the egyptian guidelines for registration of herbal medicines · dossier contents: ... even if the...
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The Egyptian Guidelines for Registration of Herbal Medicines
January 18
2016
D.S. Page 1
Contents Introduction ............................................................................................................ 2
Purpose and objectives of the guidelines .................................................................... 2
Specific objectives .................................................................................................... 2
Definition of herbal medicines ................................................................................... 3
Herbal substances: ................................................................................................... 3
Herbal preparations: ................................................................................................ 3 Classification of herbal medicines: ............................................................................. 4 References/ requirements for evidence of safely use of herbal medicines: ..................... 5
Minimum requirements for assessment of the efficacy of herbal medicines ................ 7 Efficacy claims categories for herbal medicinal products ............................................ 7
Quality assurance of herbal medicinal products ........................................................ 10
Coordinating quality control .................................................................................... 10
· Adherence to GACP, GMP and GLP guidelines: ........................................................ 10
· Setting specifications: ........................................................................................... 10
· Quality control measures. ..................................................................................... 11
Vitamins and minerals in herbal medicinal products for human use ............................. 13
Product information and labeling ............................................................................ 14
Pharmacovigilance ................................................................................................. 14
Administrative Procedures and Documentation:........................................................ 15
General Requirements ............................................................................................ 15
Applicant: ............................................................................................................. 15
The responsibilities of the local agent, applicant and manufacturer: ............................ 15
Applications .......................................................................................................... 15
Documentation ..................................................................................................... 16
Processing of applications ....................................................................................... 17
Registration........................................................................................................... 17
Dossier Contents: ................................................................................................... 19 Annex .1: Forms ................................................................................................................. 20 Application Form:.................................................................................................. 20 Product composition template :......................................................................................... 21 pamphlet template : ........................................................................................................... 23 SmPC Form: .......................................................................................................... 25 Commetiments Form: ............................................................................................ 26 Annex .2: Check lists ............................................................................................. 27 Check list no.1: New –Registration Checklist ............................................................. 27 : CHECKLIST for re –registration ......................................................... 30
Check list no.2: NODCAR CHECKLIST ........................................................................ 33 Check list no.3: STABILITY CHECKLIST....................................................................... 34 Check list no.4: PRICING CHECKLIST ......................................................................... 35 Check list no.5: FINAL REGISTRATION CHECKLIST ...................................................... 36
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Introduction
The term “herbal medicine” is medicinal products that contain as active
ingredients aerial or underground parts of plants, or other plant materials, or
combinations thereof, whether in the crude state or as plant preparations.
Herbal medicine represents an important component part of health care system
for the population that relies on natural remedies for their health care needs.
Currently, herbal medicines are used to treat a wide range of illnesses.
Purpose and objectives of the guidelines
The purpose of this document is to propose a framework for the registration of
herbal medicines. The proposed framework is based on the criteria of
pharmaceutical quality, safety of use and therapeutic efficacy; it should
accelerate the registration and circulation of standardized herbal medicines of
consistent quality and encourage the development of herbal medicines from
traditionally used Egyptian herbs and plants.
Specific objectives
The specific objectives of the guidelines are as follows:
1. To set a definition of herbal medicines;
2. To propose a classification scheme for herbal medicines;
3. To propose general minimum regulatory requirements for the registration of
herbal medicines including minimum requirement to assess safety, efficacy and
quality.
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Definition of herbal medicines Any finished, labeled medicinal product (for oral , external or inhalation uses), exclusively
containing as active substances one or more herbal substances or one or more herbal
preparations, or one or more such herbal substances in combination with one or more
such herbal preparations; Herbal medicines may contain conventional excipients in
addition to the plant-based active ingredients. In some cases, they may also contain, by
tradition, natural organic or inorganic ingredients which are not of plant origin. However,
products to which chemically-defined active substances have been added, including for
example, synthetic compounds and/or isolated constituents from herbal materials e.g.
(Atropine, Diosgenin) are not considered to be herbal medicinal products.
Herbal medicinal products may contain vitamins/minerals as supplementary
substances.
New registration of herbal medicine will be considered for products containing 1 to 5
herbal medicine components but no herbal product may contain more than five herbal
components.
WHO- EMA- MHRA
Herbal substances:
All mainly whole, fragmented or cut plants, plant parts, algae, fungi, lichen in an
unprocessed, usually dried, form, but sometimes fresh. Certain exudates that have not
been subjected to a specific treatment are also considered to be herbal substances.
Herbal substances are precisely defined by the plant part used and the botanical name
according to the binomial system (genus, species, variety and author);
Herbal preparations:
They are obtained by subjecting herbal substances to treatments such as extraction,
distillation, expression, fractionation, purification, concentration or fermentation.
These include comminuted or powdered herbal substances, tinctures, extracts,
fractions (Silymarins, Ginsenosides, Curcuminoides; ….etc.) , essential oils, expressed
juices and processed exudates.
EMA
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Classification of herbal Medicine:
Category I: Traditional herbal medicines / herbs with well-established use
Traditional herbal medicines are defined as the medicinal herbs (individually or in
combination) which are used inside Arab Republic of Egypt for a period of not less than 15
years and they should be supported by references for safety and efficacy. This category
also includes traditional medicine formulations to which minor changes have been made.
Herbs with well-established use are defined as the medicinal herbs (individually or in
combination) which are mentioned in different pharmacopeia or monographs.
Category II: New herbal medicines
Herbal medicines (single or mixture of herbs) can be considered “new herbal medicines” if
not supported by references for safety and efficacy, never used within the community or
region, used for only a short period of time, used to a very small extent (few uses in a
small number of patients), or used in a new combination of herbal substances never
combined before.
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References /Requirements for evidence of safely use of herbal medicines
(WHO References for safety of category I
Any assessment of herbal medicines must be based on a clear identification
and characterization of the constituents.
A literature search must be performed. This should include general literature such as:
Official pharmacopeia or extra pharmacopeia (e.g. Martindale) {from reference countries approved by technical committee}.
Official monographs (such as WHO monographs) {from reference countries approved by technical committee}.
Handbooks Specific to this form of therapy.
Other authoritative data related to herbal medicines, if available, database searches in online or offline databases, e.g. the WHO adverse drug reaction database, National Library of Medicine’s Medline, etc.
Articles published in scientific journals with impact factor NLT 1 (Thomson Reuter) may be submitted but they are not acceptable as the sole source of evidence to support the
safety and efficacy. Toxicological information on single ingredients should be assessed for its relevance to the herbal medicines. The need for additional data or additional new tests would be considered in light of the information requirements for new herbal medicines. Many of the tests required for these new medicines may be replaced by documented experience. However, it would be carefully considered whether all questions on toxicology raised can be answered adequately and in a plausible way by the available knowledge. Particular attention would be given to effects that cannot be readily detected empirically, e.g . genotoxicity. The assessment seeks to determine if there is sufficient information to guarantee safe use in vulnerable populations such as pregnant or lactating women and in small children. In assessing safety in pregnancy, information on traditional misuse, e.g. as an agent to induce abortion, should be assessed.
