Islamic Republic of Iran
Ministry of Health and Medical Education
Food and Drug Organization
Title: Regulations for contract manufacturing .
Type:
√ Finalized
Draft
No.: d/4113
Date of Issue: 2007/08/07
Document No.: BP-RU-98-01
Name of Office: Biologic,Deputy for Drug
Introduction:
The development of the biologic drug industries and the invention of new pharmaceuticals and the need to
state of the art technologies and instruments for production promotes the tendency of collaboration between
manufacturers through the different stages of production.
These collaborations are unavoidable in pharmaceutical industries and increase the potentiality for designing
and producing new drugs. Then the following regulations has been codified applicants who wants to
cooperate to produce biological products .
Applicants must also follow other pharmaceutical regulations, rules and standards of the drug production .
Terminology:
Contract manufacturing of biological products can be done in three forms:
1) Divided manufacturing:
Different steps of the production are divided between two or more pharmaceutical factories which
individually certified for the whole production line of the same product and each factory performs one or a
small part of the whole production.
2) Shared manufacturing:
Different steps of the production are divided between two or more pharmaceutical factories which are
certified for producing only Specific Parts of Whole Production.
3) Contract manufacturing:
License Holder (employer) transfers Specific Parts of Whole Production based on own responsibility to
another factory (contractor) in terms of a contract. All responsibilities of the finished product lie with the
certified license holder.
This document defines the regulation of contract manufacturing and doesn’t include any information about
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other kinds of production cooperation condition .
Contract manufacturing:
Qualifications of the license holder (employer):
Pharmaceutical companies (production or research) which are certificated by the ministry of health and
medical education meet conditions mentioned below can contract the production of products licensed by the
Drug Deputy . The license holder is responsible for assuring the safety ,the quality, purity and effectiveness
of the product and its conformity with the registered standards and specifications. These companies must
have the following qualifications:
1) Experienced in drug manufacturing procedures.
2) Employing specialists familiar with the production of the desired product or the similar product.
3) Utilizing enough space facilities, and equipment for required research and control which approved Drug
Deputy.
Qualifications of the contractor:
1) Applying experienced and acquainted persons in manufacturing the contracted products or similar
products available on the market.
2) Utilizing buildings, equipment ,materials ,enough knowledge and educational facilities based on the
contract context.
3) Possessing the Good Manufacturing Practice certificate (GMP) approved by the producing country’s
drug control center and the Iranian embassy.
5) Acquiring GMP from the Drug Deputy.
6) The contractor must follow the rules and regulations of the Iranian Health ministry.
Contract conditions:
The contract must be official and signed by both sides and contain these terms:
1) Detailed information (including companies addresses) of both sides of the contract.
2) Specifications of the contracted product.
3) Clear description of both sides responsibilities including quality assurance manner by the contractor
and the license holder (employer) supervision.
4) Description of distribution condition of raw materials and finished products and responsibilities between
license holder (employer) and contractor . .
5)Description the exact steps which are done by the contractor.
6) Providing complete lists of the standard operation procedures (SOP) for contract manufacturing of the
product.
7) Agreement between both sides that the contractor has to inform the license holder on any changes of
place or procedure of production in advance, including any new side products.
8) Agreement of the contractor has to inform any errors during production processes or experiment results
and sending it to the license holder.
9) license holder (employer)or the drug deputy permitted to inspect and access the factory or related
documents at any time.
10) Scheduling inspection times by the license holder.
11) Defining the procedures for receiving side effects, deviations, complains and responsibilities.
12) Scheduling the production stages.
13) Documentation procedure, responsibilities of both sides for documentation and the storage of
samples and documents.
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14) The contractor is not able to transfer the responsibilities to third one .
15) The authorized person must supervise the production and control processes of the contractor in
production site.
Stages of the contract manufacturing:
Applicants of contract manufacturing and distributing must follow the below the procedures.
1) Submit the application for initial permission includes:
1-1) Introducing the product in detail (the product must be indexed based on the Iranian official drug
list)
1-2) Detailed introduction of both sides of the contract and their résumé.
1-3) Clear description of production steps and both sides responsibilities .
1-4) Introduction of qualified personnel with their responsibilities and experiences.
1-5) GMP certificate issued by by competent authority in country of origin and other international
certificates if it is applicable.
2) Obtaining initial permission issued by Article 20 of legal commission .
3) Presenting the registration documents as follows :
3-1) Photocopy of the official approved contract.
3-2) CTD,SMF,PMF(if it is applied ) by the license holder (employer)technical director
confirmation.
3-3) International certifications of the product if it is available.
3-4) Persian Packing leaflet which is approved authorized person confirmation and a related
Memberof university scientific board.
3-4) License holder (employer) known as the manufacturer on the package. As well as name of
license holder ,in the leaflet contractor known as manufacturing site.
will be the contractor’s and the employer ,s name as the place of manufacturing.
3-5) Receipt photocopy of registration fee .
4) GMP certificate of the production site by the supervising general department of drugs and narcotics and
general department of food and drug controlling labs.
5) Accepted results for samples by the national quality control laboratory ( for thefinished products, samples
or laboratory scale.
6)Obtaining temporary production or import permission of necessary number of products for clinical and
subclinical trials and for stability studies for 2 years.
7) Presenting the results of clinical ,under clinical, stability ,validation studies and production uniformity.
8) Obtaining production and import permission from the Article 20 of legal commission and issuing
production certification
9) Presenting required documents for batch release as follow:
9-1) Necessary Documents of biological products batch release .
- One copy of this document must be kept by the employer, for at least 5 years after the product’s
expire date.
9-2) Certification of the contractor for GMP principles compliance and implementing all the necessary
processes according to the contract and registration file with any deviation, that is confirmed by
technical director of license holder or his /her deputy.
9-3) Release certificate of product issued by authorized person after review whole production steps
and documents.
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