Check List for Documents Submit for Registration Dossier
Date of Submission:
Product Name:
Applicant Name:
ApplicantRepresentative:
Biological Registration Specialist:
Prepare 5 separate dossiers as follows / Check / NotesDossier I: Core Registration Dossier
First: Administrative data
1 / Index
2 / Covering letter on applicant head letter signed and stamped by the registration general manager
3 / Copy of Box approval
4 / Copy of pricing certificate
5 / Copy of Preliminary approval
6 / C.D containing all content of thefive dossiers
7 / A certification that all data in the file is true and accurate and identical to the CD
8 / Authorization letter for the person responsible for communication on behalf ofapplicant during the procedure and this letter should be certified as truly signed
9 / Payment receipt 10000 L.E
10 / Application form for registration of biological medicinal products.
Signed by the Applicant
Stamped by the applicant(each page)
11 / Composition Certificate
On license holder letter head
Signed by the license holder
Stamped by the license holder
Notarized and Authenticated
Trade name of the product is specified
Dosage form of the product is specified
Active ingredient (s) with its (their) quantity (ies) per unit dose is (are) specified
inactive ingredient (s) with its (their) quantity (ies) per unit dose is (are) specified
Active & inactive ingredient is specified (in house specification , USP ,EU ,JP ,British pharmacopeia)
The overage should be mentioned
API name is specified (the INN, scientific, pharmacopoeia, common name accompanied by its salt or hydrate form (if any))
API Manufacturer’s name + Country + City are specified
API manufacturing site address is specified
12 / Reference:
The latest version(BNF ,Swiss compendium Rote list, Vidal)
WHO prequalification, FDA, EMA
13 / Free sale certificate or CPP issued by Competent Authorities in Country of Origin
Authenticated
Valid
The Arab Republic of Egypt is mentioned as Importing Country (Optional)
Number of product license is specified
Date of issue is specified
Trade name of the Product is specified (in COO and A.R.E)
Dosage form (s) and Strength (s) are specified.
License Holder (address, city, country) is specified
Role of License Holder is specified
Product marketed in the COO (if not, explain why marketing is lacking?)
Manufacturing site(s) is/are specified, registration for other manufacturing, packing & batch release site(s) involved in the manufacturing of the product is available (If any)
Good Manufacturing Practice (GMP) of the manufacturer is specified (or in separated certificate if manufacturing site is not in the same country, it must by valid and authenticated)
Pack Presentation and pack size(s) of the Product is (are) specified (could be as attachment)
Inner leaflet recent modification (could be as attachment)
Active Ingredient(s) by its salt or hydrate form (if any) with its (their) quantity (ies) per unit dose is (are) specified
Inactive Ingredient(s) with its (their) quantity (ies) per unit dose is (are) specified (could be as attachment)
Shelf-life of the Product is specified (could be as attachment)
Storage Conditions of the Product is specified (could be as attachment)
SPC or package insert of the product is attached
If the Name of the product may change in Egypt it must by noted or clarified by other letter.
If there are two manufacturing site in the COO it must be clarified which site will be the supplier.
14 / GMP of all the manufacturers involved in the production process
(Manufacturer of active substance, Manufacturer of finished, Manufacturer of solvent, Batch releaser, primary packager,…….)
Authenticated
Valid
The name of plant by its address should be specified
The date of the last inspection should be specified
The invalidation date should be mentioned
The production lines are specified
15 / Manufacturing license indicating production lines or equivalent
16 / TSE free certificate (if the product contains magnesium stearate, lactose, or gelatin derived from animal source)
Original letter from the company mentioning that Product is TSE free and mentioning Countries of origin of source materials
17 / Copy(s) of the Supplier company letter(s) stating the safety of substance supplied to the concerned company available
18 / Notarized copy of the certificate of suitability from the concerned authorities in the country of origin (e.g.: Certification of Suitability of Monographs of the European Pharmacopoeia) available
19 / List of the countries where the product is registered & sold, notarized from the chamber of commerce or its equivalent in the country of origin and certified from the Egyptian embassy abroad
20 / Company profile (applied once for each company) recieval letter from CAPA.
