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SITE MASTER FILE

OF

COMPANY NAME

According to EudraLex; The Rules Governing Medicinal Products in the European Union; Volume 4; Good
Manufacturing Practice; Medicinal Products for Human and Veterinary Use; Explanatory Notes on the
preparation of a Site Master File: https://health.ec.europa.eu/system/files/2016-
11/2011_site_master_file_en_0.pdf.

And according to the Pharmaceutical Inspection Convention: PE 008-4; 1 Annex; 1 January 2011;
Explanatory Notes for Pharmaceutical Manufacturers on the Preparation of a Site Master File:
https://picscheme.org/docview/3463.

And according to WHO guidelines for drafting a site master file:

https://www.who.int/docs/default-source/medicines/norms-and-standards/guidelines/distribution/trs961-
annex14-guidelinesdraftingsitemasterfile.pdf?sfvrsn=29ee9d0_2.

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REVISION HISTORY.
Version no. Prepared by Date of Preparation Changes compared to previous version
01 Name of author dd/mm/yyyy First version
xxxxxxx

Replace or remove the red texts.

It is recommended to update the SMF with an interval of two years.

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1. GENERAL INFORMATION ON THE MANUFACTURER.............................................................6

1.1 Contact information on the manufacturer......................................................................................6
1.1.1 Name of the MAH (Marketing Authorisation Holder).............................................................6
1.1.2 Name of the Contract Manufacturer (Contract Manufacturer)....................................................6
1.2 Authorised pharmaceutical manufacturing activities of the site..................................................7
1.2.1 Copy of the valid manufacturing authorisation in Appendix 1....................................................7
1.2.2 Brief description of manufacture, import, export, distribution and other activities.....................7
1.2.3 Type of products currently manufactured on-site (list in Appendix 2) where etc.......................7
1.2.4 List of GMP(HACCP/ISO etc) inspections of the site within the last 5 years............................7
1.3 Any other manufacturing activities carried out on the site...........................................................7
2. QUALITY MANAGEMENT SYSTEM OF THE MANUFACTURER.............................................8
2.1 The quality management system of the manufacturer..................................................................8
2.1.1 Brief description of the quality management systems run by the company................................8
2.1.2 Responsibilities related to the maintaining of quality system including senior management.....8
2.1.3 Information of activities for which the site is accredited and certified, including etc.................8
2.2. Release procedure of finished products...........................................................................................9
2.2.1 Detailed description of qualification requirements of the QP......................................................9
2.2.2 General description of batch certification and releasing procedure.............................................9
2.2.3 Role of Authorised Person/Qualified Person in quarantine and release of finished products.....9
2.2.4 The arrangements between Authorised Persons/Qualified Persons when several Persons etc....9
2.2.5 Statement on whether the control strategy employs Process Analytical Technology (PAT)......9
2.3 Management of suppliers and contractors....................................................................................10
2.3.1 A brief summary of the establishment/knowledge of supply chain and the external audit pr.. .10
2.3.2 Brief description of the qualification system of contractors, manufacturers of API’s and etc.. 10
2.3.3 Measures taken to ensure that products manufactured are compliant with TSE guidelines......10
2.3.4 Measures adopted where counterfeit/falsified products, bulk products, API’s or excip. etc.....10
2.3.5 Use of outside scientific, analytical or other technical assistance in relation to manufact etc...10
2.3.6 List of contract manufacturers and laboratories.........................................................................10
2.3.7 Brief overview of the responsibility sharing between the contract giver and acceptor.............10
2.4 Quality Risk Management (QRM).................................................................................................10
2.4.1 Brief description of QRM methodologies used by the manufacturer........................................10
2.4.2 Scope and focus of QRM including brief description of any activities which are performed...11
2.5 Product Quality Reviews................................................................................................................11
3. PERSONNEL.........................................................................................................................................12
3.1 Organisational chart.......................................................................................................................12
3.2 Number of employees......................................................................................................................12
4. PREMISES AND EQUIPMENT..........................................................................................................13
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4.1 Premises............................................................................................................................................13
4.1.1 Brief description of heating, ventilation and air conditioning (HVAC) systems.......................13
4.1.2 Brief description of water systems.............................................................................................13
4.1.3. Brief description of other relevant utilities, such as steam, compressed air, nitrogen, etc........13
4.2 Equipment........................................................................................................................................14
4.2.1 Listing of major production and control laboratory equipment with critical pieces of equipm.14
4.2.2 Cleaning and sanitation..............................................................................................................14
4.2.3 GMP critical computerised systems...........................................................................................14
5. DOCUMENTATION.............................................................................................................................15
5.1 Description of documentation system (i.e. electronic, manual)...................................................15
5.2 When documents and records are stored or archived off-site (incl. PV)...................................15
6. PRODUCTION......................................................................................................................................16
6.1. Type of products..............................................................................................................................16
6.2 Process validation............................................................................................................................16
6.2.1 Brief description of general policy for process validation.........................................................16
6.2.2 Policy for reprocessing or reworking.........................................................................................16
6.3 Material management and warehousing.......................................................................................16
6.3.1 Arrangements for the handling of starting materials, packaging materials, bulk and etc..........16
6.3.2 Arrangements for the handling of rejected materials and products...........................................17
7. QUALITY CONTROL (QC)................................................................................................................18
7.1 QC control and analytical tests......................................................................................................18
7.2 QC records.......................................................................................................................................18
7.3 Revision of formulation and documents........................................................................................18
8. DISTRIBUTION, COMPLAINTS, PRODUCT DEFECTS AND RECALLS................................19
8.1 Distribution (to the part under the responsibility of the manufacturer)...................................19
8.1.1 Types (wholesale licence holders, manufacturing licence holders, etc) and locations of etc....19
8.1.2 Description of the system used to verify that each customer / recipient is legally entitled etc. 19
8.1.3 Brief description of the system to ensure appropriate environmental conditions during trans..19
8.1.4 Arrangements for product distribution and methods by which product traceability is maint....19
8.1.5 Measures taken to prevent manufacturers’ products to fall in the illegal supply chain.............19
8.2 Complaints, product defects and recalls.......................................................................................19
8.2.1 Complaints.................................................................................................................................19
8.2.2 Product defects...........................................................................................................................19
8.2.3 Product Recalls...........................................................................................................................19
9. SELF INSPECTIONS............................................................................................................................20
APPENDICES................................................................................................................................................21
Appendix 1 Copy of valid manufacturing authorisation...................................................................21
Appendix 2 List of dosage forms manufactured.................................................................................22
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Appendix 3 Copy of valid GMP Certificate........................................................................................23

