GOOD MANUFACTURING PRACTICES

Modul-3
Documentation
Wayan Redja
Fakultas Farmasi Universitas Pancasila
Jakarta, 2014
 Documentation

Introduction
Types and Hierarchy of Documents
General Requirements
Document Required
Preparation of Documents
Document Control
Document Maintenance and Disposal
 Introduction
Prinsip
Document is information and its supporting medium.

Supporting medium: paper; magnetic, electronic or optical computer

disc.; etc.)

Documentation is a file or a set of documents.

Documentation is part of Management Information System and good

documentation is an essential part of QA System

Detail and clear written job descriptions should be understood by

related personnel to avoid misinterpretation and error.

Available written master formulas, procedures, methods, job

instructions, records and reports must be error-free.
 Introduction
Purpose
To support effectiveness and efficiency planning,
operation, control and evaluation (PDCA)
To enable communication of intent and consistency of
action.
To provide contributions in:
- achievement of conformity to customer requirements
and quality improvement.
- provision of appropriate training
- repeatability and traceability.
- provision of objective evidence
- evaluation of effectiveness and continuing suitability of
the QMS.
 Introduction

Purpose
To define the specifications and procedures for all
materials, products, and methods of manufacture and
control.
To ensure that all personnel know what, when and how to
do their job.
To ensure that authorized persons have all the information
necessary to release or not the materials or products.
To ensure the existence of documented evidence, and
traceability to permit investigation.
To ensure the availability of data for planning, operation,
validation, control, statistical analysis, review, and continual
improvement.
 Types and Hierarchy of Documents

Terms related to data, information and document

(ISO 9000:2015)

Data
Facts about an object (anything perceivable). Data supporting the
existence or verify of something obtained through test, measurement
etc,are called Objective Evidence

Infformation
Meaningful data. QMS network of communication channel of an
organization is called Information System.

Document
Information and the medium (paper,magnetic, electronic, etc) on
which it is contained.
Documentation is the well documented documents.
 Types and Hierarchy of Documents
Terms related to data, information and document (ISO 9000:2015)

Data
Facts about an object (anything perceivable). Data supporting the
existence or verify of something obtained through test, measurement
etc,are called Objective Evidence

Infformation
Meaningful data. It is the result of evaluatin after analysis of data.
QMS network of communication channel of an organization is called
Information System.

Document
Information and the medium (paper,magnetic, electronic, etc) on
which it is contained.
Documentation is a set of well documented documents.
Documented information shoul be contrilled and maintained.
 Types and Hierarchy of Documents
Terms related to data, information and document (ISO 9000:2015)

Spesification
Document stating requirements (e.g. Quality Manual, Quality Plan,
SOP, Work Instruction, process, test, product, product performance).

Quality Manual
Specification for the QMS of an organization.

Quality Plan
Specification of the procedures and associated resourcesto be
applied whwn and by whom to a specific object.
Procedure is specified way to carry out an activity or a process.

Record
Document stating results achieved or providing evidence of activities
performed.
 Types and Hierarchy of Documents
Terms related to data, information and document (ISO 9000:2015)

Verification
Conformation through provision of objective evidence that specified
equirements have been fulfilled..

Quality Manual
Specification for the QMS of an organization.

Quality Plan
Specification of the procedures and associated resourcesto be
applied whwn and by whom to a specific object.
Procedure is specified way to carry out an activity or a process.

Record
Document stating results achieved or providing evidence of activities
performed.
Types and Hierarchy of Documents

Hierarchy of Documents

Quality Manual
1 - QMS specification

Procedures
2 - Specifiction for interrelated activities
Work Instruction
3 - Specification for particular activities
Records
4 . Document stating results or activities
 General Requirements (WHO 2011)
Documents should be designed, prepared, reviewed; comply with
relevant parts of manufacturing and marketing authorization, and
distributed with care.

Contents should be unambiguous: the title, nature and purpose

should be clearly stated and the lay out in orderly fashion and be
easy to check.

Reproduced documents should be clear, no error, and legible.

Sufficient space should be provided if require data entries, and the

entries should be clear, legible, and indelible.

Documents should be regularly reviewed, kept up to date,

Documents or its change should be approved, signed, dated and

authorized by the appropriate responsible person.

