Before we proceed further to Quality Manual let us review documentation
system requirements given in ISO Standard and ICH Q10.
ISO 9001:2008 requires that, in
addition to documented statement of quality policy & quality objectives and
quality manual, QMS documentation shall include:
- documented procedures and
records required by this International Standard, and
- documents, including records,
determined by the organization to be necessary to ensure the effective
planning, operation and control of its processes.'
ISO 9001:2008 standard
require 6 mandatory procedure and 21 records as
given below:
S.No
ISO
Clause
Documented Procedures
1
4.2.3
Control
of documents
2
4.2.4
Control
of records
3
8.2.2
Internal
audit
4
8.3
Control
of nonconforming product
5
8.5.2
Corrective
action
6
8.5.3
Preventive
action
Sr.No
Para.
Record
Required
1
5.6.1
Management
reviews
2
6.2.2
(e)
Education,
training, skills and experience
3
7.1
(d)
Evidence
that the realization processes and resulting product fulfill requirements
4
7.2.2
Results
of the review of the requirements relating to the product and actions arising
from the review
5
7.3.2
Design
and development inputs
6
7.3.4
Results
of design and development reviews and any necessary action
7
7.3.5
Results
of design and development verification and any necessary action
8
7.3.6
Results
of design and development validation and any necessary action
9
7.3.7
Results
of the review of design and development changes and any necessary action
10
7.4.1
Results
of supplier evaluations and actions arising from evaluations
11
7.5.2
(d)
As
required by the organization to demonstrate the validation of processes where
subsequent monitoring and measurement cannot verify the resulting output
12
7.5.3
Unique
identification of the product, where traceability is a requirement
13
7.5.4
Customer
property that is lost, damaged, or otherwise found to be unsuitable for use
14
7.6
(a)
Standards
used for calibration or verification of measuring equipment where no
international or national measurement standards exist
15
7.6
Validity
of previous results when measuring equipment is found not to conform to its
requirements
16
7.6
Results
of calibration or verification of measuring equipment
17
8.2.2
Internal
audit results
18
8.2.4
Evidence
of product conformity with the acceptance criteria and indication of the
authority responsible for the release of the product
19
8.3
Nature
of the product nonconformities and any subsequent actions taken, including
concessions obtained
20
8.5.2
Results
of corrective actions
21
8.5.3
Results
of preventive actions
ICH Q10 and FDA's Guidance Document on Process
Validation expects documentation
control and knowledge management throughout the life-cycle stages of a
product. Pharmaceutical documentation starts from the R&D stage,
commercial production and continues post marketing & post product
discontinuation.
ICH Q10 emphasize on the
lifecycle approach to pharmaceutical QMS. Documentation system shall capture
this life cycle approach and this documented evidence should be
preserved. Each stage in the product life cycle has its unique set of
documents which makes control of documents a challenging task.
Fig 1: Pharmaceutical Quality System ICH Q10 (Source
Internet)
FDA's process
validation guidance document emphasizes scientific approach
to process validation and product life cycle which shall be captured
through documentation control. This guidance document defines process
validation as “the collection and evaluation of data, from
the process design stage through commercial production, which
establishes scientific evidence that a process is capable of consistently
delivering quality product. Process validation involves a series of activities
taking place over the lifecycle of the product and process.”
The guidance describes process validation activities in three
stages.
• Stage 1 – Process Design: The commercial manufacturing process
is defined during this stage based on knowledge gained through development and
scale-up activities.
• Stage 2 – Process Qualification: During this stage, the process
design is evaluated to determine if the process is capable of reproducible
commercial manufacturing.
• Stage 3 – Continued Process Verification: Ongoing assurance is
gained during routine production that the process remains in a state of
control.
Requirements of documentation are emphasized in section IV:
Documentation.
ISO Standard expects control over documents and records. The Standard requires that all the documents shall
be approved, reviewed
periodically, made available at point of use, shall remain legible and identifiable
and obsolete documents shall be controlled. The standard also requires control over documents of
external origin. Documents of external origin can be customer drawings/plans,
documents of suppliers and vendors, reference documents and standards, or any
other document which can be misused if not controlled.
The standard defines records as
special type of documents. Records
shall be controlled through a documented procedure which defines the controls
needed for the identification, storage, protection, retrieval, retention and
disposition of records. Records shall remain legible, readily identifiable and
retrievable.