Appendix 4 List of contract manufacturers and laboratories...........................................................24
Appendix 5 Organisational charts.......................................................................................................25
Appendix 6 Lay outs of production areas...........................................................................................26
Appendix 7 Schematic drawings of water systems.............................................................................27
Appendix 8 List of major production and laboratory equipment....................................................28

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1. GENERAL INFORMATION ON THE MANUFACTURER.

1.1 Contact information on the manufacturer.

1.1.1 Name of the MAH (Marketing Authorisation Holder)

Street name of the MAH
Postal code and city name
Country
Website: xxxxxxxx
Telephone No.: xxxxxxxx
Fax No.: xxxxxxxx
24 hour contact Telephone No.: xxxxxxxx (CEO)
xxxxxxxx (QP)
xxxxxxxx (QPPV)
Email: xxxxxxxx
Chamber of Commerce no.: xxxxxxxx
VAT no.: xxxxxxxx
GPS details: xxoxx’xx.xx”N; xxoxx’xx.xx”O
D-U-N-S No.*: xxxxxxxx

1.1.2 Name of the Contract Manufacturer (Contract Manufacturer)

Street name of the MAH
Postal code and city name
Country
Website: xxxxxxxx
Telephone No.: xxxxxxxx
Fax No.: xxxxxxxx
Email: xxxxxxxx
Chamber of Commerce no.: xxxxxxxx
VAT no.: xxxxxxxx
GPS details: xxoxx’xx.xx”N; xxoxx’xx.xx”O
(A)-D-U-N-S No.*: xxxxxxxx

For details see Site Master File of Name of the Contract Manufacturer.

* A D-U-N-S reference is required for Site Master Files submitted to EU/EEA authorities for
manufacturing sites located outside of the EU/EEA.

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1.2 Authorised pharmaceutical manufacturing activities of the site.

1.2.1 Copy of the valid manufacturing authorisation in Appendix 1.

Or when applicable, reference to the EudraGMP database.
If the Competent Authority does not issue manufacturing authorizations, this should be stated.
This can be the marketing authorisation of the national Chamber of Commerce or a certificate of the
National Health authorities.

