2020 FDA 483s around change

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:

1. Think change management and not just change control and document control
2. Computer change controls need to be holistic and system orientated
3. Have a process that ensures changes are appropriately reviewed and approved
4. Risk based and evaluate validation
5. A robust supplier management program is critical, plan for change

Here’s a more detailed checklist to help you evaluate your change system.