A Summary of the New MHRA ‘GXP’ Data Integrity Guidance and Definitions – March 2018

A Summary of the New MHRA ‘GXP’ Data Integrity Guidance and Definitions – March 2018

For over 20 years, there have been Health Authority regulations governing the use of Electronic Records and Electronic Signatures (eReS) for GxP purposes. These regulations (the US part 11, the EU Annex 11, and their ilk globally) are arguably among the most elegant, concise, and consistent across jurisdictions (with differences mostly limited to context and emphasis rather than substance).

That being said, there has been a considerable amount of confusion in interpreting and applying the eReS regulations as both the Regulators and those in Industry have evolved their understanding of these regulations as the various guidance documents have emerged, been rescinded, revised, re-issued, clarified, etc.

This latest guidance document (which can and should be read in its entirety here (21 pages): https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/687246/MHR), is very mature in its outlook and takes what has come before and builds upon it. The result adds a huge amount of clarity by specifically expounding on the general theme “This what we want, yes it means exactly that, and yes we understand the practical considerations and resource impact of what we want”.

Some key items in the guidance include:

  • Its application is intended across all GxP areas (Excepting Medical Devices – which I found interesting)
  • The principles of data integrity (which are separate from those of data quality) are meant to be adaptable, and are designed to evolve with Technology and promote a risk-based approach.
  • The non-technical aspects of data integrity are addressed, including the organizational responsibility to create a culture and environment (controls) that ensures that data is complete, consistent, and accurate in all forms (They focus on the oft neglected idea that PEOPLE are part of the process).
  • They revisit both ALOCA and ALCOA+ (Attributable, Legible, Contemporaneous, Original, and Accurate + Complete, Consistent, Enduring, and Available. They go on to clarify that these two acronyms are differing ways of explaining the same expectations.
  • Differing paper, electronic, hybrid scenarios are discussed as are the ideas around Risk, Risk mitigation, and documentation around both. Warnings are made about poor organizational controls and the over-reliance on a system’s validated state.
  • Challenges and considerations around designing data processes and controls are discussed in some detail.
  • Key definitions are explained in some detail for: Data, ALCOA, Raw = Source Data, Metadata, Data Integrity, Data Governance, Data Lifecycle, Recording & collection of data, Data transfer & migration, Data Processing, Data Exclusion, True Copy, Transactional data, Audit Trail, Reconstructability, Electronic Signatures, Data review and approval, Data Retention/Backup/Archival, System Access, the Admin Role, Validation, and IT Suppliers including Cloud providers).



Novartis goes digital with FocalView for ophthalmology clinical trials

(Image: Getty/demaerre)May you live in interesting times… A colleague flagged this for me. I’ll be very interested in the particulars of how this all works going forward. #ItsAllAboutApps



Source: Novartis goes digital with FocalView for ophthalmology clinical trials

Week of Mar 25th 2018 | FDA Sent These Warning Letters to Pharma Companies | FDAZILLA BLOG

Image result for fdaNew warning letters out! These are largely GMP-specific. Like no other agency, FDA is reknowned for updating regulations via warning letter (rather than the onerous process of getting an actual new or updated regulation approved)….so it is good to always keep an eye on these to be clear on “FDA’s current thinking”. YMMV. In any case, check out the full information at the link below!

Source: Week of Mar 25th 2018 | FDA Sent These Warning Letters to Pharma Companies | FDAZILLA BLOG

FDA posted 8 warning letters this week, including:


Computer System Validation (CSV) Audit Mindmap

As a break from writing, I finished the first electronic version of my CSV Audit Mindmap. The intent is for it to be a mental tickler during an audit. Rather than 10-20 pages of checklists, this would be a visual layout of related topics that fit on 1 or 2 pages (or more if you like). Click the link to look at a pdf version…and be sure to let me what you think.

CSV Audit Mindmap




New Drug Development – 1.5 Billion Dollars

I was sad (though not surprised) to hear of JnJ’s pending layoffs. I have friends who work there. However, the thing that really caught my attention in this article is that the cost to develop a new drug has moved from US $800 Million to US $1.3-1.5 Billion in just a few years. I don’t have a lot of time to expound on this, but thought it worth flagging.


J&J to slash 7,000 to 8,000 jobs

By Ransdell Pierson –

NEW YORK (Reuters) – Johnson & Johnson plans to cut up to 7 percent of its workforce in order to generate cost savings needed to finance increasingly costly drug research and to weather future challenges, the diversified healthcare company said on Tuesday.
J&J said the planned restructuring will eliminate 7,000 to 8,000 jobs and generate annualized cost savings of $1.4 billion to $1.7 billion by 2011…..[snip]

The typical cost of developing a new medicine has now climbed to between $1.3 billion to $1.5 billion, from a cost of $800 million only a few years ago, Weldon said. He noted that J&J and other drugmakers increasingly are partnering with rival companies in order to share such financial gambles…..[snip]

SQA Abstract – Impact of eSystems, etc.

I’ve submitted this abstract to the SQA for their annual meeting in April and am really hoping it is accepted. A very similar one that I posted last year was not….but this year, it seems that this sort of stuff is on their “hot topic” list. Fingers crossed.


The Impact of Electronic Systems, eHRs, and eData on Clinical Research

Although the use of electronic data in the pharmaceutical industry is by no means a new phenomenon, its impact has evolved over time. Technology has revolutionized our lives in many ways; in the way we access information, in our entertainment, in the way we do business, and in the way we interact. This technological revolution has had very pronounced impacts on the GxP industries: eRecords, eData, eSignatures, Data Processing, Data Mining and the Regulatory Standards associated with them.

