HM Medical Clinic

Dppharma.ir

DAROU PAKHSH
PHARMACEUTICAL MFG. CO.
SITE MASTER FILE
Issued Date: 09/05/2015
CODE : DPSMF422
Validation Date: 09/05/2016
Rev. No:3

This Site Master File was prepared on the basis of the PIC/S document "Explanatory notes for industry on
the preparation of a Site Master File" PE 008-4.
Contents:
Chapter 1: General information
1.1
Contact information on the manufacturer Authorized Pharmaceutical manufacturing activities of the site Any other manufacturing activities carried out on the site
Chapter 2: Quality management system
2-1
the Quality management system of DAROU PAKHSH PHARMACEUTICAL COMPANY Release procedure of finished products Management of Supplier s &contractors QRM(Quality risk management) Product quality reviews Chapter 3: Personnel
Organization of technical division
Chapter4: Premises and equipments
4-1
4-1-1 Brief description of heating, ventilation and air conditioning (HVAC) systems 4-1-2 Brief description of water systems 4-1-3 Brief description of other relevant utilities, such as steam, compressed air, nitrogen, etc. 4-2 4-2-1 Listing of major production and control laboratory equipment with critical pieces of equipment identified should be provided in Appendix 8 4-2-2 Cleaning and sanitation 4-2-3 GMP critical computerized systems Chapter 5: Documentation
Chapter6: Production
6-1
type of products(reference to appx. 2) Process validation Material management and warehousing
Chapter 7: Quality control(QC)
Chapter 8: Distribution ,Complaints, product defects and recalls
Chapter 9: Self inspections

Page 1 of 13
DAROU PAKHSH
PHARMACEUTICAL MFG. CO.
SITE MASTER FILE
Issued Date: 09/05/2015
CODE : DPSMF422
Validation Date: 09/05/2016
Rev. No:3

General appendies
Appendix 1: Copy of valid manufacturing authorization
Appendix 2: List of dosage forms manufactured including the INN-names or common name (as available)
of active pharmaceutical ingredients(API) used
Appendix 3: Copy of valid GMP Certificate
Appendix 4: List of contract manufacturers and laboratories: NA
Appendix 5: Organisational charts
Appendix 6: Lay outs of production areas including material and personnel flows, general flow charts of
manufacturing processes of each product type (dosage form)
Appendix 7: Schematic drawings of water systems
Appendix 8: List of major production and laboratory equipment



Page 2 of 13
DAROU PAKHSH
PHARMACEUTICAL MFG. CO.
SITE MASTER FILE
Issued Date: 09/05/2015
CODE : DPSMF422
Validation Date: 09/05/2016
Rev. No:3

Chapter 1: General information
DAROU PAKHSH PHARMA. MFG. CO is a subsidiary of Tamin pharmaceutical investment company
(TPICO). which is a wholly owned subsidiary o f Social Security investment Company. This company is a
registered public joint stock company according to the I.R. Iran laws.
1-1
Contact information
Name: Dr.Amjadi Kambiz(senior manager)Dr. Eimagh naeini Babak&Dr. Dolat abadi
Fateme&Dr.zamani farahani Afsane&Dr.Ahmadi Zahra.
Address: 18th Km of karaj freeway , Darou Pakhsh Manufacturing pharmaceutical company ,Tehran ,Iran
P.o.Box:11365-4388
Phone:(+98-21)44986815-16
Fax: (+98-21)44987314
Email:
1-2
Authorized Pharmaceutical manufacturing activities of the site
DAROU PAKHSH PHARMA. MFG. CO. is authorized by MOH of I.R. Iran (n° T42-74), date August 15,
1972 and ministry of Industry (n° 42- 06/60668), date Nov. 30, 1959 to manufacture, import, trade
wholesale and export medications (Appendix 1)
DAROU PAKHSH PHARMA. MFG.CO. manufactures more than 176 pharmaceutical finished products
for human and veterinary in different dosage forms: tablets, capsules, oral powders (sachets), oral liquid,
small volume parentherals (SVPs)& large volume parenterals (LVPs), Freeze dried injectables, eye-drops,
creams, ointments and suppositories, lotion, vial and dental cartridges.
For human products, manufacturing licenses are obtained from Iranian Ministry of Health (MOH). In
addition, for veterinary products, the appropriate Licenses are obtained from the veterinary organization of
Ministry of Agricultural. (Appendix 1)
The company is located in suburb of Tehran ; research and development activities , manufacturing , quality
control , marketing and dispatch activities are all carried out at this site. Recently dedicated production
areas e.g. Insulin, Mycophenolate and contrast media are added.
1-3
Any other manufacturing activities carried out on the site
The company imports nutritional supplement products and may produce cosmetics or cosmeceutical
products in future.

Chapter 2: Quality management system
2-1
the Quality management system of DAROU PAKHSH PHARMACEUTICAL COMPANY
DAROU PAKHSH PHARMA. MFG. CO. considers quality in the wide sense of the word as being one of the key-elements for its success. DAROU PAKHSH PHARMA. MFG. CO quality system design and implemented with the aim of producing high quality, healthy and effective drugs in accordance with the principles of GMP,. , the.Product quality improvement (in aspect of the customer) and the standardization of products and processes (in the way processes) are determined.as sterategic goals of company. In this regard, the company in the year 2002 towards the establishment of the ISO 9000 system action and in2010 compared to the revision 2008. Improving quality system, as the unlimited process, has done under the leadership of the Managing Director, restrict. Page 3 of 13
DAROU PAKHSH
PHARMACEUTICAL MFG. CO.
SITE MASTER FILE
Issued Date: 09/05/2015
CODE : DPSMF422
Validation Date: 09/05/2016
Rev. No:3

