Goederenon:Nangstbon 18. juli 2018

ivdek01

Pharma Greven GmbHThomas NadlerHuttruper Heide 90D-48268 GrevenGermany

Orderleveranciersnr. 2420

Brondocument lnkooporder

Bronnr. BM 80822

Expediteur

Opslagnummer OPS-027946B

Uw referentie

Orderdatum 28-05-18

Verkoper/Inkoper Lisette Jonker- Bosma

Nr. ONT~027832B

Regelnr. 10000

Ar r. Omschrijving

500511 Nystatinum

(124990)

Aantal

96,708

Vestiging BU 01 Laboratoriumcode

Zone IKG Bewaarconditiecode

Opslaglocatie >Otte Magazijnklasse

Werkzame stof

Aard beschadiging GEEN Monstergrootte

Beoordeling verpakking GOED Monstereenheid

Gevaaraanduiding Artikelkeurgroepcode

GevaaraanduidIng 2 Verhoogd risico

Intern artikelnr. 100827-114-91

Producent lotnr. Chargenr.

401 0236

lrzorgsmaatregelen

L•abine afplakken; gekleurde grondstof !!

Autom. tekstuitbreidingsregels

6x100 BOU = 16,118 Kg / 100 BOU

ex Antibiotce S.A.

600 bou = +I- 96,708 kg

Inkoopordertextregels

BATCH: 401 0236 EXP:5-2021

1 bou = € 34,657

Would you be so kind to confirm this order by mail

IMPORTANT NOTE!!!

Aanvullende keuringsinstructies

.--4PARENTERAALL alle eenheden OPId. testen

r ( 4REG-MICRO .waarde bepaling: minimaal extra 20 gram nodig •

Abnormale toxiciteit:copy AC producentn

11:1 7 ..7t-Id.monsters:alleen IR is voldoende

Gehalte eis NLT 5000 !

Fermentatie statment aanwezig van de fabrikant Antibiotice.

14F05-1301:Composition dp,nog ter evaluatie:volgende charge weer?(getolereerde deelkeuring?)

Miv 14J09-001 "getolereerde deelkeuring" op composition.

15G23-B02:00T gehalte probleem bij Eurofins. lnitiele resultaat "invalid" verklaard.Nieuwe charge wer evalueren(controleer recovery!)

16016-B05:weer OOT gehalte probleem, risicoanalyse:acceptabel. Volgende charge weer evaluerenidem probleem 16G21-009

Fagron Services B.V.Molenwerf 131911 DB UITGEEST

GerealiseerdeEenheidsco Vervaldat Week ontvangstdatum

KG 19-07-18 29 18-07-18

PROXYLAB Fabrikantnr.

KOELTRANSP

1

Ja

30 2 )

VOLL

Nee

Vervaldatum Keurstatus

2466

Antibiotice S.A.

Valea Lupului nr.1

707410 LASI

RO

18G18-001 31-05-21 Nieuw

fDatum: i•Paraaf:

'ATTENTlE• revised text Ph. Eur. 9.0

Gehalte 'dried en 'as is' laten rapporteren door het lab en beide vermelden op ons CoA.

Datum:

Paraaf:

PRODUCT NAME

PRODUCER :

TEXT DATA ON EXTERNAL BULK CONTAINERS

SUPPLIER :

• •••:,

MANUFACTURING DATE : EXPIRY DATE :

REMARKS (E.G. STORAGE CONDITION / QUALITY STANDARD / STERILITY) :

/24 ,42v, s:

INSPECTION

SORT CONTAINER: B - i, ik,,,_ , . KG/GR/L-Tit

NUMBER OF CONTAINERS :

EACH CONTAINER SHOWS PRODUCT NAME ?

GRAMS/KGSAFFERS = • , ,' _ TOTAL,

El YES • NOEACH CONTAINER SHOWS BATCH NUMBER ? 0 YES El NO —COMPLETE BATCH 1 UNIQUE LOT NUMBER ? N. YES • NO . . ..

COMPLETE BATCH SEALED ? gi YES • NONAME EMPLOYEE + DATE : - ,

1 INSPECTION PACKAGING MATERIAL

INSPECTION PROCEDURE ACCORDING TO PROCEDURE NUMBER P41.3.5

INSPECTION LABEL

INITIALS/DATE

, ,

Appearance(form;colour;dimension)Eagreed • not agreedAbsence damages • agreed El not agreed

Closure (cap;lid) El agreed E not agreed

Number of units analyzed ... ... ... ... ........

