005-Sampling-Identification-and-Testing1.pptx

8/14/2019 005-Sampling-Identification-and-Testing1.pptx

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Sampling

,

Identification and

Testing

(S.I.T.)


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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 withregulatory and Safety requirements


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Scope

Applies to all manufacturing sites

Applies to all sub-contractors

Applies to all Affiliates

Applies to Raw-materials, isolatedintermediates, APIs, excipients, medicaldevices, packaging materials, inprocessmaterials, bulk and packaged drug products

Does not apply to environmental samples andReference and Retention samples


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Reference Documents

ICH Q7 : Good Manufacturing Practice for ActivePharmaceutical Ingredients

EU GMP Part I Chapter 6 : Quality Control

EU GMP Annex 8 : Sampling of Starting and PackagingMaterials

US CFR : Subpart E-Control of Components and Drug ProductContainers and Closures : 211.80 : General requirements ;

211.84 Testing and approval or rejection of components,drug product containers, and closures ; 211.110 Samplingand testing of in-process materials and drug products,Subpart G-Packaging and Labelling Control : 211.122Materials examination and usage criteria


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Sampling General

Requirements (1)

Composite sample : justify the number of individual samples

Sampling operations recorded with specific items. Records availablefor 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.


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Sampling General

Requirements (2)

Sampling personnel initially trained andretrained on regular basis

Only qualified and authorised personnelcan sample

Any anomaly/irregularity during samplinghas to be notified and recorded.


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Sampling GeneralRequirements (3)

Sampling areas designed to protect product fromenvironment and cross contamination and protectpersonnel from the product

Appropriate areas in case of high potency, sensitizingmaterial, antibiotic, etc

Gowning instructions and personnel protective

equipment must be available

Material Safety Data Sheet (MSDS) available beforesampling.


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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.


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Containers in which samples areplaced must be clean and clearly

labelled

Sampled samples must not be

returned to the batch


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Identification General

Requirements

Identification method : described in thecurrent locally applicable Pharmacopoeia(e.g. USP, EP, JP) or approved Regulatory

File

For material identification, a NIR validated

method can be applied even if notregistered in the Regulatory File; forcountries where the practice is allowed.


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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 onsampling delegation

Place(s) where samples need to be taken oridentification : detailed in SOP

Samplingmust not be the cause of contaminationor cross-contamination

Cleaning operation in case of outer dirty container.


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Operations (3)

Each batch of incoming material forAPI product : subject for identity,

except in case of risk for health andsafety

Such kind of materials to be listedCoA obtained from supplier for each

batch.


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Operations (4)

Sampling plans or procedures minimuminformation

Version, approvers name, date of approvalName of material, amount to be sampled

Sample packaging and labelling, storageconditions

Sampling equipment, safety/handlingprecautions : sterile, noxious product,pyrogens.


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Operations (5)

Sampling plans or procedures minimuminformation (cont.)

Number of containers to be sampled

Number of samples to be taken

Sampling/Identification location within thecontainer :

Supplier pre-samples or identification locationwhen direct NIR identification

Measurement units : quantity (g, ml, mg,)


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Sampling and IdentificationOperations (6)

Sampling plans or procedures minimuminformation (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 ofsampling equipment.


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Sampling and IdentificationSpecific Rules (1)

Materials used for Manufacture of APIs:StartingMaterials, RawMaterialsandSynthesisIntermediates

Manufacturers of SM, RM, SImust be identified

If Manufacturer is certified, reduced testing isallowed

Reduced testing on hold in case of investigationand return to reduced testing only if supported byconclusion of investigation and approval fromQuality operations.


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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 eachcontainer)

* ICH = European Union, North America, Japan + EFTA:Switzerland, Norway, Iceland and Liechtenstein.


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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).


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Materials used for Manufacture of APIs(cont.)Intermediates Synthesisexternal 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).


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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.


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APIs and ExcipientsAPI not produced at company manufacturing

site and excipients with origin from the ICH

Region: sampling and identification dependupon 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 whichthey are used.


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APIs and Excipients (cont.)

API or excipient coming from single product manufactureror plant

API, excipient coming directly from manufacturer in sealedcontainers and manufacturer regularly audited

In such case : Sampling and Identification performedon a reduced number of containers according to

justified sampling plan

If previous conditions not fulfilled : identification oneach container

APIs and Excipients used for Parenterals : EACHcontainer must be identified.


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Packaging MaterialsSampling plan based on quantity received and

required, nature and criticality of material(geographical origin, primary packaging, printed

packaging), production methods, qualityassurance of manufacturerSampling place/location is dependant on supplier

status :Approved or certified supplier > sampling possible by

supplier : written sampling delegation and justifiedsampling plan are mandatory Supplier with no quality agreement > sampling by

own company manufacturing site : justified samplingplan.


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Intermediates for Drug Product, Bulk DrugProducts, 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 transportvalidation)

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, experiencewith sub-contractor

Each individual container sampled and tested for identity.


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Intermediates for Drug Product, Bulk DrugProducts, In-Process Materials and DrugProducts (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 samplingplan

In-Process Materials and Drug Products : If relevant, sampling and identification performed according

to marketing autorisation requirements or site samplingplan.


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Testing OperationsRequirements (1)

Control operations of received goods - for eachcontainer 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.


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Analytical Methods validated

Results obtained recorded and checked, calculation critically examined

Tests 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, Suppliers 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 inrespect with current pharmacopeias and/or approved dossiers.


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Packaging Materialsmost frequent defects and degree of criticality listed

Tests reduced

if certified supplier raw materials, intermediates, synthesis intermediates

and drug products manufactured within companyregardless of origin

Reduced testing not allowed raw materials used in manufacture of parenterals products

raw materials, intermediates, synthesis intermediates anddrug products with origin outside ICH region.


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GLYCEROL and Diethyleneglycol testing sites are required to:

Evaluate traceability of manufacturers/distributors

Define manufacturers location : ICH or not ICH

Declare manufacturers status certified or not certified

Evaluate the risk and decide on the need for DEG testing on each containertaking 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.


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The decision tree diagram below determines the extent of DEGtesting required:* Composite sample size: 1 composite sample derived from no more than 5 individual samples

GlycerolDirectly

Supplied byManufacturer

Suppliedfrom ICHLocation

CertifiedSupplier?

RiskAssessment

DEGTesting onCompositeSamples*

DEG Testing on Each Container

YES YESYES

NONO

NO

HIGH

RISK

LOW

RISK


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Thank You

Any Questions