"in many cases RA simply lack the technical and scientific knowledge and understanding to assess the impact of a change."
And conversely, operations personnel simply lack the regulatory knowledge and understanding to assess the regulatory impact of a change. Therein lies the challenge. I myself don't try to assess the technical impact of a technical change; that is for the operations staff to do. What I assess is the written assessment of the impact that is provided by operations personnel. This assessment really should be clear enough for a non-expert to follow, because no auditor or regulatory inspector is going to have the technical and scientific knowledge and understanding to make the experts in every type of change that can occur in operations, either.
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Julie Omohundro RAC
Durham NC
United States
Original Message:
Sent: 03-25-2014 04:25
From: Siegfried Schmitt
Subject: Regulatory Assessment in Change Control -
Though there is nothing in the regulations that would prevent RA to review changes in operations, fact is that few regulatory affairs professionals have a sufficiently profound understanding of operations and have seen operations first hand. Consequently, in many cases RA simply lack the technical and scientific knowledge and understanding to assess the impact of a change. For example, replacing one pump with another, or an analytical column with another may or may not impact critical process parameters or critical quality attributes and thus require a change in the filing.
RA's capacity (workload) planning rarely takes into account the time that would be needed to assess the multitude of changes happening in operations.
Given that RA functions are not necessarily located at the plants, this poses another obstacle to efficient and effective reviews.
Clearly RA are the experts when it comes to assess what approvals, if any, are needed as part of a change.
Regards
Siegfried
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Siegfried Schmitt
Principal Consultant
PAREXEL
Braintree, Essex
United Kingdom
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Original Message:
Sent: 03-24-2014 01:37
From: Robert Falconer
Subject: Regulatory Assessment in Change Control -
Others have made the main point - RA must assess changes vs. commitments in the marketing application.
Unfortunately I do not know of a reference article to answer the original question. Just wanted to offer some deeper points which I have found relevant in real world circumstances in drug companies-
In my own recent quality system audits of Rx drug manufacturing sites - in both US and non-US sites supplying products to highly regulated markets - it is surprising how often a firm's change control SOPs are not very specific as to how/when RA dept assessments must be done.
Change control SOPs sometimes do not include the RA dept - placing organizational responsibility on tech services, engineering/validation and QA functions to decide when RA should be consulted. In my personal experience, if a product is subject to a non-trivial change, there are two principal assurances that proper RA assessment will be performed:
(i) Change Control SOPs should explicitly require the RA function to assess. Obviously trivial changes may be excluded. However, these SOPs should clearly state that RA is integral to assessments, and should include cross-references to published EU Guidelines on Variations to dossiers, and FDA's SUPAC Guidances and "Changes to NDAs/ANDAs Guidance";
(ii) SOPs on cGMP training should explicitly require Tech Services, QA, QC, Engineering/Validation and RA functions to receive formal training on which changes are significant, when and how they need to be assessed against Marketing Application commitments.
(iii) RA assessments of spontaneous of manufacturing or QC deviations or changes are as important as planned deviations in managing regulatory impact. Cumulative "minor" changes, over months or years, can have more than "minor" impact, leaving RA groups finding out too late that a worrisome gap has developed between current practice vs. original marketing application commitments.
It is one thing to say that RA should be included, but it is most effective to embed these requirements in formal SOPs, to assure that training has occurred, and to document such training. We have all heard the compliance proverb "if it is not documented, it has not occurred."
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Robert Falconer
VP Technical Operations
Breckenridge Pharmaceutical Inc.
Henrico VA
United States
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Robert Falconer
VP Technical Operations
Breckenridge Pharmaceutical Inc.
Henrico VA
United States
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Original Message:
Sent: 03-20-2014 14:38
From: Huston Howell
Subject: Regulatory Assessment in Change Control -
Can anyone provide a reference article the contains a good descriiption of how regulatory assessment is integrated into quality manufacturing change control? All articles I have been able to find in web searches focus almost exclusively on the quality operations aspect with very little discussion of the regulatory process.
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Huston Howell
Senior Manager
DENTSPLY International
York PA
United States
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