Shakeups at Emergent
There is a lot to understand in this story. As congressional hearings unfold, and the shareholder lawsuit works the way through the courts, I hope we learn more about the how’s and the why’s.
Today Janet Woodcock issued a statement “FDA Continues Important Steps to Ensure Quality, Safety and Effectiveness of Authorized COVID-19 Vaccines” which links to the April 2021 Form 483 of the Baltimore facility.
I have requested hearings from my congressional representatives. The path where Emergent received so much money from the federal government to lead to this place is frightening.
The latest version (version 14) of the “How to do” Document – Interpretation of ICH Q7 Guide and “Review form” for APIs was published a few months back. It is intended to facilitate the implementation of the ICH Q7 Guideline and provides recommendations on interpretation.
In this version, the responsible Task Force of the Quality Group of APIC, which is a sector group of the European Chemical Industry Council (CEFIC), mainly made additions and updates in chapters 11 – Laboratory Controls, 15 – Complaints and Recalls, and in section 16 – Contract Manufacturers (incl. Laboratories).
The addition in section 11.11 for “Approval/rejection of materials” is pretty striaghtforward – have an SOP.
The changes in section 15 for recalls is pretty cosmetic.
I would re-read section 16 on contract manufacturers. Not much substantial here, but the rewrite makes it a good time to ensure compliance.
The MHRA GPvP inspectorate recently published their latest inspection metrics for the period from April 2019 to March 2020.
Someday these reports won’t take a year to write. If I took a year writing my annual reports I would receive an inspection finding from the MHRA.
There is no surprise that the five critical observations are all from risk management. Risk management is also the largest source of major findings, with quality management a close second with a lot of growth.
There are a lot of observations around the smooth and effective running of the CAPA program; a fair amount on PSMF management; and a handful on procedure, training and oversight.
Looking at the nine major observations due to deficiencies in the management of CAPA, the MHRA reports these problems:
I’m going to go out on a limb here and say some of these stem from companies thinking non-GMP CAPAs do not require the same level of control and scrutiny. Root Cause Analysis and a good CAPA program are fundamental, no matter where you fall on (or out of) the pharmaceutical regulatory spectrum.
An appropriate level of root cause analysis should be applied during the investigation of deviations, suspected product defects and other problems. This can be determined using Quality Risk Management principles. In cases where the true root cause(s) of the issue cannot be determined, consideration should be given to identifying the most likely root cause(s) and to addressing those. Where human error is suspected or identified as the cause, this should be justified having taken care to ensure that process, procedural or system based errors or problems have not been overlooked, if present.
Appropriate corrective actions and/or preventative actions (CAPAs) should be identified and taken in response to investigations. The effectiveness of such actions should be monitored and assessed, in line with Quality Risk Management principles.
EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use, Chapter 1 Pharmaceutical System C1.4(xiv)
The MHRA cited 210 companies in 2019 on failure to conduct good root cause analysis and develop appropriate CAPAs. 6 of those were critical and a 100 were major.
My guess is if I asked those 210 companies in 2018 how their root cause analysis and CAPAs were doing, 85% would say “great!” We tend to overestimate our capabilities on the fundamentals (which root cause analysis and CAPA are) and not to continuously invest in improvement.
Of course, without good benchmarking, its really easy to say good enough and not be. There can be a tendency to say “Well we’ve never had a problem here, so we’re good.” Where in reality its just the problem has never been seen in an inspection or has never gone critical.
The FDA has fairly similar observations around root cause analysis. As does anyone who shares their metrics in any way. Bad root cause and bad CAPAs are pretty widespread.
This comes up a lot because the quality of CAPAs (and quantity) are considered key indicators of an organization’s health. CAPAs demonstrate that issues are acknowledged, tracked and remediated in an effective manner to eliminate or reduce the risk of a recurrence. The timeliness and robustness of these processes and records indicate whether an organization demonstrates effective planning and has sufficient resources to manage, resolve and correct past issues and prevent future issues.
A good CAPA system covers problem identification (which can be, and usually is a few different processes), root cause analysis, corrective and preventive actions, CAPA effectiveness, metrics, and governance. It is a house of cards, short one and the whole structure will fall down around you, often when you least need it to.
We can’t freeze our systems with superglue. If we are not continually improving then we are going backwards. No steady state when it comes to quality.
Investigations of a Dog 