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Requirements for safety of category II
The safety data required for registration of new herbal medicines will be identical
for any new substance:
• Single-dose toxicity
• Repeated-dose toxicity
o Acute toxicity: to determine lethal dose in 50 %( LD50) in different species of small
animals.
o Chronic toxicity: in varying doses in large animals to determine the effect on
development, vital organ functions, blood chemistry and picture.
• Chronic toxicity
• Organ-targeted toxicity, if necessary
• Immunotoxicity
• Embryo/foetal and prenatal toxicity, if necessary
• Mutagenicity/genotoxicity, if necessary
• Carcinogenicity, if necessary
• Local tolerance.
In special circumstances, such as new combinations of well-known substances,
some of these studies may not be necessary.
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Minimum requirements for assessment of efficacy of herbal medicines Efficacy claims for herbal medicines are made with respect to:
• Acute diseases, which have a rapid onset and are of relatively short duration;
• Chronic diseases, which have a slow onset and last for a long period of time;
• Health enhancing effects,
Patients suffering from certain health conditions, e.g. loss of appetite, hay fever,
menopause, sometimes recover without any medical intervention.
The efficacy should be supported by data in existing well-established documents
such as pharmacopoeia and monographs as well as other authoritative documents
such as WHO monographs. Pre-clinical and clinical data of efficacy may or may not
be required depending on conditions shown in table 1 & 2. The efficacy should be
proven by pre-clinical data and clinical trials or well-established documentation.
D.S. Page 8
Efficacy evaluation and assessment of new herbal medicines Pharmacological screening: to determine the possible pharmacodynamics action
(mechanism of action) and the effective dose in 50% of small animals (ED50) in
different species.
Biological studies
It is indicated to determine the ingredient pharmacokinetics:
Absorption by the different routes of administration.
Distribution.
Metabolism.
Excretion.
These are determined by using sensitive assay procedures e.g. chromatography,
spectrophotometer, radioisotopes … etc.
The results are collected and introduced to an independent committee:
To be approved and allowed to be evaluated on human to be used topical, oral or
inhalation administration only other formulations e.g. injectable, ophthalmic ….etc.
are not allowed as herbal remedies.
Rationale for the Combination For each active ingredient in the formulation, a clear and logical rationale is required to support the following: • The claim being made for the combination; • The dosage of each individual active ingredient found in the multiple ingredients product; • Its safety and efficacy in combination with the other active ingredient(s) under the recommended conditions of use.
D.S. Page 9
D.S. Page 11
Quality assurance of herbal medicinal products
Quality assurance of herbal medicinal products is the shared responsibility of manufacturers and regulatory bodies.
The manufacturers have to adhere to Good Agricultural and Collection Practices (GACP), GMP and Good Laboratory Practice (GLP) standards, establish appropriate specifications for their products, intermediates and starting materials and compile a well-structured, comprehensive documentation on pharmaceutical development and testing.
The producers should make continued efforts to improve standards and adapt them to the present state of knowledge. A cooperative approach between different manufacturers, e.g. by establishing drug master-files for specifications and quality control are encouraged.
Coordinating quality control
A coordinating agency on GACP should be established to facilitate the availability of good quality herbal medicines to the market. Manufacturers and importer of herbal medicinal products who possess certificates of adherence to the GACP from their botanical suppliers are encouraged to submit it.
Adherence to GACP, GMP and GLP guidelines:
All parties involved in the production of herbal medicinal products should adhere to the principles set out in the WHO GACP guidelines for medicinal plants, GMP and GLP. Manufacturers of herbal medicines should be licensed and registered in MOH. The quality assurance system should be adequate and proportionate to the type of production and the regional situation, e.g. agricultural production or industrial production.
The implementation of a credible concept of quality assurance, e.g. identifying and eliminating potential sources of contamination, rather than implementing all individual technical aspects, should be the primary goal. The following areas should be considered: · Control of raw materials (refer to the GACP and Quality Control Methods for Medicinal Plant Products); · Control of starting materials and intermediate substances; · In-process control (Standard Operating Procedure for Processing Methods should be mentioned); · Finished product control (It should be performed with reference to the control of raw materials, starting materials and intermediate substances).
· Setting specifications:
D.S. Page 11
The basis for quality control is the establishment of appropriate specifications and standards. Information on appropriate standards can be found in official pharmacopoeias and monographs.
A comprehensive specification must be developed for each herbal substance even if the starting material for the manufacture of the herbal medicinal product is a herbal preparation.
Latin name should be given to ensure correct identification of a plant. A definition and description of the part of the plant from which the medicine is made (e.g. leaf, flower, and root) should be provided, together with an indication of whether fresh or dried processed material is used.
The active and characteristic constituents and their biological & geographical variation should be specified and, if possible, content limits should be defined. A qualitative statement should be defined about the organoleptic character(s) which includes characteristic and the macroscopic and microscopic botanical characters of the herbal substance. A comprehensive specification must be developed for each herbal preparation based on recent scientific data. A statement of the botanical source, part used, extraction solvent, the type of preparation (e.g. dry or liquid extract), and the ratio of the herbal substance to the genuine herbal preparation must be stated.
A qualitative description of the dosage form should be provided (e.g., size, shape, colour). The acceptance criteria should include the final acceptable appearance at the end of the shelf-life. If color changes occur during storage, a quantitative procedure may be appropriate.
The physical and chemical stability of the product in the container in which it is
to be marketed should be tested under defined storage conditions and the shelf-life
should be established.
The best approach that can be proposed for determining the quality of herbal
medicine is the level of active components or key biological markers. This form of
standardization, i.e., stating the content of active constituents versus drug
concentration ratio, allows for dosage to be based on active constituents.
The manufacturing procedure including (temperature effects, residual solvents),
and formula including (the quality of the herbal substance and/or herbal preparation,
amount of excipients and profile and stability of the active substance/formulation in
packaging) should be described in detail. A finished product specification should be
defined. A method of identification and quantification of the plant material in the
finished product should be defined.
· Quality control measures.
In choosing analytical methods, the availability, robustness and validity of the methods must be considered, such as microscopic identification, thin layer chromatography (TLC), titration of active substance and, if possible, a full validation of
D.S. Page 12
more sophisticated methods, such as high-performance liquid chromatography (HPLC), gas chromatography (GC), and gas chromatography-mass spectrometry (GC-MS). If such advanced methods are used, a full validation for each test would be necessary.
Tests of Foreign matter & Total ash should be applied. Water content test is important when the herbal substances are known to be hygroscopic. Foreign matter, impurities, toxic metals, radioactive elements, insecticide/ pesticides and microbial content (microbial levels, mycotoxins (aflatoxins) should be defined or limited. Voucher specimens, representing each lot of plant material processed, should be authenticated by a qualified botanist.