The site operates in conformance with GMP /PICs.
A fully documented quality system is established and maintained which ensures that products, produced,
released and sold meet the specified requirements of the relevant specifications .
Senior Management Reviews are held and use Internal Audit results, deviations,CAPA's, external audits to
determine the effectiveness of the quality system.
The Quality system include quality assurance unit,quality control unit and responsible pharmasists are
directly responsible for all aspects of the quality system including, but not limited to:
§ approval or rejection of all raw materials, components, and product batches,
§ ensuring the CAPA system is functional,
§ ensuring that maintenance and calibration systems for critical equipment are effective,
§ oversight of cleaning and sanitization systems,
§ cGMP training,
§ ensuring that quality related customer complaints are investigated and resolved,
§ organizing and monitoring recalls, and performing product quality reviews products throughout
The specifications for raw materials and finished products as well as for manufacturing and analysis
processes are set out in written procedures, which are periodically controlled.
Written reports are kept on manufacturing conditions and on the controls undertaken during manufacturing
and in the laboratories. This permits monitoring of the company's manufacturing and guarantees their
quality.
The company has certificate of ISO14001&9001 .(Appendix 1)
2-2
Release procedure of finished products
The batch may not be dispatched unless it has been released and is accompanied by a duly signed
certificate of analysis
Quality Unit personnel authorized to review batch documentation and release batches are by responsible
pharmacist of the Quality Control department for the intermediate and finished products.
The batch certification and release procedure is covered by DPWI6377009 Batch Release.
In summary, the person in charge of release reviews all pages of the completed production batch record
and the test sheets from the QC lab to ensure that all parameters were within specification, all spaces for
entering information are completed, signatures and production checks were completed, raw material
usage data is correct and complete, labels are accounted for and excess labels are destroyed, and
calculations are verified If all information is in order, the batch record is stamped "RELEASED, BY,
and DATE". Then the batch is released . None of the current control strategies Process Analytical
Technology (PAT). employ
2-3
Management of Supplier s &contractors
The evaluation of suppliers takes into account in various criteria: § The history of the company's relations with the supplier § The quality of products supplied hitherto § cGMP and ISO 9001 certification is a selection criterion (for similar offers, preference is given to a supplier with such certification) § Results of external audits undertaken by Technical director in collaboration with Industrial Logistics. Emphasis is placed on the audit of the major suppliers whose products have a significant impact on the quality of DAROU PAKHSH PHARMA. MFG. CO. finished products. Page 4 of 13
DAROU PAKHSH
PHARMACEUTICAL MFG. CO.
SITE MASTER FILE
Issued Date: 09/05/2015
CODE : DPSMF422
Validation Date: 09/05/2016
Rev. No:3
The production unit is responsible for ensuring production deviations are reported and considered; critical
deviations are investigated with conclusions and corrective actions documented,
The production unit also is responsible for ensuring the production facilities are clean in
accordance with site production and quality procedures, ensuring that calibrations are performed and
documented,
ensuring that facility and equipment are maintained and these activities are documented ,reviewing and
approving validation protocols and reports, reviewing and approving changes to products, processes, and
equipment, and ensuring that new and modified equipment are qualified as appropriate.
2-5
Product quality review
Annual Product Reviews are completed for API's and semi-finished medicinal products
Site Manager, Production Manager, Process Manager, Quality Control, and Quality Assurance reviewed
and discussed the results of all APR. The studies contain a product summary (number of batches
produced, specifications), description of deviations (in-process deviations, complaints, OOS's, etc.), a
description of change control documents, specifications and revisions, review starting and packaging
materials, process validation review, equipment and utility review, test data analysis and trends, stability
review, recalls, conclusions, and recommendations. Site meetings are held where corrective action plans
are generated where necessary.

Chapter 3: Personnel
The organization chart provided at appendixe5, outlines the structure of DAROU PAKHSH PHARMA.
MFG. CO. top chart.
3-2 The technical staffs are deployed as follows:
Production:
Quality control: Regulatory Affair 8 QA: Training strategies and policies are set according to organization's strategy and the human resource development requirements; thereby the training total program is set out. The job training needs and the main content of courses are determined through interview with subject professionals and modified periodically by job professionals in company. The employee training needs for each personnel and the training priorities are determined by questionnaire and interview with manager and direct responsible of employees, annually. All the personnel whose jobs could affect the quality of the product (Production, Maintenance, Storage, Quality Control) receive GMP training that include issues such as pharmaceutical products quality, personnel, sanitation and hygiene, premises and equipments, materials, documentation. Newly recruited production personnel (either permanent or temporary employees) receive induction training that covers good practices in production and packaging the different pharmaceutical dosage forms as well as health and safety. The quality control staffs receive previously mentioned training as well as GLP. Page 5 of 13
DAROU PAKHSH
PHARMACEUTICAL MFG. CO.
SITE MASTER FILE
Issued Date: 09/05/2015
CODE : DPSMF422
Validation Date: 09/05/2016
Rev. No:3

