Transcript Company name DEPARTMENT Management of GMP

Sampling,
Identification and
Testing
(S.I.T.)
Introduction
• Define basic principles for applying sampling,
identification and testing requirements
1) Systems and procedures
 ensuring that samples are representative of the batch when
sampled
 Correctly identified
 Tested
2) Systems and Procedures in accordance with
regulatory and Safety requirements
Scope
Applies to all manufacturing sites
Applies to all sub-contractors
Applies to all Affiliates
Applies to Raw-materials, isolated
intermediates, APIs, excipients, medical
devices, packaging materials, inprocess
materials, bulk and packaged drug products
• Does not apply to environmental samples and
Reference and Retention samples
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Reference Documents
• ICH Q7 : Good Manufacturing Practice for Active
Pharmaceutical Ingredients
• EU GMP Part I Chapter 6 : Quality Control
• EU GMP Annex 8 : Sampling of Starting and Packaging
Materials
• US CFR : Subpart E-Control of Components and Drug Product
Containers and Closures : §211.80 : General requirements ;
§211.84 Testing and approval or rejection of components,
drug product containers, and closures ; §211.110 Sampling
and testing of in-process materials and drug products,
Subpart G-Packaging and Labelling Control : §211.122
Materials examination and usage criteria
Sampling General
Requirements (1)
• Composite sample : justify the number of individual samples
• Sampling operations recorded with specific items. Records available
for evaluation as condition of batch release
• Additional sampling may be considered in case of OOS/OOT
Based on approved re-sampling protocol
• Sterile materials sampled aseptically in environmental zone A.
-
Sampling General
Requirements (2)
• Sampling personnel initially trained and
retrained on regular basis
• Only qualified and authorised personnel
can sample
• Any anomaly/irregularity during sampling
has to be notified and recorded.
Sampling General
Requirements (3)
• Sampling areas designed to protect product from
environment and cross contamination and protect
personnel from the product
• Appropriate areas in case of high potency, sensitizing
material, antibiotic, etc
• Gowning
instructions
and
equipment must be available
personnel
protective
• Material Safety Data Sheet (MSDS) available before
sampling.
Sampling General
Requirements (4)
• Sampling equipment and tools : specified, stored appropriately
protected from contamination, cleaned after use and cleaning
validation performed
• Cleanliness status of equipment identifiable
• Containers carefully opened and closed
• Containers marked when sample taken
• Identification of person who performs sampling
• Date of sampling recorded.
Sampling General
Requirements (5)
• Containers in which samples are
placed must be clean and clearly
labelled
• Sampled samples must not be
returned to the batch
Identification General
Requirements
• Identification method : described in the
current locally applicable Pharmacopoeia
(e.g. USP, EP, JP) or approved Regulatory
File
• For material identification, a NIR validated
method can be applied even if not
registered in the Regulatory File; for
countries where the practice is allowed.
Sampling and Identification
Operations (1)
• Samples must be representative of the batch of
materials or products from which they are taken
• Pre-samples allowed only from approved or
certified suppliers with written agreement on
sampling delegation
• Place(s) where samples need to be taken or
identification : detailed in SOP
• Sampling must not be the cause of contamination
or cross-contamination
• Cleaning operation in case of outer dirty container.
Sampling and Identification
Operations (2)
• Hazardous or highly toxic materials,
processing aids (solvents) or other special
material may not be sampled or tested
• CoA needed from supplier : results
conform to established specifications
• Practice to be justified and approved.
Sampling and Identification
Operations (3)
• Each batch of incoming material for
API product : subject for identity,
except in case of risk for health and
safety
Such kind of materials to be listed
CoA obtained from supplier for each
batch.
Sampling and Identification
Operations (4)
• Sampling plans or procedures minimum
information
Version, approver’s name, date of approval
Name of material, amount to be sampled
Sample packaging and labelling, storage
conditions
Sampling equipment, safety/handling
precautions : sterile, noxious product,
pyrogens.
Sampling and Identification
Operations (5)
• Sampling plans or procedures minimum
information (cont.)
Number of containers to be sampled
Number of samples to be taken
Sampling/Identification location within the
container :
Supplier pre-samples or identification location
when direct NIR identification
Measurement units : quantity (g, ml, mg,…)
Sampling and Identification
Operations (6)
• Sampling plans or procedures minimum
information (cont.)
Composite sample (number of sample for a
composite)
Sub-division of sample
Department/person - the sample is to be sent
Instructions for cleaning and storage of
sampling equipment.
Sampling and Identification
Specific Rules (1)
• Materials used for Manufacture of APIs:
Starting Materials, Raw Materials and
Synthesis Intermediates
 Manufacturers of SM, RM, SI must be identified
 If Manufacturer is certified, reduced testing is
allowed
 Reduced testing on hold in case of investigation
and return to reduced testing only if supported by
conclusion of investigation and approval from
Quality operations.
Sampling and Identification
Specific Rules (2)
• Materials used for Manufacture of APIs (cont.)
 Starting Materials, Raw Materials
1) Manufacturer within « ICH » Region*:
A justified sampling and identification plan
based on criteria such as :
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Criticality of material
Material variability
Supplier past quality history
Manufacturing factory dedication
Certification of Supplier
At least one test for Identity of each batch
(except in case of health and safety risk sample each
container)
* « ICH » = European Union, North America, Japan + EFTA:
Switzerland, Norway, Iceland and Liechtenstein.
Sampling and Identification
Specific Rules (3)
• Materials used for Manufacture of APIs (cont.)