A method for identification & assay of the constituents with known therapeutic activity or active or analytical markers in herbal preparation should be added. If identification of an active principle is not possible, it should be sufficient to identify a characteristic substance or mixture of substances (e.g. "chromatographic fingerprint") to ensure consistent quality of the preparation.
Drying conditions, residual solvents in extracts, and stability of the constituents should be defined. Water content test is important when the herbal preparations are known to be hygroscopic.
The need for inclusion of tests and acceptance criteria for Impurities including Inorganic impurities, toxic (heavy) metals, Microbial limits, Mycotoxins (aflatoxins), Pesticides, Fumigation agents, etc. should be studied during development and the manufacturing process. In finished product:
In choosing analytical methods, the availability and robustness of the method
must be considered. It may be preferable to use simple methods (such as microscopic
identification, thin-layer chromatography or titration of active substance) if a full
validation of more sophisticated methods (such as high-performance liquid
chromatography, gas chromatography and gas chromatography/mass spectrometry) is
not possible. If such advanced methods are used, a full validation for each test will be
necessary.
If the identification of an active principle is not possible, it should be sufficient to
identify a characteristic substance or mixture of substances (e.g. "chromatographic
fingerprint") to ensure consistent quality of the product. The finished product should
comply with general requirements for particular dosage forms.
Identification tests should establish the specific identity of the herbal
substance(s) and/or herbal preparation(s), in the herbal medicinal product and
optimally should be discriminatory with regard to substitutes/adulterants that are likely
to occur. In the case of herbal medicinal products containing powdered or comminuted
herbal substances, microscopical and macroscopical characterization could be used for
identification in combination with other methods, if justified.
D.S. Page 13
In the case of products containing herbal substances and/or herbal preparations
with constituents of known therapeutic activity, validated assays of the content of
these constituents are required along with details of the analytical procedure(s). In
cases where use of a non-specific assay is justified, other supporting analytical
procedures should be used to achieve overall specificity, i.e. a combination of the assay
and a suitable test for identification (e.g. fingerprint chromatography) can be used. A
specific, stability-indicating procedure should be included to determine the content of
the herbal substance(s) and/or herbal preparation(s) in the herbal medicinal product.
In the case of herbal medicinal products containing herbal substance(s) and/or
herbal preparation(s) where the constituents with known therapeutic activity are not
known, validated assays of active or analytical markers or other justified determinations
are required. The choice of such markers should be justified. In cases where a specific
assay of each active substance of a herbal medicinal product is not possible other
justified determinations are required (for example, in multi-component herbal
medicinal products for human use the same markers may be present in more than one
herbal substance/preparation).
There is a need to specify the total count of aerobic micro-organisms, the total
count of yeasts and moulds, and the absence of specific objectionable bacteria. These
microbial counts should be determined using pharmacopoeial procedures or other
validated procedures.
Impurities arising from the herbal substance(s) and/or herbal preparations e.g. contaminants such as pesticide/fumigant residues, toxic metals, if controlled during the testing of the herbal substance/preparation, it is not necessary to test for these in the herbal medicinal product. Similarly, residual solvent arising from the manufacture of the herbal preparation (e.g. an extract) need not be controlled in the herbal medicinal product provided. It is appropriately controlled in the extract specification. However, solvents used for example in tablet coating will need to be controlled in the dosage form.
Vitamins and minerals in herbal medicinal products for human use
Impurities arising from degradation of the vitamin(s) or mineral(s) should be
monitored in the herbal medicinal product for human use. When it has been
demonstrated conclusively by provision of a significant body of data (generated using
appropriate analytical methods, that the vitamin(s) and/or mineral(s) do not degrade in
the specific formulation and under the specific storage conditions proposed in the
application) degradation product testing may be reduced or eliminated upon approval
by the regulatory authority.
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Product information and labeling
This should include all necessary information on the proper use of the product.
The detailed information of the herbal medicinal products should include the following
requirements for registration:
1· Trade name and dosage form of the product
2. Physical description of the product
3. Quantitative list of ingredients; including Latin name, family of the plant(s) from
which the drug(s) has been extracted including plants part(s) used. Synonym if available
should be given. The Arabic and English name if available shall be provided.
4. Brief pharmacology of the medicines
5. Therapeutic indications
6. Dosage regimen and route of administration
7. Brief toxicological information of the medicine
8. Contra-indications
9. Warnings and precautions
10. Drug Interactions
11. Adverse reactions
12. Side Effects
13. Storage condition
14. Shelf-life and storage conditions
15. Presentation or pack size(s)
16. Date of manufacture
17. Expiry date of product
18. Lot/Batch number
19. Registration No.
20. Name of manufacturer/ company with full address.
Pharmacovigilance
Pharmacovigilance of herbal medicinal products is subjected to the guidelines issued by Egyptian Pharmaceutical Vigilance Center EPVC.
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Administrative Procedures and Documentation:
General Requirements
All application shall be made by submitting a duly filled in application form accompanied with information as prescribed in these guidelines. All documents shall be in Arabic and/or English language. Where original licenses are in another language, copies shall be presented together with certified Arabic and/or English version.
Applicant:
An application for registration of herbal medicines can be made by owner of the
product (Factory, Toll Manufacturer, Scientific Offices, Agents and Distributers)
responsible for the manufacture or to whose order the product is manufactured for
sale in Egypt.
The responsibilities of the local agent, applicant and manufacturer:
i. To monitor the product on the market and inform the Authority immediately after
the detection of any problem relating to registered product such as serious
manufacturing defects which may endanger public health.
ii. The Local Distributor shall facilitate communication between the applicant and the
Authority on matters relating to the product.
iii. Handle product recalls according to Pharmaceutical Regulatory Authority Recall
procedures.
iv. Detect and report adverse drug reactions or events to the Pharmacovigilance Center.
Applications
A separate application is required for each product. Only two applications for
each applicant are allowed monthly. Submissions are made on the announced dates of
reception. Applications shall be made by submitting a completely filled in application
form which shall be accompanied with:
i). Complete documentation as per these guidelines supported by independent expert
reports.
All ingredients must comply with specification prescribed in Pharmacopoeias. In-house
specification may be acceptable if justified by validation reports.
ii) For under license products, original notarized Certificate of Pharmaceutical Product
from the Drug Regulatory Authority of the country of origin of the product should be
submitted. This shall be accompanied with approved product information.
D.S. Page 16
iii). Copy of license of the manufacturing site for local manufacturers and toll register
for toll manufacturers.
iv) R&D samples of each package size being applied for registration (One commercial
sample for re-registration if required in case of variation) to carry out quality control
tests as declared in the dossier. The samples must be in the form and container in
which they will be marketed.
v)Stability study should be done on 3 different R&D batches on the finished product in
its final container closure system as accelerated (6 months) or long term stability (for
the required shelf life and storage conditions).