For better understanding we have divided plant documents into two
main categories:
QMS Documents:
These are the
documents which are required by ISO 9001:2008 for implementation of QMS
and continual improvement. Few other administrative documents are
also included for better understanding and demarcation.
Product Documents:
These
are the documents covering the product realization cycle or
product life cycle as defined in ISO 9001:2008 and ICH Q10 respectively. This
category includes manufacturing procedures, manufacturing formulas, product
specifications, Testing Procedures, maintenance procedures, Support processes
etc. The makeup of these documents is derived by GMP, GLP, GCP, product
requirements and other statutory and regulatory requirements. WHO provides
guidance for vaccines in Technical Report Series (WHO-TRS) and other publications series such as V&B, IVB, VSQ etc.
Templates of Documents categorized as QMS Documents to
be posted in this blog are:
Template documents categorized as Product documents to
be posted in this blog are:
Terms often used in documentation:
Quality Manual (QM): This top-level document defines the company's quality
policies and quality objectives; defines the scope of the quality system,
including details and justification for any exclusions; describes the overall
quality system, its processes, and their sequence and interaction; and
references applicable operational procedures.
Quality Operational Procedures: These are second-level documents defining specific
quality system processes. Operational procedures explain the what, when, who
and how for a process, and define what records must be established to document
the results.
Quality Forms (FORM): These are usually one-page forms or matrices defining
a "template" for establishing a record.
Work Instructions: The purpose of work instructions is to guide personnel
in performing specific tasks, such as carrying out and controlling a production
processes, handling products, calibrating measuring equipment, conducting tests
or inspections, etc.
Labeling and packaging specifications: These documents include component, sub-assembly,
assembly, and packaging drawings and specifications; bills of materials
(or lists of ingredients); compositions; formulations; diagrams; software
specifications; user manual, packaging artwork, sterilization documents (where
applicable) and other such documents defining the medical device and its
packaging. For some contracts these documents may be of external origin, e.g.
supplied by customers.
Manufacturing specifications: Documents under this category include process/
assembly lines diagrams; specifications for equipment, tools, and molds;
manufacturing environment specifications; setup procedures; operator
instructions; machine maintenance procedures; blank travelers, nonconforming
product/process forms, and other reporting forms; and other such documents
defining the manufacturing processes and the manner of production.
Quality assurance/control procedures
and specifications: Documents
under this category include process control specifications/charts; control
plans, instructions and acceptance criteria for incoming, in-process, and
finished device inspection and testing; procedures and acceptance criteria for
the verification of packaging, labeling, installation, and servicing
activities; blank forms for inspection/ testing reports and other device
history records; release document review list; and other such documents
defining how products and manufacturing processes are controlled and verified.
Standards and codes: These are international, national and local
regulations, standards, and codes that define operational, quality and product
requirements.
Device Master Record/
Master Formula Record: Engineering,
manufacturing and quality specifications, and other such documentation that
define the medical device/pharma product (or a family of similar
devices/products) and the manner of production are organized into a Device
Master Record (DMR)/ Master Formula Record (MFR). The DMR/MFR may be
in the form of one or several files or binders with the actual documents, or in
the form of an index referencing these documents and their revision status and
location. The procedure instructs how DMR’s/ MFR’s are established and
maintained.
When a DMR/MFR document is withdrawn or
superseded by a new revision, a copy of the obsolete document is retained for a
period of time at least equivalent to the lifetime of the medical
device/product, but not less than two years from the date of product release.
If this document retention policy is in conflict with relevant regulatory
requirements, the regulatory requirements shall take precedence.
References:
ISO 9001:2008 Quality
management systems — Requirements
Before we proceed further to Quality Manual let us review documentation
system requirements given in ISO Standard and ICH Q10.
ISO 9001:2008 requires that, in
addition to documented statement of quality policy & quality objectives and
quality manual, QMS documentation shall include:
- documented procedures and
records required by this International Standard, and
- documents, including records,
determined by the organization to be necessary to ensure the effective
planning, operation and control of its processes.'
