This document summarizes the key points of a presentation on sterilization requirements and strategies for compliance. The presentation covered general sterilization requirements, radiation sterilization and its impacts, and EO sterilization and its impacts. It discussed the main changes in ISO 11137 for radiation sterilization and ISO 11135 for EO sterilization, and the impacts these standards have on sterilization contractors and medical device manufacturers.
Provide recommendations and background information concerning computerised systems
Information will be of assistance to inspectors for training purposes and during the inspection
Where automated systems and electronic records are used in warehouses and similar establishments where GDP requirements are applicable, controls and disciplines outlined in this document, or a best practice alternatives are expected to be in place.
Vertically integrated companies (R&D, manufacturing and distribution) will already apply such controls and compliance measures.
International regulatory agencies have collaborated to produce this guidance.
Intended as a reference for regulated users, including their suppliers, in addition to regulatory inspectors and investigators.
Provides a logical explanation of the basic requirements for the implementation, validation and operation of computerised systems.
May be adapted to identify the criteria for a regulated user, or a regulatory agency, in an inspection of GxP computer systems.
National legislation should to be referred to when determining the extent to which the provisions laid down in this document may be applicable.
This presentation gives a summary of this guidance.
WHO Good Manufacturing Practice Requirements
Good Manufacturing Practice is the part of quality assurance that ensures that products are consistently manufactured and controlled to the quality standards appropriate to their intended use.
Provide recommendations and background information concerning computerised systems
Information will be of assistance to inspectors for training purposes and during the inspection
Where automated systems and electronic records are used in warehouses and similar establishments where GDP requirements are applicable, controls and disciplines outlined in this document, or a best practice alternatives are expected to be in place.
Vertically integrated companies (R&D, manufacturing and distribution) will already apply such controls and compliance measures.
International regulatory agencies have collaborated to produce this guidance.
Intended as a reference for regulated users, including their suppliers, in addition to regulatory inspectors and investigators.
Provides a logical explanation of the basic requirements for the implementation, validation and operation of computerised systems.
May be adapted to identify the criteria for a regulated user, or a regulatory agency, in an inspection of GxP computer systems.
National legislation should to be referred to when determining the extent to which the provisions laid down in this document may be applicable.
This presentation gives a summary of this guidance.
WHO Good Manufacturing Practice Requirements
Good Manufacturing Practice is the part of quality assurance that ensures that products are consistently manufactured and controlled to the quality standards appropriate to their intended use.
A brief presentation on the current good manufacturing practices employed in the manufacture of pharmaceuticals in the US.
Comprises of all aspects of good manufacturing practices
Qualification of Dissolution Test Apparatus and Validation of Utility System this presentation will help to enhance your knowledge in validation and qualification area.
A brief presentation on the current good manufacturing practices employed in the manufacture of pharmaceuticals in the US.
Comprises of all aspects of good manufacturing practices
Qualification of Dissolution Test Apparatus and Validation of Utility System this presentation will help to enhance your knowledge in validation and qualification area.
Validation Of Radiation Sterilization Dose For Proteases Immobilized On Aldeh...iosrphr_editor
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
Sterilization Validation for Medical DevicesDocKetchum
Every medical device produced must be sterilized before being shipped to hospitals, doctors’ offices, and other medical locations.
Random samples of these devices must then be tested to be sure the sterilization kills disease causing microbes including bacteria, fungus, and spores in every device.
These are some of the most common ways that sterilization validation is performed.
ISO 10993-6: Biological Evaluation of Medical Devices - Tests for local effec...NAMSA
ISO 10993-6 helps identify appropriate implantation sites, how long implants should remain in place during testing, implantation methods and biological responses at the macro- and microscopic level.
1. AGES-BfR-Forum "Nahrungsergänzungsmittel: Nutzen und Risiko", 30. Mai 2012
Anlässlich des 10-jährigen Bestehens der AGES und der 5-jährigen Kooperation mit dem deutschen Bundesinstitut für Risikobewertung (BfR) fand eine Spezialveranstaltung zum Thema Nahrungsergänzungsmittel (NEM) statt, bei der die bisher umfassendste Erhebung zum Thema im deutschen Sprachraum exklusiv präsentiert wurde. Risiken und Nutzen von NEM wurden aus Sicht der Lebensmittel- & Arzneimittelsicherheit, Risikobewertung & Risikokommunikation, die den Verbraucherinteressen gerecht wird, betrachtet. Die ExpertInnen von AGES und BfR diskutierten mit rund 120 Gästen aus Wissenschaft & Forschung, Wirtschaft & Industrie, Ärzteschaft & Apotheken sowie Behörden und Medien.
