{"id":452,"date":"2016-08-26T21:06:22","date_gmt":"2016-08-26T11:06:22","guid":{"rendered":"http:\/\/paulyeatman.net.au\/?p=452"},"modified":"2020-07-29T14:37:43","modified_gmt":"2020-07-29T03:37:43","slug":"notes-on-iso13408-2-2003-aseptic-processing-of-health-care-products-part-2-filtration","status":"publish","type":"post","link":"https:\/\/paulyeatman.net.au\/index.php\/2016\/08\/26\/notes-on-iso13408-2-2003-aseptic-processing-of-health-care-products-part-2-filtration\/","title":{"rendered":"Notes on ISO 13408-2 (2003) \u2013 Aseptic processing of health care products \u2013 Part 2 :  Filtration"},"content":{"rendered":"<p>I found the <a href=\"http:\/\/www.ctslab.eu\/doc\/EN_ISO_13408-2_2011_Aseptic_processing_of_health_care_products_Part_2_Filtration.pdf\">latest ISO online here<\/a>.\u00a0 As far as I can tell it is legit (in so far as allowing the ISO online for free) \u2013 it certainly is the current ISO.<\/p>\n<p>A recent HR rep from a pharmaceutical company contacted me regarding an open role I Sydney.\u00a0 After passing my details along to \u201csenior management\u201d, the response I got was \u201cWe 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\u201d.<\/p>\n<p>Such a response show a lack of foresight from the employer as they do not want the best candidate for the job.\u00a0 Do they want someone who knows their stuff?\u00a0 No.\u00a0 Do they have a commitment to training and staff development?\u00a0 No.<!--more--><\/p>\n<p>Many of the regulations, standards and guidelines are quite old.\u00a0 My relevant sterile microbiology experience pertains to standards such as this one.\u00a0 A thirteen year old standard.\u00a0 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.<\/p>\n<h3>Forward<\/h3>\n<p>States that Parts 3-6 are under preparation.\u00a0 A google search shows they have been issued as follows:<\/p>\n<ul>\n<li>ISO\u00a013408-3:2006 Aseptic processing of health care products\u00a0\u2014 Part\u00a03: Lyophilization<\/li>\n<li>ISO\u00a013408-4: 2005 Aseptic processing of health care products &#8212; Part 4: Clean-in-place technologies<\/li>\n<li>ISO\u00a013408-5: 2006 Aseptic processing of health care products &#8212; Part 5: Sterilization in place<\/li>\n<li>ISO\u00a013408-6: 2005 Aseptic processing of health care products &#8212; Part 6: Isolator systems<\/li>\n<\/ul>\n<p><em>I\u2019ll review those in due course.<\/em><\/p>\n<h3>Introduction<\/h3>\n<p>This docco replaces clause 20 of 13408\/1<\/p>\n<h3>1 Scope<\/h3>\n<p>Does not apply to removal of viruses or fluids where effective ingredient larger than pore size of a filer.<\/p>\n<h3>3 Terms and definitions<\/h3>\n<p>17 definitions given.\u00a0 All are applicable to microbiological testing or validation of filters.<\/p>\n<h3>5 Selection of filters and filter assemblies bases on filter manufacturer\u2019s data<\/h3>\n<p>Should be the most suitable filter, be certified by the supplier (quality certificate) and be non-shedding (fibre releasing).<\/p>\n<h3>6 Fluid-specific selection criteria based on filter user&#8217;s data<\/h3>\n<p>Filters to be evaluated on-site for suitability (validated) and they should not be altered by the fluid being filtered.<\/p>\n<p>6.2 details what to take into account for filter characterisation.<\/p>\n<h3>7 Filtration Process<\/h3>\n<p>Process parameters to be established, qualified and documented and the process validated.\u00a0 Factors to be defined or specified are stated in 7.1.1<\/p>\n<p>7.1.2 Integrity testing procedures need to be established.<\/p>\n<p>\u201cThe 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\u2026\u201d<\/p>\n<p>7.1.3 Appropriate wetting fluid(s) to be selected (shall be the filter manufacturer\u2019s recommended fluid or the fluid being filtered.\u00a0 <em>In my experience it would either be the flushing fluid or the test sample.<\/em><\/p>\n<h3>7.2 Validation of fluid-specific microbial retention by filters<\/h3>\n<p>7.2.1 Bacterial challenge test<\/p>\n<p>Need to validate (worse case) sterilizing capability of filter.\u00a0 Can scale it down and do it in the lab.\u00a0 All failures need an investigation.\u00a0\u00a0 7.2.1.4 details what to take into account when simulating worse case conditions.<\/p>\n<p>\u201c7.2.1.5 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\u201d<\/p>\n<p>7.2.2 Challenge fluid and challenge microorganisms<\/p>\n<p>Details what is required to ensure one can recover microbes within the product.