1.2.2 Brief description of manufacture, import, export, distribution and other activities.
Describe here the actions of the MAH/Manufacturer regarding the above items.

1.2.3 Type of products currently manufactured on-site (list in Appendix 2) where not covered by Appendix
1 or EudraGMP entry.
Describe the kind of products which are not covered by the authorisation certificate in appendix 1.

1.2.4 List of GMP(HACCP/ISO etc) inspections of the site within the last 5 years.
Inspection date Competent Authority Number Main remarks

A copy of current GMP certificate (Appendix 3). (Or HACCP/ISO certificate)

1.3 Any other manufacturing activities carried out on the site.

If, in addition to the GMP medicines, e.g. nutritional supplements are produced, please describe the
work carried out here; if only medicines are produced, the text "Not applicable" is sufficient.

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2. QUALITY MANAGEMENT SYSTEM OF THE MANUFACTURER.

2.1 The quality management system of the manufacturer.

2.1.1 Brief description of the quality management systems run by the company.
You can take e.g. the text below:
The policy consists of implementing the objectives regarding quality in all divisions and on all levels
to obtain maximal involvement of all employees. These objectives generally mean that Name of the
MAH operates fully in accordance with Good Manufacturing Practices (GMP) and with HACCP
(based on Codex Alimentarius and Guideline 93/43/EEG) guidelines.

2.1.2 Responsibilities related to the maintaining of quality system including senior management.
For example, the texts below can be used, or (partly) changed:
The responsibilities of the QA manager’s and possible assistants are:
 Authorization of specifications for starting materials, packaging components and finished
products.
 Dispatch of the complaints together with QP.
 Check the maintenance, premises and equipment of the production department.
 Changing formulations in consultation with general manager, QP and production manager.
 Organizing validation of production methods, and writes the validation report.
The responsibilities of Qualified Person are:
Before certifying a batch prior to release the QP doing so should ensure, with reference to the
guidance, that at least the following requirements have been met:
 The batch and its manufacture comply with the provisions of the marketing authorisation
(Registration file) (including the authorisation required for importations were relevant).
 Manufacture has been carried out in accordance with GMP or, in case of a batch imported
from a third country, in accordance with GMP standards at least equivalent to EC GMP.
 The principal manufacturing and testing processes have been validated; account has been
taken of the actual production conditions and manufacturing records.
 Any deviations or planned changes in production or quality control have been authorised by
persons responsible in accordance with a defined system. Any changes requiring variation to
the marketing or manufacturing authorisation have been notified to and authorised by the
relevant authority.
 All necessary checks and tests have been performed, including any additional sampling,
inspection, tests or checks initiated because of deviations or planned changes.
 All necessary production and quality control documentation has been completed and
endorsed by the staff authorised to do so.
 All audits have been carried out as required by the quality assurance system.
 The QP should in addition take into account any other factors of which he is aware which are
relevant to the quality of the batch.

2.1.3 Information of activities for which the site is accredited and certified, including dates and contents of
accreditations, names of accrediting bodies.

See Appendix 2

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2.2. Release procedure of finished products.

2.2.1 Detailed description of qualification requirements (education and work experience) of the Authorised
Person(s) / Qualified Person(s) responsible for batch certification and releasing procedures.
The Authorised Person / Qualified Person (QP) is xxxxxx and is responsible for batch certification
and releasing procedures.
Educational background:
Xxxxxxx
Courses:

Occupational experience:

2.2.2 General description of batch certification and releasing procedure.

For Pharmaceutical products; e.g.:
The QP compares the batch record with the registration file to control whether the product is
manufactured according to the registration file, and evaluates the analytical results of each batch. A
document for release of the finished product is written and signed by the QP. This release document
is attached to the batch documents and available for clients.
For Food-supplements; e.g.:
The QA Manager evaluates the batch records and, if available, analytical results of each batch. A
document for release of the finished product is written and signed by the QA manager or by
competent authorised staff personnel. This release document is attached, together with the pack-bon,
to the goods for transport to the client (for distribution). A copy of the release document is attached
to the production files.