Dokumentation der Fachtagung mit Präsentationen:
http://www.ages.at/ages/ages-akademie/stakeholderveranstaltungen/wien-nahrungsergaenzungsmittel/
Disclaimer:
Die Inhalte dieses Vortrages sind die Privatmeinung der Vortragenden und sind keine offizielle Aussagen der AGES MEA bzw. des Bundesamtes für Sicherheit im Gesundheitswesen
Understanding How Bioburden and Sterilization Affect Medical DevicesPacific BioLabs
This presentation covers:
Bioburden- what is it and how it can affect a device development program and sterilization validation program.
Sterilization: methods and the bioburden-sterilization connection.
Benefits of minimizing the sterilization dose for your device.
Importance of monitoring bioburden.
Case study: sterilization failure and tracking down root cause.
How to monitor and reduce bioburden levels.
Bioburden is the measure of living microbes on a surface that has not yet been sterilized. It is usually tested for on medical devices and other products that come in contact with patients during care at a medical facility.
Cleaning, Disinfection, and Sterilization Validations of Reusable Medical Dev...Pacific BioLabs
This presentation provides important details on how to save time and money in the process of reusable medical device design. The main focus is on how device material choice and design affects the cleaning and disinfection process, and what considerations design engineers need to make when creating reusable medical devices.
Lernen Sie, wie Sie Schritt für Schritt zum CE-Zeichen für Ihr Medizinprodukt kommen und dass es kein CE-Audit und keine Zulassung gibt.
Die Präsentation beschreibt den Weg von der Zweckbestimmung, über die Wahl des Konformitätsbewertungsverfahrens, die Klassifzierung, den Nachweis der grundlegenden Anforderungen mit harmonisierten Normen über die Konformitätserklärung und das Anbringen des CE-Zeichens bis zur Post-Market-Phase.
From May 2017, NQA is able to carry out transition audits to the revised medical device standard as a part of your next assessment.
Every organization which wishes to maintain certification to this standard must undergo a transition audit before March 2019 including resolution of any/all non-conformances raised during
the transition audit. To help get you started, the helpful annexes in the new standard have been expanded to give you more detail on where to focus your attention to understand and implement the
required changes. The work required will of course depend on your products/services and the nonapplicable cause specific to your QMS.
This webinar goes over the major changes of the new ISO 13485:2016 standard, including the upgrade process. Program Manager Rick Burgess presented and responded to questions live on the webinar.
Single use technology: a regulatory perspectiveTGA Australia
An overview of the regulation of single use technology including Good Manufacturing Practice requirements and the types of deficiencies and issues observed at inspections
This presentation will provide elements for creating a comprehensive passivation validation package and understanding the different options to passivate.
Optimizing the Sterilization Process in compliance with standardsRushyanthKR1
Sterilization optimization involves improving the process of sterilization to ensure it is efficient, effective, and safe123. Sterilization itself is a process that destroys or eliminates all forms of microbial life and is carried out in healthcare facilities by physical or chemical methods.
U.S.F.D.A. was the pioneer in the concept of process validation.
Validation had proven to be an important tool for quality management of pharmaceutical according to ISO 9000:2000.
U.S.F.D.A. was the pioneer in the concept of process validation.
Validation had proven to be an important tool for quality management of pharmaceutical according to ISO 9000:2000.
This document has been prepared to provide a summary on the changes between ISO 13485:2003 and ISO 13485:2016. The documents contains the following:
a. Benefits of the new version of the standard.
b. Few key definitions
c. Mapping between the versions as per ISO.org.
d. Summary of key changes between the versions of the standard
How to Prepare for the New EU Medical Device Regulations (MDR)Greenlight Guru
The new MDR is expected to be formally published in late 2016 or early 2017, and there will be a three-year transition period to be compliant.
Many forward thinking medical device companies are already developing their plans for compliance now to gain strategic advantages over their competitors.
