Ensure Your Informed Consent Forms Comply With New Requirements

For those sponsors conducting clinical trials that need to comply with FDA regulations, remember that from 7th March 2012 your informed consent documentation must comply with the new 21 CFR § 50.25(c) requirement. This requires the informed consent form to inform the clinical trial subject about the clinicaltrials.gov website. Specifically, it has to include the following statement word-for-word:

“A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. Law. This Web site will not include information that can identify you. At most, the Web site will include a summary of the results. You can search this Web site at any time.”

A guidance document on the new requirements is available from the FDA website by following this link.

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GMP Directive (2003/94/EC) to cover active substances?

The European Commission are proposing to extend the scope of Directive 2003/94/EC to cover active substances, including the manufacture of active substances. The intent is to bring cohesion of requirements for active substances and medicinal products. However, since all of the provisions for medicinal products would then also apply to active substances, there are significant implications, including requirements for document and records management.

A consultation process on the impact of this proposed change has now opened, with responses requested by 20 April 2012. Click HERE to download the concept paper.

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Is it OK to “manipulate” PDFs to improve records management?

This is a question that I hear posed fairly frequently, I guess as a result of organisations managing electronic records rather than – or in addition to – traditional paper records. A typical scenario is an electronic document received into the Records Centre as two individual components; is it legitimate for the Records Manager to combine the individual files into a single PDF. Another scenario I’m often asked about is a large report that is circulated as a hard-copy for signature. Is it OK for the Records Manager to scan just the signature page and integrate it into an existing PDF of the same report; scanning of the whole paper document would create a file that was too large to manage and would not necessarily be text searchable.

For the regulated pharmaceutical and biotechnology sectors, I have been unable to locate a regulation or law that deals specifically with these scenarios (if anyone can point me to one, please comment below!). So to answer the question we really need to look at the regulations and guidance to identify any predicate rules or principles for us to base an answer upon. The best guidance that I think is relevant here is a reflection paper from the European Medicines Agency on “Expectations for Electronic Source Documents Used in Clinical Trials“. This paper also refers to the CDISC Standard for Electronic Source Data Within Clinical Trials which discusses a group of 12 high-level principles which, if adhered to, provide a good basis for the acceptability of electronic source data. Compliance with these principles helps us to answer the question posed.

Regulated documents need to be trustworthy. Furthermore, their trustworthiness must be able to withstand scrutiny, either by an auditor, a regulatory inspector or legal counsel. The EMEA reflection paper requires that documents are: accurate; legible; contemporaneous; original; attributable; complete; consistent; enduring; and available. The CDISC standard also adds ‘not modified’.

Whilst the manipulation of PDF files is well meant and helps to reduce duplication and encourage good records management working practices, it has the potential to introduce a question as to the reliability and authenticity of the record. Take the example of the signed study report. The signatory did not read, review and sign the content of the PDF file. Although the Records Manager knows that the content of the PDF and the hard-copy are the same – or assumes that they are – , the signature was not applied to the PDF and should therefore not be attached or associated with it. This would be akin to taking the signature page from a hard-copy study report and stapling it to an alternative version. Or taking the signature from one contract and attaching it to a paper version of a different copy. An alternative approach for signatures is to create a standalone signature sheet where the signatory affirms his/her approval of the content of a separate document that he/she has reviewed.

The example of combining different PDF files has similar problems. Although the Records Manager knows that the files should be combined, this process has the potential to call into question the validity of the concatenated document. If we use the analogy of the study report again, this process is like having the individual components reviewed but the Records Manager assembling the final study report and archiving it with no final approval. Following report assembly, the sponsor and investigator review and approve the compiled document.

To conclude, I said at the outset that I could not locate specific regulations on this. There will always be exceptions and the final decision has to be taken following a risk-based approach. However, my recommendation would be to identify document management processes that avoid the need to manipulate signature pages and/or manipulate individual components of a document. Our goal is always to create and manage reliable, authentic, trustworthy records.