In case of re-registration, the stability study is done on at least one production batch in
the final container closure system as accelerated stability study (6 months) or long term
stability study.
vi) Patient Information Leaflet draft and Artwork (Mock-ups)
vii) An appropriate and complete index/ list of the various sections and documents of
submission.
viii) Non-refundable fee per product to be registered.
It should be noted that fees may be changed as shall be prescribed under the Fees and Charges Regulations.
Documentation
Paper type and binding
1. Data shall be presented on A4 paper with readable letters of at least 12 font sizes.
Every page shall be numbered sequentially.
2. Extension sheets, tables, diagrams and other supporting documents shall be as far as
possible be of the same size, well annotated, numbered and appropriately referenced
or cross referenced.
3. All registration sections must be bound separately and arranged sequentially in or more
file covers depending on the number of pages contained in a chapter.
Official References, Texts
When direct reference is made to specification, quality control procedures, test
methods, data etc. in official compendia, texts or standard publication other than the
current pharmacopoeias, reprints or authenticated copies of relevant pages shall be
enclosed. References to pharmacopoeias should specify the year of issue.
D.S. Page 17
Processing of applications
Processing of applications shall only be done on complete applications; incomplete
applications shall not be processed.
The Authority may during evaluation of the product request for clarification or
additional data or samples.
Once a query has been raised, the processing may be halted until the query has been
clarified.
Immediately after the processing is completed applicants will be informed with
preliminary approval of the scientific committee to proceed in Naming of the product
and pay the registration fee.
Official letter of approval by the final product name will be issued to the applicant.
If the application is refused, official letter of refusal will be issued and supported with
reasons.
After approval; the applicant must proceed in registration procedure of, analysis in NODCAR, submitting stability study, pricing. For export products:
In order to encourage the exportation, product will be registered in fast track procedures without affecting their safety, efficacy and quality assurance.
Only stability study will be needed on 3 different R&D batches on the finished product in its final container closure system as accelerated (6 months) or long term stability (for the required shelf life and storage conditions).
In case of re-registration, the stability study is done on at least one production batch in the final container closure system as accelerated stability study (6 months) or long term stability study.
Analysis can be done on the first production batch which will not be released before conformity of the analysis. Naming and Pricing are not needed.
Registration
After the applicant has finished all the procedures of the registration, the
applicant shall submit the requirements mentioned in checklist (5). The complete file
will be submitted to the Technical Committee and a product registration license shall be
issued after committee approval.
Validity of registration
The registration of a product shall be valid for (10 years) with fulfilling all
conditions and rules including routine activities.
Renewal of Registration
The registration of a product shall be renewed during the last year of the
registration license validation before invalidation of the license.
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Termination of product registration
The Technical committee has the right to refuse re-registration of the product
during the re-evaluation of the product & reasons of refusal will be mentioned.
The license will be terminated if the applicant didn't submit the product for re-
registration during the allowed period.
The license will be terminated if any changes occur to the data of the license
without informing CAPA.
The license will be suspended or cancelled or revoked if MAH / applicant is not
complied with regulation.
The license will be cancelled or revoked by giving writing letter from minister of
health in case of the product is found to represent a serious public health
hazards no previous notice is given.
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Dossier Contents: Section no. Details Comments
Section 1. Application
1. Table of content of accompanied documents 2. Application Form 3. Accompanied documents (according to checklist no.1)
checklist no.1 (registration checklist)
Section 2. Safety Requirements
Herbal medicines shall submit safety data according to what mentioned above in Minimum requirements for assessment of safety of herbal medicines section.
Section 3. Efficacy requirements
Herbal medicines shall submit efficacy data according to what mentioned above in Minimum requirements for assessment of efficacy of herbal medicines section depending on conditions shown in table 1 & 2.
Section 4. Quality requirements documentation
1. Table of content of the analysis file. 2. Analysis file (according to checklist no.2) 3. Results of the analysis by NODCAR 4. Certificate of analysis of the finished product by the
manufacturer
*Analysis file is submitted to NODCAR by the applicant acc. To NODCAR guidance * checklist no.2 (NODCAR checklist)
Section 5. Herbal medicine Stability
1. Table of content of the stability study file. 2. stability file (according to checklist no.3) 3. Final report of the stability study by stability committee
*stability file is submitted to stability department by the applicant acc. To stability guidance * checklist no.3 (stability checklist)
Section 6. Herbal medicine pricing
1. Table of content of the pricing file.
2. pricing file (according to checklist no.4)
3. pricing license by pricing committee
*pricing file is submitted to pricing department by the applicant acc. To pricing guidance * checklist no.4 (pricing checklist)
Section 7. Variations
It includes all variations and documents support this variations
Section 8. Summary of product characteristics (SmPC Form)
1. Trade name and dosage form of the product 2. Physical description of the product 3. Quantitative list of ingredients; including Latin name, family of the plant(s) from which the drug(s) has been extracted including plants part(s) used. Synonym if available should be given. The Arabic / English name if available shall be provided. 4. Brief pharmacology of the medicines 5. Therapeutic indications 6. Dosage regimen and route of administration 7. Brief toxicological information of the medicine 8. Contra-indications 9. Warnings and precautions 10. Drug Interactions 11. Adverse reactions 12. Side Effects 13. Shelf-life and storage conditions 14. Presentation or pack size(s) 15. Storage Condition
(SmPC Form) *To be completed by the applicant after finishing all the procedures of the registration. *To be submitted with the results of analysis and stability decision and pricing license *It should summarize all the data of the product including variation if any.
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Annex .1; Forms i. Application Form
ػشجي غجيغهت رسجيم يسزذعش
Application for Registration of herbal medicinal Product
Re-Registration New Registration Status
Previous Reg. no. Expiry date of Reg.
In English Product Name & Dosage form ثبنهغخ انؼشثيخ
Applicant
License Holder
Manufacturer
Packager
Local Toll Under license F.Toll Type of License
Similars (In case of new products)
Indications
Dose
Composition:
Each5 ml / Tablet/ F.C.T/ S.G.C/ H.G.C. /Sachet contains
Representative:
Name
Tel.
Official mail
Signature
THIS PART SHOULD BE SIGNED BY THE PRODUCT OWNER I hereby declare that:
1-All the information supplied is true
2-Any documents will be furnished upon request
3-All the dietary ingredients are manufactured, packed & held under conditions proposed by GMP
4-No product advertisement will be made before the approval of the technical committee
5- The product public Price won’t be raised unless the ministry of health is notified
6- If the Product possession is transferred to another owner both the Previous & the new owner should notify the ministry of health within 8 days from
the date of transfer
7-No Qualitative or Quantitative Data of the active or inactive ingredients- approved by the subcommittee-should be changed before submission to the
ministry of health for Re registration
8- No False or misleading sentences will be written on the label.
