Applied Clinical Trials reported this week news that Janssen Research & Development are establishing a global, cross-pharmaceutical Investigator Databank to improve the efficiency of industry-sponsored clinical trials. The Investigator Databank, to be hosted by DrugDev.org, will hold key information about clinical investigator sites including their infrastructure and “good clinical practice (GCP) training records”.
As these types of initiatives are developed and become more commonplace, it remains to be seen whether the expectation of regulatory inspectors will be that the industry sponsors maintains a copy of training records and CVs for trial staff, or whether it would be acceptable to cite the Investigator Databank as the official repository for such information. The latter would certainly remove one of the administrative burdens of managing trials, namely ensuring that an up-to-date CV is on file for key trial site personnel. It would of course be necessary to have certain guarantees that the records held at DrugDev.org were kept up-to-date and retained for the required period of time.
As collaborative efforts across industry increase, I’m sure we’ll see more of these issues arising. The challenge will be whether or not regulatory authorities and industry can accommodate a paradigm shift in terms of record maintenance and ownership.
We have been maintaining Trial Master Files for many years with increasing levels of consistency and quality since the introduction of Good Clinical Practice guidelines in the 1990’s and more latterly, the publication of European Directives and Regulations that make compliance a legal obligation. However, a quick review of published agency inspection findings shows that industry and clinical sites are still making many mistakes when it comes to document management. So do we really understand what the regulatory requirements and, importantly, how to comply with them in an efficient and cost effective way? Add to this the advent of technological solutions that now make it possible to manage our TMF content electronically, and we have a whole realm of other challenges to face.
For example, do you understand:
- what type of file structure the regulatory agencies may expect to find when they inspect your trial master file?
- what the indexing requirements are for the trial master file?
- what records related to third parties you are expected to maintain when you outsource trial activities?
- how you file emails, email conversation threads and email attachments?
- where you file documents such as the DSUR which may appear in several places (Ethics, Regulatory, Safety)?
- what the validation expectations are for an electronic trial master file (eTMF)?
- whether electronic signatures are permitted and if so, how they should be implemented?
- whether it is allowed to destroy paper original documents after they have been scanned into an eTMF?
- how you can provide the site with an electronic investigator site file (eISF) and what regulations you need to follow?
These questions – and many more – will be answered at a one-day workshop dedicated entirely to the subject of trial master files and electronic trial master files. The workshop is being run on Wednesday 28th November in Munich immediately prior to the 13th DIA Electronic Document Management Conference. Your workshop presenters are Eldin Rammell, Managing Director, Rammell Consulting Ltd and Karen Redding, Business Development Director, Phlexglobal Ltd. The workshop content has recently been re-written to include latest industry and agency experiences, more focus on electronic signatures and eTMF implementation challenges. This content-packed workshop is great value as a stand-alone training event at €550 (approx. £440) but can also be taken as an optional extra to the DIA EDM Conference. The workshop fee is fixed but if you also plan to attend the conference please note that the closing date for the conference early-bird discount is approaching fast. This workshop held in previous years has been fully booked!
On 24th September 2012 the Medicines and Healthcare products Regulatory Agency (MHRA) published a Good Clinical Practice Guide. Containing 542 pages, this is an essential reference book for anyone involved in some way with the conduct of clinical trials of medicines for human use in the UK. In addition to a chapter entitled “Key Trial Documentation” (chapter 4), it has a whole 29 pages devoted to the trial master file and archiving (chapter 10).
There are no great suprises in the guide. However, the guide states very clearly in black-and-white the MHRA viewpoint on many of the issues that have caused controversy and discussion over the years. I have picked out just a few examples to whet your appetite:
- The contents of the TMF should be sufficient to adequately reconstruct the trial, along with key decisions
- The TMF will be more than just the documents identified in ICH GCP as essential documents
- Signatures are only recommended where they add value. The guide also acknowledges that wet-ink signatures are usually just down to internal requirements; if your SOPs don’t mandate that a signature is required, it is likely that your documents don’t need to be signed!
- Ideally, the TMF should be a stand-alone set of documents rather than distributed across different file systems or electronic systems
- Emphasises the need for a document management plan when using a CRO
- Describes the inspectors’ expectations for “maintaining the TMF in a timely manner”
- Emphasises the unacceptability of an electronic Investigator Site File (eISF) to be held by the sponsor at the end of a trial which the site accesses via a portal (the ISF must be controlled by the site)
- Describes what is meant and required by QC of scanned images
- Describes the requirements of an electronic trial master file (eTMF)
- Confirms that destruction of original records following scanning is not ruled out, subject to several caveats
I think this will become an indispensable guide for the clinical records manager, clinical trial administrator and others involved in clinical trial activities. At £45, it may be beyond some budgets so I’d recommend getting a copy for your organization / company and taking a look through. Happy reading!
