Tag: compliance

The GxPs – a brief definition

Jargon is something we should work hard to avoid, and yet there is an awful lot of it we find difficult to let go. Right at the top is the GxPs.

GxP is a general abbreviation for the “good practice” quality guidelines and regulations. The “x” stands for the various fields, including the pharmaceutical and food industries, for example good manufacutiring practice, or GMP.

There are a lot of GxPs, though we tend to focus on 5(ish), depending on where you are.

We tend to argue a lot about them. Even to the GxP vs GXP. Or GPvP vs GVP. Or GdocP or GDP (so damn confusing, there is another GDP – Good Distribution Practices). Or if Good Storage Practice is its own body or part of the GMPs and GDPs. And…and…and.. The arguing can be fun.

The Five big ones in pharma and medical devices are GLP, GCP, GMP, GDP and GPvP. Some of the others like GACP are pretty intesting in their application.

Some like GDocP and GAMP are more specific threads that go across the GxPs.

By nature the GxPs are tied to the phase of the pharmaceutical pipeline.

The GxPs are all about ensuring compliance and are informed from a wide range of sources, starting with law and regulations.

Being in the age of globalization, there are many many sources to draw from.

This can also draw from beyond the health authorities (for example in the US USDA for GACP or the DEA for parts of the GDPs).

At the end of the day, GxPs answer to five important criteria.

EMA Publishes 2021 GCP Compliance Report

The EMA has published the Annual Report of the Good Clinical Practice (GCP) Inspectors Working Group (IWG) 2021.

Beyond wishing for an 11 month cycle of writing and approval on my annual reports, there is some valuable information there.

In 2021, three CHMP GCP inspections were conducted entirely remotely, and three inspections were conducted in a hybrid setting. A total of 286 deficiencies, comprising 24 critical, 152 major and 110 minor findings were recorded for the 27 CHMP requested inspections conducted in 2021. This represents an average of 10-11 findings per site inspected. The three top categories were: “General”, “Trial Management” and “Computer System”. An increase in findings related to computer systems (e. g. Audit Trail and Authorized Access, Computer Validation, Physical Security System and Backup) is noted compared to the last reports.

More information is available at EMA´s Good Clinical Practice Inspectors Working Group website.

Under organisation and personel we see “Delegation of tasks to inappropriate team members.” This reinforces the needs for strong cv and job descriptions, and linking to both hiring and personnel qualification.

The computer systems observations are the greatest hits of data integrity, and should be a wakeup call to any company that treats GCP and GMP computer systems differently.

Let the 2022 annual GCP training development begin. And make sure you get that training done on time!

The Great Man Fallacy and Pharmaceutical Quality

Primary Investigator, Study Director, Qualified Person, Responsible Person – the pharmaceutical regulations are rife with a series of positions that are charged with achieving compliance and quality results. I tend to think of them as a giant Achilles heel created by the regulations.

The concept of an individual having all the accountability is nowhere near universal, for example, the term Quality Unit is a nice inclusive we – though I do have some quibbles on how it can end up placing the quality unit within the organization.

This is an application of the great man fallacy – the idea that one person by the brunt of education, experience, and stunning good looks can ensure product safety, efficacy and quality, and all the other aspects of patient and data integrity of trials.

That is, frankly, poppycock.

People only perform successfully when they are in a well-built system. Process drives success and leverages the right people at the right time making the right decisions with the right information. No one person can do that, and frankly thinking someone can is setting them up for failure. Which we see, a lot in the regulatory space.

Sure, the requirement exists, we need to meet it failing the agencies waking up and realizing the regulations are setting us up for failure. But we don’t need to buy into it. We build our processes to leverage the team, to democratize decisions, and to drive for reliable results.

Let’s leave the great man theory in the dustbins where it belongs.

dissolving crown

FDA 2021 483s – Bioresearch Monitoring

The FDA has released the 2021 483 data. With my mind being mostly preoccupied with bioresearch monitoring inspection preparation, let’s look at that data, focusing on the top 10.

CFR Reference in 2021# 483s 2021#  483s 2020# 483s 2019
21 CFR 312.609058127
FD-1572, protocol compliance8454119
Informed consent648
21 CFR 312.62(b)483060
Case history records- inadequate or inadequate483060
21 CFR 312.62(a)131117
Accountability records121116
Unused drug disposition (investigator)1#N/A1
21 CFR 50.27(a)937
Consent form not approved/signed/dated726
Copy of consent form not provided211
21 CFR 312.64(b)967
Safety reports967
21 CFR 312.668719
Initial and continuing review626
Unanticipated problems246
21 CFR 312.20(a)513
Failure to submit an IND513
21 CFR 58.130(a)423
Conduct: in accordance with protocol423
21 CFR 312.503716
General responsibilities of sponsors3414
21 CFR 50.20358
Consent not obtained, exceptions do not apply314
Comparison of 2021 Top 10 BIMO 483 categories with 2020 and 2019 data

Based on comparison of number of inspections per year, I am not sure we can really say there was much COVID impact in the data. COVID may have influenced observations, but all it really seemed to do is excaerbate already existing problems,

Key lesson in the data? The GCPs are struggling at accountability of documentation and decision making.

Quality Goes Way Beyond a Few Regulations

The quality profession in the pharmaceutical industry is wider than the overseeing regulations from health authorities. The GXPs are truly a starting point, not an ending point which is why we often use that little “c” for “current.”

The GXPs (and the regulations behind them) serve an important purpose. But they are the start of excellence and not the end.

The GXPs are an outline. When we start with these requirements and then fill in the details we build a robust and beautiful engine for quality.

The 5Ps of GXPs: People, Procedure, Product, Premise, and Principles.

This is often why we talk about compliance being the start of quality, and not the end.