The presentation was given by the TGA at the 2014 ARCS Scientific Congress, and covers the microbiology requirements for various medical products

1. Microbiology data requirements for Submissions for
registration of sterile products
Joanne Wilson
Senior Microbiologist, Microbiology Section, Office of Laboratories & Scientific Services,
Monitoring & Compliance, TGA
ARCS Scientific Congress 2014
10 September 2014

2. Microbiology data requirements
• Terminally sterilised products
– Moist heat (steam) sterilised
– EO or radiation sterilised
• Aseptically manufactured products
• Finished product testing
• Multidose products
• Common deficiencies
Microbiology Data Requirements for Submissions for 1
Registration of Sterile Products

3. Microbiology data requirements
This is nothing new
Microbiology Data Requirements for Submissions for 2
Registration of Sterile Products

4. Terminally sterilised products
• Usually moist heat (steam) sterilised (autoclaving)
• Sometimes EO or radiation (usually for implants) sterilised
A minimum Sterility Assurance Level (SAL) of 10-6
must be demonstrated
• This information also applies to sterile drug substances
3

5. Terminally sterilised products
Moist heat (steam) sterilisation
• Pre-sterilisation bioburden information
• Physical and microbiological validation information, including:
– Cycle parameters and validation parameters
– Details of empty chamber studies
– Heat distribution and penetration studies
– Details of the Biological Indicator used
– BI configuration
– Confirmation of BI enumeration
– Calculations of SAL
– Frequency of revalidation
• Information required for every site
• Definition of a ‘batch’
Microbiology Data Requirements for Submissions for 4
Registration of Sterile Products

6. Terminally sterilised products
• Guidance available:
– ISO 11135-1:2007 for EO
– ISO 11137 Parts 1-3 for radiation
• Other methods need to demonstrate a minimum SAL of 10-6
• Bioburden information
• Validation report
• Information required for every site
5
Ethylene Oxide and radiation sterilisation
Microbiology Data Requirements for Submissions for
Registration of Sterile Products

7. 6
Aseptically manufactured products
• Products sterilised by filtration and then aseptically filled
• Some products manufactured completely aseptically
Microbiology Data Requirements for Submissions for
Registration of Sterile Products

8. Aseptically manufactured products
• Bioburden information
• Sterilising filter integrity testing
• Sterilising filter validation – including bacterial retention studies applicable to conditions of use
• Parameters and validation of depyrogenation/sterilisation processes applied to the containers and closures
– A minimum SAL of 10-6 is expected for product contact parts
• Media fills
– Worst case conditions
– Sterile hold and filling times
– Acceptance criteria
– Results from the past 12 months
• Container closure integrity
• Information required for every site
• Definition of a ‘batch’
Microbiology Data Requirements for Submissions for 7
Registration of Sterile Products

9. 8
Finished product testing
• Sterility testing
– Pharmacopoeial Test for Sterility
– Rapid methods (refer Ph.Eur. 5.1.6)
• Parametric release – in-process testing
Microbiology Data Requirements for Submissions for
Registration of Sterile Products

10. 9
Multidose products
• Preservative efficacy testing to comply with TGO 77
– Beginning of closed shelf life
– End of closed shelf life
• Justification of open shelf life with microbiological simulated in-use testing

11. Common deficiencies
• Validation studies not provided in English
• Extracts of studies submitted that do not provide enough relevant information to allow evaluation
• Bacterial retention studies for the sterilising filter not provided
• Results of media fill runs provided that are many years old
• For moist heat (steam) sterilisation, physical validation information only – microbiological data must be
included
• Container/closure integrity validation not provided
• Information not provided for all sites of finished product manufacture
• For multidose products, simulated in-use studies absent or without microbiological results
Microbiology Data Requirements for Submissions for 10
Registration of Sterile Products

12. 11
Problems understanding data requirements?
• Check the TGA website
• Call the Information Line 1800 020 653
We can’t assess data before you submit it, but we can provide some advice
Microbiology Data Requirements for Submissions for
Registration of Sterile Products