The yearly database of 483s has been updated by the FDA. Lots will be written on themes as we end the year, so I decided to give a few of my immediate observations.
I find that over time what I focus in on changes, as my jobs evolve and change, and the interests I have shift. However, some things never change, so let us talk change.
|Reference Number||Short Description||Long Description||2020 Frequency||2019 Frequency||2018 Frequency|
|21 CFR 211.100(a)||Changes to Procedures Not Reviewed, Approved||Changes to written procedures are not [drafted, reviewed and approved by the appropriate organizational unit] [reviewed and approved by the quality control unit]. Specifically, ***||8||13||9|
|21 CFR 211.160(a)||Lab controls established, including changes||The establishment of [specifications] [standards] [sampling plans] [test procedures] [laboratory control mechanisms] including any changes thereto, are not [drafted by the appropriate organizational unit] [reviewed and approved by the quality control unit]. Specifically, ***||4||18||17|
|21 CFR 212.20(c)||Adverse effects of changes made||You did not demonstrate that any change does not adversely affect the [identity] [strength] [quality] [purity] of your PET drug. Specifically,***||1||1||1|
I think its fair to say the decreases as a result of the pandemic and the reduced inspections.
Over on the device side of things we see:
|Reference Number||Short Description||Long Description||Frequency|
|21 CFR 820.30(i)||Design changes – Lack of or Inadequate Procedures||Procedures for design change have not been [adequately] established. Specifically,***||26|
|21 CFR 820.40(b)||Document change records, maintained.||Records of changes to documents were not [adequately] maintained. Specifically, ***||6|
|21 CFR 820.70(b)||Production and Process Change Procedures, lack of or Inad.||Procedures for changes to a [specification] [method] [process] [procedure] have not been [adequately] established. Specifically, ***||5|
|21 CFR 820.75(c)||Process changes – review, evaluation and revalidation||A validated process was not [reviewed and evaluated] [revalidated] when changes or process deviations occurred. Specifically, ***||5|
|21 CFR 820.40(b)||Change records, content||Records of changes did not include [a description of the change] [identification of the affected documents] [the signature of the approving official(s)] [the approval date] [when the change became effective]. Specifically, ***||3|
|21 CFR 820.50(b)||Supplier notification of changes||There is no agreement with [suppliers] [contractors] [consultants] to notify you of changes in the product or service. Specifically, ***||3|
|21 CFR 820.75(c)||Documentation – review in response to changes or deviations||There is no documentation of the [review and evaluation of a process] [revalidation of a process] performed in response to changes or process deviations. Specifically, ***||1|
I’m a firm believer that pharma should always pay attention to the medical device side for 483s. A lot of us are combination products now (or will be) and there is always good trends to be aware of.
My key takeaways:
- Think change management and not just change control and document control
- Computer change controls need to be holistic and system orientated
- Have a process that ensures changes are appropriately reviewed and approved
- Risk based and evaluate validation
- A robust supplier management program is critical, plan for change
Here’s a more detailed checklist to help you evaluate your change system.
2 thoughts on “2020 FDA 483s around change”