WELCOME
TO THE
TRAINING
Shah Sharfin
Manager, Quality Assurance
Volume 4 - Guidelines for good
manufacturing practices for
medicinal products for human and
veterinary use
2
EU GMP
•Part I - Basic Requirements for Medicinal Products
• Chapter 1 - Pharmaceutical Quality System (2013)
• Chapter 2 - Personnel (2014)
• Chapter 3 - Premise and Equipment (2015)
• Chapter 4 - Documentation (2011)
• Chapter 5 - Production (2015)
• Chapter 6 - Quality Control (2014)
• Chapter 7 - Outsourced activities (2013)
• Chapter 8 - Complaints and Product Recall (2015)
• Chapter 9 - Self Inspection
3
TODAY’S TOPIC
EU GMP_ Chapter 4: Documentation
Effective from:
30 June 2011
4
Basic Principle of Documentation
Principle of Documentation
Good documentation constitutes an essential
part of the quality assurance system and is key
to operating in compliance with GMP
requirements.
Principle of Documentation
The various types of documents and media used
should be fully defined in the manufacturer's
Quality Management System.
Documentation may exist in a variety of forms,
including paper-based, electronic or
photographic media.
Principle of Documentation
The main objective of the system of
documentation utilized must be to establish,
control, monitor and record all activities which
directly or indirectly impact on all aspects of the
quality of medicinal products
Principle of Documentation
There are two primary types of documentation
used to manage and record GMP compliance:
instructions (directions, requirements) and
records/reports. Appropriate good documentation
practice should be applied with respect to the
type of document.
Principle of Documentation
Suitable controls should be implemented to
ensure the accuracy, integrity, availability and
legibility of documents.
Instruction documents should be free from errors
and available.
Required GMP documentation (by type)
Required GMP documentation
• Site Master File
• Instructions (directions, or requirements) type
• Specifications
• Manufacturing Formulae, Processing, Packaging
and Testing Instructions
• Procedures
• Protocols
• Technical Agreements
Required GMP documentation
• Record/Report type
• Records
• Certificates of Analysis
• Reports
Generation and Control of Documentation
Generation & Control of Documentation
• All types of document should be defined.
• Complex systems need to be understood, well
documented, validated, and adequate controls should
be in place.
Generation & Control of Documentation
• Many documents (instructions and/or records)
may exist in hybrid forms, i.e. some elements
as electronic and others as paper based.
• Relationships and control measures for master
documents, official copies, data handling and
records need to be stated for both hybrid and
homogenous systems.
Generation & Control of Documentation
• Appropriate controls for electronic documents
such as templates, forms, and master
documents should be implemented.
• Appropriate controls should be in place to ensure
the integrity of the record throughout the retention
period.
Generation & Control of Documentation
• Documents should be designed, prepared, reviewed,
and distributed with care.
• Documents containing instructions should be
approved, signed and dated by appropriate and
authorized persons.
• Documents should have unambiguous contents and
be uniquely identifiable.
• The effective date should be defined.
Generation & Control of Documentation
• They should comply with the relevant parts of
Product Specification Files, Manufacturing and
Marketing Authorization dossiers, as appropriate.
• The reproduction of working documents from
master documents should not allow any error to
be introduced through the reproduction process.
Generation & Control of Documentation
• Documents containing instructions should be laid
out in an orderly fashion and be easy to check.
• The style and language of documents should fit
with their intended use.
• Standard Operating Procedures, Work Instructions
and Methods should be written in an imperative
mandatory style.
Generation & Control of Documentation
• Documents within the Quality Management
System should be regularly reviewed and kept
up-to-date.
• Documents should not be hand-written; although,
where documents require the entry of data, sufficient
space should be provided for such entries.
Good Documentation Practices
Good Documentation Practices
• Handwritten entries should be made in clear,
legible, indelible way.
Good Documentation Practices
• Records should be made or completed at the time
each action is taken and in such a way that all
significant activities concerning the manufacture of
medicinal products are traceable.
Good Documentation Practices
• Any alteration made to the entry on a document
should be signed and dated; the alteration should
permit the reading of the original information.
Where appropriate, the reason for the alteration
should be recorded.
Good Documentation Practices
Good Documentation Practices
Good Documentation Practices
Good Documentation Practices
Good Documentation Practices
Retention of Documents
Retention of Documents
• It should be clearly defined which record is
related to each manufacturing activity and where
this record is located.
• Secure controls must be in place to ensure the
integrity of the record throughout the retention
period and validated where appropriate.
Retention of Documents
• Specific requirements apply to batch
documentation which must be kept for one year
after expiry of the batch to which it relates or at
least five years after certification of the batch by
the Qualified Person, whichever is the longer.
Retention of Documents
• For other types of documentation, the retention
period will depend on the business activity which
the documentation supports.
Retention of Documents
• Critical documentation, including raw data (for
example relating to validation or stability), which
supports information in the Marketing
Authorisation should be retained whilst the
authorization remains in force.
Retention of Documents
• It may be considered acceptable to retire certain
documentation (e.g. raw data supporting
validation reports or stability reports) where the
data has been superseded by a full set of new
data. Justification for this should be documented
and should take into account the requirements for
retention of batch documentation.
Retention of Documents
• For example, in the case of process validation
data, the accompanying raw data should be
retained for a period at least as long as the
records for all batches whose release has been
supported on the basis of that validation exercise.
Retention of Documents
• The quality management system should describe
all documents required to ensure product quality
and patient safety.
Specifications
• There should be appropriately authorised and
dated specifications for starting and packaging
materials, and finished products.
Specifications
Specifications
Manufacturing Formula & Processing
Processing Instructions
Packaging Instructions
Procedures and records
Procedures and records
• Sampling
• There should be written procedures for sampling,
which include the methods and equipment to be
used, the amounts to be taken and any
precautions to be observed to avoid
contamination of the material or any deterioration
in its quality.
Procedures and records
• Testing
• There should be written procedures for testing
materials and products at different stages of
manufacture, describing the methods and
equipment to be used.
• The tests performed should be recorded.
Procedures and records
• Written release and rejection procedures should be
available for materials and products, and in particular
for the certification for sale of the finished product by
the Qualified Person(s).
• All records should be available to the Qualified
Person.
Procedures and records
• A system should be in place to indicate special
observations and any changes to critical data.
Procedures and records
• Records should be maintained for the distribution of
each batch of a product in order to facilitate recall of
any batch, if necessary.
Procedures and records
• There should be written policies, procedures,
protocols, reports and the associated records of
actions taken or conclusions reached, where
appropriate, for the following examples:
- Validation and qualification of processes,
equipment and systems;
- Equipment assembly and calibration;
- - Technology transfer;
- - Maintenance, cleaning and sanitation;
Procedures and records
• - Personnel matters including signature lists, training
in GMP and technical matters, clothing and hygiene
and verification of the effectiveness of training. -
Environmental monitoring; - Pest control; -
Complaints; - Recalls; - Returns; - Change control; -
Investigations into deviations and non-
conformances; - Internal quality/GMP compliance
audits; - Summaries of records where appropriate
(e.g. product quality review); - Supplier audits.
Procedures and records
• Clear operating procedures should be available for
major items of manufacturing and test equipment.
Procedures and records
• Logbooks should be kept for major or critical
analytical testing, production equipment, and areas
where product has been processed.
Procedures and records
• They should be used to record in chronological
order, as appropriate, any use of the area,
equipment/method, calibrations, maintenance,
cleaning or repair operations, including the dates
and identity of people who carried these operations
out.
Procedures and records
• An inventory of documents within the Quality
Management System should be maintained.
Q&A
58