In this presentation you will learn:
-Why the European regulations are changing
-An overview of the text being voted on
-What does the new regulation mean for manufactures
-Examine the risk based approach to classification
-Strategy for technical documentation preparation
-Changes to clinical evidence for devices
-Post market surveillance and vigilance for medical devices
-What you can do to start preparing now
-What are all the significant changes
You can watch the recording of this presentation here: https://www.greenlight.guru/webinar/eu-medical-device-regulations-mdr
2. Topics
• General Requirements
• Radiation Sterilization
– Impact to Subcontractors
– Impact to Manufacturers
• EO Sterilization
– Impact to Subcontractors
– Impact to Manufacturers
• Summary
3. Introduction
• Presentation covers • Presentation does not
– Gap Analysis between cover
current version and – All differences – only
previous version of the most significant
standards – The steps for
– Compliance sterilization or
information validation of
– References sterilization processes
Copyright
laws
prevent
MedTech
Review
and
MEDTEC
China
Conferences
from
providing
copies
of
standards
to
conference
par;cipants.
5. General Requirements
• Aligned somewhat with the requirements
of ISO 13485:2003
– Document and Record Retention
• Procedures for development, validation, routine
control and release (ISO 13485:2003, Clause 4)
– Management Responsibility
• Authority, responsibility, including contractors (ISO
13485:2003, Clause 5)
6. General Requirements
– Product Realization
• Procedures for purchasing, identification and
traceability, and calibration are required (ISO
13485:2003, Clause 7)
– Measurement and Improvement
• Controls for non-conforming material and
corrective actions (ISO 13485:2003, Clause 8)
7. Sterilization by Radiation
• ISO 11137:2006
– Part 1
• Requirements for development, validation, and
routine control of a sterilization process for medical
devices (approved 15 April 2006)
– Part 2
• Establishing the sterilization dose (approved 15
April 2006)
– Part 3
• Guidance on dosimetric aspects (approved 15 April
2006)
8. Sterilization by Radiation
• ISO 11137:2006 is now mandatory and
fully implemented in the EU (as of April
2009)
– The following standards are now OBSOLETE
• EN 552
• ISO 11137:1995
• AAMI TIR 27:2001
• ISO/TIR 13409:1996
• TIR 15844:1998
9. Certification
• Contract sterilization companies who carry
out irradiation processing can include
EN ISO 11137-1:2006 within the scope of
their ISO 13485 registration.
• EN ISO 11137 Parts 2 and 3 cannot be
included.
10. ISO 11137:2006 – Main Changes
• Clause 3 – Definitions
– Processing category
• Group of different products that can be sterilized
together, based on
– Composition
– Density
– Dose requirements
11. ISO 11137:2006 – Main Changes
– Product family
• Group of different products that can be given the
same sterilization dose based on the nature of the
– Raw materials
– Components
– Manufacturing processes
– Equipment
– Environment
– Location
It
would
be
helpful
for
the
manufacturer
to
develop
a
process
map
or
decision
tree
to
consistently
address
the
requirements
and
document
the
ra8onale
for
groupings.
12. ISO 11137:2006 – Main Changes
• Clause 5 – Sterilizing Agent
Characterization
– New requirements for environmental
considerations
Are
there
environmental
impacts
such
as
discharges
into
the
air
or
water
that
may
adversely
impact
the
environment?
How
are
these
controlled?
13. ISO 11137:2006 – Main Changes
• Clause 6 – Process and Equipment
Characterization
– Requirements have been expanded –
irradiator and its method of operation shall be
specified.
Can
be
addressed
under
vendor
contract
/
purchasing
control
/
internal
control
procedures
such
as
process
control,
equipment
valida8on
and
equipment
change
control.
14. ISO 11137:2006 – Main Changes
• Clause 7 – Product Definition
– New requirements emphasize control of product
AND packaging AND control of bioburden
– New requirements – defining product families in
establishing dose and dose audit based on
• Bioburden
• Representative product
• Master product
• Equivalent product
• Simulated product
Product
families
must
be
established
with
documented
criteria,
maintained
(i.e.,
reviewed)
and
risks
in
using
product
families
must
be
addressed
15. ISO 11137:2006 – Main Changes
• Clause 8 – Process Definitions
– Incorporates Method 1, Method 2 and Vdmax
Method (15 and 25)
– New Means for dose transference
SOPs
need
to
include
requirements
for
establishment
of
max
dose
and
steriliza8on
dose;
manufacturers
need
to
document
the
appropriate
method
used
and
process
for
valida8on.
