sterilization standards update: strategies for compliance

Sterilization requirements: Strategies

for Compliance

presented by John Beasley

Owner & Sr. Consultant MedTech Review

Topics

•  General Requirements •  Radiation Sterilization

–  Impact to Subcontractors –  Impact to Manufacturers

•  EO Sterilization –  Impact to Subcontractors –  Impact to Manufacturers

•  Summary

Introduction

•  Presentation covers –  Gap Analysis between

current version and previous version of standards

–  Compliance information

–  References

•  Presentation does not cover –  All differences – only

the most significant –  The steps for

sterilization or validation of sterilization processes

Copyright laws prevent MedTech Review and MEDTEC China Conferences from providing copies of standards to

conference par;cipants.

Sterilization Processing by IR or EO

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)

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)

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)

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

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.

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


– 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.


•  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?


•  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.


•  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


•  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.


•  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


•  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

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.


•  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 – Auditing for safety

These items can be reviewed and covered during preven8ve

maintenance ac8vi8es and supplier audits.


•  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?


•  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.”


•  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.


•  Each of the previous items must be audited in addition to – Personnel training – Dosimetery – Radiation cell refueling

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

Regarding China

•  GB18280-2007 - Sterilization of health care products requirements for validation and routine control of radiation sterilization –  idt ISO 11137:2006

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

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

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.

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

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

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

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

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.

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

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

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

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

Regarding China

•  GB 18279-2000 ethylene oxide sterilization of medical equipment validation and routine control –  idt ISO 11135:1994

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.

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.

Thank You

John Beasley Owner & Sr. Consultant MedTech Review, LLC

www.medtechreview.com Email: [email protected]

SKYPE: medtechreview

sterilization standards update: strategies for compliance

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