Name of CEO:
Signature:
Stamp:
/ / رذشيشا في :
Active Ingredients concentration Specifications Functions
Inactive Ingredients concentration Specifications Functions
Capsule Shell (In case of H.G.C.) Cap Body Specifications Functions
Capsule Shell (In case of S.G.C.) concentration Specifications Functions
Film Coat Composition
(In case Film Coated Tablet)
concentration Specifications Functions
Proposed Total weight
Proposed Color of capsule
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ii. Product Composition Template
1) Name of product:
2) Dosage Form:
3) Composition:
*For capsules: Each hard/soft gelatin capsule contains:
*For syrup: Each 5 ml of syrup contains:
*For tablets: Each tablet/enteric coated/film coated tablet contains:
*For sachets: Each 5 gm sachet contains:
I) Active ingredients:
Name of active ingredient
Concentration Specification Function (active)
A. In case of extracts:
*Latin name
*Extraction type: liquid extract / powder extract
* Part of plant used: Root/Stem/Leaves/Seeds/Fruit/Bark …..etc.
* Type of solvent: Aqueous, alcoholic, or hydro-alcoholic, …….etc
* Ratio of extraction: ( ___:___)
* Standardization: (Standardized as NLT_______ % of active ingredient)
Note :
In case of powder :
*Latin name
* Part of plant used: Root/Stem/Leaves/Seeds/Fruit/Bark …..etc.
* Standardization: (Standardized as NLT_______ % of active ingredient)
In case of oils :
Latin name
Part used
Mark of oil
B. In case of Vitamins:
*All vitamins must be written in mg except for vitamins A, D, K, B12, folate, and Biotin which
are written in µg.
*For Vitamin D3, activity must be written ( _____ I.U./mg)
*For vitamins A, D, and E must be clarified in equivalents:
e.g.: dl-alpha tocopheryl acetate _____ mg or mcg
(Eq. to ___ I.U of Vitamin E).
C. In case of Minerals:
*All minerals are written in mg except for Molybdenum, Iodine, Chromium, Copper, and
Selenium which are written in µg.
*must be clarified in equivalents
D.S. Page 22
II) Inactive ingredients:
Name of inactive ingredient
Concentration Specification Function
A) For colors: C.I.No. (Not less than four digits) must be written.
B) For hydrogenated oils: Type I or Type II must be specified.
C) In case of capsules and tablets:
C-1) For hard gelatin capsules: Cap: Body:
C-2) For soft gelatin capsule: Capsule shell composition:
C-3) For film coated tablet : Film coat composition:
4) End Color of Capsule:
5) Total weight of Capsule Or Tablet:
6) Manufactured by (Factory name) For (Company name)
7) Production Manager or R& D Manager, or Quality Control Manager:
A. Name
B. Signature
C. Date
خزى انصغ (8
D.S. Page 23
iii. Pamphlet template
النشرة تكون على ورق الشركة صاحبة المستحضر
1. TRADE NAME OF HERBAL MEDICINE: The product name should be followed by both the strength if applicable and the pharmaceutical form. 2. QUALITATIVE AND QUANTITATIVE COMPOSITION: As mentioned in composition template The quantity of the active substance should be expressed per dosage unit, per unit volume, or per unit of weight . for example : *For capsules: Each hard/soft gelatin capsule contains:
*For syrup: Each 5 ml of syrup contains:
*For tablets: Each tablet/enteric coated/film coated tablet contains:
*For sachets: Each 5 gm sachet contains 3. CLINICAL PARTICULARS:
4.1 Therapeutic indications: 1-Define the target disease 2- Treatment (symptomatic, curative or modifying the evolution or progression of the disease) , prevention (primary or secondary) and diagnostic indication. 3- Define the target population especially when restrictions to the patient populations apply.
4.2 Posology and method of administration:
U- method/route of administration 2- Frequency of dosing should be expressed using time units (e.g. once or twice daily or every 6 hour) Or as directed by physician OR as the physician prescribed.
4.3 Contraindications: 1-Excluded patients from the studies. 2- If pregnancy or breastfeeding is contraindicated. 3- A contraindication in the paediatric population should be listed without a sub-heading. 4-Hypersensitivity to the active substance or to any of the excipients should be included, hypersensitivity extended to other plants of the same family or to other parts of the same plant .
4.4 Special warnings and precautions for use: The order of warnings and precautions should in principle be determined by the importance of the safety information provided.
To be used under medical supervision )acc. To the committee descision )
Keep out of reach of children
4.5 Interaction with other medicinal products and other forms of interaction:
Interactions affecting the use of the product should be given first, followed by those interactions resulting in clinically relevant changes on the use of others. Information on other relevant interactions such as with other herbal medicinal products, food, alcohol, smoking, or pharmacologically active substances not used for medical purpose, should also be given . With regard to pharmacodynamic effects where there is a possibility of a clinically relevant potentiation or a harmful additive effect, this should be stated. If no interaction studies have been performed, this should be clearly stated.
4.6 Fertility, pregnancy and lactation: 4.7 Effects on ability to drive and use machines: 4.8 Undesirable effects:
It is important that this part is worded in concise and specific language and does not include information such as claims regarding the absence of specific adverse reactions, comparative frequency statements other than as described below, or statements of general good tolerability such as “well tolerated”, “adverse reactions are normally rare”, etc. Statements on lack of proof of causal association should not be included .
D.S. Page 24
In order to provide clear and readily accessible information, section 4.8 should be structured according to the following recommendations : a. Summary of the safety profile b. Tabulated summary of adverse reactions c. Description of selected adverse reactions d. <Paediatric population > e. <Other special population(s)>
4.9 Overdose: Describe acute symptoms and signs and potential sequelae of different dose levels of the product based on all available information including accidental intake, mistakes and suicide attempts by patients . Taking into account all relevant evidence, describe management of overdose in man, e.g. in relation to monitoring or use of specific agonists/antagonists, antidotes or methods to increase elimination of the product such as dialysis. However, there should not be any dosage recommendation of other medicinal products (e.g. antidotes) as it could create conflict with the SmPCs of those other products . If applicable, counteractive measures based on genetic factors should be described. 4. PHARMACOLOGICAL PROPERTIES: Parts 5.1 – 5.3 should normally mention information, which is relevant to the prescriber and to other health-care professionals, taking into account the approved therapeutic indication(s) and the potential adverse drug reactions. Statements should be brief and precise . The parts should be updated regularly when new information becomes available, especially in relation to the paediatric population. 5.1 Pharmacodynamic properties 5.2 Pharmacokinetic properties 5.3 Preclinical safety data 5. PHARMACEUTICAL PARTICULARS:
6.1 List of excipients A list should be given of the excipients, expressed qualitatively only. All excipients, which are present in the product, should be included, even those present in small amounts, such as printing inks. The ingredients in excipient mixtures should be listed individually Ingredients that may or may not be added for the pH adjustment should be followed by the parenthesis ‘(for pH-adjustment). Abbreviations for excipients should not be used. However, where justified for space considerations, abbreviations for excipient names may appear on the labeling.
6.2 Incompatibilities Information on physical and chemical incompatibilities of the product with other products with which it is likely to be mixed or co-administered should be stated.. If appropriate, the standard statement, ‘Not applicable’, should be included .
