Sampling - PowerPoint Presentation

Slide1

Sampling, Identification and Testing(S.I.T.) Slide2

IntroductionDefine 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 requirementsSlide3

ScopeApplies to all manufacturing sitesApplies 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 samplesSlide4

Reference DocumentsICH Q7 : Good Manufacturing Practice for Active Pharmaceutical IngredientsEU 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 criteriaSlide5

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.Slide6

Sampling General Requirements (2)Sampling personnel initially trained and retrained on regular basisOnly qualified and authorised personnel can sample

Any anomaly/irregularity during sampling has to be notified and recorded.Slide7

Sampling General Requirements (3)Sampling areas designed to protect product from environment and cross contamination and protect personnel from the productAppropriate areas in case of high potency, sensitizing material, antibiotic, etc

Gowning instructions and personnel protective equipment must be available

Material Safety Data Sheet (MSDS) available before sampling.Slide8

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.Slide9

Sampling General Requirements (5)

Containers in which samples are placed must be clean and clearly labelled

Sampled samples must

not

be returned to the batchSlide10

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.Slide11

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.Slide12

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.Slide13

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.Slide14

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

.Slide15

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,…)Slide16

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.Slide17

Sampling and Identification Specific Rules (1)Materials used for Manufacture of APIs: Starting

Materials

,

R

aw

M

aterials

and

S

ynthesis

I

ntermediates

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.Slide18

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 :

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.Slide19

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).Slide20

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).Slide21

Sampling and Identification Specific Rules (5)APIs and ExcipientsAPI 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.Slide22

Sampling and Identification Specific Rules (6)APIs and ExcipientsAPI 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.Slide23

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.Slide24

Sampling and Identification Specific Rules (8)Packaging MaterialsSampling plan based on quantity received and required, nature and criticality of material (geographical origin, primary packaging, printed packaging), production methods, quality assurance of manufacturerSampling 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.Slide25

Sampling and Identification Specific Rules (9)Intermediates for Drug Product, Bulk Drug Products, In-Process Materials and Drug ProductsIntermediates 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.Slide26

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.Slide27

Testing Operations Requirements (1)Control operations of received goods - for each container check/perform and documentContainer status and cleanliness

Correct storage conditionsDamages, 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.Slide28

Testing Operations Requirements (2)Analytical Methods validatedResults obtained recorded and checked, calculation critically examinedTests performed must be recorded with following data:

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.Slide29

Testing Operations Requirements (3)Packaging Materialsmost frequent defects and degree of criticality listedTests reduced

if certified supplierraw 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.Slide30

Testing Operations Requirements (4)GLYCEROL and Diethyleneglycol testing sites are required to:

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:

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.Slide31

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

Supplied from ICH Location

Certified Supplier?

Risk Assessment

DEG Testing on Composite Samples*

DEG Testing on Each Container

YES

YES

YES

NO

NO

NO

HIGH RISK

LOW RISKSlide32

Thank YouAny Questions