Subjects such as GMP, which the legal obligations require their retraining, are retrained timely. The
specialty issues are retrained in updated cases, which are determined at annually need assessment or are
requested by managers.
Health & safety and environment unit under supervision of Human Resource Department is responsible for
checking employee's health & safety and hygiene. Base on person's job and work place hazard DAROU
PAKHSH PHARMA. MFG. CO. has especial physical examination interview and Para-clinic tests
(Eudiometry, Spirometry, Optometry and.). There is periodic employee examination base on their job.
DAROU PAKHSH PHARMA. MFG. CO. has special sickness registration system that report yearly.
For hi-risk jobs there are special protocols for following and all employees have special examination before
and during their work. DAROU PAKHSH PHARMA. MFG. CO. has special registration system for
worker during return the work after disease. Those who work in aseptic and clean areas have clinical
examination twice a year and examination has different.
QC clothing in the laboratory is white. Standard clothing in the production buildings is a blue overall, a
cap/hat and working blue shoes or overshoes. Mechanics who undertake dirty work wear dark blue
overalls.
Overall are washed and pressed once a week inside the company; each collaborate has a set of 2-5 overalls,
permitting once change.
Depending on the type of work and its localisation (for example laminar flow, aseptic arias, controlled
arias, etc) each collaborator wears specific clothing (for example sterilised overall, mask, hood, specific
shoes and gloves).
Chapter4: Premises and equipment
4-1
premises
DAROU PAKHSH PHARMA. MFG. CO. is located in the suburb of Tehran with more than ……. buildings on a 191/650 m2 (see location site in appendix6). Floor plans are provided in the Appendix 6 The premises are situated, designed, constructed, adapted and maintained in a manner to facilitate manufacturing, control and cleaning operation. Manufacturing, packaging, quality control and storage operations are undertaken in buildings. The Main production building from 1959 houses mainly pharmaceutical production and R&D & quality control laboratories From 2010 , renovation have been done in main production buildings under latest GMP and environmental standards for example sterile production unit and liquids production unit and QC laboratories departments have been done Also 3 new production units have been constructed : 1) Insulin production line 2) Growth hormone production line 3) Vial production line In near future , packaging of solids unit , central weighing departments and semisolids unit will be renewed. Training center & Clinic buildings These buildings are located outside of the production area and used for personnel training and healthcare. Page 6 of 13
DAROU PAKHSH
PHARMACEUTICAL MFG. CO.
SITE MASTER FILE
Issued Date: 09/05/2015
CODE : DPSMF422
Validation Date: 09/05/2016
Rev. No:3

4-1-1 HVAC SYSTEM:
Each unit has its own separated HVAC and if necessary dedusters. In all units fresh air is available
according to unit requirements and in solid unit full fresh air exists. HVAC's have F9,F7 & G4 and in case
of GMP guidelines H13 filters .
Tempreture , pressure and humidity are monitored and control system creats optimal conditions
4-1-2 Water systems
Water that derivated from well after passing sandy filters is chlorinated by DP(Darou pakhsh) to 0.6ppm.
Chlorinated water is used for general consumption in the company. All units are equipped with pure water
generator which turn the chlorinated water to pure water by RO equipments.
The input water for RO passes through carbon filters for dechlorinating & water softner for reducing
hardness and after passing through membrance filters turns into pure water.
If injectable water is needed, it can be produced from pure water and distillation process.
The water specifications for this unit are those set out in the BP monograph
4-1-1 Steam /Compress air/ Oxygen/ Nitrogen:
Compressed air :
Compressed air is generated by 2 oil-free compressors that work frequently. It is stored in storage tanks
through dryers and then transferred to all units via pips for their usage. All the compressors and
requirements are located in main power plant of the company
Steam:
There is 2 kinds of steam system in DP :
1) Industrial steaming in which steam is generated in the boilers and then transferred through pipes to all
2) Clean steaming in which by using industrial steaming and pure water in the unit itself, clean steaming is producer and used. -The available oxygen in compressed air after passing through oxygen generator is separated from
Nitrogen with the purity of 99% and stored in feeding tanks and reached to units that need pure oxygen
vice pipes. This generator is located in the main powerplant of the company
-Nitrogen:
The available nitrogen is compressed air is separated from oxygen with purity of 99.5% when passes
through Nitrogen generator and is stord in storage tanks. This Nitrogen transfer to those units in need of it
via pipes. This generator is located in main powerplant of the company.
4-2
Equipment
The materials used for the construction of apparatus machines used in production are appropriate for their
use (for example, various types of stainless steel); flexible silicon pipes can be sterilized. Production
phases requiting aggressive treatments (for example alkaline) are undertaken on materials resistance to
such conditions.
4-2-1 Description of production and control equipment
The Lists of major production and control laboratory equipment are in appx. 3
Page 7 of 13
DAROU PAKHSH
PHARMACEUTICAL MFG. CO.
SITE MASTER FILE
Issued Date: 09/05/2015
CODE : DPSMF422
Validation Date: 09/05/2016
Rev. No:3

4-2-2 Equipment cleaning
The manufacturing areas are cleaned and if necessary disinfected after each manufacturing run by the
manufacturing personal according to the current operating procedure.
Large pieces of apparatus are designed to facilities cleaning and/or sterilization in place; small or easily
dismantled pieces of equipment are cleaned by hand or in washing machines (glassware) before being
disinfected or sterilized, if necessary.
The cleaning of the HVAC systems is undertaken regularly with a varying frequency variable depending
on the type of installation.
The microbiological laboratory monitors the microbiological quality of the air in the different
manufacturing and control premises.
The frequencies of the controls and the limits set for warnings / actions depend on the type of premises.
A microbiological control of the surfaces is also undertaken in the atmosphere – controlled areas.
4-2-3 Electronic monitoring systems:
These systems function as logical control by using PLC. (Programmer logical controller)and HMI(Human
machine Interface) that ultimately lead to control.
EMS system for monitoring and controlling of environment conditions can be accessible locally as well as
an Internet and local Intranet.
Systems for checking staff personnel , materials and products can be programmed by Access control on the
network and assure that only authorized personnel can have access to certain units.
Chapter 5: Documentation DAROU PAKHSH PHARMA. MFG. CO. has established a document
management system. This system organize the different types of documents, i.e.
§ Quality Manual
§ process profiles
§ instruction&/or procedures of doing the process
§ the process instruction &/or procedures of controls and monitoring
§ Recordes and documents of above
Control of Documents
Quality system documents are controlled both manual and semi electronic. the format, Coding, content, approval, distribution, revision, and control of documents describes in procedures and ensures that only the most current versions of quality system documents are used. Procedures are in place for manufacturing processes, the quality control laboratory, and all general site quality procedures. Each controlled procedure is assigned a unique document number, and each document contains the effective date, revision number, expire date(valid until) signature blocks for the issuer and approvals , QA manager, and a revision history. Responsible pharmacist's signature required for all documents pertaining to production as defined within the document control SOP's. Control of Records
Procedures for filing, storage, and disposal of quality system records are defined in the Quality Records Management Procedure (DPPR424007). All written operating area and laboratory records are completed during activities The following are described in the documentation: Page 8 of 13
DAROU PAKHSH
PHARMACEUTICAL MFG. CO.
SITE MASTER FILE
Issued Date: 09/05/2015
CODE : DPSMF422
Validation Date: 09/05/2016
Rev. No:3

