Basic Principles of GMP
Documentation
Part 2
15
Documentation
Labels
What must be labelled?
Containers, equipment, premises
Label information?
Clear, unambiguous, company format
Intermediates and bulk products
Colours can be used, e.g. green (accepted), red (rejected)
15.10
Basic Principles of GMP
Different types of labels,
e.g. cleaning status,
production stage, status of
materials
Other types of labels?
Basic Principles of GMP
Labels can indicate the
status of materials such
as "quarantine"
Documentation
Finished Product Label
National legislation, but includes:
Name
Active ingredients and amounts
Batch number
Expiry date
Storage conditions, precautions if necessary
Directions for use, earnings
Name and address of manufacturer
15.11
Documentation
Reference standards
Label to include:
Name
Potency or concentration
Date of manufacture
Expiry date
Date the closure is first opened
Storage condition
Control number
15.12
Documentation
Specifications
Specifications:
Authorized, approved, signed and dated
Starting materials and packaging materials
include tests on identity, content, purity, quality
Finished products
Intermediates and bulk
Water, solvents and reagents
QC, QA or documentation centre 15.14, 15.15
Documentation
Specifications and Test Procedures
Test Procedures:
Validated (facility and equipment) before routinely used
Specifications:
Periodic review
15.13, 15.16 -15.17
In compliance with current pharmacopoeia
– Pharmacopoeia, reference standards and spectra should be available
Documentation
Specifications: Starting and packaging materials
Include:
Name (e.g. INN) and internal code
Pharmacopoeia (if applicable)
Qualitative and quantitative requirements and limits
Other data may include:
Supplier
Sampling procedure or reference
Storage conditions, precautions
Retest date 15.18 -15.19
Basic Principles of GMP
Can you list which
documents are associated
with / needed for sampling of
starting materials?
And for packaging materials?
Documentation
Specifications: Finished products
Include:
Name and code reference
Names of actives (e.g. INN)
Formula
Dosage form, package details
Reference to sampling
Qualitative and quantitative requirements and limits
Storage conditions and precautions
Shelf life 15.21
Documentation
Master Formulae - I
Master formula for each product and batch size
Manufacturing instructions include:
Name of product with product reference code
Dosage form, strength and batch size
List of starting materials including quantities and unique
reference code
Expected final yield with acceptable limits (and intermediate
yields)
Processing location and principal equipment
15.22 – 15.23
Documentation
Master Formulae - II
Manufacturing instructions - continued
Equipment preparation (e.g. cleaning, assembling,
calibrating, etc.)
Detailed stepwise processing instructions and checks,
pre-treatments, sequence of additions, times,
temperatures, etc.
In-process control instructions and their limits
Storage requirements and special precautions
Any special precautions if needed
15.22 – 15.23
Documentation
Master Formulae - III
Authorized packaging instructions for each product, pack size
and type, and to include:
Name of the product
Dosage form, strength and method of application
Pack size (number, weight or volume of product in final
container)
List of all packaging materials (quantities, size, types and
code number)
15.24
Documentation
Master Formulae – IV
Packing instructions - continued
Examples of printed packaging materials, with location of
batching information
Special precautions, including area clearance checks
(before and after operations)
Description of the packaging operation including equipment
to be used
In-process controls, with sampling instructions and
acceptance limits
15.24
Documentation
Batch Processing Record – I
Record kept for each batch processed
Based on the master or specifications (e.g. copied to avoid
errors)
Before start of process - check suitability of area and equipment
clear of previous products, documents, materials
Checks recorded
15.25 – 15.26
Documentation
Batch Processing Records – II
Information recorded during processing include:
Name of the product, batch number
Dates and times (e.g. start, major steps, completion)
Name of person responsible for each stage of production
Name of operators carrying out each step (check signatures)
Theoretical quantities for materials in the batch
Reference number and quantity of materials used in the batch
15.27
Documentation
Batch Processing Records – III
Information recorded during processing include (cont.):
Main processing steps and key equipment
In-process controls carried out, person's initials, and results
obtained
Yield at each stage with comments on deviations
Expected final yield with acceptable limits
Comments on any deviations from process
Area clearance check
Instructions to operators 15.27
Documentation
Documentation
Batch Packaging Records – I
For every batch or part of a batch
Based on approved packaging instructions
Can be copied or computer generated
Before start – checks that equipment and work station suitable
and clean, no previous product
– Line clearance (opening)
– Recorded
15.28, 15.29
Documentation
Batch Packaging Records – II
Contents:
Name of the product, batch number and quantity to be packed
Batch number, theoretical quantity and actual quantity of
finished product
Actual quantity obtained – reconciliation
Dates and times of operation
Name of person responsible for packaging, initials of operators
carrying out each step
15.30
Checks, and in-process results
Documentation
Batch Packaging Records – III
Contents:
Details of packaging operation, including equipment and line
used
Returns to store
Specimen of printed packaging materials, with batch coding
approval (batch number and expiry date)
15.30
Deviations and actions taken; and authorization
Reconciliation of packaging materials, including issues, use,
returns and destruction
Documentation
Documentation
Standard Operating Procedures (SOP) - I
What is an SOP?