6.3 Pack: 6.4 Storage :
Keep at temparture not exeeding 30 c + Special precautions for storage
Manufactured By …….. for……….
D.S. Page 25
iv. SmPC Form
TRADE NAME & DOSAGE FORM The product name should be followed by both the strength if applicable and the pharmaceutical form
QUALITATIVE AND QUANTITATIVE COMPOSITION
PHYSICAL DESCRIPTION OF THE PRODUCT A visual description of the appearance of the product (color, markings, etc.) should be given, in a separate paragraph to the standard term, including information on the actual size of a solid oral formulation
CLINICAL PARTICULARS Therapeutic indications
Posology and method of administration Contraindications
Special warnings and precautions for use Interaction with other medicinal products and
other forms of interaction
Fertility, pregnancy and lactation Effects on ability to drive and use machines
Undesirable effects Overdose
PHARMACEUTICAL PARTICULARS Shelf life
Storage conditions Pack
BRIEF PHARMACOLOGICAL PROPERTIES It should mention information, which is relevant to the prescriber and to other health-care professionals, taking into account the
approved therapeutic indication(s) and the potential adverse drug reactions. Statements should be brief and precise .
The parts should be updated regularly when new information becomes available, especially in relation to the pediatric
population.
MARKETING AUTHORISATION HOLDER Name and permanent address or registered place of business of the Marketing Authorization Holder.
Telephone, fax numbers or e-mail addresses may be included (not websites or emails linking to Websites).
MANUFACTURER Name and address of manufacturer Telephone, fax numbers or e-mail addresses may be included (not
websites or emails linking to Websites).
REGISTRATION NUMBER
DATE OF FIRST AUTHORISATION For example : Date of first 25uthorization: 3 April 1985 Date of latest renewal: 3 April 2000
RENEWAL OF THE AUTHORISATION
DATE OF REVISION OF THE TEXT Leave blank in case of a first Marketing Authorization SIGNATURE AND STAMP
REGISTRATION MANAGER NAME Dr.
C.E.O. NAME Dr.
D.S. Page 26
v. Commitments Form
التعهدات
السيد األستاذ الدكتور/رئيس اإلدارة المركزية للشئون الصيدلية
00000...........رئيس مجلس إدارة شركة د / أناأتعهد
بخصوص مستحضر ............................................ باالتي :
0سالمة البيانات المقدمة ومسئولية الشركة القانونية عن عدم صحة أى منها
اإلعالن عن المستحضر إال بعد الرجوع للجنة الفنية لمراقبة األدوية.عدم
: صحة اللوجو المستخدم فى الختم وعلى العبوات الخارجية وشكله كاآلتى
كالتالي :مصدر المادة الخام
اسم المادة اسم المورد )المصنع( بلد المنشأ – عنوان المورد
1
2
. سارية وذلك عند التقدم الستيراد المادة الخام من اإلدارة المركزية للشئون الصيدلية GMPكما تتعهد الشركة بتقديم شهادة ال
وتتعهد الشركة بأن المستحضر السابق ذكره يتم توزيعه عن طريق الشركات اآلتية....
وأن مكان تخزين المستحضر هو......وعنوان المخزن..........
تتعهد الشركة بأن الجيالتين المستخدم فى المستحضر من مصدر نباتى أو حيوانى وخالى فى حالة وجود مادة الجيالتين و
من مسببات األمراض
وفى حالة وجود مادةmagnesium stearate خالى من مسببات جنون البقرمن مصدر حيوانى أنهاب الشركة تتعهد
.
توقيع رئيس مجلس إدارة الشركة
ختم الشركة
D.S. Page 27
Annex .2; Checklists
Check list no.1
New- Registration Checklist
Comment File Documents
Covering Letter
ذىليع سئيس –يحرىياخ انهف -انشكم انصيذن-)اسى انسرحضش
انششكحخرى -يجهس إداسج انششكح
Payment Receipt
جي رسجيم جذيذ 0111
يظخ ث اسى انسزذعش،اسى انششكخ، خزى االداسح انبنيخ
االدش
نههف ثبنزسجيم)االغالع ػه االصم( رفيط انذة انمذو
Application
(Including indication & dose)
SmPC
Naming List
نهسزذعش انشكم انصيذن+رليغ يذيش انزسجيميظخ ثب االسى انجذئ
انجدح ػهي انلغ sopsغجمب نم
Leaflets (Arabic/English)
-
………………………………………………
………………………………………………
………………………………………………
………………………………………………
………………………………………………
………………………………………………
………………………………………………
………………………………………………
………………………………………………
………………………………………………
………………………………………………
………………………………………………
………………………………………………
………………………………………………
………………………………………………
………………………………………………
Composition )تيا انرشكية عه وسق انششكح او عه وسق انصع
او يذيش انرسجيم( CEOاو ال R&Dيىلع ي يذيش االراج او ال
ف حانح ا انىاد تها يىاصفاخ دسرىسيح يجة االنرزاو تها.-
Certificates of analysis
for each active ingredients
)رمذو فمػ ف دبنخ اناد انغيش دسزسيخ فمػ(
يرى كراتح دسرىسي او غيش دسرىسي-أ
يجة ا يزكش االذ: Extractsتانسثح نم -ب
1-trade name & physical character
latin name 2-
part used 3-
Solvent 4-
extraction ratio 5-
standardization 6-
:powder & oilتانسثح نم -ج
يا سثك 6و 3و 2و 1يرى ركش انمطح Scientific references for each active ingredients
احضاس انىاصفاخ انذسرىسيح ا وجذخ-
يشاجع نأليا و انفاعهيح و انجشعح و دواع االسرعال-
ن يزى اسزالو انهف check listف دبنخ ػذو اسزيفبء انششكخ ال ي انمػ انزكسح ف ال
Company name:………………
…………………………………
File name:………………
Serial No.:.………………
Date of revision Type of Product
Contact e-mail Under licence Toll (F) Toll Local
D.S. Page 28
( Specification)انفؼبنخ انبدح ياصفبد إظبفخ
في ثيب انزشكيت شبدح انسد
خزى جيغ االساق انمذيخ ي لجم انششكخ ثخزى انششكخ
انزؼذ ا انادج انخاو غيش دسرىسيح ف حانح عذو وجىدها-1
ف اي ي انذساذيش انذواء
ف يشجع عه يعرذ، يجة standardف حانح عذو وجىد ال-2
احضاس ذعهذ تاالنرزاو تانىاصفاخ انزكىسج ف شهادج انىسد
انمذيح ي لثم انششكح
Reference Product ف أحذ انىالع االنكرشويح نهجهاخ انشسيح جيزكىسأو انرشكيثح
يع ذىضيح انكىاخ و اسى نهذول انشجعيح انعرذج صحيحان
انششكح انصعح و تهذ انشأ
Comment Company & Factory documents
سخصخ انصغ
