Changenotification_AB@sartorius.com
May 25th, 2016
Sartorius Stedim Switzerland AG
Ringstrasse 24a
8317 Tagelswangen
T:+41 52 354 36 36
Sartorius Stedim Biotech GmbH.
August-Spindler-Straβe 11
37079 Göttingen, Germany
t:+49.(0)551.3080
f:+49.(0)551.308.3289
www.sartorius-stedim.com
Sartorius Stedim Biotech GmbH, 37079 Goettingen Germany
Notification letter
ECN 40216: Modification of the Certificate of Compliance for Flexsafe® RM Bags and
implementation of Quarterly Dose Audit (ECN40316)
Registered Office Goettingen
Local Court of Registration:
Amtsgericht Goettingen
HRB No. 200266
Dear Valued Customer,
Introduction
As an international leading supplier of process technologies to the bio-pharmaceutical
industry, Sartorius Stedim Biotech is committed to a continuous improvement of its products
and services in order to serve our customers in an optimal way.
This notification letter is intended to inform you about modifications in the Certificate of
Compliance (CoC) for Flexsafe® RM Bags including the implementation of the Quarterly Dose
Audit.
Change description
Certificate Modification
In order to harmonize the documentation of Sartorius products, the Certificate of Compliance
(CoC) for all Flexsafe® RM bags will be renamed to Certificate of Release (CoR) and updated to
add the following claims:
Table 1: Comparison current Certificate of Compliance to future Certificate of Release
Attributes
Current
After Changer
Description
Physicochemical Test
TSE/BSE free Status
Cell Growth Status
Visual
Inspection
Statement
Bioburden
Certificate of Compliance (CoC)
n.a.
n.a.
n.a.
Yes
Certificate of Release (CoR)
yes
yes
yes
Included in Batch Testing
Batch Testing
Addresses
All bag types and sizes were
tested over a period of 2 years
Leak Testing
Company headquarter and
manufacturing site
* See below
Change ECN 40216
Page 1 of 6
Only 20L bags (most sold) and
200L bags (worst case design)
are being tested*
Amended wording to Pressure
Hold Test
Manufacturing site
Implementation of Dose Audits
The sterilization process is validated based on ISO 11137.
In the past, sterility of Flexsafe® RM Bags was guaranteed by parametric release testing.
Beginning of 2016, Dose Audits have been implemented for Flexsafe® RM Bags. Dose Audits
are performed with 20L Flexsafe® RM Bags (most sold bag size).
Sterility
Current situation
After Change
Parametric Release*
Dose Audit*
*See definitions below
Parametric Release:
A system of release that gives the assurance that the product is of the intended quality
based on information collected during the manufacturing process and on the compliance
with
specific
GMP
requirements
related
to
Parametric
Release.
(general definition according to PIC/S)
According to the PDA (Parenteral Drug Association) following aspects need to be respected
and qualified:
- Sterility Assurance Level (SAL) >10-6
- Definition of Critical Process Parameters
- Sterilization
- (Bio-) Indicators
- Bioburden (before sterilization)
- Process Validation
- Product Release
- Minimal Absorption Dose of 25kGy
The European Pharmacopoeia states that the Parametric Release is of higher safety than
the testing for Sterility.
Dose Audit:
The dose audit is a test method to check / monitor the sterilization dose. Dose audits
confirm that the previously determined verification dose still achieves sterility (an SAL of
10-6).
Bioburden Results:
The amount of bioburden load during the last 2 years has been determined with different bag
types (basic, optical, perfusion) and bag sizes (2L, 10L, 20L, 50L, 200L). The different bag sizes
remain in the same range for bioburden loads. As het Flexsafe® RM 20L basic is the most sold
bag, itwill be used as representative, therefore is being applied for Dose Audits.
Bioburden testing will be executed with Flexsafe® RM 200L basic or optical bags (worst case
design as 200L bags are the largest available size).
Bioburden results from Dose Audits (Flexsafe® RM 20L basic) and bioburden testing (Flexsafe®
RM 200L) will continuously be compared.
This change has no impact on the fit, form or functionality of the product.
Change ECN 40216
Page 2 of 6
Affected Product Lines
Our records indicate that all Flexsafe® RM Bags, made by Sartorius Stedim Biotech for your
company are impacted by this change.
The impacted part numbers are listed in appendix 1.
Change Implementation
This change is controlled internally and is governed by our change management procedures.
Dose Audits are being executed since beginning of 2016.
The new Certificate of Release will be available in Q3 2016.
We thank you for your trust and your continuous use of Sartorius Stedim Biotech products.
Sincerely,
Stefan Schlack
Senior VP Global Marketing BPS
Sartorius Stedim Biotech GmbH
Klaus Walter
Vice President Global Quality
Sartorius Stedim Biotech GmbH
Change ECN 40216
Page 3 of 6
Appendix 1 : List of impacted products
Flexsafe® RM Basic
Flexsafe® RM Optical
Flexsafe® RM Perfusion
Flexsafe® RM ViaMass
DFB001L
DFB002L
DFO002L
DFO002L----01SC
DFP200L--AT
DFP002L--AT
DFB010L----VM
DFB020L----VM
DFB002L----01SC
DFB010L
DFB010L----01SC
DFB020L
DFB020L----01SC
DFB050L
DFB050L----01SC
DFO010L
DFO010L----01SC
DFO010L----VM
DFO020L
DFO020L----01SC
DFO050L
DFO050L----01SC
DFP002L--SM
DFP010L--AT
DFP010L--ATVM
DFP010L--SM
DFP020L--AT
DFP020L--SM
DFP050L--AT
DFB050L----VM
DFO010L----VM
DFO020L----VM
DFO050L----VM
DFP010L--ATVM
DFP010--SMVM
DFP020L—ATVM
DFB050L----01US
DFB100L
DFB200L
DFC200L----03NO
DFO100L
DFO200L
DFP050L--SM
DFP100L--AT
DFP200L--AT
DFP020L--SMVM
DFP050L—ATVM
DFP050L--SMVM
DFP100L—ATVM
DFP200L--ATVM
Flexsafe® RM customized
DFC002L----01LA
DFC002L----01PT
DFC050L----01MK
DFC050L----01PT
DFC002L----01SE
DFC010L----01GT
DFC020L----01LO
DFC020L----01ME
DFC020L----01MK
DFC020L----01NO
DFC020L----01PT
DFC050L----01SE
DFC050L----01WE
DFC050L----02BI
DFC050L----02CE
DFC050L----02CR
DFC050L----02GK
DFC050L----02WE
DFC020L----01SE
DFC020L----01WE
DFC020L----02NO
DFC020L----02WE
DFC050L----01BI
DFC050L----01CR
DFC050L----01GK
DFC050L----01GT
DFC050L----01ME
DFC050L----04CR
DFC100L----01GA
DFC100L----01NO
DFC100L----02NO
DFC100L----03NO
DFC200L----01GK
DFC200L----01NO
DFC200L----02NO
DFC200L----04NO
Change ECN 40216
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Appendix 2: Certificates
Current Certificate of Compliance (Example):
Change ECN 40216
Page 5 of 6
New Certificate of Release (Example):
Change ECN 40216
Page 6 of 6