16. ISO 11137:2006 – Main Changes
• Clause 9 – Validation
– IQ / OQ / PQ requirements have been
expanded
– Dose mapping (both container and product)
– Process specifications established directly
from validation; requirements detailed
– Defined sample sizes required
17. ISO 11137:2006 – Main Changes
• Clause 12 – Maintaining process
effectiveness
– Standard defines a more flexible approach for
maintaining effectiveness of process
• Bioburden specifications (number and type)
– 1 month, 3 month, each batch
• Dose audits – frequency; rationale
• Failure Investigation and actions
18. Impact to Sterilization Contractor
• Requirements for environmental
considerations
“The
poten8al
effect
on
the
environment
of
the
opera8on
of
the
radia8on
steriliza8on
process
shall
be
assessed
and
measures
to
protect
the
environment
shall
be
iden8fied.
This
assessment,
including
poten8al
impact
(if
any)
shall
be
documented
and
measures
for
control
(if
iden8fied),
shall
be
specified
and
implemented.
19. Impact to Sterilization Contractor
• Think about all of the possible environmental
impacts that might occur in the event of a
failure of the radiation control system.
– Maintenance of the source material and its
storage (pool water levels, alarms, testing)
– Control of access to the cell
– Care and maintenance of the source racks/
carriers
– Control room alarms These
items
can
be
reviewed
and
covered
during
preven8ve
– Auditing for safety maintenance
ac8vi8es
and
supplier
audits.
20. Impact to Sterilization Contractor
• Process interruptions
– What happens when there is an interruption in the
exposure?
– What is the impact of stopping and restarting the
cycle and the timing? How are under-dosing and
overdosing prevented?
– What is the additional exposure to the product
resulting from the travel time of the source material
rising up and lowering down, possibly multiple times?
– Is there a risk of product or package degradation
caused by the changes in temperature while in the
cell due to the interruptions?
21. Impact to Sterilization Contractor
• Partial containers – dose mapping
“If
par8ally-‐filled
irradia8on
containers
are
to
be
used,
the
effect
of
par8al
filling
on
dose
distribu8on
within
irradia8on
containers
or
in
other
irradia8on
containers
present,
shall
be
determined
and
recorded.
When
a
carrier
is
not
completely
full,
the
density
of
the
load
becomes
inconsistent,
and
therefore
the
delivered
dose
can
vary.
By
properly
mapping
par8al
carrier
loads,
equivalent
dose
distribu8on
can
be
assured.”
22. Impact to Sterilization Contractor
• Procedures for review and product release
• 11.1 – Any specific periodic tests, calibrations,
maintenance tasks and necessary re-qualifications
need to be documented.
• 11.2 – Procedures for review of records and
product release from sterilization need to be
written.
When
a
steriliza8on
process
is
found
to
not
meet
specifica8ons,
taking
into
account
the
uncertainty
of
the
measurement
system(s),
then
the
product
shall
be
handled
as
nonconforming.
23. Impact to Sterilization Contractor
• Each of the previous items must be
audited in addition to
– Personnel training
– Dosimetery
– Radiation cell refueling
24. Impact to Manufacturer
• VDMax 25
– Bioburden testing unchanged (<1000 CFU per
device); verification does set to 10-1; sterility
testing on 10 units
• VDMax 15
– Bioburden control limits extremely low (<1.5
CFU per device)
• ISO 15843 – Dose audit frequency
– Quarterly -> Semi-annually -> Annually
25. Regarding China
• GB18280-2007 - Sterilization of health
care products requirements for
validation and routine control of
radiation sterilization
– idt ISO 11137:2006
26. Sterilization by EO
• ISO 11135-1:2007
– Requirements for development, validation,
and routine control of a sterilization process
for medical devices (approved 01 May 2007)
• ISO 11135-2:2008
– Guidance on the application of ISO
11135-1:2007
27. Sterilization by EO
• ISO 11135 is now mandatory and fully
implemented in the EU (as of May 2010)
– The following standards are now OBSOLETE
• EN 550:1994
• ISO 11135:1994
28. Certification
• Contract sterilization companies who carry
out EO processing can include
EN ISO 11135-1:2007 within the scope of
their ISO 13485 registration.
