Who is the FDA?
The Food and Drug Administration (FDA) is the US regulator responsible for protecting the public health by ensuring the safety, efficacy, and security of drugs for human use. They regulate a variety of different markets but for the purpose of this article we will focus on the rules relating to drugs associated with clinical trials.
Throughout this post, we’ll also make reference to the Code of Federal Regulations (CFR) which is a codification of the general and permanent rules published in the Federal Register in the US. Title 21 of the CFR (CFR 21) is reserved for rules of the FDA.
Does the Trial Master File impact US sponsors?
The Trial Master File (TMF or its electronic counterpart, the eTMF) is often referenced in many clinical regulations around the world – for example it is referenced in the upcoming EU Regulation 536/2014 on clinical trials. However, the FDA do not reference the TMF/eTMF within CFR 21 or any of their regulations relating to the management of clinical data.
That said, should a US organisation look to distribute into the EU, or sell a drug to a biotech in order to re-sell, a TMF/eTMF will be required.
Additionally, many consider the creation and maintenance of a TMF good practice and supports a healthy approach to a QMS.
So, which data retention rules should you be aware of?
Broadly speaking, 21 CFR Part 11 is the FDA’s regulation for electronic documentation and electronic signatures. However, when it comes to your data retention and management, there are several sub-sections of 21 CFR you should be aware of:
- 21 CFR 11.10 states that “electronic records and electronic signatures are treated the same as paper records and handwritten signatures.”
- FDA 21 CFR 211.180 prescribes that all records required under this part, or copies of such records, shall be readily available for authorised inspection during the retention period
- FDA 21 CFR part 58 specifies good laboratory practices for conducting non-clinical laboratory studies.
- FDA 21 CFR 58.190 requests that only authorised personnel shall enter the archives.
Let’s break it down further and explain how these relate to your data retention and archiving strategy.
1 – Archiving
The regulations seek to ensure all documentation relating to a clinical trial are archived appropriately to allow for future access and potential inspections.
You can be forgiven for thinking that this is a rather broad request, but the FDA have drilled into this further within FDA 21 CFR part 58. This section relays that archives must be limited to access by authorised personnel only and should contain all raw data, documentation, protocols, specimens, and final reports during, or at the close, of the study.
From an archiving perspective, this means that the organisation holding the related data and documents must have an appropriate solution whereby user access can be assigned internally and externally to your organisation.
2 – Preservation
Switching back to Part 11, is the requirement to ensure digital assets are stored in a manner that maintains them in “human-readable form”.
“You should allow inspection, review, and copying of records in a human readable form…”
Why does the FDA request this? Because over time, file formats can become corrupt, lost and even, obsolete. When you consider that these documents may be retained for several years or decades it may become the case that when your organisation or an inspector retrieves a particular file, they can no longer open or read it.
As such, your eTMF solution should encompass the ongoing automatic process of file normalisation to prevent this from happening. Normalisation is a process whereby a copy of each original digital asset is created and maintained in a format that can be opened and read by future hardware and software. This essentially means that whatever has been uploaded will remain in a readable and usable format for as long as it is retained.
You must have access to a complete audit trail for all assets held within the digital archive. 21 CFR 11.10 exerts the requirement for the use of secure, time-stamped audit trails for each document archived which records the date and time of operator entries and actions that create, modify, or delete electronic records.
According to our recent research, 83% of respondents claim to be unable to use their archive to provide clear audit trails.
You should ask yourself – or your provider – is your data being stored in-line with data best practices ALCOA and GCP guidelines? Can an inspector gain access to an audit trail relevant to any piece of documentation they wish to analyse?
A purpose-built solution is the only solution
As we’ve outlined above, there are several regulatory stipulations regarding the long-term management of associated clinical data but they all have the integrity and safeguarding of that data as their focus point.
There are various data storage options you could look at but there is only one purpose-built option – a digital archive and preservation solution.
Only this tool can provide the long-term safeguarding, access and readability of your data.
If you have any concerns or queries, please contact our expert team.
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