Notes on ISO 13408-2 (2003) – Aseptic processing of health care products – Part 2 : Filtration

I found the latest ISO online here.  As far as I can tell it is legit (in so far as allowing the ISO online for free) – it certainly is the current ISO.

A recent HR rep from a pharmaceutical company contacted me regarding an open role I Sydney.  After passing my details along to “senior management”, the response I got was “We have had some discussion with senior quality managers about your profile and unfortunately they feel your relevant experience in Sterile Micro going back 10 years is a little too long for us ideally”.

Such a response show a lack of foresight from the employer as they do not want the best candidate for the job.  Do they want someone who knows their stuff?  No.  Do they have a commitment to training and staff development?  No.

Many of the regulations, standards and guidelines are quite old.  My relevant sterile microbiology experience pertains to standards such as this one.  A thirteen year old standard.  To strengthen my scientific knowledge, I have reviewed this standard anew and what follows are the salient points for QA/QC microbiology from the ISO which are either stated or paraphrased for reference when the ISO is in your possession.


States that Parts 3-6 are under preparation.  A google search shows they have been issued as follows:

  • ISO 13408-3:2006 Aseptic processing of health care products — Part 3: Lyophilization
  • ISO 13408-4: 2005 Aseptic processing of health care products — Part 4: Clean-in-place technologies
  • ISO 13408-5: 2006 Aseptic processing of health care products — Part 5: Sterilization in place
  • ISO 13408-6: 2005 Aseptic processing of health care products — Part 6: Isolator systems

I’ll review those in due course.


This docco replaces clause 20 of 13408/1

1 Scope

Does not apply to removal of viruses or fluids where effective ingredient larger than pore size of a filer.

3 Terms and definitions

17 definitions given.  All are applicable to microbiological testing or validation of filters.

5 Selection of filters and filter assemblies bases on filter manufacturer’s data

Should be the most suitable filter, be certified by the supplier (quality certificate) and be non-shedding (fibre releasing).

6 Fluid-specific selection criteria based on filter user’s data

Filters to be evaluated on-site for suitability (validated) and they should not be altered by the fluid being filtered.

6.2 details what to take into account for filter characterisation.

7 Filtration Process

Process parameters to be established, qualified and documented and the process validated.  Factors to be defined or specified are stated in 7.1.1

7.1.2 Integrity testing procedures need to be established.

“The standardized bacterial-retention tests should use a challenge level of at least 10 to the power of 7 colony-forming units per square centimetre of effective filtration area…”

7.1.3 Appropriate wetting fluid(s) to be selected (shall be the filter manufacturer’s recommended fluid or the fluid being filtered.  In my experience it would either be the flushing fluid or the test sample.

7.2 Validation of fluid-specific microbial retention by filters

7.2.1 Bacterial challenge test

Need to validate (worse case) sterilizing capability of filter.  Can scale it down and do it in the lab.  All failures need an investigation. details what to take into account when simulating worse case conditions.

“ Revalidation shall be performed whenever filters or filtration conditions are altered to be outside the worst-case conditions tested during validation.7.2.2 Challenge fluid and challenge microorganisms”

7.2.2 Challenge fluid and challenge microorganisms

Details what is required to ensure one can recover microbes within the product.  Makes not of using Brevundimonas dimunuta as it might be small enough to get through the product filter.  States what to do if a smaller microbe is suspected.  Changes need to be justified to make auditor happy/ensure end-user safety.

7.2.3 Acceptance criteria

No challenge microbes growing in the filtrate.  So here you validating the ability of the filter to clear microbes from the fluid. This is not the validation of the recovery method.

8 Filtration system design

Everything to be documented.  Everything to be justified.

Filtration system not to adulterate the fluid being filtered.

If air or gas, pay attention to avoiding (unintentionally) wetting/moistening the filter or filter equipment.

Design the system for minimum number of aseptic connection. Less points of failure.

In-place integrity testing should be permitted by design.

9 Routine Process

Document it.

9.2 points a-g detail what to include.

Pre-sterlization bioburden shall be determined for every batch (with some provisos).  This is where the Microbiology lab will require bioburden samples.

10 Process documentation

Critical process parameters to be documented and form part of the batch record.

10.2 points a-3 detail what to include.

11 Maintenance and change control

Any changes to the validated documented procedure needs to be made using the defined and documented change control procedure.

11.3 There shall be a written agreement between the filter user and filter manufacturer that they will comply with this requirement. This should be verified by the filter user through audits of the filter manufacturer.  The QA dept needs to make sure things happen here.

12 Operator training

For each filter type, operators need documented training for points a-e.

Annex A is informative and has contains basic information and quality certificates for filter cartridges.

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