2.2.3 Role of Authorised Person/Qualified Person in quarantine and release of finished products.
Finished pharmaceutical products are quarantined, e.g. waiting for the next production or packaging
step, or waiting for analytical results. Batch release takes only place after approval and signing of the
batch release document by the QP. (or QA in case of food-supplements)

2.2.4 The arrangements between Authorised Persons/Qualified Persons when several Persons are involved.
Not applicable.
Or in case of more QP’s you can use the following text:
All xx QP’s are qualified and registered at the Authorities.
The first QP is xxxxx; with possible a short explanation.
The second QP is xxxx; also, with a short explanation.
Etc.

2.2.5 Statement on whether the control strategy employs Process Analytical Technology (PAT).
In case of the use of data loggers, use the following text:
Environmental control for temperature and humidity is collected out by data-loggers. These loggers
are periodically read on the computer.
Weighing prints are attached to the production documents.
Analytical data like spectra and chromatograms are collected digital and can be used for calculations.
In case no information is digital collected, use the following text:
No manufacturing or analytical information is digital collected.

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2.3 Management of suppliers and contractors.

2.3.1 A brief summary of the establishment/knowledge of supply chain and the external audit program.
All manufacturers of Active Pharmaceutical Ingredients (API's), excipients and packaging materials
intend for Registered Pharmaceutical Products should be sufficient be certificated (GMP).
Manufacturers are audited according to the regulations.
Or in case of the manufacturing of food-supplements:
Suppliers of starting materials and packaging materials are qualified and periodically assessed with
regard to their quality.

2.3.2 Brief description of the qualification system of contractors, manufacturers of API’s and other critical
materials suppliers.
A questionnaire, containing a checklist, is sent to the suppliers concerning quality, liability and
certificates. The questionnaire has to be signed and returned to the “Name of the Applicant”.
Certificates of the supplier (like GMP, ISO, HACCP etc.) are collected in the supplier’s file. Non-
certificated suppliers will be audited or rejected. Approved suppliers are reported on a list.

2.3.3 Measures taken to ensure that products manufactured are compliant with TSE guidelines.
The API’s of the Registered Pharmaceutical Products are ensured through the DMF (or ASMF) and
audits. For all other API’s, not intend for registered Pharmaceutical Products, and all excipients,
produced from animal sources, a TSE statement from the manufacturer is required.

2.3.4 Measures adopted where counterfeit/falsified products, bulk products, API’s or excipients are
suspected or identified.
All ingredients (API’s and excipients are tested for identity. Ingredients from new unknown
manufacturers are tested more extended.

2.3.5 Use of outside scientific, analytical or other technical assistance in relation to manufacture and
analysis.
In case Name of the Applicant is not able to perform analytical testing on raw materials or end
products, external laboratories will be used to perform these tests.

2.3.6 List of contract manufacturers and laboratories.

Including the addresses and contact information and flow charts of supply-chains for outsourced
manufacturing and Quality Control activities; e.g. sterilization of primary packaging material for
aseptic processes, testing of starting raw-materials etc., is presented in Appendix 4.

2.3.7 Brief overview of the responsibility sharing between the contract giver and acceptor.
The contract acceptors are laboratories which have to be authorized by the Competent Authorities.
The contract giver is supplied with full details of the method to be used.
2.4 Quality Risk Management (QRM).

2.4.1 Brief description of QRM methodologies used by the manufacturer.

Risk assessment: Risk assessment consists of the identification of hazards and the analysis and
evaluation of risk associated with exposure to those hazardous quality risk assessments begin with
the well-defined problem description or risk question.

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Risk control measures: Risk control measures include decision making to reduce and / or accept the
risk. The purpose of risk control is to reduce the risk to an acceptable level. The amount of effort
used for risk control should be proportional to the significance of the risk.

2.4.2 Scope and focus of QRM including brief description of any activities which are performed.
Critical parameters, steps and quality attributes are identified and controlled in each product specific
process. Decisions of managing risks in manufacturing are based on scientific knowledge, experience
and understanding of the process. Good Manufacturing Practice principles as contained in the SOP’s
ensure that identified risks are reduced to acceptable levels.
2.5 Product Quality Reviews.

At the end of the year complaints, change controls and other quality related subjects are discussed
within the company and for as far as needed changes will be made.
Methodologies of Product Quality Reviews for pharmaceutical products include:
• Quality of starting and packaging materials.
• In-process controls and finished product results.
• Deviations, nonconformance, out of specification (OOS) results and batch rejections.
• Changes to processes or analytical methods.
• Changes to Marketing Authorisations.
• Stability testing and review of retention samples.
• Returns, complaints and results.
• Adverse events.
• Process and equipment validation results.
• Supplier and contractor audits.
• Technical / Quality Agreements with suppliers and contractors.