21 / Certificates clarifying the relationship between the manufacturing company, the importing company & the distributor (for imported products)
i.e Authorization letter or Agency agreement
22 / Certificate of the scientific office ( if scientific office is the applicant)
mentioning the name of the companies affiliating the scientific office
23 / A letter from the manufacturing company in the country of origin authorizing packaging & registration of product in Egypt (for bulk products)
24 / Tax Card
25 / Commercial register
27 / Certificate of importers register
28 / Certificate of approval of chamber of medicinal industries (for local products)
29 / Outer label of the Product (for the COO product and the proposed A.R.E product) 3 original packs and 4 layouts
Trade Name is typed in the same way and style, identical to the CPP or the approved one.
The Pharmaceutical Form is identical to the CPP or the approved one
The Pack Size is identical to the approved by pricing committee
Active ingredients with their quantities are mentioned on the Outer pack, are identical to the CPP or the approved one, under the trade name
Manufacturer, license holder or any other participant in the manufacturing process, the name, address, city, country, (phone, Fax, web site) must maintained in addition to the specific logo or trade mark.
The brief indication or the therapeutic class is maintained
Route of administration (in case of (IV, IM. SC, Ia, infusion…) injection, vaginal supp., Rectal supp., eye only, ear only, eye/ ear, vaginal or external cream/ ointment)
Special precaution for handling (if any, as Shaking, dilution…)
If the dosage form or the product related to special population (infant, Children, adults)
Different concentration should have different printing color for easier identification
Unit of the dosage form present in the container or box (the priced unit)
The legalized price / unit
Registration Number of Egyptian ministry of health / Year of registration
Batch number is mentioned on the Outer pack
Manufacturing date is mentioned on the Outer pack
Expiry date is mentioned on the Outer pack
In case, the product submitted for export only , export and tender, hospital use (must maintained)
Storage conditions are mentioned on the Outer pack
Contains the warning/ presence of some ingredients (for exp.: Aspartame. Sunset yellow, Benzalkonium chloride and others) if not mentioned in the package insert (leaflet)
A clarification letter stating that the submitted samples are the COO or for registration purpose only, if these samples are not intended for the Egyptian market use.
30 / Inner Label of the product 3 original labels and 4 layouts
The manufacturer and / or the license holder by their logo should specified
The trade name and strength are specified
Batch number is specified
Manufacturing date is specified
Expire date is specified
31 / Package Insert (leaflet) of the Product (for the COO product and the proposed A.R.E product) 2 original and 2 word copies
On Company letter-head
Contains the Composition of the product {Active ingredient(s) with quantity(ies) }
Contains list of the Inactive ingredient(s)
Contains the Pharmaceutical Form (s)
Contains Storage Conditions
The Storage Conditions are identical to the one available in the file & identical to the one mentioned on the outer pack and inner pack
Powder for reconstitution: The Storage Conditions before reconstitution and after reconstitution are mentioned in the insert.
All Pack size (s) is (are) mentioned
Manufacturer and License holder full name and address are mentioned
Package insert reference no. and date of issue/revision are available
32 / Reference for the insert (innovator insert)
33 / Declaration letter that the submitted insert is the most updated and is the one marketed in the COO
Second: Ingredients & packaging materials
A)Active ingredients:
34 / Specifications of the active ingredients and the relevant tests.
Justification of Specification
35 / Certificate of Analysis
Original & Signed by the Company or the concerned center or laboratory that held the analysis
Stamped by the Company or the concerned center or laboratory that held the analysis
Product name, strength and form are specified
Manufacturing date is specified
Expiry date is specified
Batch number is specified
36 / Methods of analysis and validation (soft copy only)
37 / Supplier name & origin
b) Excipients:
38 / Specifications of the inactive ingredients and the relevant tests.
39 / Certificate of Analysis
Signed by the Company or the concerned center or laboratory that held the analysis
Stamped by the Company or the concerned center or laboratory that held the analysis
Product name, strength and form are specified
Manufacturing date is specified
Expiry date is specified
Batch number is specified
40 / Methods of analysis and validation (soft copy only)
41 / Supplier name & origin
42 / d)Packaging material:
Type of packaging materials.
Specifications of packaging materials.
Supplier name & origin
Third: Finished product
43 / Specifications of the finished product and the relevant tests
44 / Certificate of Analysis of finished products
Signed by the Company or the concerned center or laboratory that held the analysis (Authenticated and Notarized)
Stamped by the Company or the concerned center or laboratory that held the analysis
Product name, strength and form are specified
Manufacturing date is specified
Expiry date is specified
Batch number is specified
45 / Methods of analysis and validation (soft copy only)
46 / Supplier name & origin of finished products
If the materials entering in the product formulation are from blood derivatives , the following will be presented besides the previous: (47-50)
47 / Official certificates declaring plasma source
48 / HV-1,HV-2,HBsAG,HCV freedom certificate for the plasma
49 / Flow chart indicating sites and steps of product manufacture.
