Islamic Republic of Iran
Ministry of Health and Medical Education
Food and Drug Organization
Title: Pattern for preparing file summary for plasma-derived products
Type:
√
Finalized
Draft
No.:
Date of Issue:
Document No.: 102-60-03
Name of Office: Biologic,Deputy for Drug
Drug name:
Manufacturing company and country of origin:
Importing company:
Date of request:
Remarks:
unit:
Name of technical in-charge:
Number of correspondence:
Check the following items prior to submission of documents:
1- The product is compatible with the official index of Iranian drug in terms of name, form, and amount of
active ingredient.
2- Basic approval from the legal commission for importation
3- Drug master file
4- Plasma master file
5- Site master file
6- Certificate of pharmaceutical product, confirmed by embassy
7- List of countries purchasing the drug
8- GMP certificate by inspectors of the supreme department
9- Response of drug control laboratory (are documents and the specimen submitted to the lab?)
10- History of import
Brand name:
Generic name:
Drug unit:
Drug form:
Manufacturer name:
Manufacturer address:
Further remarks:
Minimum Required Product Information
Drug Master File
1- General information regarding the product:
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 Formulation, with mention of amounts and function of each constituent for a drug unit
 Number and volume of packaging
 Filled volume
 Storage and transportation conditions
 Route of administration
 Indications
 Product cautions
 Further remarks:
Expert opinion:
2- Information regarding the manufacture process:
 Formulation amounts for one batch
 Manufacture process, including all stages of preparation, isolation and purification
 Controls during manufacture
 Process evaluation with mention of results
 Proof of manufacture homogeneity
 Description of equipment and method of maintenance and cleaning
 Further remarks:
Expert opinion:
3- Information regarding auxiliary substances
 Source of obtaining
 Control methods
 Reference used
 Analysis sheet
 Further remarks:
Expert opinion:
4- Control of intermediate substances (if production is not consecutive)
 Control methods
 Reference used
 Analysis sheet
 Further remarks
Expert opinion:
5- Control of final product:
 Control method
 Reference used
 Evaluation of control methods
 Analysis sheet
 Further remarks:
Expert opinion:
6- Control of solvent in final product
 Control method
 Reference used
 Analysis sheet
 Further remarks
Expert opinion:
2
7- Information regarding product packaging
 Type and materials
 Analysis sheet of packaging materials
 Color sample label
 Color sample packaging
 Sample brochure
 Sample product
 Further remarks:
Expert opinion:
8- Information regarding solvent packaging:
 Type and materials
 Analysis sheet of packaging materials
 Color sample label
 Further remarks
Expert opinion:
9- Information regarding stability of final product:
 Name and address of the laboratory where the test is conducted (if tests are conducted outside the factory)
 Batch numbers tested, alongside manufacture date and size of batch
 Test procedure
 Storage conditions of tested samples
 Packaging type of samples
 Interval of tests and duration of stability
 Tests conducted and their results
 Final result
 Further remarks
Expert opinion:
10- Information regarding stability of solvent in product
 Name and address of the laboratory where the test is conducted (if tests are conducted outside the factory)
 Batch numbers tested, alongside manufacture date and size of batch
 Test procedure
 Storage conditions of tested samples
 Packaging type of samples
 Interval of tests and duration of stability
 Tests conducted and their results
 Final result
 Further remarks
Expert opinion:
11- Information regarding stability of solution after preparation
 Name and address of the laboratory where the test is conducted (if tests are conducted outside the factory)
 Batch numbers tested, alongside manufacture date and size of batch
 Test procedure
 Storage conditions of tested samples
 Packaging type of samples
 Interval of tests and duration of stability
 Tests conducted and their results
 Final result
3
 Further remarks
Expert opinion:
12- Information regarding clinical and subclinical studies
 Method of studies
 Cases studied
 Results
 Further remarks:
Expert opinion:
13- Product deviralization
 Procedure of deviralization and its conditions
 Further remarks
Expert opinion:
14- Evaluation of deviralization methods:
 Name and address of site of deviralization evaluation and brief history of the company’s activities of valid
certificates
 Determination of steps of deviralization
 Type and species of viruses used
 Test procedure
 Method of low scaling and its evaluation
 Preliminary and final titers of viruses added
 Methods used for virus quantification
 Reductive factors in each step
 Statistical analyses and diagrams
 Final RF and interpretation of findings
 Original version of confirmation of evaluating studies of deviralization process
 Further remarks
Expert opinion:
15- Reagents used in production
(Biologic substances used in the manufacture process, e.g. monoclonal antibodies for purification, enzymes etc.)
