Appendix I

Plant Master File

NOTE: The manufacturer shall prepare a succinct document in the form of site master file
containing specific information about the production and/or control of device manufacturing
carried out at the premises. It shall contain the following information,-:

Sr. No Requirements Information

A GENERAL INFORMATION
I Brief information on the site In not more than 250 words, outline the company's
(including name and activities, other sites (if any), in addition to the site
address), relation to other that is the subject of registration.
sites
II Manufacturing activities as 1. Indicate whether the site has been approved by
licensed by the Competent national authority, or any foreign Competent
Authorities Authority (if the latter, name the authority and state if
approval granted is for the manufacture of Medical
Device of the same or different description from that
in the application).
2. Quote the relevant document (licence) as issued by
the Competent Authority. State the period of validity
of licence/certificate document (if the validity of the
document is given in the country concerned). Any
conditions and/or restrictions should be stated.
Submit valid copy of manufacturing/establishment
licence/plant registration certificate.
III Any other operations carried This covers both medical device related and non-
out on the site medical device (including medicinal products) related
activities.
IV Name and exact address of 1. Name of company, site address and mailing
the site, including telephone, address (if different from site address)
fax numbers, web site URL
and e-mail address 2. Telephone, fax nos. and email address of contact
person
V Type of medical devices 1. Quote the type of medical devices handled,
handled on the site and specifying if the medical device is handled under a
information about contractual agreement with a contract giver.
specifically toxic or
hazardous substances 2. Note any toxic, hazardous, highly sensitizing
handled, mentioning the substances handled e.g. antibiotics, hormones,
way they are handled cytostatics. Note hether special precautions were
and precautions taken taken for such medical device (List the appropriate
license numbers where applicable)
VI Short description of the 1. Provide a map indicating the location of the site(s)
site (size, location and and the surrounding area. Mark the site(s).
immediate environment 2. Other activities on the site.
and other activities on
the site)

VII Number of employees Area of No of No of

engaged in Production, Operation Permanent/regular Contractual
Quality Control, employees employees
warehousing, and
distribution 1. Production
2. Quality
Control
3.Warehousing
4. Storage
5. Distribution
6. Technical &
Engineering
Support
Services

Total of the
above

VIII Use of outside scientific, For each work process outsourced or sub-
analytical or other technical contracted(including contract delivery companies),
assistance in relation to give:-
the design, manufacture and 1. Name, address, telephone no. and fax. no. of
testing contractor
2. Brief outline of the activity being undertaken in
more than 250 words.

IX Short description of the (Not more than 750 words).

quality management 1. State the company's Quality Policy
system of the company 2. Define the responsibility of the Quality Assurance
function
3. Describe the elements of the QA system e.g.
organizational structure, responsibilities, procedures
processes
4. Describe the audit programmes (self-inspection or
audits by external organisations undertaken).
5. Describe how results are reviewed to demonstrate
the adequacy of the quality system in relation to the
objective i.e. quality, efficacy and safety of the
product.
 6. Describe vendors qualification/validation policy.
When suppliers of critical starting materials and
packaging materials - actives, excipients, containers,
closures and printed packaging materials are
assessed, give details of how this is done
7. Record if the company has been certified to
industry standards (e.g. ISO9000, ISO 13485:2003)
8. Describe the release for sale procedure for finished
products

X Devices details registered State name of the devices along with the name of the
with foreign countries countries where the device is approved/registered.
XI brief description of testing Manufacturer Brief Details require
facility
B PERSONNEL
I Organization chart showing Organogram listing key personnel (Quality
the arrangements for key Assurance, Production, and Quality Control) has to
personnel be constructed.
Record senior managers and supervisors only
II Qualifications, experience 1. Brief details of qualifications and years of relevent
and responsibilities of key experience since qualifying.
personnel 2. Job descriptions for the key personnel