Superseded version of the revised document be retained for a

specific period of time, and the system should prevent reuse of it.
 General Requirements
Alteration of documents should be signed, dated, and the original
information still can be read, where appropriate the reason for
alteration should be recorded.
Data may be recorded by electronic data-processing system, or by
photographic or any reliable means.
Only authorized persons are allowed to enter or modify data in the
computer, and there should be a record of changes and deletions.
Access should be restricted by passwords or other means and the
entry of critical data should be independently checked.
Batch records stored electronically should be protected by back up
transfer on magnetic tape, microfilm, proper print out or other
means, and during the period of retention the data are readily
available.
Records should be traceable, and be made or completed when any
action is taken.
Records be retained for at least one year after expire date of the
finished product.
 Document Required

Specifications
- for Starting and Packaging Materials
- for Intermediate, Bulk, and Finished Products
Labels
Master Formulae
Standard Operating Procedures (SOPs)
Testing Procedures
Packaging Instructions
Records:
- Receipt of Materials Records
- Analysis Records
- Batch Processing Records
- Batch Packaging Records
 Document Required
Specifications of Materials
Specifications for Starting Materials, Primary and Printed
Packaging Materials, should provide a description, including:
Name and internal code reference
Reference to a pharmacopoeial monograph (if any).
Qualitative (identity) and quantitative requirements (purity, impurity,
content) with acceptance limits, including specifications for water,
solvent, acids, and bases used in production.
Depending on the company, other data may be added, e.g.
- the producer name of the materials,
- a specimen of printed materials,
- direction for sampling and testing, or a reference to
procedure,
- storage conditions and precautions,
- re-testing time.
 Specifications of Products
Intermediate, Bulk, and Finished Products
Specifications for intermediate similar to starting materials

Specifications for bulk products similar to finished products

Specification for finished products should include:

- Name and code reference,
- Name(s) of the active ingredient(s),
- the formula or a reference to the formula,
- a description of the dosage form and package details,
- direction for sampling and testing or a reference to procedure,
- the qualitative (identity) and quantitative requirements (impurity,
performance, content) with acceptance limits,
- the storage conditions and precautions, where applicable,
- the shelf life.
 Labels
Labels should be clear, unambiguous, and colored to indicate status,
e.g. yellow for quarantine, etc.

Labels of finished product conform national regulation, bearing at least:

- the name of the drug product,
- a list of the content of active ingredients, and a statement of the net
contents (e.g. number of dosage units, weight, volume),
- the batch number,
- the expiry date,
- any special storage conditions and handling precautions,
- directions for use, warnings, and precautions,
- the name address of the manufacturer, company, or the person
responsible for placing the product on the market.

For reference standards, the labels and/or accompanying documents

should indicate: potency or concentration, manufacturing date, expiry
date, first opened date, storage conditions, and control number.
 Master Formulae
A formally authorized master formulae should exist for
each product and batch size to be manufactured.
The specification of master formulae should include:
- the product name, with product reference code
- description of dosage form, strength of the product and batch size.
- a list of all starting materials and the amount of each.
- the expected intermediate and final yield with the acceptable limits
- a statement of the processing location and the principal equipment.
- the methods for preparing and operating critical equipments, e.g.
cleaning, assembling, calibrating, sterilizing, use.
- detailed step-wise processing instructions (e.g. checks on material,
pretreatments, sequence for adding materials, mixing times,
temperatures).
- the instructions for IPC with their limits.
- requirements for storage, including the container, the labeling and
any special storage conditions.
- any special precautions to be observed.
 Standard Operating Procedures

SOP(s) and records of actions taken should be

available for:
- equipment assembly and validation,
- analytical apparatus and validation,
- calibration, maintenance, cleaning and sanitization.
- personnel matters: qualification, training, clothing and
hygiene,
- environmental monitoring,
- pest control,
- complaints,
- recalls,
- returns
The SOP(s) should be placed in close proximity to the
equipment.
SOP(s) for Batch Numbering System

There should be detailed SOP(s) of the batch (lot)

numbering system specific for each of intermediate, bulk
and finished products.
Batch numbering applied to processing stage and
packaging stage should be related to each other.
The same batch number must not be used repeatedly,
including reprocessing.
Batch number allocation should be immediately recorded,
e.g in a log book, and should include:
- date of allocation,
- product identity
- batch size.
 SOP(s) for Sampling

The sampling instruction should include:

