Eldin Rammell is managing director at Rammell Consulting Ltd, a sub-contractor of Phlexglobal Ltd.

Eldin Rammell

The past year has seen significant consolidation of mid-size CROs, with many of them being bought or put up for sale. In particular, the top six or seven CROs seem to be signing more preferred partner deals, such as Pfizer teaming with Parexel and ICON, and Takeda’s deals with Covance and Quintiles, which is driving mid-size CROs growth through major acquisitions. There has also been a big shift in outsourcing services to preferred partnerships, with large CROs outsourcing niche services to small CROs on a functional basis. Sponsors are also assessing their current tasks and outsourcing those that require non-core expertise. One niche area that companies do not always consider outsourcing is document control. Document management is essential in the pharma industry but can be difficult to optimise, so working with an outsourcing partner can be valuable. 

Karen Redding. Global business development director at Phlexglobal Ltd.

Good records management is crucial in the pharma industry. One of the most common problems we see is individuals and teams retaining their own copy of documents rather than utilising a single central source, preferably made available via an electronic document management system (EDMS). In our highly regulated environment, demonstrating the reliability and authenticity of documentation is critical, so individuals making use of a central definitive source for their records is particularly important. In addition, much time and money is wasted through duplication and mismanagement of documents when carried out in an uncontrolled manner.

In some industry sectors, management have introduced strict controls over where and how documents may be saved. Some organisations, for example, prevent documents from being saved anywhere except in an authorised EDMS. Perhaps this is one step too far, but good document control is necessary to achieve regulatory compliance.

Another problem we often see is poor version control, particularly for draft documents. As there may be a need to demonstrate appropriate review of draft documents, it is essential that any review signatures and comments be unambiguously linked to the associated document. This requires a formal system of version control within the organisation.

Eldin Rammell. Managing director at Rammell Consulting Ltd, a sub-contractor of Phlexglobal Ltd.

Once a pharmaceutical process has been completed—whether a clinical trial or the production of a batch of drugs—the only thing remaining to demonstrate regulatory compliance is the documentation audit trail. This is why adequate quality control is so important. It is not enough just to have a record of what happened; regulatory authorities have an expectation that you can demonstrate those records to be accurate, legible, contemporaneous, original, attributable, complete, consistent, enduring and available when needed  (1). A well-designed quality system will ensure that documentation being sent off to the archive is “fit for purpose”.

Poor quality control can be recognised when a sponsor is notified of an impending regulatory inspection. All too often, there is a mad panic as documentation is retrieved from various filing systems and hours are spent checking files for completeness. This is wasted effort and diverts key personnel from their core activities. A robust quality control system should eliminate the need for these eleventh-hour activities and result in inspection-ready files. Furthermore, quality control should ideally be embedded within existing processes rather than being introduced as an additional process. It is better to prevent poor quality records from being generated rather than identifying poor quality records and having to expend effort in fixing them. 

The vast majority of regulatory requirements worldwide actually say very little about records management, which has been a bone of contention for years. On the one hand, records management professionals prefer the need for explicit guidance so that there is assurance they are operating within the permitted boundaries, but on the other hand, the lack of explicit guidance gives freedom to define company-specific processes and systems. However, it would be helpful for regulators to provide more specific guidelines in areas that are troubling industry the most, particularly where they see commonly occurring inspection deficiencies. 

The bottom line is the need to have documented processes and robust document management systems (either electronic or physical) that permits the demonstration of the above-mentioned attributes. The most common regulatory failures are an inability to locate requested documents (because they have not been generated, have been lost or destroyed, or stuck in a chaotic filing system) and poor quality records. Inspection findings related to quality typically cite a lack of appropriate signatures, missing pages, and missing document attributes, such as no page numbers, dates or document reference identifiers. As previously stated, the best processes are ones where quality is checked before a document is signed off or used; poor quality records never find their way into the files as they are corrected before they become final. 

One of the key points to note is that few regulations have thoroughly addressed the electronic environment that we are now working in. As such, it is extremely important that organisations pay attention to the predicate rules — those regulations and guidance documents that are applicable to traditional hard-copy data and documents. Moving into the electronic arena, perhaps the most important requirements are the need to use appropriately validated systems  (2) and to design data and document management systems that maintain the integrity, authenticity and completeness of the content for the full term of the retention period.

Regulations mandate that some data be retained for the marketed life of a product. In these cases, it can be challenging to address the potential problem of software, operating system and hardware obsolescence (i.e., the ability to retrieve and read data in ten, twenty and thirty years’ time). One solution is data migration or the use of enduring file formats. Data migration requires the regular transformation of data from one file format and/or hardware platform to another across the retention period, ensuring each data migration is complete, checked and fully validated. An alternative approach is to choose a file format and storage medium that is likely to remain accessible over the retention period, such as PDF/A, TIFF, ASCII or XML. This is often a lower cost option, but can result in loss of metadata and functionality, such as the inability to re-process data. 

The challenge for industry is that whilst some guidance on long-term electronic archiving exists (3) , guidance from the regulatory agencies is sparse and often inconsistent. In the absence of guidance, the recommended strategy is to adopt a risk-based approach in determining electronic archiving solutions and processes. It is also essential that decision-making processes are formally documented. This documentation should be retained as part of the validation package, which may be requested in the event of regulatory inspections. 

1. EMA, “Reflection paper on expectations for electronic source data and data transcribed to electronic data collection tools in clinical trials” (June 2010).PIC/S, “Good Practices for Computerised Systems in Regulated “GXP” Environments” (September 2007). 

2. Guidance on the Archiving of Good Clinical Practice Material (Scientific Archivists Group, September 2007). 

Articles

The past year has seen significant consolidation of mid-size CROs, with many of them being bought or put up for sale. In particular, the top six or seven CROs seem to be signing more preferred partner deals, such as Pfizer teaming with Parexel and ICON, and Takeda?s deals with Covance and Quintiles, which is driving mid-size CROs growth through major acquisitions.