50 / Certificate of release from Health authority
51 / Method of manufacture including in process control & validation (soft copy only)
Manufacturing Process Development
Manufacturer (s) (Name, address, responsibility of each manufacturer including contractors, and each proposed production site or facility involved in manufacturing and testing should be provided)
Information should be provided on the manufacturing process, which typically starts with a vial(s) of the cell bank, and includes cell culture, harvest(s), purification and modification reactions, filling, storage and shipping conditions.
Controls of critical steps and intermediates (Tests and acceptance criteria performed at critical steps of the manufacturing process to ensure that the process is controlled should be provided)
52 / Site master file (soft copy only)
53 / Description of cold chain maintenance procedure
Dossier II: Stability Studies of The Finished Product / Submitted to stability department
1 / Authorization letter for the person responsible for communication on behalf of applicant during the procedure and this letter should be certified as truly signed
2 / Copy of the Preliminary approval
3 / Composition Certificate (5 copies)
4 / Copy of the Free sale certificate or CPP issued by Competent Authorities in Country of Origin
5 / Stability summary sheet (on website in stability committee)
6 / Stability report
7 / Certificate of Analysis of finished product
8 / Stability decision (3 copies) (on website in stability committee)
9 / stability report (on website in stability committee)
10 / Certificate of the lab where the stability studies id done ( for local products)
11 / Declaration of responsibility on the storage conditions
12 / C.D containing all content of the stability dossiers
13 / Letter (on company head letter) confirm the all the documents inside the C.D is identical to stability dossier (use the form on the website)
14 / NORCB analysis report (if issued)
15 / stability study (every paper should be stamped)
16 / M.O.A of active substance in the finished product
17 / Validation of the M.O.A of active substance in the finished product
18 / Declaration if the product is multi or single dose i.e immediate use or there is stability after opening
19 / Description of the packaging material
Dossier III: Inspection Dossier
1 / Site master file (stamp each paper)
Covering letter from the License holder declaring that the submitted SMF is the most updated and approved signed, stamped and Authorized
2 / Active substance master file
3 / GMP of all the manufacturers involved in the production process
(Active substance, Manufacturer of finished, Manufacturer of solvent, Batch releaser, primary packager,…….)
4 / Manufacturing license indicating production lines
5 / Copy of CPP of the product
6 / Manufacturing process for Active substance and Finished product
7 / CD contains all contents the Inspection dossier
Dossier IV: Quality Dossier
1 / Copy of application form for biological products
2 / Copy of composition
3 / Copy of Preliminary approval
a)Active ingredients:
4 / Specifications of the active ingredients and the relevant tests.
Justification of Specification
5 / Certificate of Analysis
Signed by the Company or the concerned center or laboratory that held the analysis
Stamped by the Company or the concerned center or laboratory that held the analysis
Product name, strength and form are specified
Manufacturing date is specified
Expiry date is specified
Batch number is specified
6 / Methods of analysis and validation
7 / Supplier name & origin
b)Excipients:
8 / Specifications of the Excipients and the relevant tests.
9 / Certificate of Analysis
Signed by the Company or the concerned center or laboratory that held the analysis
Stamped by the Company or the concerned center or laboratory that held the analysis
Product name, strength and form are specified
Manufacturing date is specified
Expiry date is specified
Batch number is specified
10 / Methods of analysis and validation
11 / Supplier name & origin
12 / c)Packaging material:
Type of packaging materials.
Specifications of packaging materials.
Supplier name & origin
d)Finished product:
13 / General Information
Nomenclature (as INN, compendial name if relevant, chemical Name,…)
Structure (Structural formula, relative & absolute stereochemistry, Molecular formula,..).
Biotech :
The schematic amino acid sequence indicating glycosylation sited or post translational modifications.