These impacts have been most apparent in the cGMP and GLP areas and there is a fair level of comfort with eData and Validation in those areas. Increasingly however, the impact of eData and the need for controls around its use can be seen in the GCP area. Due to its large reliance on external sources of data, Clinical Research has some unique challenges. This session will cover:

I. Technology in Pharma and Validation Overview: a discussion of these concepts (which are widely felt to be cGMP artifacts) and relating them to the GCP area through analogies.

II. Centralized GCP Technology: The use of centralized eData and eSystems, primarily on the “sponsor side” has some unique challenges due to very short timelines and the external nature of clinical data inputs. Also the challenges of study-specific validation activities will be addressed.

III. De-Centralized GCP Technology – “Technology at the Clinic”: The advent of electronic Health Records (eHRs) has had a profound impact on Clinical Research and the way in which source data is handled, however the adoption of eHRs has been uneven, piecemeal, and largely independent of any research concerns . Resultantly, source data at clinical sites varies widely in format, from purely paper systems through purely electronic integrated source systems. However, a large and growing number of sites use a hybrid paper/electronic model with various sources of data, scans of source destroyed by hospital systems, paper notes, dictated notes, email notifications, and central sponsor data collection systems. Some ideas on how to address various hybrid source data scenarios will be presented.

Level: Basic Validation, Intermediate Clinical
Key Words: GCP, Electronic Data, Hybrid Source, Validation


sqaThe Society of Quality Assurance is a great professional society for those of us working in Quality Assurance, etc. in Pharma and related industries. I just received email notification that the Quality Assurance Journal from April is now online……This is the one that contained all the abstracts from the annual meeting. A bit slow to move from print to electronic, but I suppose better late than never:

Quality Assurance Journal Volume 12, Issue 2 Content Alert
Dear SQA Colleague:

The Quality Assurance Journal, Volume 12, Issue 2 is now available online! To access the content, please log into the SQA members-only website at http://www.sqa.org and visit the My Membership page from the menu at the top. The link to the Journal is available on the right side of the page under Publications. SQA Members do not need a separate login to access the Journal through the SQA website. The content listing for this issue is available below. All paid members of SQA receive an online subscription to the QA Journal, included with membership in SQA. If you are interested in contributing to the Journal, please review the information regarding submissions available on the SQA website.

We hope you find this information useful.


Elliott Graham, RQAP-GLP, Executive Director

Allison Travis, Program Director

Society of Quality Assurance
154 Hansen Rd, Suite 201, Charlottesville, VA 22911 USA
Phone – +1.434.297.4772 Fax – +1.434.977.1856
Web Site | Privacy Policy | Send to a friend | Unsubscribe

Additionally, I would encourage any Quality professional (in the Pharma or related space) who does not yet belong to SQA to consider joining. You can learn a lot and remind yourself of things you already know.

Oh, I nearly forgot. There is also an SQA group on LinkedIn. I encourge you to join that as well.


Not a real blogger?

When I first started this blog up, I was flattered that Shel Israel picked up on it. He was excited to find a real Pharma blogger. He actually wanted to interview me for some project or other he was working on, but his interest fizzled as he saw how my blog developed. It wasn’t the content (at least I hope it wasn’t), rather it seemed that he had hoped that it would be a real-time interaction, that I would post often and with reckless abandon, that I would name names, and put it all out there.

Shel (if you’re reading this and I’m sure you are since I linked to you), let me remind you:  I work in PHARMA….And to add to that, I work in one of the most sensative areas of any Pharma company, Quality Assurance – I handle our dirty laundry. Maybe that’s why you found my blog so intriguing at first, you thought I was going to put it out there anyway. Maybe I’m overstating your disappointment. You’re a busy guy (I know, I follow you on Twitter), but I think I’m at least 80% right on this.

Enough picking on Shel. He’s not alone in his disappointment. Pharma, being subject to what is arguably the most demanding body of regulation of any industry, will continue to frustrate the Web 2.0/interactive social media evangelism/technologist/Twitterite set. Pharma is conservative. Pharma is a late adopter of new technologies and paradigms.

Pharma is very, very gun-shy about being served by a regulatory body, fined, demonized, sued, condemned by congress, or otherwise censured. I have former colleagues who have had to testify before congress about questionable clinical data…not a fun time and I’d like to avoid the experience (at least in that context)

So in conclusion, maybe I’m not a real blogger. Maybe I’m a self-edited, self-published, web columnist who publishes on a very sporadic schedule…that’s a mouth full. I guess I’ll just call myself a pseudo-blogger. And I’m ok with that…at least for now.


Super Busy

My time has been largely booked with work. Travel has been quite extensive. In-house projects have been non-stop. As a result, there hasn’t been much time left for discretionary writing (i.e., this site). There is a light at the end of the tunnel, however.

Our HR group has posted a new position for our group (and another has tentative approval for 3rd/4th quarter). If you have any interest in Celgene, stop by the website and look in the Careers section…or drop me a line (my email address is in the comments below).

Bringing on more resources will definitely help out and hopefully clear some time for some writing. I’ve been thinking about a good number of topics that would make good discussion points. With any luck, I’ll have them up here soon.


21 CFR part 11 Update

Folks, it looks like some of our US regulations and guidance documents have been flagged for update by FDA….including everyone’s favorite, 21 CFR part 11 (source Cerulean’s email newsletter). I don’t anticipate major changes, just clarification on their intent.  Everyone enjoy your Friday.

New Guidance Agenda for 2009 Released by FDA

The FDA’s CDER has published its list of expected guidance documents and revised regulations to be issued this year (2009).

Readers of our 2009 forecast will find many items on the list familiar:

· 21 CFR Part 11

· Process Validation

· Adaptive Clinical Trial Design

· Contract manufacturing

· Various marketing, promotional and labeling guidance

· “Dear Healthcare Professional Letters” for recalls