Product specification
Raw material specification
Packaging material specification
Operating procedure describing the different manufacturing steps, including packaging
Analytical methods
Procedure for batch release
The documents for follow-up of manufacturing and analysis, which constitute the batch process
record(BPR).
The BPRs are revised and controlled by the heads of manufacturing divisions, thus certifying that the
batch has been manufactured according to the operating procedures, that all the manufacturing process
controls have been performed and that all the documents released by that division and constituting the BPR
have been correctly and completely filled in. They ensure that any incident has been recorded in the BPR
and reported to Quality Control Department
Each manufacturing run is subject to an output calculation (archive in the BPR) allowing identification of
any abnormal losses.
The BPR are then forwarded to Quality Control Department and submitted to a documented control.
The batch records is in paper version and kept for 1 year after expiry date of batch.
Change Control
A Management of Change procedure (DPPR824005) is in place to ensure that all changes affecting
quality are reviewed and approved prior to implementation.
It is applicable, but not limited to changes in raw materials or packaging and their sources,
material specifications, test methods, manufacturing and analytical equipment, production processes,
and manufacturing or packaging sites. All such changes that potentially impact product
quality require approval of the Quality unit.
Chapter 6: Production
Type of products
The list of the products, which manufactured by DAROU PAKHSH PHARMA. MFG. CO. is provided in the appendix. 2. in a list of human & veterinary & under investigation 6-1-1 Toxic substances An immunosuppressive drug , Mycophenolate ,is classified as hazardous
6-1-2 Dedicated line
Recently Insulin and Mycophenolate production lines are added as dedicated lines
6-2
process validation
6-2-1 general policy of process validation
process validation newly started and is in progress. 6-2-2 Batch reprocessing
If necessary, batch reprocessing is done according to the defined procedure under deviation and OOS managment (the procedure is defined by Technical Director, head of QC & QA and Head of Production). Page 9 of 13
DAROU PAKHSH
PHARMACEUTICAL MFG. CO.
SITE MASTER FILE
Issued Date: 09/05/2015
CODE : DPSMF422
Validation Date: 09/05/2016
Rev. No:3
Material Management &warehousing
6-3-1 Handling of starting materials, packaging materials, intermediate, semi finished and finished
products, including sampling, quarantine, release and storage.
After reception of any raw and packaging material is put in a quarantine zone and labelled accordingly. Each delivered article is identified by its article number, its supplier batch number and its internal DAROU PAKHSH PHARMA. MFG. CO. code number. The delivered batch is sampled (under laminar flow for the raw materials If necessary) according to procedures and the sampling plan. The samples are transmitted to the Quality Control laboratories and analysed. The batch is released or rejected, the labels (under test) covered by another label specifying its new status and among others its expiration date. A certificate of analysis is edited and signed by the head of Quality Control Department The Planning division manages the raw materials stock and designates the batches, which will be delivered to the production division. They will be weighed, mainly in the central weighing facility then delivered to the manufacturing departments. The key manufacturing parameters are described in the manufacturing protocols in the form of columns to be completed, the operators records the controls carried out: these can therefore found in the Batch Processing Record. The authorized operator undertakes empty line checks and controls during the course of manufacturing and packaging, these controls are recorded in the Batch Processing Report. Intermediate, semi-finished products are sampled according to the current procedures and analysed by the Quality Control Department. The laboratories control that the products meet the physico-chemical, and microbiological specifications, and if applicable biological control and activity specifications, as well as the primary and secondary packaging specifications. As the intermediate and semi- finished products constitute the key step of the production process, the Quality Control department puts them in quarantine until release or rejection. This is also the case for all finished products. A certificate of analysis signed by the heads of the Quality Control department and a label (Approved) or (Rejected) is affixed. Acceptance or rejection is made on the basis of: § Batch analysis result § Review of the Batch Processing Record § Evaluation of possible non-conformities related to the manufactured batch The storages areas are buildings, which guarantee the security and the quality of the raw materials and products stored (limited access, fire detection and extinguisher system, temperature control). Samples are taken if necessary in sampling rooms under laminar flow. Raw materials are stored in containers, which protect them from dust. The storage area is equipped with air- conditioned rooms for raw materials and products that are sensitive to temperature variations and there is a cold room for the storage for sensitive raw materials. Page 10 of 13
DAROU PAKHSH
PHARMACEUTICAL MFG. CO.
SITE MASTER FILE
Issued Date: 09/05/2015
CODE : DPSMF422
Validation Date: 09/05/2016
Rev. No:3