III Outline of arrangements for Give brief details of the training programme and
basic and in-service training include induction and continuous training as follows
and how records are 1.Describe how training needs are been identified and
maintained by whom.
2.State the form of training eg.in house, external, and
how practical experience is gained and which staff
are involved.
4. Explain training evaluation procedures.
5.Explain how retraining needs are identified.
6.Give brief details of training records kept.
IV Health requirements for Give brief details of the following:
personnel engaged in 1. Who is responsible for checking health of
production employees?
2.Is there a pre-employment medical examination?
3. Are employees routinely checked from time to
time depending on the nature of their work?
4. Is there a system for reporting sickness or contact
with sick people before working in a critical area?
5. Is there a system of reporting back after illness?
6. Are those who work in clean areas (Grade A-D)
subject to additional monitoring?
V Personnel hygiene Give brief details of the following:
 requirements, including 1. Are there suitable washing, changing and rest
clothing areas?
2.Is the clothing suitable for the activity undertaken?
Briefly describe the clothing
3. Are there clear instructions on how protective
clothing should be used and when it should be
changed? Is in-house or external laundry used?
C PREMISES AND FACILITIES
I Layout of premises with Layout of premises
indication of scale 1. Manufacturing Plant Layout with men and material
flow,
2. Clean room classification where relevant (e.g.as
per ISO 14644-1).
3. Describe the controls available to prevent
unauthorized access.
4. Provide a simple plan of each area with indication
of scale.
Label areas and annotate plan with names.
5. Plans should be legible
II Nature of construction, Nature of construction should include type of
finishes/fixtures and flooring, walls, roof, doors, windows etc. Details
fittings should be provided for all processing areas,
packaging areas and critical storage areas.
III Brief description of Brief description of ventilation systems etc.
ventilation systems. More Brief description of ventilation systems etc.
details should be given for
critical areas with potential Note 1: More details should be given for critical areas
risks of airborne with potential risks of airborne contamination.
contamination (including Note 2: To reduce the narrative, schematic drawings
schematic drawings of the should be used.
Systems). Classification
of the rooms used for The following data should be given:-
the manufacture of sterile Design criteria e.g.
products should be .Specification of the air supply
mentioned .Temperature
.Humidity
.Pressure differentials and air change
rate
.Single pass or recirculation (%)
Filter design and efficiency e.g.
.Bag 99% efficiency
.HEPA 99.997% efficiency
.Details of any alarms on the ventilation
System should be given.
3. The limits for changing the filters should be given.
4. Give the frequency of revalidation of the system
IV Special areas for the Follow the same layout as above for description
handling of highly toxic, of areas specially designated for the handling of
hazardous and highly toxic, hazardous and sensitizing
sensitizing materials materials.

V Brief description of water Brief description of water system, including

systems (schematic drawings sanitation should include following:
of the systems are desirable) 1. The schematic drawing must go back to the
including sanitation city supply system
2. The capacity of the system (maximum
quantity produced per hour).
3. Construction materials of the vessels and pipe
work
4. Specification of any filters in the system must
be given
5.If water is stored and circulated, the
temperature at the point of return
6.The specification of the water produced
(Chemical, Conductivity and microbiological)
7. The sampling points and frequency of testing
8. The procedure and frequency of sanitation

VI Maintenance Maintenance Note: For the purpose of this guide,

(description of planned "Maintenance" is carried out by the company
preventive maintenance and "servicing" is by an outside contractor.
programmes for 1. Describe the planned preventive maintenance
premises and recording programme.
system) 2. Are there written procedures and contractual
details for outside work?
4. Are there written procedures and suitable
reporting forms for maintenance and servicing?
Do the documents record type/frequency of
service/checks, details of service, repairs
and modifications?
5. Have the maintenance routines that could
affect medical device quality been clearly
identified?
6. Are the reports made known to the users?

D EQUIPMENT
I Brief description of major Makes and model numbers of the equipment are
production and quality control not required
laboratories equipment (a list However the following points should be
of the equipment is required) addressed:
1. Is the machinery constructed of appropriate
material(e.g. AISI grade 316 stainless steel for
product contact equipment)?
2. Have other materials been suitably validated
e.g. polypropylene, chrome-plated brass, PVC,
nonreactive plastic materials?
3. Is the equipment designed with ease of
 cleaning in mind?
4. A brief general description is required. If the
equipment has additional devices, these should
be recorded
5. In particular give brief information on the use
of computers, microprocessors etc. in the
premises

II Maintenance Following points should be addressed:

(description of planned 1. Who is responsible for maintenance and
preventive maintenance servicing?
programmes and 2. Are there written procedures and contractual
Recording system). details for outside work?
3. Are maintenance routines which could affect
product quality clearly identified?
4. Are records kept of
.type and frequency of service/check
.details of service repairs and modifications
5. Are reports made known to the users?

III Qualification and calibration, Following points should be addressed:

including the recording 1. Briefly describe the company's general policy
system. Arrangements for and protocols for qualification and validation
computerized systems (prospective and retrospective).
Validation. 2. Is there regular revalidation of critical
equipment?
3. An outline of process validation may be given
here or cross-referenced to Production
4. Describe the system for the release for sale or
supply of development and validation batches.
5. What are the arrangements for computer
validation, including software validation?
6. Describe equipment calibration policy and
records kept

E SANITATION
I Availability of written Cleaning procedures for the manufacturing areas
specifications and and equipments should include:
procedures for cleaning
the manufacturing areas 1. Are there written procedures for cleaning and
and equipments specifications for cleaning agents and their
concentration for the method of cleaning and the
Frequency?
2. Are cleaning agents changed from time to
time?
3. Have the cleaning procedures been validated
 and what was the method of evaluating the
effectiveness of cleaning?
4. Are cleaning methods monitored routinely by
chemical and/or microbiological methods?
5. What are the cleaning methods (and their
frequency)for the water system, air handling
system and dust extraction system?