يىضح تها خظ اراج انسرحضش انمذو
loca
l
To
ll
صسح ي ػمذ انزصيغ انثك ي انشئ
انمبيخ ػه ا ال يك لذ يش ػهي اكثش ي
ساد خس
(األصم ) اإلطالع عه
صسح ي يهذك ػمذ ثبسى انسزذعش انمزشح
انمبيخ انشئ ي يثك انزصيغ
) اإلغالع ػه األصم(
يهحك تاسى انسرحضش انثذئ انمذو نهرسجيم و
يىضح ته انشكم انصيذن)ال ضشوسج نزكش تيا
انرشكية(يع ذمذيى ذعهذ ترغييش االسى لثم انحصىل
عه االخطاس(
سجم ثبنزصيغ نذ انغيشليذ
Toll Card) اإلغالع ػه األصم(
شبدح غشفخ صبػخ انذاء نهششكخ أ نهصغ
يجت أ يزكش شبغ انزصيغ نذ انغيش ف انسجم-
نهششكخ انزجبس
F ا يؼبيخ applicantسخصخ يصغ ال--t
oll
ػمذ انكبنخ
Un
der
Lic
ense
registration & manufacturingث يزكس
authorization يثك ي انسفبسح انصشيخ ,
chamber of commerce
اإلغالع ػه األصم
رشجخ انؼمذ ي يكزت ػه يؼزذ
D.S. Page 29
Free sale(or CPP) انصشيخ انسفبسح ي أصم يثك
انضساػخ أ انصذخ صاسح
ثبنخبسج انغزاء ا انجيئ
يظخ ث ا انسزذعش is freely sold , is sold , is
currently sold , is legally
sold , is marketed , may be
sold , can be sold , is
distributed in the country
of origin under the same
name & composition غجمب (
نمشاس انهجخ انفيخ ثجهسخ
22/5/2112 )
ثب ثيب انزشكيتيشفك
ذ ثبنسديرؼ
ف دبن ا شبداد انسد
نيسذ ػه سق انششكخ صبدجخ
انسزذعش ثبنخبسج
ادعبس رؼذ ي انششكخ ثبنخبسج
ثأسبءانسدي نكم يبد اى
فس انسدي نهخبيبد
انسزخذي ثبنسزذعش ثبنخبسج
انصشيخ انسفبسح ي يثك
chamber of commerce Product sample
D.S. Page 31
Check List for Re – Registration
Comment File Documents
Covering Letter
Payment Receipt
الػبدح انزسجيمجي 4111
رفيط انذة نهزسجيم
نهذة انمذو نههف)االغالع ػه االصم(
Application
(Including indication & dose)
SmPC
------------------------------------------------------------------------------------------
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-----------------
Composition
)تيا انرشكية عه وسق انششكح او عه وسق
او يذيش CEOانصع يىلع ي يذيش االراج او ال
انرسجيم(
Certificates of analysis
for each active ingredients
يرى كراتح دسرىسي او غيش دسرىسي-أ
يجة ا يزكش االذ: Extractsتانسثح نم -ب
1-trade name & physical character
latin name 2-
part used 3-
Solvent 4-
extraction ratio 5-
standardization 6-
:powder & oilتانسثح نم -ج
يا سثك 6و 3و 2و 1يرى ركش انمطح
Scientific references for each active
ingredients
انفؼبنخ انبدح ياصفبد إظبفخ (Specification )
انسد شبدح انزشكيت ثيب في
ن يزى اسزالو انهفcheck listف دبنخ ػذو اسزيفبء انششكخ ال ي انمػ انزكسح ف ال
Company name:………………
…………………………………
File name:………………
Serial No.:.………………
Date of revision Type of Product
Contact e-mail Under licence
Toll (F) Toll Local
D.S. Page 31
انزؼذ
ػذو دبنخ ف دسزسيخ غيش انخبو انبدح ا-0
انذاء انذسبريش ي ا جدب ف
يشجغ ف standardال جد ػذو دبنخ ف-2
ثبناصفبد ثبالنزضاو رؼذ ادعبس يجت يؼزذ، ػه
انششكخ لجم ي انمذيخ انسد شبدح ف انزكسح
انششكخ نجيب رشكيت يخزهف ػ ف دبنخ رمذيى -3
يظخ انزغييش cover letterانسبثك يجت رمذيى
أسجبث إ جذد
ف حانح مم انرصيع او مم انهكيح او كهيها يرى ذمذيى
انىافماخ انرىرثثد رنك ف انهف تذءا ي انصع و
انانك انزكىسي تاالخطاس
ذمذيى يىافمح ذعذيم ف حانح ذعذيم تيا انرشكية يرى
تيا انرشكية
Product sample
انزسجيم انسبثك صسح اخطبس
اإلغالع ػه األصم
سبثمانؼبيم ان صسح يطبثمخ
ثيب انزشكيت انطبثك انصبدس ي انؼبيم
اإلغالع ػه األصم
انلف ي انزسؼيش
Comment Company & Factory documents
انصغسخصخ
انمذو انسزذعش ازبج خػ ثب يظخ
local
انمبيخ انشئ ي ػمذ انزصيغ انثك
5 ي اكثش ػهي يش لذ يك ال ا ػه
األصم ػه ساد اإلغالع
Toll
ثبسى انسزذعش انزصيغ يهذك ػمذ
انمزشح يثك ي انشئ انمبيخ
) اإلغالع ػه األصم(
انسرحضش انثذئ انمذو يهحك تاسى
نهرسجيم و يىضح ته انشكم انصيذن)ال
ضشوسج نزكش تيا انرشكية(يع ذمذيى ذعهذ
ترغييش االسى لثم انحصىل عه االخطاس
ليذ سجم ثبنزصيغ نذ انغيش
) اإلغالع ػه األصم( Toll Card
شبدح غشفخ صبػخ انذاء نهششكخ أ
نهصغ
ػمذ انكبنخ
Un
der
Lic
ense
& registrationث يزكس
manufacturing authorization
, يثك ي انسفبسح انصشيخ
chamber of commerce
اإلغالع ػه األصم
رشجخ انؼمذ ي يكزت ػه يؼزذ
D.S. Page 32
Free sale (or CPP) انصشيخ انسفبسح ي أصم يثك
ا انغزاء انضساػخ أ انصذخ صاسح
ثبنخبسج انجيئ
يظخ ث ا انسزذعش is freely sold , is sold , is
currently sold , is legally sold , is
marketed , may be sold , can be
sold , is distributed in the
country of origin under the
same name & composition غجمب (
( 22/5/2112نمشاس انهجخ انفيخ ثجهسخ
يشفك ثب ثيب انزشكيت
ذ ثبنسديرؼ
ف دبن ا شبداد انسد نيسذ ػه
سق انششكخ صبدجخ انسزذعش
ثبنخبسج
ادعبس رؼذ ي انششكخ ثبنخبسج
ثأسبءانسدي نكم يبد اى فس
انسدي نهخبيبد انسزخذي
انسفبسح ي ثبنسزذعش ثبنخبسج يثك
chamber of انصشيخ
commerce Product sample
D.S. Page 33
Checklist no.2
NODCAR CHECKLIST
المستندات و المتطلبات المطلوبة لتسليم ملف التسجيل المرفق بالعينات الواردة
للهيئة القومية للرقابة و البحوث الدوائية
موافقة االدارة العامة للتسجيل باالدارة المركزية للشئون الصيدلية .1 مستوفاة البيانات 11استمارة صحة .2
نسخ( 6بيان تركيب المستحضر مضاف إليه المعايرة ) .3
المواصفات و الحدود الكمية للمواد الفعالة بالمستحضر النهائي .4
نسخ( 6شهادة تحليل المستحضر النهائي ) .5
شهادات تحليل المواد الخام مع ارفاق مواصفات المواد الفعالة و ذكر المعايرة .6
نسخ( 6طرق التحليل كاملة ) .1
. (validation) تقديم ما يفيد صحة طريقة التحليل مع ضرورة ارفاق الكروماتوجرام .8
عند استخدام طرق الكروماتوجرافي في التحليل يراعي االتي : .9
ارفاق الكروماتوجرام
ق اعمدة الفصل المستخدمة في طريقة التحليل ارفا
النشرة الداخلية المرفقة بالمستحضر باللغة العربية او االنجليزية او االثنين معا .10
صورة االيصال الدال علي تسديد نفقات تحليل المستحضر .11
قرص مدمج يشمل محتويات الملف .12
عينات التحليل و المواد المرجعية مادة قياسية مرفق بها المواصفات و شهادة التحليل بما يتناسب و طريقة التحليل و الموافقة الصادرة من االدارة .13
المركزية
يرفض الملف في حالة عدم استيفاء البيانات و المتطلبات .