The materials in quarantine are stored in a reserved and labeled area.
The status of raw materials, packing materials, intermediate, semi –finished and finished products is
indicated by a system of labeling which indicates clearly whether a material or a product is in quarantine,
released or rejected.
Raw materials are used on a "First In, First Out" (FIFO) basis, as indicated by their expiration date. The
finished products follow in general this principle (except in the case indicated above, when a batch is
reserved for a particular client).
6-3-2 Handing of rejected products and materials
Rejected products are clearly labelled (red labels); they are stored in an area designed for this purpose. When a sufficient quantity of materials to be destroyed has accumulated, they transported to an incineration center and destructed according to the guidelines of MOH.
Chapter 7: Quality Control
7-1
Physico-chemical laboratory:
Physico-chemical control and analysis of the quality of the starting materials. intermediate and finished
products.
7-2
Biology laboratory
Microbiological control and analysis of the quality of the raw materials, intermediate and finished
products.
Control of the microbiological quality of the Water ,environment (air, surfaces) and utilities.
Biological control and analysis of raw materials, intermediate, and finished products.
7-3
In – process QC laboratory
In – process control of packaging materials, production procedures, finished products and other differential
important Parameters such as Temperature, Humidity, Pressure, Air Particle counting and … .
7-4
Biotechnology laboratory
Biological assay of insulin , growth hormone , heparin ,enoxoparine and similar drugs.
Chapter 8: Distribution Complaints', PRODUCT DEFECTS & RECALLS
The distribution companies that The DAROU PAKHSH PHARMACEUTICAL MFG. Co. is deal with are:
Darou Pakhsh distribution Company, Momtaz Distribution Company, Exir Company, Poorapakhsh
Company, Darougostar Razi Company, Hejrat Company, Behresan Darou Company, Mahya Darou
Company.
8-1
Batches of products packed are stored; After releasing the batches and when an order arrives, the quantity required is taken from stock. The distribution follow- up system allows a batch to be traced from manufacturing to the customer (date of delivery, quantity, name and address of the customer). Page 11 of 13
DAROU PAKHSH
PHARMACEUTICAL MFG. CO.
SITE MASTER FILE
Issued Date: 09/05/2015
CODE : DPSMF422
Validation Date: 09/05/2016
Rev. No:3
Complaints and Recalls
There is a written procedure for dealing with quality complaints. This procedure describes in particular the actions to be taken in case of compliant and the responsibilities of the persons that make up the committee for handling complaint, which include among others: § The Technical Director who has responsibility for setting up a centralized documentation of all information, reports, forms, minutes of meeting, etc.… and for assembling the batch record concerning each complaint, for determining the exact nature of the complaint and for finishing its cause. § The head of Marketing Department, whose task is to provide a list of customers who have received the incriminated batch and establish an inventory of remaining stocks within the company. § The head of Quality Control who is responsible for labeling and control of storage of the incriminated batch, for verifying reference samples, for using or developing control methods in order to complete the inquiry. Reports are prepared for the different stages in handling the complaint; a final report closes the matter. The reports are submitted to the compliant handling committee; the members of this committee receive a copy of the final report; this system ensures the control of these documents. Each compliant file is retained for at least 2 years after expiring date of the product. The above-mentioned procedure is also used in case of recalls; it describes the process to be followed when compliant - internal company information or a demand from the authorities – justifies a recall. This procedure mentions in particular the sequence of actions to be taken and who is responsible for: § Tracing distribution § Information customers (and how) § Receipt, separate storage and labeling of the returned batch § Inquiring into the cause of the recall § Proposing corrective actions § Coordinating operations related to the recall (establishing the cause of the compliant, contacts with the authorities, writing of the communications to be issued to the media, report on the progress of return of the batch). The decision – making scheme describe in this procedure allows to evaluate the risk, and if necessary to
inform the authorities.
The procedure refers to the classification of the quality defects According to MOH of Iran guideline for
setting the mode of recall.
Chapter 9: Self inspection
9-1
Internal audit
The internal audit system is managed by the Responsible pharmasist and /or QA manager and is subject to a Written Instruction (WI). The division involved in manufacturing, storage and controls are regularly audited by the Responsible pharmacist and /or QA manager based on a program. In addition, internal audits may be required in particular cases, for example in the case of a recall, when products are repeatedly rejected, or at the introduction of a new production. The observed weak points are subjected to corrective actions whose implementation and follow – up are the responsibility of the head of the audited division and of the the Responsible pharmasist and /or QA manager, respectively. Page 12 of 13
DAROU PAKHSH
PHARMACEUTICAL MFG. CO.
SITE MASTER FILE
Issued Date: 09/05/2015
CODE : DPSMF422
Validation Date: 09/05/2016
Rev. No:3

Archiving of the internal audit files (records, reports, follow- up on corrective actions, etc …) is done by
the Responsible pharmacist and /or QA manager.
Page 13 of 13
Appendix 1
Copy of valid manufacturing

DAROU PAKHSH
PHARMACEUTICAL MFG. CO.
SITE MASTER FILE
Issued Date: 09/05/2015
CODE : DPSMF422
Validation Date : 09/05/2016
Rev. No:3
Page 1 of 2