• EN ISO 11135-2:2008 cannot be included.
29. Sterilization by EO
• Cycle Development
– Several methods for cycle development
offered in Annex
– Use of developmental chambers as well as
production chambers for process
development expanded
– Chamber and process equivalency
– Clarification of microbiological and physical
PQ provided
30. Sterilization by EO
• Main Changes
– Clause 5 – Sterilizing Agent Characterization
• New requirements for microbicidal effectiveness if
EO outside range of widely recognized
compositions or if novel diluents are to be used
• Effects of EO on the product to be documented
• Environmental considerations
31. Sterilization by EO
– Clause 6 – Process and Equipment
Characterization
• Generally relates to the requirements of the
contractor; responsibility lies with the manufacturer
to ensure contractor sterilizer complies with these
specific requirements
• Process Characterization is a result of the OQ
• Equipment Characterization is a result of the IQ
32. Sterilization by EO
– Clause 7 – Product Definition
• Product and packaging must meet the specified
requirements for safety, quality, and performance
following the sterilization process at the most
challenging process parameters
– Useful Standards
• ISO 10993 (relevant parts) for biological safety and
EO residuals following exposure
• AAMI TIR 28:2001; Product Adoption and Process
Equivalency for EO Sterilization
33. Sterilization by EO
• ISO 11737-1:2006 specifies requirements and provides
guidance for the enumeration and microbial
characterization of the population of viable micro-
organisms on or in a medical device, component, raw
material or package.
• ISO 17664:2004 specifies the information to be
provided by the medical device manufacturer on the
processing of medical devices claimed to be
resterilizable, and medical devices intended to be
sterilized by the processor.
• ISO 11607-1:2006 specifies the requirements and test
methods for materials, preformed sterile barrier
systems, sterile barrier systems and packaging
systems that are intended to maintain sterility of
terminally sterilized medical devices until the point of
use.
34. Sterilization by EO
– Clause 8 – Process Definition
• Process parameters clearly defined
• Appropriateness of BI and process challenge
device to be defined and documented to
demonstrate and support SAL
35. Sterilization by EO
– Clause 9 – Validation
• The number of sensors in PQ (temperature,
humidity, BIs) in the load is based on product load
volume as opposed to usable chamber volume.
• The number of sensors in IQ/OQ is based on
chamber volume.
– Clause 10 – Routine Monitoring and Control
• New requirements for additional levels of reviews
when parametric release is to be used
36. Sterilization by EO
– Clause 11 – Product Release
• Conventional release and parametric release are
more harmonized
– Clause 12 – Maintaining Process
Effectiveness
• Justification for requalification requirements /
intervals of requalification
37. Sterilization by EO
– Requalification Review to include
• Verify appropriateness of BIs
• Verify loading patterns remain unchanged
• Verify no changes to design, materials, load
configuration or manufacturing process
• Verify no change in bioburden or characterization has
occurred
• Verify temperature distribution and chamber operation
remain unchanged
• Review of sterilization process history demonstrates
repeatability
• Review of preventive maintenance programs
demonstrate no change to sterilizing equipment
Recommended
reduce
microbial
performance
qualifica;on
studies
are
performed
at
least
every
two
years
to
verify
the
documented
paperwork
review
has
captured
any
changes
in
the
product
or
steriliza;on
review
38. Regarding China
• GB 18279-2000 ethylene oxide
sterilization of medical equipment
validation and routine control
– idt ISO 11135:1994
39. Summary
• While techniques of sterilizing medical
devices have not changed much over the
past 25 years, the levels at which
sterilization processes are monitored and
controlled have changed significantly.
40. Summary
• Sterilization Validation is DYNAMIC
– ISO 14937:2009 specifies the elements of a
Quality Management System which are
necessary to assure the appropriate
characterization of the sterilizing agent,
development, validation and routine
monitoring and control of a sterilization
process.
• It provides a standardized procedure for validating
new sterilization technologies.
41. Thank You
John Beasley
Owner & Sr. Consultant
MedTech Review, LLC
www.medtechreview.com
Email: john@medtechreview.com
SKYPE: medtechreview