Posted in Compliance, e-records, Litigation, Records management practice, Regulations | 1 Comment

Certification by a qualified person and batch release – Consultation

A concept paper on revising Annex 16 of the guide to good manufacturing practice: certification by a QP and batch release is currently open for consultation until 31/01/2012 using the following link to the EMA website: http://bit.ly/yTocBW

The concept paper succinctly describes some of the challenges in certifying batches of manufactured drug product for release in an environment where different parts of the manufacturing process are often conducted in different places around the globe and frequently by different companies. This also presents a challenge from a document management perspective; it is not always clear who has responsibility for maintenance of the constituent parts of the product specification file and which records, if any, the QP is expected to maintain, be responsible for or simply to just have access to. It could be argued that this clarification best sits in Chapter 4 of Volume 4 GMP Guidelines but perhaps the scope of the revision to Annex 16 should also cover documentation?

Any comments on the concept paper should be submitted to the EMA by end-January.

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Are Copies as Acceptable as Original Documents?

This is a question that I seem to be hearing with increasing frequency! I think the reason for this is that an increasing number of companies and organizations are introducing electronic document management systems (EDMS). Where there are hard-copy records generated, these are digitized (scanned) and the resulting electronic files uploaded into the EDMS. The question then remains: What do I do with the original source paper records?

On Thursday 1st December this question will be addressed at the Drug Information Association (DIA) Electronic Document Management conference in Zurich. Lisa Mulcahy (Mulcahy Consulting) and Steve Scribner (International Life Science Solutions) will be presenting a framework that has been developed by a Special Interest Area Community to facilitate the destruction of original records following digitization. Of course, there are caveats to this process and Lisa/Steve will be outlining what some of those caveats are, including the certification of copies to provide assurance that the copy is a complete and accurate representation of the original record.

Incidentally, this question was put to FDA GCP Questions some time ago with the following response given:

“The scanning of study records to CDs and/or pdf files is acceptable for clinical trials provided the scanning process ensures that the resulting copy contains all of the original attributes and information found in the original records and someone certifies, after verification, that the records are an accurate and complete reflection of the original.

If you wish to use the scanned copies in lieu of the paper source data, (i.e. destroy the paper source data) then the scanned copies would have to meet the definition of a certified copy as described in our guidances. If you wish to retain these copies in electronic form in lieu of paper your computer system would have to comply with part 11 [21CFR11]. 

Certification should be accomplished by having the person who makes the copy, sign or initial and date the copy to indicate it meets the requirements of a certified copy as described above. This should be described in the SOP and can be accomplished by initialing and dating each copy or by initialing and dating a document certifying copies in bulk. Whichever method is used the SOP should describe the procedure.”

I find the reference to certifying copies in bulk particularly interesting as companies often ask whether each individual page or individual document needs to be certified. The process of certifying documents in batches or in bulk has long been the practice in the world of microfilming so it makes absolute sense to accept the same principle in the world of electronic digitization too.

Posted in Compliance, e-records, Litigation, Records management practice, TMF | 2 Comments

MHRA Opens Public Consultation on Review of UK Medicines Legislation

On 25th October, the MHRA opened a consultation period of 12 weeks for their review and consolidation of UK legislation pertinent to manufacture and use of medicines. Many requirements relating to the creation, management and retention of medical records are covered by the regulations within scope. However, an initial review of the proposed changes do not appear to reveal anything specifically about this topic.

Of note, the requirements for clinical trials is explicitly excluded from this exercise. The consultation document states:

“There are ongoing negotiations at a European level about the introduction of a Directive that would require substantial changes to the regulation of clinical trials. In addition, on 23 March the Chancellor of the Exchequer announced that the Government will review the UK’s implementation of the Clinical Trials Directive in order to reduce perceived gold-plating and to increase the proportionality of the system. We intend to leave the existing UK legislation regulating clinical trials as it is for the moment, rather than consolidate it now and then amend it substantially not long afterwards.”

Those records managers with an interest in GCP records need to look out for the subsequent review

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eTMF Vendors – Who Has the Largest Market Share?

This is a question just sent through to us….. which vendor has the largest market share of the eTMF solution vendors? I guess the answer will depend on whether we’re talking about most client licenses/seats or highest volume of sales and whether we’re also including the likes of EMC and others who build bespoke eTMF solutions.

If any readers would like to comment on this question, please submit a comment below.

Posted in e-records, TMF | 2 Comments