- the sampling plan,
- the method of sampling,
- the equipment to be used,
- the type of sample container (s) (aseptic or normal
sampling, and labeling),
- any precautions to avoid cross-contamination and
deterioration of materials,
- the amount of sample to be taken,
- instruction for any required subdivision of the sample,
- any specific precautions to the sampling of sterile or
noxious materials
 SOP(s) for Quarantine, Storage,
Sampling and Testing,

There should be SOP(s) for labeling, quarantine and

storage of materials.
Thee should be SOP(s) for sampling, which specify the
authorized person.
There should be written procedures for testing materials
and products at different stages of manufacture.
Testing procedures should be validated in the context of
available resources.
Pharmacopoeias, reference standards, reference
spectra and other reference materials should be
available in the QC laboratory.
Written release and rejection procedures should be
available, and release for sale by an authorized person
 Packaging Instructions
Packaging instructions for each batch, packed size and
type, should include:
- the name of the product,
- a description of its dosage form, strength, and method of
application,
- the pack size, weight, and volume of the product in the final
container,
- a complete list of all packaging materials used including:
quantities, size and types, the code or reference number relating to
the specifications for each packaging material,
- an example or reproduction of the relevant printed packaging
materials and specimens, indicating where the batch number and
expiry date have been marked,
- special precautions to be observed, to ascertain the line clearance
before and after packaging operations,
- a description of the packaging operation,
- details of IPCs with instruction for sampling and acceptance limits.
 Records

Records of operations for major and critical equipment,

include:
- validations,
- calibrations,
- maintenance,
- cleaning,
- repair,
- date and the identity of the person who carried
these operations out.
Records of the use of major and critical equipment, and the
areas where the products have been processed, should be
recorded in chronological order.
 Records of Receipts of Materials

The records of receipts of starting materials, primary and

printed packaging material should include:
- the name of materials,
- the “in-house” name and code (if different from the name
on the delivery note),
- the date of receipt,
- the supplier and manufacturer name (if possible),
- the manufacturer’s batch or reference number,
- the quantity and number of containers received,
- the batch number assigned after receipt,
- the relevant comment (e.g. state of the containers)
 Analysis Records
Analysis records should include:
- the name of material and product,
- the batch number, manufacturer / supplier.
- references to specifications and testing procedures,
- the results, observations and calculations, and reference to
specifications (limits),
- date(s) and reference number(s) of testing,
- the initial of person who performed the testing.
- the date and initials of the person who verified the testing and
calculations.
- a clear statement of release or rejection (or other status
decision) and the dated signature of the designated
responsible person.
Records of distributed batches should be maintained in
order, to anticipate actions in case of product recall.
 Batch Processing Records
Line clearance before any processing begins.
The following information should be recorded at the time
each action is taken:
- the name of the product,
- the number of the batch being manufactured,
- dates and times of commencement, significant intermediate
stages, and of completion of production,
- the name of the person responsible for each production stages,
- the initials of operators and the person(s) who checked the
operations, e.g. weighing,
- the batch number and analytical control number
- the quantity of each starting material actually weighed (including
the batch number and amount of any recovered or reprocessed
material added).
 Batch Processing Records (continuation)

The following information should be recorded at the time

each action is taken (continuation):
- any relevant processing operation or event and the major
equipment used,
- the IPC(s), results obtained, the initials of person(s) carrying them
out,
- the yield at different stages, and comment for significant deviations
from the expected yield.
- notes on special problems including details, with signed authorization
for any deviation from the master formula.

The record should be dated and signed by the

responsible person after completion of the process.
The processing records of each batch should be kept for
at least one year after the expiry date of the batch.
 Batch Packaging Records

Line clearance should be carried out before any

packaging operations begins.
The following information should be recorded at the time
each action is taken:
- the name of the product,
- the batch number and the quantity of the bulk product to be
packed,
- the batch number and the planned quantity of finished product,
the quantity actually obtained and the reconciliation,
- the date(s) and time(s) of the packaging operation,
- the name of the related responsible person,
- the initials of the operators of the different steps,
 Batch Packaging Records

The following information should be recorded at the time

each action is taken (continuation):
- the results of in-process controls,
- details of packaging operations,
- samples of printed packaging materials used,
- notes of any special problems, including any deviations with
written authorization,
- the quantities and reference number or identification of all printed
packaging materials and bulk product issued, used, destroyed or
returned to stock,
- the quantities of the product obtained to permit an adequate
reconciliation.
Packaging record of each batch should be kept for at
least one year after the expiry date.