazosin Hydrochloride Capsules
Primidone Tablets, Oral Suspension
Procainamide Hydrochloride, Capsules, Tablets, ER Tablets
Quinidine Sulfate Capsules, Tablets, ER Tablets
Quinidine Gluconate Tablets, ER Tablets
Theophylline Capsules, ER Capsules, Tablets, ER Tablets
Valproic Acid Capsules, Syrup
Divalproex, Sodium DR Capsules, DR Tablets
Warfarin, Sodium Tablets
Others (Specify & submit reference document from EMA or US FDA)
۳۳
1st Edition of Egyptian Variation Guidelines 2/2018
• Appendix VII: Reference List.
Reference
The Website
Country
http://www.accessdata.fda.gov/scripts/cder/daf/?source
FDA =govdelivery&utm_medium=email&utm_source=govdelive
ry
Spain - https://www.aemps.gob.es/cima/fichasTecnicas.do?meto
AEMPS do=detalleForm
France (
http://agence-prd.ansm.sante.fr/php/ecodex/index.php
ANSM )
Belgium http://www.fagg-afmps.be/fr/items/banque_donnees
Australia (
https://www.ebs.tga.gov.au
TGA )
https://health-products.canada.ca/dpd-bdpp/index-
Canada
eng.jsp
http://www.mhra.gov.uk/spc-pil/?prodName=DO-
UK ( MHRA
DO%20CHESTEZE&subsName=&pageID=ThirdLevel&sea
)
rchTerm=theophylline#retainDisplay
https://www.pharmnet-bund.de/dynamic/en/drug-
Germany
information-system/index.html
Swissmedic http://ch.oddb.org
http://db.cbg-
The
meb.nl/ords/f?p=111:1:0:::SESSION:P0_DOMAIN,P0_LA
Netherland
NG:H,EN
http://www.produktresume.dk/docushare/dsweb/helpd
Denmark
esk
https://farmaci.agenziafarmaco.gov.it/bancadatifarmaci/
Italy
cerca-per-principio-attivo
Ireland https://www.hpra.ie/homepage/medicines/medicines-
( HPRA ) information/find-a-medicine
Sweden https://lakemedelsverket.se/english/
Portugal http://app7.infarmed.pt/infomed/inicio.php
۳٤
New
http://www.medsafe.govt.nz/regulatory/DbSearch.asp
Zealand
Norway https://legemiddelverket.no/English
http://www.fimea.fi/web/en/databases_and_registeries/
Finland
spcs/human_medicinal_products
http://www.pmda.go.jp/english/review-
Japan
services/reviews/approved-information/drugs/0002.html
https://aspregister.basg.gv.at/aspregister/faces/aspregis
Austria ter.jspx?_afrLoop=45028630015782264&_afrWindowMod
e=0&_adf.ctrl-state=1b7ups43h2_4
Iceland https://www.serlyfjaskra.is
http://www.ema.europa.eu/ema/index.jsp?curl=pages/i
EMA ncludes/medicines/medicines_landing_page.jsp&mid=WC
0b01ac058001ce7e
http://www.pdr.net/browse-by-drug-name
PDR
Eudra http://eudragmdp.ema.europa.eu/inspections/gmpc/sea
Inspection rchGMPCompliance.do
FDA
https://www.accessdata.fda.gov/scripts/inspsearch/
Inspection
۳٥
• Appendix VIII: Abbreviations.
NODCAR: The National Organization for Drug Control & Research

N: Notification
VDA: Variation Department Approval
VCA: Variation Committee Approval
TCA: Technical Committee Approval
CPP: Certificate of pharmaceutical products
COA: Certificate of Analysis
BE: Bioequivalence
MAH: Market Authorization Holder
۳٦

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1 st Edition of Egyptian Variation Guidelines 3/2018

Egyptian Variation Guidelines

Requirements to be fulfilled according to the type of change in the guidelines:

Composition: For Non- Sterile Products

The total additive effect of all

Change in weight of capsule shell

Formulation changes : Modified Requirements

Calculations of Premix on company paper

Change in Finished Product Specification:

Change in Physical Character of Finished Product:

Changing / Clarifying Active Ingredient Specification:

Common Administrative Documents:

Payment receipt. 1000 LE

Variation Notification form According to template attached

NODCAR certificate of analysis

Previous importation approvals In case of clarification of salt equivalence / Premix

Comparison table between old and According to attached template

Declaration letter from the license holder

Pack: Non Sterile

1 Changes - Adding or • The Change

2 Changes 1-Change in the -Liquid or semi

2-Change in size -Liquid or semi

3. Deletion of a - Solid dosage

4-Change to a new -The new

4 Adding / 1. For solid dosage -Same primary

2. For liquid or -Same primary

Change in any part of the • Not affecting

*New pack size should

Common Pack Administrative Documents:

Payment receipt. 1000 LE

Variation Notification form According to template attached

Declaration letter from the license holder

Manufacturer of Active Ingredient(s)

* Requirements (where AI and D1 are Conditions of release) are done on first

• Within the period of license validity For Tentative License.

Change in Applicant N None N VDA

Change in Name/Address of N None N VDA

Change in Name of Manufacturer N None N VDA

* Requirements (where AI is Condition of release) are done on first three

** Analysis registration (AR) must be done on the first production batch if

*** Accelerated Stability Study (6M) must be submitted at:

• Within the period of license validity For Tentative License.

• Appendix I: Declaration Letter.

• Appendix II: Variation Notification form.

• Appendix III: Composition Form

• Appendix IV: Comparison Composition Form

• Appendix V: Dosage Form List

• Appendix VI: Narrow Therapeutic Range Drugs.

• Appendix VII: Reference List.

• Appendix VIII: Abbreviations.

‫‪• Appendix I: Declaration Letter.‬‬

‫اﻟﺴﯿﺪ اﻟﺪﻛﺘﻮر ‪ /‬رﺋﯿﺲ اﻹدارة اﻟﻤﺮﻛﺰﯾﺔ ﻟﻠﺸﺌﻮن اﻟﺼﯿﺪﻟﯿﺔ‪.‬‬

• Appendix II: Variation Notification form.

 Category of the change:

Variation Department Approval (VDA)

Variation Committee Approval (VCA)

 I declare that there are no other changes except mentioned above.

‫ﺧﺘﻢ اﻟﺸﺮﻛﺔ‬ ‫رﺋﯿﺲ ﻣﺠﻠﺲ ادارة اﻟﺸﺮﻛﺔ‬

Appendix III: Composition Form

Total Weight Must be Mentioned

11. N.B: * Please write the Composition Per:

1gm 1ml 5ml Dosage Form

• Appendix IV: Comparison Composition Form