\u00a0 Makes not of using<em> Brevundimonas dimunuta<\/em> as it might be small enough to get through the product filter.\u00a0 States what to do if a smaller microbe is suspected.\u00a0 Changes need to be justified <em>to make auditor happy\/ensure end-user safety<\/em>.<\/p>\n<p>7.2.3 Acceptance criteria<\/p>\n<p>No challenge microbes growing in the filtrate<em>.\u00a0 So here you validating the ability of the filter to clear microbes from the fluid. This is not the validation of the recovery method.<\/em><\/p>\n<h3>8 Filtration system design<\/h3>\n<p>Everything to be documented.\u00a0 Everything to be justified.<\/p>\n<p>Filtration system not to adulterate the fluid being filtered.<\/p>\n<p>If air or gas, pay attention to avoiding (unintentionally) wetting\/moistening the filter or filter equipment.<\/p>\n<p>Design the system for minimum number of aseptic connection. <em>Less points of failure.<\/em><\/p>\n<p>In-place integrity testing should be permitted by design.<\/p>\n<h3>9 Routine Process<\/h3>\n<p>Document it.<\/p>\n<p>9.2 points a-g detail what to include.<\/p>\n<p>Pre-sterlization bioburden shall be determined for every batch (with some provisos).\u00a0 <em>This is where the Microbiology lab will require bioburden samples.<\/em><\/p>\n<h3>10 Process documentation<\/h3>\n<p>Critical process parameters to be documented and form part of the batch record.<\/p>\n<p>10.2 points a-3 detail what to include.<\/p>\n<h3>11 Maintenance and change control<\/h3>\n<p>Any changes to the validated documented procedure needs to be made using the defined and documented change control procedure.<\/p>\n<p>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.\u00a0 <em>The QA dept needs to make sure things happen here.<\/em><\/p>\n<h3>12 Operator training<\/h3>\n<p>For each filter type, operators need documented training for points a-e.<\/p>\n<p><strong>Annex A<\/strong> is informative and has contains basic information and quality certificates for filter cartridges.<\/p>\n<p><strong>Did you find this informative or useful? Please consider a small donation so I can expand and improve on what I deliver.<\/strong><\/p>\n<p><input title=\"PayPal - The safer, easier way to pay online!\" alt=\"Donate with PayPal button\" name=\"submit\" src=\"https:\/\/www.paypalobjects.com\/en_AU\/i\/btn\/btn_donateCC_LG.gif\" type=\"image\" \/><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/www.paypal.com\/en_AU\/i\/scr\/pixel.gif\" alt=\"\" width=\"1\" height=\"1\" border=\"0\" \/><\/p>\n","protected":false},"excerpt":{"rendered":"<p>I found the latest ISO online here.\u00a0 As far as I can tell it is legit (in so far as allowing the ISO online for free) \u2013 it certainly is the current ISO. A recent HR rep from a pharmaceutical company contacted me regarding an open role I Sydney.\u00a0 After passing my details along to [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[5,2],"tags":[29,36,12,40,35],"class_list":["post-452","post","type-post","status-publish","format-standard","hentry","category-documentation","category-the-regs","tag-documentation","tag-filtration","tag-guidelines","tag-iso","tag-standards"],"_links":{"self":[{"href":"https:\/\/paulyeatman.net.au\/index.php\/wp-json\/wp\/v2\/posts\/452","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/paulyeatman.net.au\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/paulyeatman.net.au\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/paulyeatman.net.au\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/paulyeatman.net.au\/index.php\/wp-json\/wp\/v2\/comments?post=452"}],"version-history":[{"count":6,"href":"https:\/\/paulyeatman.net.au\/index.php\/wp-json\/wp\/v2\/posts\/452\/revisions"}],"predecessor-version":[{"id":1215,"href":"https:\/\/paulyeatman.net.au\/index.php\/wp-json\/wp\/v2\/posts\/452\/revisions\/1215"}],"wp:attachment":[{"href":"https:\/\/paulyeatman.net.au\/index.php\/wp-json\/wp\/v2\/media?parent=452"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/paulyeatman.net.au\/index.php\/wp-json\/wp\/v2\/categories?post=452"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/paulyeatman.net.au\/index.php\/wp-json\/wp\/v2\/tags?post=452"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}