DAROU PAKHSH
PHARMACEUTICAL MFG. CO.
SITE MASTER FILE
Issued Date: 09/05/2015
CODE : DPSMF422
Validation Date : 09/05/2016
Rev. No:3
Page 2 of 2
Appendix 2
List of dosage forms manufactured
including the INN names or common
name of API used
DAROU PAKHSH
PHARMACEUTICAL MFG. CO.
SITE MASTER FILE
Issued Date: 09/05/2015
CODE : DPSMF422
Validation Date :09/05/2016
Rev. No:3
Product List
Darou Pakhsh Pharmaceutical Mfg. Co.
Category
Product name
Dosage form
Packaging
Dipifen®
Acetaminophen Codeine Chew. Tab. 100mg 10 A.S.A Codeine 11 Celexib® ( Celecoxib ) 12 Celexib® ( Celecoxib ) Analgesics, Antipyretics 13 Children Cold Diclen® ( Diclofenac ) 15 Diclen® ( Diclofenac Sodium ) Amp. 25mg/ml, 3ml 16 Diclofenac Sodium 17 Diclofenac Sodium 22 Methyl Salicylate Top. Oint. 30%, 30g Top. Gel 0.5%, 60g Amp. 0.5mg/ml, 2ml Amp. 0.5mg/ml, 5ml Atracurium besylate Amp. 10mg/ml , 2.5ml 30 Atracurium besylate Amp. 10mg/ml , 5ml 31 Fentanyl citrate Amp. 50mcg/ml, 2ml Anesthesia adjuncts 32 Fentanyl citrate Amp. 50mcg/ml, 10ml Persocaine-E® ( Lidocaine + Amp. 5mg/ml, 1ml Page 1 of 10
DAROU PAKHSH
PHARMACEUTICAL MFG. CO.
SITE MASTER FILE
Issued Date: 09/05/2015
CODE : DPSMF422
Validation Date :09/05/2016
Rev. No:3
Amp. 5mg/ml, 3ml 37 Dentanest® ( Prilocaine + Felypressin ) Cartridge 1.8ml Amp. 5mcg/ml, 2ml Amp. 5mcg/ml, 5ml Top. Gel 0.1%, 30g Top. Sol. 1%, 60ml 42 Metronidazole Top. Gel 0.75%, 30g Lotion 0.05%, 15ml Top. Gel 0.025%, 15g Top. Gel 0.05%, 15g Antiasthmatic agents Anti-Cancer agents Ursodeoxycholic Acid Inj.6000 IU/0.6 ml Inj.10000 IU/ ml Anticoagulant agents 52 Heparin Sodium Inj. 5000IU/ml, 1ml 53 Heparin Sodium Inj. 10000IU/ml, 1ml 58 Oxcarbazepine 60 Phenobarbital 65 Amitriptyline 66 Amitriptyline 67 Amitriptyline 68 Tripline® ( Amitriptyline ) Antidepressants Antipsychotics 73 Doxipen® ( Doxepin ) Doxipen® ( Doxepin ) Page 2 of 10
DAROU PAKHSH
PHARMACEUTICAL MFG. CO.
SITE MASTER FILE
Issued Date: 09/05/2015
CODE : DPSMF422
Validation Date :09/05/2016
Rev. No:3
76 Nortriptyline 77 Nortriptyline Amp. 5mg/ml, 1ml 83 Venlafaxine S.R. Venlafaxine S.R. Vial (70IU NPH+30IU Dipisulin-(70/30)® ( Insulin 70/30 ) Regular)/ml, 10ml 88 Dipisulin-N® ( Insulin NPH Human ) Vial 100IU/ml, 10ml Dipisulin-R® ( Insulin Regular Human ) Vial 100IU/ml, 10ml Antidiabetic agents 95 Atropine Sulfate Amp. 0.5mg/ml, 1ml Anticholinergic Antispasmodic 96 Atropine Sulfate Amp. 10mg/ml, 2ml Amp. 1mg/ml, 1ml Amp. 1mg/ml, 3ml 100 Metoclopramide Amp. 5mg/ml, 2ml 101 Metoclopramide Oral Drop 4mg/ml, 15ml 102 Griseofulvin 103 Ketoconazole 104 Ketoconazole Top. Cream 2%, 30g Top. Sol. 1%, 10ml Syr. 5mg/5ml, 60ml 109 Chlorpheniramine Amp. 10 mg/ml, 1ml 110 Chlorpheniramine 111 Cyproheptadine 112 Diphenhydramine Elixir 12.5mg/5ml, 60ml 113 Fexofenadine* Syr. 10mg/5ml, 120ml Page 3 of 10
DAROU PAKHSH
PHARMACEUTICAL MFG. CO.
SITE MASTER FILE
Issued Date: 09/05/2015
CODE : DPSMF422
Validation Date :09/05/2016
Rev. No:3
Syr. 5mg/5ml, 60ml 119 Pediatric Grippe 120 Atorvastatin 121 Atorvastatin Antihyperlipidemia 122 Atorvastatin Anti-inflammatory 126 Amikacin Sulfate Amp. 50mg/ml, 2ml 127 Amikacin Sulfate Amp. 250mg/ml, 2ml 128 Ciprofloxacin 129 Ciprofloxacin Amp. 150mg/ml, 2ml 131 Co-trimoxazole Amp. 10mg/ml, 2ml Antibacterial agents Amp. 40mg/ml, 1ml Amp. 40mg/ml, 2ml 137 Moxifloxacin 141 Ergotamine-C 144 Megrif®* (Sumatriptan+Naproxen) 145 Pyrvinium Pamoate Susp. 50mg/5ml, 50ml 146 Calcipotriol Top. Oint. 0.005%, 30g 147 Diphenhydramine compound 148 Expectorant Codeine Top. Oint. 10%, 5g 152 Aminophylline Amp. 25mg/ml, 10ml Amp. 1mg/ml, 1ml Amp. 0.1mg/ml, 10ml Syr. 2mg/5ml, 120ml Page 4 of 10
DAROU PAKHSH
PHARMACEUTICAL MFG. CO.
SITE MASTER FILE
Issued Date: 09/05/2015
CODE : DPSMF422
Validation Date :09/05/2016
Rev. No:3
