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Reference Materials: Certificates Of Analysis März 2009 Dr .

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Reference materials: Certificatesof analysisMärz2009Dr. Christian Zeine(Basic concept byDr. Julian Schwarz)WebinarWbiS i 2013,Series2013May 23rd, 2013

Quick guide to the webinart ltools2

Agenda Definition for ‘CertificateCertificate of analysis’analysis ISO 31: Certificate Content and Structure Certificates–––––Certified reference materials (CRMs)Primary pharmaceutical reference standardsSSecondarydpharmaceuticalhti l referencefstandardst d dImpurity reference standardsResearch materials Summary3

What is a certificate (of analysis)?4

Definition ISO Guide 31:2000 defines certificates as:“Document containing all the information which isessential to the use of a certified referencematerial” Please also note:“Without the certificate, the material (the CRM),however costly its production, is valueless.”“The certificate should not be parted from the CRM.”5

Definition ISO Guide 31:2000– Defines content and structure of certificatesCurrently under revision!6

Content of a certificate Possible content acc. to ISO Guide –Name and address of certifying organisationTitle of the documentName of the documentCode and batch numberDescription – relevant informationIntended useInstructions for useHazardous situationLLevell off hhomogeneityitCertified property values and uncertaintyTraceabilityDate of certificationPeriod of validityStability, transportation and storage instructionsShelf life/expiry date .CAN be included with a CRM!Not a MUST!7

Agenda Definition for ‘CertificateCertificate of analysis’analysis ISO 31: Certificate Content and Structure Certificates–––––Certified reference materials (CRMs)Primary pharmaceutical reference standardsSSecondarydpharmaceuticalhti l referencefstandardst d dImpurity reference standardsResearch materials Summary8

CertificatesCet cates – NISTS CCRM9

CertificatesCet cates – USUSP CCRMCertified Property Value: 1.000 0.001 mg/mg10

CertificatesCet cates – USUSP CCRM Caution with uncertainty:– Very small, looks good on a first glance– However,However in this case: Uncertainty does not take into accountwater content, needs to be determined by user through KarlFischer-titration– Was raising discussions in the pharmaceutical community Smaller than comparable materials from metrology institutes(see NIST CofA) Traceability “hidden”, as with the NIST CofA as well– Both materials only traceable to NIST resp. USPin house methods– Info on traceabilitiy can be more detailed with CRMs from othersources (e.g. some ERM materials)11

USP – Will tthereUSe e be furtherut e CCRMs?s Pertaining discussion on CRMs inside USP:„„TheUSP Reference Standard projectp jteam seems to have mixedfeeling whether or not the CRM would add value to current practicesfrom Industry perspective.“(Comment at: unity aapspharmaceutica com; Feb 2009) No further CRMs for the USP-NF since more thanthree years12

Agenda Definition for ‘CertificateCertificate of analysis’analysis ISO 31: Certificate Content and Structure Certificates–––––Certified reference materials (CRMs)Primary pharmaceutical reference standardsSSecondarydpharmaceuticalhti l referencefstandardst d dImpurity reference standardsResearch materials Summary13

Primary pharmaceuticalreference standards Previous webinar: Recommended approach forprimary RS (see also EP General text 5.12.)– UsuallyUll purityit off 95%95%– Full characterization and documentation of Identityy (with(several qqualitative techniques:qNMR, MS, IR, UV/VIS,Elemental analysis, where appropriate X-ray structure analysis) Purity (with HPLC impurity profile)Identify peaks with area percentage 0.1%M b checkMaybeh k relativel ti response factorf t off impurityiit behindb hi d peakk. continued14

Primary pharmaceuticalreference standards Recommended approach for primary RS(continued)– Full characterization and documentation of Residual solvents by GC-Headspace methodsWater content by Karl-Fischer titrationLoss on drying (sum of water and residual solvents)Melting point (rough purity/identity information)Sulphated Ash (inorganic impurities) Assay, for primary RSs from purity calculation (with the results from allrelevant examinations) plus at least one additional independent method(e.g. titration)15