F PRODUCTION
I Brief description of Describe the production operations using flow
production operations charts. The following points should be
using, wherever addressed:
possible, flow sheets 1. Describe the operations capable of being
and charts specifying carried out at the site with the existing facilities
important parameters and specify the types of medical devices
2. When only packaging is undertaken, give a
brief description only, e.g. labeling, filling etc.
and the nature of containers used
3. When only packaging is undertaken, give a
brief description only, e.g. labeling, details of
packaging materials used etc.

II Arrangements for the The following points should be addressed:

handling of starting 1. Control of manufacturing
materials, packaging Checks on key parameters during manufacture
materials, bulk and Records of key parameters
finished products, In-process checks
including sampling, Records of in-process checks
quarantine, release and Compliance with the Marketing Authorization
Storage. 2. Packing
Release of bulk, semi-finished products,
packing materials
Confirmation of identity and line clearance
checks
3. Quarantine and release of finished products;
Compliance with Marketing Authorization.
4. Explain the role of the Authorized Person(s).
III Arrangements for What arrangements are in place for reprocessing
reprocessing or rework or reworking batches of products
IV Arrangements for the The following points should be addressed:
handling of rejected
materials and products Are rejected materials and products clearly
labeled?
Are they stored separately in restricted
Area?
Describe arrangements for sentencing the
 Materials and their disposal. Is destruction
recorded?

V Brief description of An outline of process validation policy only is

general policy for required
process validation
VI Brief description of Provide Brief description of sterilization facility
sterilization facility;
G QUALITY Assurance
I Description of the The following points should be addressed:
Quality Control system 1. Describe the activities of the QC system e.g.
and of the activities of specifications, test methods, analytical testing,
the Quality Control packaging, component testing, biological and
Department. Procedures Microbiological testing and other quality related
for the release of data collection.
finished products 2. Outline the involvement in the arrangements
for the preparation, revision and distribution of
documents in particular those for specification
test methods, batch documentation and release
criteria.
H STORAGE
I Policy on the storage of The following points should be addressed:
medical device 1. How are the medical devices stored e.g. pallet
racking?
2. Describe any special storage or handling
condition such as cold chain management.
I DOCUMENTATION
I Arrangements for the Arrangement for the preparation, revision and
preparation, revision and distribution of documentation should include:-
distribution of necessary Is there a description of the documentation
documentation, including system?
storage of master documents 2. Who is responsible for the preparation,
revision a distribution of documents?
3. Where are the master documents stored?
4. Is there a standard format and instruction of
how documents are to be prepared?
5. How is the documentation controlled?
6. For how long are the documents kept?
7. Detail any arrangement for electronic or
microfilmed records.
J MEDICAL DEVICE
COMPLAINS AND FIELD
SAFETY CONRRECTIVE
ACTION
I Arrangements for the handling Following points should be included:
of complaints Is there a written procedure for medical device
 complaints?
Who is responsible for:-
Logging
Classifying
Investigating complaints
Are written reports prepared?
Who reviews these reports?
For how long are complains records kept?
II Arrangements for the Following points should be included:
handling of field safety 1. Is there a written procedure which describes
corrective action the sequence of actions to follow including:-
a. Retrieval of distribution data;
b. Notification to customers;
c. Receipt/segregation/inspection of
returned medical devices;
d. Investigation/reporting of cause.
e. Reporting corrective action.
2. Who is responsible for coordinating medical
device field safety corrective actions?
3. Who notifies the Competent Authority of field
Safety corrective actions?
4. Canfield safety corrective actions be effected
Below wholesale level?
5. Is there written procedure for destruction of
defective/unsafe devices?
K SELF INSPECTION / Internal
Audit:
I Short Description of the Following points should be included:
internal audit system 1. Describe how the internal audit system
verifies that those activities that have a bearing
on medical device quail comply with the planned
arrangement.
2. Are there documented procedures for the
internal a diet system and for the follow-up
actions?
3. Are the results of the internal audit
documented, brought to the attention of the
personnel having responsibility for the
area and activities inspected?
4.Does the system ensure that those responsible
for the real or activity take timely corrective
action on the deficiencies found?
L CONTRACT ACTIVITIES
I Description of the way Describe briefly the details of the technical
in which the compliance contract between the contract giver and acceptor
of the contract acceptor is and the way in which t e QMS compliance, or
 assessed compliance with other appropriate standards, is
assessed. The selected standards should be
assessed for the suitability of its application. The
type of activities undertaken by the contract
acceptor should be specified.

NOTE:

1. Any information which is not relevant may be stated as ‘Not Applicable’ in the relevant
Sections/Columns of the above format, and reasons for non applicability should be
provided.
2. The above information should be submitted in the form f one or more bounded form (like
spiral binding or hard binding).