157 Theophylline ER 158 Theophylline ER Syr. (50+30)mg/5ml, 159 Theophylline G 161 Amlodipine 5/Atorvastatin 20 Cardiovascular agents 168 Dipix® (Clopidogrel) 170 Lozaten® ( Losartan Potassium ) 171 Lozaten® ( Losartan Potassium ) 172 Lozaten-H® ( Tab. (50+12.5)mg Losartan+Hydrochlorothiazide ) Oral Sol. 33.3%, 120ml Cognitive enhancer 178 Barex® ( Barium Sulfate ) 179 Gadopentetate dimeglumine Vial. 469mgI/ml, 20ml Vial. 150mgI/ml, 20ml Vial. 150mgI/ml, 50ml Vial. 270mgI/ml, 20ml Vial. 270mgI/ml, 50ml Vial. 320mgI/ml, 50ml Vial. 300mgI/ml, 20ml Contrast media agents Vial. 300mgI/ml, 50ml Vial. 370mgI/ml, 20ml Vial. 370mgI/ml, 50ml 189 Iopaque® ( Iohexol ) Amp. 240mgI/ml, 10ml 190 Iopaque® ( Iohexol ) Amp. 240mgI/ml, 20ml 191 Iopaque® ( Iohexol ) Vial. 240mgI/ml, 20ml 192 Iopaque® ( Iohexol )* Vial. 240mgI/ml, 50ml 193 Iopaque® ( Iohexol ) Amp. 300mgI/ml, 10ml 194 Iopaque® ( Iohexol ) Amp. 300mgI/ml, 20ml Page 5 of 10
DAROU PAKHSH
PHARMACEUTICAL MFG. CO.
SITE MASTER FILE
Issued Date: 09/05/2015
CODE : DPSMF422
Validation Date :09/05/2016
Rev. No:3
195 Iopaque® ( Iohexol ) Vial. 300mgI/ml, 20ml 196 Iopaque® ( Iohexol )* Vial. 300mgI/ml, 50ml 197 Iopaque® ( Iohexol ) Amp. 350mgI/ml, 20ml 198 Meglumine Compound 199 Meglumine Compound* 200 Meglumine Compound 201 Meglumine Compound* Dementia symptoms 207 Rivastigmine 208 Rivastigmine 209 Hydrochlorothiazide Erectile Dysfunction 212 Esomeprazole* 214 Mebeverine E.R.* Gastrointestinal agents 216 Rabeprazole* Amp. 25mg/ml, 2ml 219 Dipitropin® (Somatropin)* Top. Oint. 10%, 30g Hypopigmenting agents Immunosuppressant agents 222 Cytocept® (Mycophenolate Mofetil) 223 H.C.G. (Human Chorionic Gonadotrophin) H.C.G. (Human Chorionic Infertility therapy adjuncts 225 H.C.G. (Human Chorionic for Inj. 75IU LH+75IU H.M.G. (Menotropin) 227 Dextrose 3.33%, NaCl 0.3% 228 Dextrose 3.33%, NaCl 0.3% Infusions & Irrigation 231 Dextrose 5%, NaCl 0.9% 232 Dextrose 5%, NaCl 0.9% 233 Dextrose 50% Page 6 of 10
DAROU PAKHSH
PHARMACEUTICAL MFG. CO.
SITE MASTER FILE
Issued Date: 09/05/2015
CODE : DPSMF422
Validation Date :09/05/2016
Rev. No:3
236 Sodium Chloride 0.45% 237 Sodium Chloride 0.45% 238 Sodium Chloride 0.9% 239 Sodium Chloride 0.9% 240 Sodium Chloride 0.9% Sol. For Irrigation 500ml 241 Sodium Chloride 0.9% Sol. For Irrigation 1Lit. 242 Sterile water for Injection 243 Sterile water for Injection 244 Bromhexine HCl Elixir 4mg/5ml, 60ml 246 Codeine Phosphate Amp. 5mg/ml, 1ml Syr. 25mg/5ml, 250ml Dispersible Tab. 20mg Dispersible Tab. 40mg 254 Morphine Sulfate Amp. 10mg/ml, 1ml Tincture 1%, 250ml Nasal Drops, 0.05%, Nasal Decongestant Ophthalmic Drops 0.1%, Ophthalmic Drops 0.2%, 5ml Ophthalmic Drops 2%, 259 Cromolyn Sodium Ophthalmic Drops 0.1%, Ophthalmic Drops 2%, 5ml Ophthalmic Drops 0.3%, Ophthalmic agents Ophthalmic Drops 0.025%, 5ml Ophthalmic Sol. Ophthalmic Drops 0.1%, Ophthalmic Drops 0.1%, Ophthalmic Drops 0.5%, Page 7 of 10
DAROU PAKHSH
PHARMACEUTICAL MFG. CO.
SITE MASTER FILE
Issued Date: 09/05/2015
CODE : DPSMF422
Validation Date :09/05/2016
Rev. No:3
Ophthalmic Drops 0.5%, Oral electrolyte 270 Methocarbamol Amp. 100mg/ml, 10ml Skeletal muscle relaxants 271 Methocarbamol 272 Pancuronium Bromide Amp. 2mg/ml, 2ml 273 Phenytoin Sodium Top. Cream 1%, 30g Skin healing agents Top. Oint. 25%, 30g 275 Betamethasone Amp. 4mg/ml, 1ml 276 Betamethasone Top. Cream 0.1%, 15g 277 Betamethasone Top. Lotion 0.1%, 20ml 278 Betamethasone Top. Oint. 0.1%, 15g 279 Betamethasone L.A. Top. Cream 0.05%, 15g Top. Lotion 0.05%, 25ml Top. Oint. 0.05%, 15g 283 Dexamethasone Amp. 4mg/ml, 2ml Steroidal anti-inflammatory Amp. 40mg/ml , 1ml 285 Dipimedrol®*(Methylprednisolone vial. 40mg/ml , 1ml 286 Fluocinolone Acetonide Top. Cream 0.025%, 15g 287 Fluocinolone Acetonide Top. Oint. 0.025%, 15g 288 Hydrocortisone Top. Oint. 1%, 15g 289 Hydrocortisone sodium phosphate Amp. 50mg/ml, 2ml Hydrocortal® (Hydrocortisone sodium 291 Triamcinolone Amp. 40mg/ml, 1ml Sweetening agents Prostatic hyperplasia therapy Uterine relaxant 295 Borage Oil (RP Scherer) Calcium-D Fort® (Calcium Caplet 500mg+400IU carbonate+Vit.D3) Caplet 500mg+200IU 298 Clear Vision Eye Care (RP Scherer) Vitamins, Minerals & Dietary 299 Cod Liver Oil (RP Scherer) 300 SeaPearl® (Cod liver oil) 301 SeaPearl® (Cod liver oil) 303 Quzyme® (CoQ10)* 304 Energy Plus (RP Scherer) Page 8 of 10