D.S. Page 34
Checklist no.3
STABILITY CHECKLIST
Sample Product Name:
Date : Prepared by : Dr/
رفيط ثزبثؼخ يهفبد دساسبد انثجبد خطبة انزذيم ي االداسح انخزصخ C.P.P. (Imported) إلخطبس في دبنخ اإلػبدح اصسح
Cert. of analysis summary sheet of Stability file
) Composition: صس 4أصم(
Stability report Certificate of responsibility
رؼذ ظشف انزخضي CD CD+االلشاس انخبص ثبل
ػمذ دساسخ انثجبد في دبنخ ػذو ػم دساسخ ثجبد في انصغ
رؼذ ػذو انزغييش
Stab. Study items Results: ) يزى انشاجؼخ ي االخزجبساد انزكسح ثبنماػذ انظخ(
Cert. of analysis NODCAR Stability tables
1- Colour & shape& average wt.:
2- Type of Pack:
3-Company name:
4-Chemical Analysis:
5-microbiological Analysis:
Assay Chromatograms at all time intervals for all batches
Others: Spectro. GC TLC U.V HPLC Method of analysis:
Validation items:
Precision Accuracy Spec. Official:
Chromatogrms:
Rugged. Linearity Precision Accuracy Spec. Non Official:
Chromatograms:
Other comments:--------------------------------------------------------------------------------------------------------
انمشاس ثؼذ انشاجؼخ
اسزمجبل اسزكبل
إلسزيفبء انطهجبد.في دبنخ رمذيى يهف انثجبد غيش كبيم ال يزى اسزالي رؼط انششكخ يهخ نذح شش ادذ فمػ ي ربسيخ انزمذو
في دبنخ ػذو إدعبس انهف بئيب خالل انشش يزى انؼشض ػه انهجخ انفيخ إلرخبر انالصو
D.S. Page 35
Checklist no.4
PRICING CHECKLIST
خطاب عمي ورق الشركة مختوم بختم الشركة وتوقيع مدير التسجيل )أو المفوض من الشركة بالتعامل مع اإلدارة المركزية لمشئون الصيدلية وارفاق صورة التفويض( يحتوي عمي :
اسم الشركة مقدمة الطمب : تاريخ تقديم الطمب :
وتركيزه و الشكل الصيدلي :المستحضر اسم :بيان التركيب
العبوة المطموب تسعيرىا : تاريخ الحصول عمي الموافقة عمي السير في إجراءات التسجيل :
نوع اإلنتاج : التسعيرة المبدئية المقترحة من الشركة :
المستندات المطموبة : : )مستحضر جديد(
.لممستحضرصورة من قرار الموافقة عمي السير في إجراءات التسجيل -1وتركيزه والشكل الصيدلي والعبوة التي تمت عمل الدراسة المستحضر الدراسة السعرية لممستحضر )قائمة التكمفة( موضحا بيا اسم -2
عمييا . صورة من فواتير شراء الخامات و مواد التعبئة أو عرض أسعار . -3 . الجرعة و دواعي اإلستخدام ( موضحا بيا 17صورة من )صحة -4 إيصال دفع الرسوم المطموبة . -5)مذكورا بيا طرق صورة من بيان التركيب عمي ورق الشركة مطابقا لما تم عرضو عمي المجنة العممية المتخصصة لألغذية الطبية -6
قبل إدارة المعايرة لممواد الفعالة , وفي حالة وجود فيتامينات أو معادن تكون موضحة عمي ىيئة ممح و مكافئ ( مختوما ومعتمدا من غذائية والشركة .المكمالت التسجيل
)تعديل بيان التركيب( : نفس المستندات المذكورة بعاليو باالضافة الى:
صورة من بيان التركيب القديم عمي ورق الشركة مطابقا لما تم عرضو عمي المجنة العممية المتخصصة لألغذية الطبية مختوما -1 غذائية والشركة .الالت مكمالومعتمدا من قبل إدارة تسجيل
)إعادة تسجيل( : :نفس المستندات المذكورة بعاليو باالضافة الى
صورة من اخطار التسجيل القديم + العبوة المسجمة موضحا عمييا السعر. -1أصل خطاب موجو من إدارة التفتيش عمى المكمالت الغذائية الى الشركة صاحبة المستحضر يوضح بو السعر المتداول بو -2
المستحضر فى السوق المحمى وذلك فى حالة تسعير مستحضر مكمل غذائى جبرى.
D.S. Page 36
Checklist no.5
FINAL REGISTRATION CHECKLIST
No. Section Details
Comments
1 NODCAR conformity Issued from NODCAR with analyzed composition
2 Stability report Issued from stability department
3 Pricing license Issued from pricing department
4 C.O.A. of the finished
product by
manufacturer
Original, signed and stamped
5 C.O.A. of raw materials
+ GMP of supplier
6 Pack + Label /Al-Foil
7 SmPC
8 Commitments form
9 Sheet 17
chick listفى حالة عدم استيفاء الشركة الى من النقط المذكورة فى ال لن يتم االستام
Company name:………………
…………………………………
File name:………………
Serial No.:.………………
Date of revision Type of Product
Contact e-mail Under licence Toll (F) Toll Local