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3. PERSONNEL.
3.1 Organisational chart.
The organizational structure of the “Name of the Applicant” is shown in Appendix 5.
Tasks and responsibilities of the various positions are detailed in job descriptions below:

Name Function Education / Degree Experience

x yr

3.2 Number of employees.

Engaged in the quality management, production, quality control, storage and distribution
respectively.

Quality Assurance: x (including QP)

Production: x
Laboratory: x
Storage and distribution: x
Technical & Engineering Support Services: x
Packaging: x
Scientific consultants: x
Administrative employees: x
Regulatory Affairs and Pharmacovigilance: x
IT department: x
Housekeeping: x

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4. PREMISES AND EQUIPMENT.

4.1 Premises.
 Short description of plant; size of the site and list of buildings.
Warehouse area: x m2
Production area: x m2
Packaging area: x m2
Laboratory: x m2
Offices: x m2
Canteens: x m2
Total area: x m2
 Simple plan or description of manufacturing areas:
Warehouse: Storage of starting materials, packaging and finished products.
Weighing-cabin: Weighing of the starting substances.
Mixing-cabin: Mixing and or granulation of the substances.
Tabletting-cabin: Production of tablets by pressing the tablet mixture.
Capsulating-cabin: Filling the capsules with the capsule mixture.
Coating-cabin: Coating of the product.
Packaging-cabin: Packaging of the finished product.
 Lay outs and flow charts of the production areas (in Appendix 6).
 Lay-outs of warehouses and storage areas, with special areas for the storage and handling of
highly toxic, hazardous and sensitising materials indicated, if applicable;
In Appendix 6 or Not Applicable.
 Brief description of specific storage conditions if applicable, but not indicated on the lay-outs;
Not Applicable or describe the specific storage conditions like below 4oC.

4.1.1 Brief description of heating, ventilation and air conditioning (HVAC) systems.
For example:
Specification of the air supply: Production cabins have 15 Pa under-pressure versus the hallway. The
air refresh rate is at least 20 times per hour. The air is recirculated for 90% and 10% fresh air is
added. The temperature and relative humidity are controlled in the range of not more than 25 oC and
between 30 to 75% RH.

4.1.2 Brief description of water systems.

Water of pharmaceutical grade is generated by means of a purification system based on reversed
osmosis and filtration. Water will be used instantaneously after it has been purified up to its
pharmaceutical grade. The microbiological quality of the water is obtained by filtering the water
through a 0.1 µm filter and with the inclusion of continuous recirculation of the typical treated water
quality will be between 15 to 18 MΩ.
Schematic drawings of the systems in Appendix 7.
Or in case of only dry production use the text:
Not Applicable.

4.1.3. Brief description of other relevant utilities, such as steam, compressed air, nitrogen, etc.
Not applicable.
Or describe these special utilities.

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4.2 Equipment.

4.2.1 Listing of major production and control laboratory equipment with critical pieces of equipment.
See Appendix 8.

4.2.2 Cleaning and sanitation.

E.g. The cleaning of all equipment is performed manually. The equipment will be dry-=cleaned as
good as possible. Afterwards, cleaning with hot water and detergent is performed. The last rinse will
be done with hot water only. Finally, the equipment will be cleaned and dried with a tissue
containing disinfecting alcohol. The alcohol will be removed by evaporation.

4.2.3 GMP critical computerised systems.

E.g. Computer systems and software are considered to be validated by the computer and software
supplier. Computer and software are protected by an up-to-date virus scanner.
Or: For environmental control (temperature and humidity) is made use of data-loggers which can be
read with a special software application.

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5. DOCUMENTATION.
5.1 Description of documentation system (i.e. electronic, manual).
The documentation is located on the company’s server, and regularly backed up.
The main documents are
 Manual or Quality Handbook; Describes the general activities concerning the quality.
 SOP’s; Standard Operation Procedures, with concerning forms.
 Batch records; Describes the detailed production information of the product.
 Certificates of Analysis; Describes the analytical results of the starting materials or finished
product.
 Product Dossier; Describes information of collegiate or magistral manufactured products.
 Registration Dossier; ECTD format application to obtain official marketing authorisation.