 Name of substances
 Name of purchase site
 Nature and function of substances in manufacture
 Results of tests conducted
 Further remarks
Expert opinion:
16- Specific cases of animal-derived products (final product or used in formulation)
 Properties of the animal used
 Health history of the animal
 Geographical location of animal’s raising environment
 Manufacture procedure
 Certificate of BSE health
 Further remarks
Expert opinion
17- Specific cases of products derived from blood and plasma (final product or used in formulation)
4
 Plasma master file
 Original version of plasma safety certificate by manufacturing company, including confirmation of selection of
healthy donor, deviralization, and other measures taken for provision of healthy product
 Further remarks:
Expert opinion:
18- Sample protocol summary of the product:
 Further remarks
Expert opinion
19- DMF appendices
 Original sample signatures of individuals in-charge with confirmation of Iranian embassy in the country of
origin
First time/ evaluating expert
date of evaluation
Revision/ evaluating expert:
date of evaluation
Complementary documents/ evaluating expert
date of evaluation
Number: BC-104/82
Minimum Requirements for Plasma used in Manufacture
(Plasma Master File)
Since using healthy plasma, with acceptable quality and free from any contamination is the first and most crucial
step in guaranteeing health and quality of plasma-derived products, the producer must submit sufficient
information to prove the compatibility of conditions of plasma collection and control with current standards.
The information must at least include the following:
 Name of country or countries providing the plasma
 Name of the company providing the plasma and registration number of the company in the country of origin
 List of blood donation centers with their address and permit number
 Date of last inspection from blood donation centers and interval between inspections
Acceptable standard: The interval between inspections must preferably be not more than two years and the
inspections must be conducted by reliable governmental centers.
 Epidemiologic information regarding the rate of transmissible infections observed in clients and donated
bloods in the blood donation center
 Measures taken for selection of health donor, such as completing a questionnaire, physical examination and
medical tests
Accepted standard: All three items above must be performed.
 Approval or rejection criteria for donor
Accepted standard: The donor must be health for transmissible diseases and must not belong to high-risk
groups.
 Screening tests on each blood donation sample and decision on responses
Accepted standard: It is mandatory to run Anti HCV, Anti HIV, and HBS antigen with reliable kits and ALT and
syphilis tests.
 Complete information of kits used for virus detection in each donor
 Complementary tests on pool plasma and decision on responses
Accepted standard: It is mandatory to run Anti HCV, Anti HIV, and HBS antigen and HCV RNA with reliable kits.




Complete information of kits used for virus detection in pool plasma
Validation studies of methods and kits used for virus detection
Name and address of the laboratory and its registration number
Quarantine system
Accepted standard: Quarantine system is not mandatory for approved regular donors; however, donations from
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new donors must be quarantined until proven healthy in subsequent sessions of donation.




Information of plasma carrying vessels
Storage and transportation conditions
Qualitative indices of plasma
Follow-up system of blood donor
Accepted standard: In case of infection in donor, the follow-up system must be able to eliminate the infected
donated plasma or recall of infected product from market, if necessary.
Further remarks:
Expert opinion:
First time/ evaluating expert
Revision/ evaluating expert:
Complementary documents/ evaluating expert
date of evaluation
date of evaluation
date of evaluation
Minimum Required Factory Building and Installations Information
Site Master File
Since quality of the final product cannot be guaranteed unless the manufacture procedures and their
compatibility with GMP principles are considered, the factory must provide sufficient information to confirm their
conformity to GMP, which ensures an appropriate quality assessment system. The maps, flowcharts, protocols
and other documents which contain the minimum required information are as follows:
 Address of manufacture site
 Organizational chart
 Brief history and current status of the factory
 Number of personnel, their education, experience and competences
 Educational programs and system of archiving educational backgrounds
 Health condition and hygiene of personnel
 Location of the factory building and position of the building used for manufacture and control
 Location of different classes of work and conditions of each class
 Circulation of personnel, raw materials and products in the factory
 Processes of quality control and quality assurance
 System of report documentation and registration
 System of process evaluation
 Method for drug recall and retrieval from market
 List of important equipment and machinery
 Plan for building and equipment maintenance and service
 Facilities for labeling and packaging
 Facilities and processes of storage and quarantine of raw materials, packaging materials, intermediate
materials, bulk materials and final product
 System of water, energy and vapor provision
 Sewage and waste handling systems
 Cleaning processes and their control
 Facilities of the vivarium
 Name of factory and laboratories that collaborate with the factory and their functions
In order to ensure that the building, facilities, processes and activities are compatible with the registration
documents, the factory reports must be reviewed. However, if no report is available or no inspection has been
performed, the factory must be inspected prior to registration.
Further remarks:
Expert opinion:
First time/ evaluating expert
date of evaluation
Revision/ evaluating expert:
date of evaluation
Complementary documents/ evaluating expert
date of evaluation
6
Correspondences:
Number of letter received
Date
Subject
Number of letter dispatched
7
Date
Subject