ISO 9001:2008 standard
require 6 mandatory procedure and 21 records as
given below:
S.No
|
ISO
9001:2008
Clause |
Documented Procedures
|
1
|
4.2.3
|
Control
of documents
|
2
|
4.2.4
|
Control
of records
|
3
|
8.2.2
|
Internal
audit
|
4
|
8.3
|
Control
of nonconforming product
|
5
|
8.5.2
|
Corrective
action
|
6
|
8.5.3
|
Preventive
action
|
Sr.No
|
Para.
|
Record
Required
|
1
|
5.6.1
|
Management
reviews
|
2
|
6.2.2
(e)
|
Education,
training, skills and experience
|
3
|
7.1
(d)
|
Evidence
that the realization processes and resulting product fulfill requirements
|
4
|
7.2.2
|
Results
of the review of the requirements relating to the product and actions arising
from the review
|
5
|
7.3.2
|
Design
and development inputs
|
6
|
7.3.4
|
Results
of design and development reviews and any necessary action
|
7
|
7.3.5
|
Results
of design and development verification and any necessary action
|
8
|
7.3.6
|
Results
of design and development validation and any necessary action
|
9
|
7.3.7
|
Results
of the review of design and development changes and any necessary action
|
10
|
7.4.1
|
Results
of supplier evaluations and actions arising from evaluations
|
11
|
7.5.2
(d)
|
As
required by the organization to demonstrate the validation of processes where
subsequent monitoring and measurement cannot verify the resulting output
|
12
|
7.5.3
|
Unique
identification of the product, where traceability is a requirement
|
13
|
7.5.4
|
Customer
property that is lost, damaged, or otherwise found to be unsuitable for use
|
14
|
7.6
(a)
|
Standards
used for calibration or verification of measuring equipment where no
international or national measurement standards exist
|
15
|
7.6
|
Validity
of previous results when measuring equipment is found not to conform to its
requirements
|
16
|
7.6
|
Results
of calibration or verification of measuring equipment
|
17
|
8.2.2
|
Internal
audit results
|
18
|
8.2.4
|
Evidence
of product conformity with the acceptance criteria and indication of the
authority responsible for the release of the product
|
19
|
8.3
|
Nature
of the product nonconformities and any subsequent actions taken, including
concessions obtained
|
20
|
8.5.2
|
Results
of corrective actions
|
21
|
8.5.3
|
Results
of preventive actions
|
ICH Q10 and FDA's Guidance Document on Process
Validation expects documentation
control and knowledge management throughout the life-cycle stages of a
product. Pharmaceutical documentation starts from the R&D stage,
commercial production and continues post marketing & post product
discontinuation.
ICH Q10 emphasize on the
lifecycle approach to pharmaceutical QMS. Documentation system shall capture
this life cycle approach and this documented evidence should be
preserved. Each stage in the product life cycle has its unique set of
documents which makes control of documents a challenging task.
Fig 1: Pharmaceutical Quality System ICH Q10 (Source
Internet)
FDA's process
validation guidance document emphasizes scientific approach
to process validation and product life cycle which shall be captured
through documentation control. This guidance document defines process
validation as “the collection and evaluation of data, from
the process design stage through commercial production, which
establishes scientific evidence that a process is capable of consistently
delivering quality product. Process validation involves a series of activities
taking place over the lifecycle of the product and process.”
The guidance describes process validation activities in three
stages.
• Stage 1 – Process Design: The commercial manufacturing process
is defined during this stage based on knowledge gained through development and
scale-up activities.
• Stage 2 – Process Qualification: During this stage, the process
design is evaluated to determine if the process is capable of reproducible
commercial manufacturing.
• Stage 3 – Continued Process Verification: Ongoing assurance is
gained during routine production that the process remains in a state of
control.
Requirements of documentation are emphasized in section IV:
Documentation.
ISO Standard expects control over documents and records. The Standard requires that all the documents shall
be approved, reviewed
periodically, made available at point of use, shall remain legible and identifiable
and obsolete documents shall be controlled. The standard also requires control over documents of
external origin. Documents of external origin can be customer drawings/plans,
documents of suppliers and vendors, reference documents and standards, or any
other document which can be misused if not controlled.
The standard defines records as
special type of documents. Records
shall be controlled through a documented procedure which defines the controls
needed for the identification, storage, protection, retrieval, retention and
disposition of records. Records shall remain legible, readily identifiable and
retrievable.
For better understanding we have divided plant documents into two
main categories:
QMS Documents:
These are the
documents which are required by ISO 9001:2008 for implementation of QMS
and continual improvement. Few other administrative documents are
also included for better understanding and demarcation.