5.2 When documents and records are stored or archived off-site (incl. pharmacovigilance data).
Describe name, address and contact information here of the extern stored documentation.

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6. PRODUCTION.
6.1. Type of products.
 Type of products manufactured including:
- list of dosage forms of both human and veterinary products which are manufactured on the
site. See Appendix 2.
- list of dosage forms of investigational medicinal products (IMP) manufactured for any
clinical trials on the site, and when different from the commercial manufacturing,
information of production areas and personnel. E.g. “Not Applicable”.
 Toxic or hazardous substances handled (e.g. with high pharmacological activity and/or with
sensitising properties); e.g. Highly toxic substances are stored in a locked cabinet; the key is kept
by head warehouse. Toxic or hazardous substances (e.g. with high pharmacological activity
and/or with sensitising properties) are handled with care gloves and breath protection according
to production protocols.
 Product types manufactured in a dedicated facility or on a campaign basis, if applicable; e.g.
describe these conditions or use the text “Not Applicable”
 Process Analytical Technology (PAT) applications, if applicable: general statement of the
relevant technology, and associated computerized systems; ; e.g. describe these PAT
applications or use the text “Not Applicable”.
6.2 Process validation.

6.2.1 Brief description of general policy for process validation.

See "EMA/CHMP/BWP/187338/2014: Guideline on process validation for the manufacture of
biotechnology-derived active substances and data to be provided in the regulatory submission".
https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-process-validation-
manufacture-biotechnology-derived-active-substances-data-be-provided_en.pdf.
e.g. Four basic steps are necessary to validate a process:
 A validation protocol will be written;
 Three production batches are produced to establish the final formulation;
 The production validation of these three batches concerns the mixing process by testing different
mixing times, the influence of tableting/capsulating time by testing samples taken at the start,
half-way and the end of the process on physical parameters, content uniformity and dissolution.
 These three batches are tested on stability in the marketed packaging as part of the validation of
the packaging.

6.2.2 Policy for reprocessing or reworking.

e.g. Products, rejected for physical properties or low contents can be milled and re-worked controlled
by the heads of production and QA/QP.
Calculations, quantities, batch-numbers and procedures are reported on the production file.
6.3 Material management and warehousing.

6.3.1 Arrangements for the handling of starting materials, packaging materials, bulk and finished products
including sampling, quarantine, release and storage.
e.g. All starting materials will be placed in quarantine after receipt. Documentation accompanying
the shipment will be reviewed and stored afterwards by the warehouse employee. Upon receipt, all
incoming goods are immediately identified by the supplier’s batch number. QC samples of the
starting materials and finished products are stored in the reference sample archive. Certificates of

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analyses (CoA’s) of the starting materials and of the finished products are compared with the
specifications and approved through the signature by the qualified person for release. Starting
materials, packaging materials, bulk and finished products will be stored in a closed warehouse
waiting for use or transport.

6.3.2 Arrangements for the handling of rejected materials and products.

 Rejected products not suitable for re-working, for example caused by chemical or
microbiological contamination or decomposition (e.g. visible by appearance) will be destroyed.
The total quantity destroyed is recorded.
 All rejected materials (substances, finished products and packaging) are labelled (In the national
language: “REJECTED”) and stored in a separated area in the warehouse.
 Materials not suitable for re-working will be destroyed, product name, batch-number, quantity
and reason for destruction will be reported.

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7. QUALITY CONTROL (QC).

7.1 QC control and analytical tests.
The starting materials are visual checked, the starting substances are tested for identity before
release. During the production process physical tests, like average weight, measurements of the
product, friability, hardness, and disintegration, are carried out.
The finished product is analysed on physical properties and chemical analysed according the
requirements.
7.2 QC records.
Batch manufacturing and packaging records are reviewed by the production manager to ensure that
they are all present, properly completed and that in-process and reconciliation check if the results are
satisfactory. The QA manager reviews also the documents, controls the analytical records and issues
a signed release document. The release document is added to the production file.
7.3 Revision of formulation and documents.
Both the production manager and the QA manager are jointly involved in the preparation and
revision of production documents. The QA manager/QP approves specifications, test-methods and
release criteria as described in the Registration File.

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8. DISTRIBUTION, COMPLAINTS, PRODUCT DEFECTS AND RECALLS.