General Properties (Physicochemical and other relevant properties)
14 / Specifications of the finished product and the relevant tests
15 / Certificate of Analysis of finished products
Signed by the Company or the concerned center or laboratory that held the analysis
Stamped by the Company or the concerned center or laboratory that held the analysis
Product name, strength and form are specified
Manufacturing date is specified
Expiry date is specified
Batch number is specified
16 / Methods of analysis and validation of finished product
Validation information including experimental data used to test drug substance)
17 / Supplier name & origin of finished products
18 / Summary protocol
19 / Pre-clinical data (soft copy only)
20 / Clinical data (Soft copy only)
21 / CD contains all contents the Quality dossier
Dossier V: Scientific Committee Dossier / Submitted to biologicals scientific committee team
1 / Covering Letter to Biological Manager (signed and stamped on company Letter head)
2 / CD contains all contents of the Scientific documents of the dossier
3 / List of countries where the product is being registered and marketed indicating the registration number & date in each country
4 / Copy of CPP in addition to SPC
5 / Copy of reference(BNF 61,Vidal,Swiss Compendium,Rote liste)
6 / Covering Letter to EPVC Manager (signed and stamped on company Letter head)
7 / PSUR (periodic safety update report)( Most updated)
Soft Copy ( 2 CDs)
8 / Approved or Suggested price
(signed and stamped on company Letter head)
9 / plasma master file &viral inactivation (plasma derived product)
10 / Summary of the Quality, Pre-clinical and Clinical data including the following ( all soft copy except clinical overview hard & soft copy)
Quality Overall Summary
Introduction
Drug substance
General Information
Manufacture
Characterization
Control of Drug Substance
Reference Standards or Materials
Container/Closure System
Stability
Drug Product
Description and Composition of the Drug Product
Pharmaceutical Development
Manufacture
Control of Excipients
Control of Drug Product
Reference Standards or Materials
Container/Closure System
Stability
Appendices
Facilities and Equipment
Adventitious Agents Safety Evaluation
Novel Excipients
Regional Information
Nonclinical Overview
Overview of the Nonclinical Testing Strategy
Product Development Rationale
Overview of Biopharmaceutics
Overview of Clinical Pharmacology
Overview of Efficacy
Overview of Safety
Benefits and Risks Conclusions
References
Non clinical written and tabulated summaries: Pharmacology, pharmacokinetics, Toxicology
Introduction
Pharmacology Written Summary
Brief Summary
Primary Pharmacodynamics
Secondary Pharmacodynamics
Safety Pharmacology
Pharmacodynamic Drug Interactions
Discussion and Conclusions
Tables and Figures
Pharmacology Tabulated Summary
Pharmacokinetics Written Summary
Brief Summary
Methods of Analysis
Absorption
Distribution
Metabolism (interspecies comparison)
Excretion
Pharmacokinetic Drug Interactions
Other Pharmacokinetic Studies
Discussion and Conclusions
Tables and Figures
Pharmacokinetics Tabulated Summary
Toxicology Written Summary
Brief Summary
Single-Dose Toxicity
Repeat-Dose Toxicity
Genotoxicity
Carcinogenicity
Reproductive and Developmental Toxicity
Local Tolerance
Other Toxicity Studies (if available)
Discussion and Conclusions
References
Toxicology Tabulated Summary
Clinical Summary
Summary of Biopharmaceutic and Associated Analytical Methods
Background and Overview
Summary of Results of Individual Studies
Comparison and Analyses of Results Across Studies
Appendix
Summary of Clinical Pharmacology Studies
Background and Overview
Summary of Results of Individual Studies
Comparison and Analyses of Results Across Studies
Special Studies
Appendix
Summary of Clinical Efficacy
Background and Overview of Clinical Efficacy
Summary of Results of Individual Studies
Comparison and Analyses of Results Across Studies
Study Populations
Comparison of Efficacy Results Across All Studies
Comparison of Results in Sub-Populations
Analysis of Clinical Information Relevant to Dosing Recommendations
Persistence of Efficacy and/or Tolerance Effects
Appendix
Summary of Clinical Safety
Exposure to the Drug
Overall Safety Evaluation Plan and Narratives of Safety Studies
Overall Extent of Exposure
Demographic and Other Characteristics of Study Population
Adverse Events
Analysis of Adverse Events by Organ System or Syndrome
Narratives
Clinical Laboratory Evaluations
Vital Signs, Physical Findings, Observations Related to Safety
Safety in Special Groups and Situations
Intrinsic Factors
Extrinsic Factors
Drug Interactions
Use in Pregnancy and Lactation
Overdose
Drug Abuse
Withdrawal and Rebound
Effects on Ability to Drive or Operate Machinery or Impairment of Mental Ability
Post-Marketing Data
Appendix
References
Synopses of Individual Studies
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