Product Documents:
These
are the documents covering the product realization cycle or
product life cycle as defined in ISO 9001:2008 and ICH Q10 respectively. This
category includes manufacturing procedures, manufacturing formulas, product
specifications, Testing Procedures, maintenance procedures, Support processes
etc. The makeup of these documents is derived by GMP, GLP, GCP, product
requirements and other statutory and regulatory requirements. WHO provides
guidance for vaccines in Technical Report Series (WHO-TRS) and other publications series such as V&B, IVB, VSQ etc.
Templates of Documents categorized as QMS Documents to be posted in this blog are:
1.
Preparation of SOP
2.
Control of Documents
3.
Control of Records
4.
Competence, awareness and
training
5.
Job Responsibilities of Key
personnel
6.
Procedure for vendor
approval with classification of materials
7.
Customer/ Market Complaint
8.
Product recall
9.
Internal Audit
10.
Handling of Non Conformance
(Deviation and OOS)
11.
Change Control
12.
Corrective and Preventive
Action
Template documents categorized as Product documents to
be posted in this blog are:
1.
Shipping Qualification
2.
Shipping Validation
3.
Validation Policy
4.
Calibration Policy
5.
Autoclave Performance
Qualification
6.
Incubators and Environment
Chamber Qualifications
7.
Cold Room Qualification
8.
HVAC, LAF and BSC
Qualification
9.
DHS and Tunnel
Qualification
10.
Aseptic Media Fill, Process
Simulation Study
11.
Cleaning Validation Policy
12.
Sterile Filtration
Validation
13.
Environmental Monitoring
14.
Warehouse Thermal Mapping
15.
Stability Plan
Terms often used in documentation:
Quality Manual (QM): This top-level document defines the company's quality
policies and quality objectives; defines the scope of the quality system,
including details and justification for any exclusions; describes the overall
quality system, its processes, and their sequence and interaction; and
references applicable operational procedures.
Quality Operational Procedures: These are second-level documents defining specific
quality system processes. Operational procedures explain the what, when, who
and how for a process, and define what records must be established to document
the results.
Quality Forms (FORM): These are usually one-page forms or matrices defining
a "template" for establishing a record.
Work Instructions: The purpose of work instructions is to guide personnel
in performing specific tasks, such as carrying out and controlling a production
processes, handling products, calibrating measuring equipment, conducting tests
or inspections, etc.
Labeling and packaging specifications: These documents include component, sub-assembly,
assembly, and packaging drawings and specifications; bills of materials
(or lists of ingredients); compositions; formulations; diagrams; software
specifications; user manual, packaging artwork, sterilization documents (where
applicable) and other such documents defining the medical device and its
packaging. For some contracts these documents may be of external origin, e.g.
supplied by customers.
Manufacturing specifications: Documents under this category include process/
assembly lines diagrams; specifications for equipment, tools, and molds;
manufacturing environment specifications; setup procedures; operator
instructions; machine maintenance procedures; blank travelers, nonconforming
product/process forms, and other reporting forms; and other such documents
defining the manufacturing processes and the manner of production.
Quality assurance/control procedures
and specifications: Documents
under this category include process control specifications/charts; control
plans, instructions and acceptance criteria for incoming, in-process, and
finished device inspection and testing; procedures and acceptance criteria for
the verification of packaging, labeling, installation, and servicing
activities; blank forms for inspection/ testing reports and other device
history records; release document review list; and other such documents
defining how products and manufacturing processes are controlled and verified.
Standards and codes: These are international, national and local
regulations, standards, and codes that define operational, quality and product
requirements.
Device Master Record/
Master Formula Record: Engineering,
manufacturing and quality specifications, and other such documentation that
define the medical device/pharma product (or a family of similar
devices/products) and the manner of production are organized into a Device
Master Record (DMR)/ Master Formula Record (MFR). The DMR/MFR may be
in the form of one or several files or binders with the actual documents, or in
the form of an index referencing these documents and their revision status and
location. The procedure instructs how DMR’s/ MFR’s are established and
maintained.
When a DMR/MFR document is withdrawn or
superseded by a new revision, a copy of the obsolete document is retained for a
period of time at least equivalent to the lifetime of the medical
device/product, but not less than two years from the date of product release.
If this document retention policy is in conflict with relevant regulatory
requirements, the regulatory requirements shall take precedence.
References:
ISO 9001:2008 Quality
management systems — Requirements
ICH
Q10 Pharmaceutical Quality System
Food and Drug
Administration: Guidance for Industry- Process Validation: General
Principles and Practices (2011)
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