About LMK’s How-To Series
LMK’s commitment to education inspires our most popular and most important service offering: TMF University. TMF University is LMK’s industry-first TMF training program, offering a wide range of courses to suit all needs; from beginners just learning to identify common regulatory documents to professionals seeking to hone their expertise.
Celebrating TMF University’s renewed focus on taking TMF action, LMK is happy to present this how-to blog post, the third post in a multi-week how-to series. You can read the series’ last post here. In the coming weeks we’ll continue to dispense with complexity and focus on what it takes to achieve a basic TMF skill we think every clinical research professional should know.
What is an original document? Are copies acceptable for filing?
Confusion surrounding what constitutes a true original document results from a simple fact: document formats, storage media, and technology evolve quickly while regulation drags decades behind. When TMFs were only paper, one would need to consider what documents should be kept as originals and what could be photocopied or faxed. Now, with eTMF or hybrid arrangements, it’s not always clear where a document first originated or what document should be considered the original. As discussed in our last post, new technology allows documents to enter the TMF from many sources: attached to an email, scanned, created in an eTMF directly, sent from a phone app, or generated as a report or output from many types of clinical trial tools. The story of a document can be complex and is not usually apparent to the individual responsible for its filing. To understand if a document is acceptable for filing, a TMF professional must know the current regulatory landscape and follow a few common-sense principles.
Discussion of what documents should be collected as an original usually provokes controversy and anxiety. As with the last how-to topic, FDA has chosen a hands-off approach. No FDA regulation identifies any specific documents that must be kept as a paper original. ICH E6 R2 contains the strongest guidance surrounding document handling. 21 CFR Part 11 also comes into play when documents are generated or stored electronically.
The foundation of discussion for this topic is found in ICH E6 R2, specifically in the addendum on page eight. A certified copy is defined as “a copy (irrespective of the type of media used) of the original record that has been verified (i.e., by a dated signature or by generation through a validated process) to have the same information, including data that describe the context, content, and structure, as the original.” The term certified copy is then incorporated into the definition of source data on page seven, resolutely confirming that electronic copies can be ICH GCP compliant.
The following guidance documents are also helpful when looking to piece together the FDA’s and the MHRA’s thinking:
The FDA speaks little about regulatory document requirements. The document linked focuses mostly on source documents and data. Regulatory documents, however, are included through general language. Just as with e-signatures, the FDA expects that electronic records, “meet the same fundamental elements of data quality (e.g. attributable, legible, contemporaneous, original, and accurate) that are expected of paper records”. In this guidance, the FDA specifically states, the “FDA is allowing original documents to be replaced by copies provided the copies are identical and have been verified as such”.
In this guidance, the FDA defines an electronic record as, “any combination of text, graphics, data, audio, pictorial, or other information represented in digital form that is created, modified, maintained, archived, retrieved, or distributed by a computer system.” Both an eCRF and an electronically created regulatory document would be considered an example of an electronic record. This guidance also specifies that source data can be retained as a certified copy, however, “When data elements are transcribed from paper sources into an eCRF, the clinical investigator(s) must also retain the paper sources, or certified copies, for FDA review.” This does not mean that the paper original needs to be archived, but rather a certified copy (which could be electronic) of the original source would be acceptable.
This 2017 draft guidance clarifies the FDA’s 2003 guidance in light of technological advances. Although the document focuses on data handling and validation, question 6 confirms that, “FDA permits the interchangeable use of electronic records and paper records for the archiving and protection of records provided that recordkeeping and retention requirements are met.” The FDA specifies that a process should be in place to certify that the electronic copy is a correct representation of the original (echoing ICH E6 R2). Importantly, the FDA notes that a sponsor could destroy the paper source data if the certified copy archival process is compliant with 21 CFR Part 11 regulations.
At a recent TMF summit, attendees were given the opportunity to attend a question and answer session with MHRA Inspector, Andrew Fisher. The Drug Information Association (DIA) Document and Records Management Community was kind enough to post minutes of this session on the TMF Reference Model webpage. The Inspector confirmed that a certified copy could replace an original paper document. Interestingly, he noted that failure to destroy the paper document after certifying an original could be cause for further investigation, and could spur investigators to request the available paper documents.
Practical Advice: ICH E6 R2 greatly reduces the confusion surrounding the terms ‘copy’ and ‘original’. A copy of a document is acceptable for filing in the TMF if it is a certified copy. The FDA doesn’t define a method for certifying copies but mandates that you must have one. This can be accomplished through SOPs and clear documentation showing you’ve followed the process outlined by the SOP. For a regulatory professional, this means that your organization’s strategic thinkers and IT leaders have likely already provided you the tools necessary to create certified copies of your own through the implementation of 21 CFR Part 11 compliant systems and ratification of compliant SOPs. Your use of ALCOA (Attributable, Legible, Contemporaneous, Original, Accurate) good documentation principles, therefore, is likely enough to ensure a document (whether certified copy or original) belongs in the TMF.