 Starting Materials, Raw Materials
2) Manufacturer outside « ICH » Region:
Sampling of each container, identification on composite
sample and full testing
(Identification on each container not required, in case of deviation/OOT:
investigation to be performed and concluded).
Sampling and Identification
Specific Rules (4)
• Materials used for Manufacture of APIs
(cont.)
Intermediates Synthesis – external manufacturer
3) Regardless of geographical origin:
Sampling on each container to make a
composite sample
– For identification
– For full testing
(Identification on each container not required, in case of deviation/OOT :
investigation to be performed and concluded).
Sampling and Identification
Specific Rules (5)
• APIs and Excipients
API produced within company: sampling and
identification limited to one container (process
validation demonstrates homogeneity,
container integrity)
API not produced within company and
excipients with origin outside the ICH region
– Identification of material on each container
– Composite sample for later full testing.
Sampling and Identification
Specific Rules (6)
• APIs and Excipients
API not produced at company manufacturing
site and excipients with origin from the ICH
Region: sampling and identification depend
upon following parameters:
– Supplier nature and status : when supplier is
certified
– Supplier quality assurance system
– Manufacturing and control conditions
– Nature of API, excipient and drug product in which
they are used.
Sampling and Identification
Specific Rules (7)
• APIs and Excipients (cont.)
– API or excipient coming from single product manufacturer
or plant
– API, excipient coming directly from manufacturer in sealed
containers and manufacturer regularly audited
• In such case : Sampling and Identification performed
on a reduced number of containers according to
justified sampling plan
• If previous conditions not fulfilled : identification on
each container
• APIs and Excipients used for Parenterals : EACH
container must be identified.
Sampling and Identification
Specific Rules (8)
• Packaging Materials
Sampling plan based on quantity received and
required, nature and criticality of material
(geographical origin, primary packaging, printed
packaging), production methods, quality
assurance of manufacturer
Sampling place/location is dependant on supplier
status :
– Approved or certified supplier > sampling possible by
supplier : written sampling delegation and justified
sampling plan are mandatory
– Supplier with no quality agreement > sampling by
own company manufacturing site : justified sampling
plan.
Sampling and Identification
Specific Rules (9)
• Intermediates for Drug Product, Bulk Drug
Products, In-Process Materials and Drug Products
 Intermediates and Bulk drug product produced by
same company and received at another site :
– sampling and identification limited to one container (due to
homogeneity demonstrated by process validation and by transport
validation)
– Each container perfectly sealed at receipt
 Intermediates and Bulk drug product not produced by
same company:
– Sampling depending upon parameters : criticality of product,
manufacturing in a dedicated facility, quality of sealing, experience
with sub-contractor
– Each individual container sampled and tested for identity.
Sampling and Identification
Specific Rules (10)
• Intermediates for Drug Product, Bulk Drug
Products, In-Process Materials and Drug
Products (cont.)
Intermediates and Bulk drug product not
produced by same company:
– Tests other than identity, sampling can be reduced or
performed on each container, based on justified sampling
plan
In-Process Materials and Drug Products :
– If relevant, sampling and identification performed according
to marketing autorisation requirements or site sampling
plan.
Testing Operations
Requirements (1)
• Control operations of received goods - for each
container check/perform and document
 Container status and cleanliness
 Correct storage conditions
 Damages, closures integrity, potential tempering,
homogeneity of containers
 Labelling in comparison with delivery documentation
 Number of containers
 Materials reconciliation and weight discrepancies
 1 lot per pallet.
Testing Operations
Requirements (2)
•
Analytical Methods validated
•
Results obtained recorded and checked, calculation critically examined
•
Tests performed must be recorded with following data:
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Material name, dosage form
Batch number, Manufacturer/Supplier if appropriate
References of specifications and testing procedures
Results, calculations, Supplier’s CoA
Testing date(s)
Initials of personnel who performed testing and verification
Release or rejection decision and signature of manager
Tests records and raw data archived
•
All IPC must be performed and recorded with QC approval
•
Raw materials tested in accordance with written procedures and specifications in
respect with current pharmacopeias and/or approved dossiers.
Testing Operations
Requirements (3)
• Packaging Materials
 most frequent defects and degree of criticality listed
• Tests reduced
 if certified supplier
 raw materials, intermediates, synthesis intermediates
and drug products manufactured within company
regardless of origin
• Reduced testing not allowed
 raw materials used in manufacture of parenterals products
 raw materials, intermediates, synthesis intermediates and
drug products with origin outside ICH region.
Testing Operations
Requirements (4)
• GLYCEROL and Diethyleneglycol testing sites are required to:
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Evaluate traceability of manufacturers/distributors
Define manufacturer’s location : ICH or not ICH
Declare manufacturer’s status certified or not certified
Evaluate the risk and decide on the need for DEG testing on each container
taking into account the following:
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Regular audits, no critical observation, no major related to traceability
Manufacturing & packaging conditions
Traceable distribution channels
Transportation
Good quality history
Containers sealing integrity
Containers aspect/integrity and labelling
Use for parenteral (note : If yes, then high risk)
Good service history
 Evaluate the risk of fraud
 Decide on the DEG testing.
Testing Operations
Requirements (5)
• The decision tree diagram below determines the extent of DEG
testing required:
* Composite sample size: 1 composite sample derived from no more than 5 individual samples
Glycerol
Directly
Supplied by
Manufacturer
YES
Supplied
from ICH
Location
YES
Certified
Supplier?
YES
NO
NO
NO
Risk
Assessment
HIGH
RISK
DEG Testing on Each Container
LOW
RISK
DEG
Testing on
Composite
Samples*
Thank You
Any Questions