Certificates – Primarypharmaceutical reference standards16

Certificates – Primarypharmaceutical reference standards17

Certificates – Primarypharmaceutical reference standards18

Certificates – Primarypharmaceutical reference standards19

Certificates – Primarypharmaceutical reference standards20

Certificates – Primarypharmaceutical reference standards21

Certificates – Primarypharmaceutical reference standards22

Certificates – Primarypharmaceutical reference standards23

Certificates – Primarypharmaceutical reference standards24

Agenda Definition for ‘CertificateCertificate of analysis’analysis ISO 31: Certificate Content and Structure Certificates–––––Certified reference materials (CRMs)Primary pharmaceutical reference standardsSSecondarydpharmaceuticalhti l referencefstandardst d dImpurity reference standardsResearch materials Summary25

Secondary pharmaceuticalreference standards FDA guidance from previous webinar– . A working standard (i.e. in-house(!) or secondarystandard) is a standard that is qualified against and usedinstead of the reference standard .– Desired qualificationsf No requirement of full proof of structureProof of identity (e.g. by IR or MS) against primary RS sufficient Determination of assay of secondary RS against original primary RS26

Secondary pharmaceuticalreference standards – Certificates27

Secondary pharmaceuticalreference standards – Certificates28

Secondary pharmaceuticalreference standards – Certificates29

Agenda Definition for ‘CertificateCertificate of analysis’analysis ISO 31: Certificate Content and Structure Certificates–––––Certified reference materials (CRMs)Primary pharmaceutical reference standardsSSecondarydpharmaceuticalhti l referencefstandardst d dImpurity reference standardsResearch materials Summary30

CofA: Impurity RS31

CofA: Impurity RS32

CofA: Impurity RS33

CofA: Impurity RS34

CofA: Impurity RS35

CofA: Impurity RS36

CofA: Impurity RS37

Agenda Definition for ‘CertificateCertificate of analysis’analysis ISO 31: Certificate Content and Structure Certificates–––––Certified reference materials (CRMs)Primary pharmaceutical reference standardsSSecondarydpharmaceuticalhti l referencefstandardst d dImpurity reference standardsResearch materials Summary38

CofA: ResearchCoesea c materialate a39

CofA: ResearchCoesea c materialate a40

Agenda Definition for ‘CertificateCertificate of analysis’analysis ISO 31: Certificate Content and Structure Certificates–––––Certified reference materials (CRMs)Primary pharmaceutical reference standardsSSecondarydpharmaceuticalhti l referencefstandardst d dImpurity reference standardsResearch materials Summary41

Summary Certificates– . are important documents relevant for the correct use of acertified reference material O a standard,Ort d d or a researchh materialt i l Content of certificate– . is relevant for the corresponding use i.e. a research material with poor purity/assay information not suitablefor qquantitative ppurposesplike determination of API‘s assayy figuresgorimpurity levels For both applications high risks of overestimation of analyte42

ClosingCos g remarkse a s PDF of presentation downloadable from our websitehttp://pharma.lgcstandards.com/g– When on website, look under ‘Events’– PDF is approx. 5 MB This webinar last one of our Spring series of webinars– We will repeat it in Autumn 2013 for Europe and Asia The last webinars had more than 100 registrants, so we are quite happyabout the success– We will also present the highlights soon for our Americancustomers43

Thank you for your attention!FINLANDN. IRELANDTurkuBelfastUKIRELANDSt lmereNETHERLANDSLuckenwaldeWeselPOLANDCZECHGERMANY rcelonaSPAINUAEDubaiINDIASOUTH AMERICAAhmadabadHyderabadSao PauloBangaloreKyalamiSOUTH AFRICAQuestions?christian.zeine@lgcstandards.com44

Agenda Definition forDefinition for ‘Certificate of analysisCertificate of analysis ’ ISO 31: Certificate Content and StructureISO 31: Certificate Content and Structure Certificates – Certified reference materials (CRMs) – Primary pharmaceutical reference standards – Sd h tilf tddSecondary pharmaceu tical reference s tandards – Impurity reference standards