DAROU PAKHSH
PHARMACEUTICAL MFG. CO.
SITE MASTER FILE
Issued Date: 09/05/2015
CODE : DPSMF422
Validation Date :09/05/2016
Rev. No:3
305 Evening Primrose Oil (RP Scherer) 306 Evening Primrose Oil (RP Scherer) 307 Evening Primrose Oil+Vitamin E nat. Softgel 500mg+6.71mg Oral Drops 25mg/ml, 308 Feriron® (Ferrous Sulfate) 309 Feriron® (Ferrous Sulfate) 310 Lipex® (Fish oil) 311 Quzyme Fort® (Fish Oil+CoQ10+Selenium)* (500+100+75.2)mg 312 Glucosamine Sulfate 313 Arthriflex-C® Soflet (500+400)mg 314 Glucosamine+chondroitin Caplet (500+400)mg 316 L-Carnitine/CoQ10 317 Lecithin (RP Scherer) 318 Multivitamin 319 Multivitamin for skin (RP Scherer) 320 Multivitamin M* 321 Multivitamin P* 322 Multivitamin plus Mineral 323 Multivitamin Therapeutic 324 Omega-3 (RP Scherer) 325 Royal Jelly+Ginseng (RP Scherer) 326 Soy Isoflavone (RP Scherer) Vitamin ACE+Selenium yeast (RP 329 Vitamin B complex 330 Vitamin B complex Vitamin B1/B6/B12 (100+100+1)mg/3ml, 3ml Amp. 100mcg/ml, 1ml Amp. 1000mcg/ml, 1ml Amp. 50mg/ml, 2ml Amp. 100mg/ml, 3ml Amp. 100mg/ml, 5ml Chew. Tab. 250mg Amp. 300000IU/ml, 1ml Page 9 of 10
DAROU PAKHSH
PHARMACEUTICAL MFG. CO.
SITE MASTER FILE
Issued Date: 09/05/2015
CODE : DPSMF422
Validation Date :09/05/2016
Rev. No:3
Chew. Tab. 100IU 343 Evital® (Vitamin E) 344 Evital® (Vitamin E) 345 Vitamin E nat. (RP Scherer) Softgel 134mg, 200IU 346 Vitamin E nat. (RP Scherer) Softgel 268mg, 400IU 347 Wheat Germ Oil (RP Scherer) 348 Zinc Gluconate-C-E (RP Scherer) Softgel (5+60+12)mg Oral Sol. 1000ml 350 Betamethasone Amp. 8mg/ml, 10ml 351 Betamethasone* Vial. 8mg/ml, 50ml 352 Bromhexine HCl 353 Bromhexine HCl 356 Dexamethasone Amp. 4mg/ml, 10ml 357 Dexamethasone* Vial. 4mg/ml,50ml 358 Dextrose 3.33%, NaCl 0.3% 359 Dextrose 3.33%, NaCl 0.3% Veterinary Products Amp. 50mg/ml, 10ml Vial. 50mg/ml, 50ml 364 Pregnan® (H.C.G.) 366 Neomycin Sulphate Top. Oint. 1%, 15g 367 Promethazine Amp. 25mg/ml, 10ml 368 Promethazine* Vial. 25mg/ml, 50ml 369 Vit. B Complex 370 Vit. B Complex* *Will be in the market soon Page 10 of 10
Appendix 3
Copy of valid GMP Certificate
DAROU PAKHSH
PHARMACEUTICAL MFG. CO.
SITE MASTER FILE
Issued Date: 09/05/2015
CODE : DPSMF422
Validation Date : 09/05/2016
Rev. No:3
Page 1 of 2
DAROU PAKHSH
PHARMACEUTICAL MFG. CO.
SITE MASTER FILE
Issued Date: 09/05/2015
CODE : DPSMF422
Validation Date : 09/05/2016
Rev. No:3
Page 2 of 2
Appendix 5
Organisational chart
DAROU PAKHSH
PHARMACEUTICAL MFG. CO.
SITE MASTER FILE
Issued Date: 09/05/2015
: DPSMF422
Validation Date: 09/05/2016
Rev. No:3
Board of Directors
Strategic Planning Manager
Strategic Plans Committee
Auditing Committee
Auditing Manag er
Managing Director
Consultants
Secretarial
Operation VP
Quality Assurance VP
Logistics VP
Finance & Economy VP
Business
Public Relation
Responsible
Scientific Research
Commercial
Security
Development
& International
Pharmacists
& Marketing
Contracts
Affairs Manager
Studies Manager
DAROU PAKHSH
PHARMACEUTICAL MFG. CO.
SITE MASTER FILE
Issued Date: 09.05.2015
CODE: DPSMF422
Validation Date:09.05.2016
Rev. No: 3
Managin g
D irector
Biologic & Biotechnology
Semisolid & Oral Liquid &
Sterile Products Responsible
Solid Responsible
Products Responsible
supplements Responsible
Pharmacist
Pharmacist
Pharmacist
Pharmacist
Secretarial
Secretarial
Secretarial
Secretarial
Responsible
Responsible
Responsible
Responsible
Pharmacist Expert
Pharmacist Expert
Pharmacist Expert
Pharmacist Expert

Source: http://www.dppharma.ir/CorporateSite/media/daroupakhsh-media/pdf/SMF.pdf