Anger and the job in difficult times

On Wednesday the United States set a devastating new record in the coronavirus pandemic: 3,124 people dead in one day. This was the first time the daily number of deaths has exceeded 3,000 but I fear it will not be the last. There are over 260k deaths in the US so far, over 1.5 million deaths worldwide. This is crippling, and it is difficult to go day-by-day with the pain of this suffering.

And yet, we need to work, support our families and communities. Get the job done. Amidst all that it is important to remember that is important to grieve and it is okay to be angry.

People grieve in diverse ways with different emotions, from anger, to depression to hopelessness, to resentment over what has been taken from them. Combined with the isolation of the pandemic, this is a recipe for poor mental health and poor coping mechanisms. And then there is a question of just how much and what sort of coping is good. Two-hundred-and-sixty thousand people are dead and there is a lot of evidence this is an underreport and a lot more people are going to die.

I hope you understand that I am angry. All day long. And it is a struggle not to bring that anger to work, not to let it twist my relationships. Yet that anger always exists.

I linked earlier this week to an article on mental health. It is particularly important to make this part of our organizations. Burnout must have a systematic fix.

What we need to give permission to, give space to, is a recognition that we are not in an okay state. And it may not be okay for a very long while, long after vaccines are widely available, and we return to the office.

It is okay to have taken a step back from obligations. I have not, for example, been writing much on this blog. It just did not work for me. Be kind to yourself and be okay with the things you must do less of. And when you are ready, go back to it.

Anger and Culture

Our organizational cultures are full of anger. What we must do is work to establish mechanisms to assure that anger is directed at issues or situations, not people. This will build psychological safety, enable good decisions and enhance our problem solving culture.

Some things we should do:

Acknowledge what is happening: Senior leadership needs to be working from compassion and generosity and taking real steps to address.
Treat toxic positivity as a bias: Toxic positivity is the assumption, either by one’s self or others, that despite a person’s emotional pain or difficult situation, they should only have a positive mindset. This is especially important as we have talent discussions, evaluate performance, and perform other managerial tasks.
Have systems around burnout
Focus on decision making quality
Build employee judgement feedback loops

We are not done. This winter will be very hard for many. As leaders we need to be ensuring our organizations can get through this and then leverage what we’ve learned to build a better culture.

Warning Letter for Aurolife demonstrates failures in process validation

The FDA commented in a Warning Letter to Aurolife Pharma that the manufacturer lacked data showing that the process was in “state of control” before batch release. The 483 pointed to the FDA’s guidance document Process Validation: General Principles and Practices, and found the company lacks a state of control of the process, which comes back to change control.

They also found major deficiencies in their OOS and cleaning programs.

2020 483s on data integrity

Data integrity continued to be a focus of the FDA, though the reduced inspections definitely led to fewer 483s.

Reference Number	Short Description	Long Description	2020 Frequency	2019 Frequency	2018 Frequency
21 CFR 211.194(a)	Complete test data included in records	Laboratory records do not include complete data derived from all tests, examinations and assay necessary to assure compliance with established specifications and standards. Specifically, , ***	15	38	33
21 CFR 211.194(a)(4)	Complete Test Data	Laboratory records are deficient in that they do not include a complete record of all data obtained during testing. Specifically, ***	10	24	28
21 CFR 211.68(b)	Backup data not assured as exact and complete	Backup data is not assured as [exact] [complete] [secure from alteration, erasure or loss] through keeping hard copy or alternate systems. Specifically, ***	6	6	71
21 CFR 211.194(a)(4)	Data secured in course of each test	Laboratory records do not include a complete record of all data secured in the course of each test, including all [graphs] [charts] [spectra] from laboratory instrumentation, properly identified to show the [specific component] [drug product container] [closure] [in-process material] [lot tested] [drug product tested]. Specifically, ***	4	1	28
21 CFR 211.68(b)	Written record not kept of program and validation data	A written record of the program along with appropriate validation data has not been maintained in situations where backup data is eliminated by computerization or other automated processes. Specifically, ***	1	6	71

483s related to data integrity

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

483s related to changes

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

Device 473s around change

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.

Mental Health and Culture

I’ve been thinking a lot today of this article by McKinsey by Jeffrey Pfeffer and Leanne Williams “Mental health in the workplace: The coming revolution.” It is a fascinating read, not just because we are in the midst of this pandemic which has certainly caused a lot of mental health issues, including depression, in many people. I know I’ve certainly been wrestling with it myself. I’m hopeful this issue remains on the agenda as I think it will provide long term benefits to culture.

I’ve written on how we need to build processes to support our employees in issues like burnout. Mental health is definitely a wicked problem, and will require systematic efforts to address. I am glad that the senior leaders I work with are thinking about this, and I look forward to deepening the conversation.