Single-Use Systems Shipping
40 BioPharm International eBook June 2018 www.biopharminternational.com
• Visual inspection of the emptied
bag—no leak
• Dye penetration test on emptied
bag—no leak.
Results of shipping liquid-filled
bags using ASTM D4169 cycle 12 &
14, level II after storage during 72
hours at 4 °C (39.2 °F) and at 40 °C
(104°F) are shown in
Table V.
BUYER BEWARE:
END-USERS ARE RESPONSIBLE
Shipping is a complex and chal-
lenging f unction. The end-user
should not simply rely on system
or material vendors' claims (e.g.,
of their products being "ISTA cer-
tified" or "ASTM compliant"). It is
important to understand what is
behind each vendor's claim for its
products. In addition, each claim
should be verified to ensure that it
is applicable to the intended use of
the biopharmaceutical product.
Finally, the end-user should
understand the trial conditions used
in the vendor tests and compare
them closely to conditions for their
specific application. The acceptance
criteria (for both bag and shipper),
the test protocol, and trial conditions
must also be closely considered.
Shipping va lidat ion must be
caref ully defined. This requires
close collaboration between the
end-user and vendor, with param-
eter setting linked to actual use.
Collec ting v ibration data on
real shipments will help the end
user and vendor to understand the
physical constraints of the ship-
ping mode and select the best
protocol to replicate them in labo-
ratory testing. The limits of the
system should be defined using
knowledge of the safety margin
and be tested under real packaging
and real transport conditions.
REFERENCES
1. FDA, Guidance for Industry Process
Validation: General Principles and
Practices (January 2011), fda.gov, /
www.fda.gov/downloads/drugs/
guidances/ucm070336.pdf.
2. EMA, Guideline on Process Validation
for the Manufacture of Biotechnology
derived Active Substances and Data
to be provided in the Regulatory
Submission (London, April 2014),
ema.europa.eu, www.ema.europa.
eu/docs/en_GB/document_library/
Scientific_guideline/2016/04/
WC500205447.pdf
3. Parenteral Drug Association
(PDA) "Technical Report Number 66,
Application of Single-Use Systems
to Pharmaceutical Manufacturing,"
store.pda.org, 2014,
store.pda.org/
T
ableOfContents/TR66_TOC.pdf
4. ASTM D4169: Standard Practice
for Performance testing of Shipping
Containers and Systems, 2014, astm.
org, www.astm.org/Standards/
D4169.htm
5. ISTA: Guidelines for Selecting and Using
ISTA Test Procedures and Guidelines,
General Simulation Performance
Tests, ista.org, www.ista.org/docs/
ISTA_2017_Guidelines.pdf
6. Technical Report of Flexsafe 3D Bags
Qualification for Liquid Shipping
according to ASTM D4169 – Sartorius
Stedim Biotech, Publication N°:
SPT1105-e161201, Order N°: 85037-
557-48, Ver.: 12|2016
BP
Number of shakes
perceived during real
transportation, ASTM
all levels and ISTA
Grms graph providing
the acceleration
perceived by the system
during real, ASTM and
ISTA conditions.
Number Shakes
Gms
PSD
Level
(g
2
/Hz)
Cycle #1 - 1 Rack
Cycle #2 - Rack 1
ASTM Level 1
Response ASTM D4169-09 Truck Level I
Continuous envelope 200L (all road)
Frequency (Hz)
Response ISTA-3E
Response ASTM D4169-09 Truck Level ll
Response ASTM D4169-09 Truck Level lll
PSD graph for real, ASTM all levels and ISTA
High envelope 200L (all road)
Level 1
Level ll
Level lll
lSTA
Eur 2
Eur 2
India
Real data recorded
ISTA3E - alone
ASTM Truck - alone
ASTM Truck - 1/pallet ISTA3E - 1/pallet
covering the entire
transportaion duration
India
Eur 1
ASTM Level 3
ISTA3E
ASTM Level 2 Cycle #2 - Rack 2
Figure 8. Data analysis for a 200-L shipping system.
Characterization tests
allow the definition
of which norm should
be used for the final
qualification by
assessing the most
stringent testing
program possible.