In many ways, the management of electronic records is no different from the management of paper records. But – and it is a big ‘but’ – there are a few significant differences and one of these is the approach that is taken with archiving of electronic records. For sure there are parallels betweeen the paper and the electronic world. For example, we have to consider the environmental protection of archived physical records just as we have to think of the protection of electronic records. However, there are some important challenges in the e-world.
These challenges can be categorised into system – or technical – issues, process issues and records management issues. The Scientific Archivists Group has recently been getting to grips with these issues and is shortly to release a draft guideline for electronic records and electronic archiving, structured around these three key areas. What is becoming apparent is the need for organizations to develop a digital preservation strategy that addresses each of these three areas, touching on software, hardware and storage media obsolescence as well as understanding the long-term information access requirements of the organization.
To find out more about this important topic, I recommend that you attend the forthcoming Scientific Archivists Group Conference. This is being held on 11th and 12th October in Bristol, United Kingdom. The agenda includes a detailed explanation and discussion on the draft guideline contents as well as the DGGF digitization White Paper and a presentation from Christine Gray, MHRA on the UK MHRA GLP Monitoring Authority view on these issues. This is also a great conference for networking with like-minded professionals. At £337.50, the full conference fee – including 1 night accommodation, all refreshments, drinks reception and conference dinner – represents great value for money. See you there…. but register quickly as there are limited places!!
Just a quick note to mention that a few more vendors providing solutions for electronic trial master files (eTMFs) have been added to our growing list. In addition to this list of packages solutions, there is also a large selection of technology companies and specialist consultancies who will custom build an eTMF solution for you. As this list is huge, we have not attempted to compile the list but this omission does not imply that their products are in any way inferior to the off-the-shelf solutions. It should also be noted that most of the off-the-shelf solutions will need configuration and may also need customization to meet your business needs.
As always, if anyone has any additions to the list, let me know in the comments box below and I’ll provide an update.
The challenge of ensuring the long-term accessibility, reliability and authenticity of archived electronic records has been with us for some time, particularly in an industry where retention times can be in excess of 15 years…. sometimes for the marketed life of a drug or device product. There are various strategies to help overcome the problems of software, hardware and operating system obsolescence as well as media failure. However, this task is made even more difficult in an industry that uses so many proprietary file formats. In comparison, the retention of Microsoft office documents is child’s play!
Help could be on its way with the initiation of a Pharmaceutical Common File Format industry group, championed by digital preservation specialists Tessella. The group, currently with six companies represented, intends to explore the challenges involved in the identification and characterization of pharmaceutical-specific file formats. These are formats which are currently not dealt with particularly well by tools such as DROID. Identification and characterization is the first step to developing a strategy for preserving these formats, either by monitoring the availability of software to access the content or by migrating the content to a compatible, more stable file format.
Feel free to contact Tessella directly to get involved. The wider participation there is in this initiative, the more likely it is that the deliverables will be representative of the industry and will be of value.
The British Standard BS 5454 Recommendations for the Storage and Exhibition of Archival Documents has been in existence in one form or other since the late 1970’s. Throughout this period, it has been a fairly succint document (last revision contained just 25 pages) and has been primarily used to give guidance on archival conditions for long-term preservation, for example, museum conditions. In this respect, it has often been misquoted as a general standard for the design and operation of business archives.
The British Standards Institute has now withdrawn this standard, together with the associated guide PD 0024:2001, and have instead made available a Published Document PD 5454:2012 Guide for the Storage and Exhibition of Archival Materials (pub. March 2012). This new document is a more subsantial publication, being 76 pages, and really brings the previous standard up-to-date. Although it still has an emphasis on preservation of valuable documents – such as manuscripts – and the exhibition of such documents, it is now much more applicable in a business archive scenario. It also addresses storage of digital media.
The document begins with detailed guidance on the nature of documents and best practice for their storage and use. This includes topics such as environamental ccontrols for different media, protection against mould, infestation and pollution, environmental monitoring, environmental control, packaging and security. The guide then goes on to describe the repository building and measures that can be taken in the design and build of an archive facility. This section includes hazard avoidance, security, construction, environmetal stability, fire and water protection, load distribution, shelving and lighting, to name but a few.
I think this new publication is a more useful document than the old British Standard and has a much wider scope of application. However, care should be taken to avoid treating the content as a standard, expecting absolute compliance. Indeed, the cover warns “This publication is not to be considered a British Standard”. PD 5454:2012 can be obtained from the BSI Online shop (£244.80 non-member price / £122.40 member price).