SAMPLING

CONTROL PRODUCER LOTNR / INTERNAL LABELS FSNL_

PARAAF/DATUM: . _..

dNUMBER X UNIT FAGRON

- , X /ML/PACK.,,....-- Monster

, X1GR/ML/PACK. ' -

., 1.1-.,„rs t a t i n um

X_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ .,.)

GR/ML/PACK.

: s.,-, PH . EUR .

,INITIALS/DATE. ‘

Batch No. : Artik..1nr . : Volqnr. :18G18-B01 500511/12,1990 M01.2

RELOCATION AND RECORDING number: . , initials/date: ' '- ;:f- ,, J - ,

0 R/LTR --+ KG/GR/LTR ---›

\ ' KOGR/LTR , . ,, ,,, , , KG/GR/LTR ---›,

,: , .

KG/GR/LTR ---> -• '''' ' ,, ,, , KG/GR/LTR -->3 ,

KG/GR/LTR --› KG/GR/LTR —›

KG/GR/LTR —÷ KG/GR/LTR ---›

KG/GR/LTR --+ KG/GR/LTR —+

KG/GR/LTR, --> KG/GR/LTR ---›

INITIALS/DATE

Certificate of Analysis

Productname: Nystatinum

Number of analysis/lnspection Code MON-177381B

Batchnumber: 18G18-1301

Reference code / No.: 2466

Analysed according to: PFLEUR 9.5

KEUR-164984B

/ 401 0236

Tests Requirement Result Unit Standard remark

Appearance Yellow or slightly brown powder Conform Hygroscopic

Fermentation According to Fermentation products Ph. Eur_ Conform Data producer

Identification B Conform Conform IR-spectrum

identification E Conform Conform HPLC

Absorbance >= 0,60 0,7 305nm, 0.001%m/V HAc / MeOH

Composition Conform Conform HPLC

Nystatin A1 >= 85,0 94,6 %m/m

Any other compound <= 4,0 1,8 3/0

Loss on drying <= 5,0 4,1 % 3 h 60"C in vacuo

Sulphated ash <= 3,5 =0,1 °A

Assay Nystatin >=5000 7853 ILJ/mg Microb_ assay of antib_, dried

Abnormal toxicity Conform Conform . According to supplier

Metallic residues CHMP/ICH/353369/2013 Conform Data producer

Residual solvents CPMP/ICH/82 260/06 Conform Data producer

TSE/BSE-statement: - No contamination with TSE/BSE-risk materials Conform Data producer

Release:dr. M.J. Vincenten - van MaanenPharmacist - Qualified Person

03-09-18

Expiration: 05-2021

Conclusion: APPROVED

This document has been produced electronically from our quality system and is valid without signature.

irk '

Science and soul

CERTIFICATE OF ANALYSIS No. 3597,

Product NYSTATIN

Analysis Record: 10.05.2018 Batch No. 401 0236 Quantity:162500 g

We S.C. ANTIBIOTICE S.A., as a manufacturer of Nystatin hereby certify that this bazch has been produced by us in full compliancewith the Certificate of GMP Compliance of Manufacturer No. 043/2016/RO issued by NANWD, valid starting with 29.11.2016.This batch has been manufactured, packaged and tested in accordance with EU GMP Guideline volume 4 part II (ICHQ7).

ANALYSES PERFORMED

Appearance

Solubitity

Identification

identification A.:A 230 / A 260

A 291 / A 309

A 319 / A 305

identification, Ultraviolet Absorption: A 250 / A 279 (sh)

Identification; B, C, D, EAbsorbance at 305 nmLoss on drying: - USP 40

- BP 2017, Eur. Ph. 9'1' EditionHeavy metalsSulphated ashAssay: - USP 40

- BP 2017 / Eur. Ph. 9' Edition

Abnormal toxicitySuspendibilityCr taltinitypH (3.0 % aqueous suspension)Composition:USP 40: - Nystatin Al

- Any other individu2J componentBP 2017/Eur. Ph. 9thEdition:

- Nystatin Al- Any other compound

CONDITIONS

Mfg. Date: 05.2018Exp. Date: 05.2021

Yettow or slightly brownish powder, hygroscopic.Yellow to light tan powder, having an odor suggestive of cereals. ishygroscopic, and is affected by •long exposure to light, heat, andair.Freely solubie in dimethylformamide and in dimethylsulfoxide;sparingly to slightly soluble in methanol, in n-propyl alcohol,and in n-butyl alcohol; practically insoluble in water and inalcohol; insolubte in chloroform and in etherAbsorption rnaxima at 230 nm, 291 nm, 305 nm and 319 nm, and ashoutder at 280 nm.