Who is responsible for preparing SOPs?
What is the format for an SOP?
Which activities require SOPs?
Where should SOPs be stored?
Are SOPs associated with records?
15.31
Documentation
Standard Operating Procedures - II
Which activities require SOPs?
Equipment and analytical apparatus:
– Assembly, validation
– Calibration
– Internal labelling, quarantine and storage of materials
– Operation
– Maintenance and cleaning
Personnel matters:
• Qualification
• Training
• Clothing
• Hygiene 15.31
Documentation
Standard Operating Procedures - III
Which activities require SOPs?
Environmental monitoring
Pest control
Complaints
Recalls
Returned goods
15.31
Documentation
Standard Operating Procedures - IV
SOP and records for receiving materials
Name of material as on delivery note
Name and in-house code
Date of receipt
Supplier's and manufacturer's name
Batch number
Quantity and number of containers received
State of container and other information
15.33
Documentation
Standard Operating Procedures - V
Other SOPs include:
Internal labelling, quarantine and storage of materials
Operation, maintenance, calibration and cleaning of all
instruments and equipment – production and QC
Sampling of materials
Batch numbering systems
Material testing at all stages of production
Complaints, recalls
15.31, 15.32
Documentation
Standard Operating Procedures - VI
Which activities require SOPs? (Continued)
Batch release or rejection
Maintenance of distribution records
Equipment assembly and validation
Maintenance, cleaning and sanitation
Personnel recruitment, training, clothing and hygiene
Environmental monitoring
Pest control
15.31
…and many more…
Documentation
Standard Operating Procedures - VII
SOP for sampling:
– the method of sampling and the sampling plan
– equipment to be used
– precautions to avoid contamination
– amount(s) of sample(s) to be taken
– instructions for any required subdivision of the sample
– type of sample container(s) to be used
– specific precautions
…and many more…
15.37
Documentation
Records
What should be recorded?
Where should records be stored?
Why are the records important?
Documentation
Records
Different types of records should be kept
For defined periods of time
Production records and packaging records
Quality control records
Distribution records
Equipment records
15.32
Documentation
Records
Records of receipt of materials
Name of material, “In-house” name and/or code of material
Date of receipt, supplier’s and manufacturer’s name
Batch or reference number, quantity, and number of containers
received;
Comment (e.g. state of the containers).
15.33
Documentation
Records
Analysis records to include:
– Name of material / product
– Batch number
– Reference to specification and test procedures
– Test results
– Dates
– Equipment references for traceability
– Initials / names of analysts and supervisors who checked
the data
15.43
– Statement of release or rejection
Documentation
Records
Include also:
Cleaning and use
Qualification and validation
Calibration
Maintenance
Preventive maintenance etc…
15.35
Documentation
Group Session I
Documentation
Docum entation W orkshop – M odel Toy assembly
Specifica First attem pt (score/5) Second attempt (score/5)
-tions Team 1 Team 2 Team 3 Team 4 Team 1 Team 2 Team 3 Team 4
M eets toy
description
Aesthetic
Beautiful
Safe
for kids
Kept to the
time lim it
No pieces left
over
Performance
test – robust
Total
First attempt Second attem pt
Total all groups
Im provement (if any)
Documentation
Group Session II
From your own experience of factory inspections, how do
documentation systems in this country compare with the WHO
model?
Identify gaps and reasons
What will help and/or hinder the process of eliminating these
gaps?