8.1 Distribution (to the part under the responsibility of the manufacturer).

8.1.1 Types (wholesale licence holders, manufacturing licence holders, etc) and locations (EU/EEA, USA,
etc) of the companies to which the products are shipped from the site.
All distribution activities of the company are in compliance with the "Guidelines of 5 November
2013 on Good Distribution Practice of medicinal products for human use" (https://eur-
lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:C:2013:343:0001:0014:EN:PDF).
E.g. In most cases, the finished product is shipped to authorized wholesalers, and from there on to
retailers such as pharmacies and drugstores.

8.1.2 Description of the system used to verify that each customer / recipient is legally entitled to receive
medicinal products from the manufacturer.
E.g. Customers / recipients like wholesalers should send their valid GDP certificate to the QA of the
company. OTC products may send to drugstores while other medicines may only send to pharmacies.

8.1.3 Brief description of the system to ensure appropriate environmental conditions during transit, e.g.
temperature monitoring/ control.
Describe here whether the product is cooled during transport and whether temperature and humidity
are monitored during transport.

8.1.4 Arrangements for product distribution and methods by which product traceability is maintained.
E.g. Transport documents with reporting the product-name and batch-number ensures the
traceability.

8.1.5 Measures taken to prevent manufacturers’ products to fall in the illegal supply chain.
E,g, Pharmaceutical products are only transported by trusted transporters to authorised
customers/recipients.
8.2 Complaints, product defects and recalls.

8.2.1 Complaints.
After receiving the complaint, the QA manager classifies and investigates the complaints, clinical
related complaints are immediately sent to the QPPV, quality complaints are discussed with the
production manager. QA manager and Production manager are responsible resolving the quality
complaints. The QA manager responses to the person from which the complaint came. Complaint
records are kept for ten years by QA.

8.2.2 Product defects.

Product defects are detected during production of after reviewing the analytical results, the product
will not be released and destroyed of reworked.

8.2.3 Product Recalls.

For the recall the recall procedure will be started. All substances used in this batch can be used in
other products/batches. If these suspected substances are used these products/batches will also be
recalled. The authorities are informed, and the authorities decided the form of the recall. The QA
manager is responsible for coordinating product recalls.

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9. SELF INSPECTIONS.

As a rule, qualified personnel of the Corporate Compliance organization conduct self-inspections on

a regular basis. The self-inspections are planned, performed and documented according to an SOP.
The purpose of self-inspections is outlined below:
 Checking of all relevant GMP and Quality Management System requirements on regular basis
and the degree of their Implementation in order to define the effectiveness of the Quality
System.
 Identification and documentation of weaknesses and observations.
 Listing of weaknesses as open issues with deadlines for amendment.
 Information of the responsible persons and of upper management by distribution of the audit
report and the list of observations.
 To ensure corrective action by regular check of deadlines and measures.
Self-inspections cover GMP and Quality Management System issues. The handling of non-
conformance identified during inspections as well as definition, approval and implementation control
of corrective actions is set out in an SOP (CAPA).

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APPENDICES
Appendix 1 Copy of valid manufacturing authorisation.

Place the Chamber of Commerce registration here.

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Appendix 2 List of dosage forms manufactured.

Including the INN-names or common name (as available) of active pharmaceutical ingredients (API) used.
MA Form is the country-code followed with the application number. Date of subscription.

Product-name and Form INN (API) MA Form Date

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Appendix 3 Copy of valid GMP Certificate.

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Appendix 4 List of contract manufacturers and laboratories.

Including the addresses and contact information, and flow-charts of the supply-chains for these outsourced
activities.

Contract manufacturer (for ………..)

Name of the company
Street name of the MAH
Postal code and city name
Country
Website:
Telephone No.:
Fax No.:
Email:

Contract Laboratory (for …………)

Name of the Laboratory.
Street name of the MAH
Postal code and city name
Country
Telephone No.
Fax No.
Email

Contract Pharmacovigilance
Name of the PV company or name of the QPPV.
Street name of the MAH
Postal code and city name
Country
Telephone No.
Fax No.
Website
Email

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Appendix 5 Organisational charts.

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Appendix 6 Lay outs of production areas.

Including material and personnel flows, general flow charts of manufacturing processes of each product
type. (dosage form).

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Appendix 7 Schematic drawings of water systems.

Place a schematic drawing of the water purification system here or place the text "Not Applicable".

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Appendix 8 List of major production and laboratory equipment.

Production equipment Brand and type no.

Laboratory equipment Brand and type no.

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