0.83 to 1.250.61 to 0.730.83 to 0.960.90 to 1.25in conformity with BP 2017 and Eur, Ph. 9'EditionNot less than 0.60

Not more than 5.0 %Not n-iore than 20 ppmNot rnore than 3.5 %Not less than 4400 USP Nystatin Units/mg, or, where intendedfor use in the extemporaneous preparation of oral suspensions,not less than 5000 USP Nystatin Units/mg 6205

RESULTS

yellow powder,hygroscopic; having anodor suggestiveof cereals

corresponds

corresponds

1.010.670.921.03corresponds0.81481.83.6< 200.6

Minimum 4400 1U/ mg (dried substance) and minimum5000 lUlrng (dded substance) if intended for orat administration 1 6437In conformity with BP 2017 and Eur. Ph. 9'Edition (2.6.9.) I corresponds

92.16Not less than 90.0 %It reveals birefringenceBetween 6.0 and 8.0

Minimurn 85.0 %I_Maximum 4.0 %

Minimum 85.0 %Maximum 4.0 %

corresponds7.9

90,431.52

91.111.52

Microbiological quality- TAMC, CFU/g

TYMC, CFU /gSpecified micro-organisms:

Not more than 10iNot more than 102

- Bile-tolerant gram-negative bacteria/ g Absent- Escherichia coli/g Absent- salmonella/ g Absent- Pseudomonas aeruginosal Absent- Staphylococcus aureus/g Absent

Residual sotvents: - Methanol Not n-iore than 0.3 %- Acetone Not more than 0.5 %

30<

absentabsentabsentabsentabsent0.010.20

Particle size,45 pm % As per ctient requirements

•

'This anaLysis s carried out periodically (1 batch for every 4 batches manufactured) 08,06,2,01895.29

STORAGE: Store in an airtight container, protected from tight at a temperature of 2°C to 8°C.pmpties with ttle--peciijcation of the BP 2017, Eur. Ph. 9t1] Edition and USP 40.

, C ,

Quality of,Quatity Control DepartmentMa rylagOY Ph-hico-Chernical Analyses

Giariiri Bu-Aileac• •

\ Wine! Miftode

.•1,, • „ ,r, „7.r, ),(-), . >-- \\D\ ,\-/-• ,

, I 1i

\ l . V a isp,2 L\e‘i 12;155i 7 0 74-la a rti I ar..0

+40 232 209 000+40 372 065 000~40 232 209 633

Head of Quality Control DepartmentMicrobiologiical and Pharmacodynarnical Analyses

Carmen Ruxandari

••• (.„ s•-•••••.,

office@antibioticelo• • ,

Product sample name Nystatinum; 500511Client-code 129Projt-c:-..ocie 0109641Batch numper 18G18-BOI

Ph. Eur. 01/7017:0517Version 1

estnb2,racters

ickritity B

Identity E.

Absorbance

Composition

Test methodMeafilid.MINIMMMIPMEWINIIMIM

Appearance

22.24

2.229

2.225

-9

Loss on dryin2 2.2„32.

sulfatt--,d

Assay

eecilication

Y e i i e w

te f"_,..,rence

Comlpared refi-Terice

powder

Ce Anaïysis

ResultÝe po\vder

CompliesLYP'.s

Conform (5x) Y '..;---. _-,

rinng,---rn,.._, ... , ,,,, , I ,.,.1 Yes

r ‘ --7,-,,..., . 1, Yes

NysLalin. Al: 85 .',r.",1 / 0 94.6 % Yesether ,oempound: 4 . o 1.8 % Yes

< 0/0 4.1 % v es

.5 % < 0.1 % Yes

7851, nijrng Yes3000 IU/mg

QA-staternent:This sradv met the criteria ft)r a valid test and. was performed in compliance ‘vith the Good control Laboratory Practiceas defined in the Guide to Good ManufacturinE Practice for Medicinal Products in the European Community.The r orrc=d ccssdts adeccuatelyr-fle-7,t thc raw data of t.h. study.

Conciusion-_The results do comply with the spezifications

This certificate is approved. by Manag r OA on 29 Auzust 201

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