BIOTECHNOLOGY 13


Why were 483 deficiencies not detected internally? Mention this in your response letter, noting your commitment to QC/QA audit management. Te definitive guide to what FDA inspectors are looking for (at least in theory) is the agency’s Investigations Operations Manual accessible at: http://www.fda.gov/ ICECI/Inspections/IOM/default. htm  If you need clarification, seek it-in writing and from the correct party. Ideally, when the investigator gave you the Form 483 after the inspection you asked a lot of questions to clarify each observation. Try to be sure you are clear on each observation before the inspector leaves your facility and make notes while he/she is explaining the observations.


If your questions involve policy, contact the FDA headquarters - do not contact your local FDA because policy is set at HQ.  You may need an industry expert. Tere are many companies who specialise in creating and implementing regulatory strategy, whether from the ground up or from your existing quality and regulatory systems. If it is worth doing, it may be worth hiring someone who knows how to do it really well.


As regulatory compliance issues grow more complex, many


References: 1


alarming system would provide secure, gap-free temperature data recording. Data loggers with long- life batteries (up to 10 years) can continue to record temperature at the point of measurement, rendering environmental data immune to network or power failures.


Regarding the blood bank 483 example, the storage units can be validated with the same equipment used to monitor.


Self-contained data loggers with internal sensors, memory and battery can be equipped for “periodic testing” or mapping the temperature distribution of the containers.


Above: Monitoring, alarming and reporting are only as good as the measured data -accurate and continuous


companies have been created to provide solutions in common compliance areas like: response to agency queries and help with agency meetings, regulatory gap analysis and remediation, internal GLP/ GMP auditing and pre-approval inspections.


Ideally, your regulated environments and equipment are always in full compliance with FDA regulations. An automated monitoring and alarming system providing high accuracy data at the point of measurement with back-up


recording – can make your QA/ QC efficient, optimal and ready for any critical evaluation, internal or external. Te continuous records that this type of system should provide could help be part of your detailed response to quality concerns outlined in a Form 483 letter.


For example, in the 483 excerpt of the CMO, which noted that ‘documentation that stability samples are maintained at the designated temperature’.


A validated monitoring and


In regard to the observations on the OTC Pharmaceutical manufacturer, the challenge of not having adequately documented temperature conditions would be solved by following the detailed IQ/OQ and SOPs provided with the monitoring, alarming and reporting system.


Every monitoring system should have a detailed IQ/OQ change control document make validation a straightforward process.


Parts of this article were sourced, with permission, from two documents 1) “FDA 483 Responses- Compliance Considerations” by Richard Poska and Ballard Graham, as published in the Journal of Validation Technology, Winter 2010 “ available with subscription at: http://www.gxpandjvt. com/ivtnews/templates/IVTNews.aspx?articleid=1896&zoneid=27 and the FDA Presentation 2) “Writing An Effective 483 Response” presented by Anita Richardson, Associate Director for Policy, Office of Compliance & Biologics Quality at the 5th Annual FDA University RI Pharma Conference, January 2009 available at: http://www.fda.gov/downloads/BiologicsBloodVaccines/NewsEvents/


WorkshopsMeetings Conferences/UCM102921.pdf 2


January 2010 3


“FDA’s Enforcement Crackdown To Increase Inspections, Delays”, Drug GMP Report - Issue No. 210,


From the FDA’s Warning Letter web page: “Inspections, Compliance, Enforcement, and Criminal Investigations” http://www.accessdata.fda.gov/scripts/warningletters/wlSearchResult.cfm?filter=tempera


ture&sortColumn=&qryStr=21+CFR+Part+11) 4


WarningLetters/default.htm 5


See the ORA FOIA Electronic Reading Room at: http://www.fda.gov/ICECI/EnforcementActions/


http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatory Information/Guidances/ UCM070279.pdf


Some organisations compliant with GMP still use chart recorders or manual methods to track temperature and humidity. Te issues with these methods are beyond the scope of this article, but as more facilities automate processes within quality assurance and regulatory compliance, relying on older technologies is and will continue to be problematic.


Te FDA, with its ‘strong recommendations”, cannot insist that organisations upgrade to any given technology. But, a commitment to using industry- best instrumentation and systems in FDA-regulated research and manufacturing processes can stave off misgivings about a facility’s commitment to quality.


Ken Appel is VP of Regulated Markets,


Veriteq, a Vaisala company, Richmond, BC, Canada. www.veriteq.com


www.scientistlive.com


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