How to Ensure TMF Inspection Readiness in 2019
We recently sat down with Marie-Christine Poisson-Carvajal, Head of TMF Operations to discuss how Pfizer ensures the quality and compliance of their TMF across various different trials and users through the use of their own in-house Quality Management System (QMS).
HOW CAN COMPANIES MAKE SURE THAT THEIR TMF OPERATIONS ARE INSPECTION-READY AND COMPLIANT WITH THE REGULATIONS?
A company can use a quality management system (QMS) to ensure that their TMF system is not only inspection ready, but of course, compliant.
In addition to aforementioned, there should be performance indicators set up to assist the study team and the functional lines in the company to measure the health of the TMF. Common TMF health indicators are completeness, timeliness and quality. Most companies should set up a framework similar to the above in order to remain inspection-ready and compliant with regulations.
WHY IS IT IMPORTANT TO BUILD A STRONG TEAM WHO CAN BRIDGE COMMUNICATIONS BETWEEN INTERNAL AND EXTERNAL OPERATIONS?
A study trial master file is an ensemble of documents coming from all partners involved in the execution of the clinical trial. Sources include different functional lines within the sponsor side, vendors or CROs.
These sources have to be consistent and well connected to ensure that the documentation for the study is aligned, complete and compliant. Strong communication is crucial when gathering the right documentation and information at the right time. Good communication can happen with positive interaction and relationship among the study team members and other partners involved in the execution of a clinical trial.
In order to effectively support all different sources, it’s important for us an organisation, to be aligned, harmonized and standardized in all aspects of what we do. If we are unified in our approach then we can provide consistent continuous support to the different partners and constantly assess the performance of our process control systems. Again, communication is the key to everything.
HOW CAN COMPANIES BUILD A GOOD TEAM WHO CAN BRIDGE COMMUNICATIONS?
In my opinion, companies can build a good team and encourage strong communicaton through leadership. For example, at Pfizer, we have a clinical project manager (CPM) who is the point person to coordinate and establish the interactions with all the functional lines, partners and vendors on behalf of the study team. The CPS has to lead, monitor and ensure that there’s a good dynamic at the study-team level.
When it comes to TMF, we have a dedicated TMF study owner, who is the TMF point person for the study team. Together, the CPM and the TMF study owner must drive everything and ensure that there’s effective communication at the team level to facilitate activities that are related to TMF.
WHY DID PFIZER THINK OF CREATING AN IN-HOUSE TMF? WHAT WERE THE DRIVERS BEHIND THIS DECISION?
At Pfizer, we are on our second eTMF. We moved from paper to electronic as early as 2002. The main driver behind that was to establish a more controlled environment for the management of TMF documents and build visibility and transparency of documents that are expected. As you know, a TMF is one of the key deliverables of a clinical trial and the TMF is what is used by auditors and inspectors that a study was conducted in compliance with GCP, regulatory requirements, to confirm data integrity and reliability and also to ensure patient’s rights and safety were protected during the execution of the study. Therefore, as a sponsor we have an obligation to design and implement a TMF system, process and requirements that provide the organisation a very controlled environment to manage clinical trial documentation.
Answering the in-house TMF question, our second generation eTMF at Pfizer was developed with an external vendor and after a couple of years in implementation we decided to maintain our eTMF internally.
However, I think whether it’s in-house or not, every company needs to have some sort of customization. The companies need to customize their TMF to ensure that it is consistent and in agreement with their own internal processes and requirements.
Companies that want to adopt an eTMF should certainly use the DIA TMF reference model and determine the level of customization needed to ensure their list of artefacts support their internal processes and requirements.
DO YOU THINK TRAINING YOUR INTERNAL TEAMS IS CRUCIAL IN ENSURING THAT EVERYONE IN THE COMPANY KNOWS WHAT IS EXPECTED BY THE REGULATORY BODY? DOES PFIZER PROVIDE SUCH TRAINING FOR INTERNAL TEAMS?
Yes, absolutely! We have different levels and types of training at Pfizer. Some of the training is generic and completed when people are on-boarded via a suite of training courses. There are some variations, depending on job roles, but we have a set of core training courses about GCP, regulations, inspection readiness and compliance.
We have some requirements to re-take training, every two years or so. In addition to that, when it comes to TMF, we have continuous education on trial master files such as TMF requirements and regulatory requirements that are specific to TMF and how the impact the way we manage the TMF. Our targeted audience is Pfizer colleagues, contractors, vendors – i.e, all individuals generating and/or collection documents/documentation relevant to clinical trials.
It is important to ensure that training is not a one-time thing. There needs to be continuous educations because the organisation around us is always changing. People come and go, and the level of knowledge and understanding is at different places. You want to make sure that you can provide continuous education through the organisation.
WHAT WOULD BE YOUR TOP THREE TIPS TO OPTIMISE THE QUALITY AND COMPLIANCE OF TMFS ACROSS TRIALS AND USERS, IN ORDER TO BE INSPECTION-READY?
My first tip is to centralize and automate everything that can be. The Companies should think about centralizing TMF tasks, such as indexing, QC of documents, in other words transactional tasks that do not touch on content of documents. Such transactional tasks can be performed by dedicated resources in order to ensure consistency in terms of filing of documents and quality of documents. It also frees up time for the study teams or the functional lines to focus on what matters the most for them, which is the collection, authoring and finalization of their documents.
My second tip is to stay on top of the regulations, including the country requirements, in order to ensure that everything is accounted for in the TMF specifications. As you establish your TMF specifications or list of expected artifacts it is important to give full visibility to the functional lines, as to what is required and when.
My third tip is around educations. Educate the study teams and functional lines within your organisation, to review the study TMF against the study execution itself and not only rely on metrics.
Way too often there are examples of study teams that go through an inspection or an audit and have findings of missing documents. They are surprised because they say: we don’t understand, our TMF completeness metric is within the threshold, and we still have missing documents.
Therefore, it’s important to understand that a metric is an indicator; it doesn’t mean that you have everything. Again, I cannot say enough how important it is to review the completeness of a study TMF against the study execution, against any events that may have happened, or decisions that have been made, to ensure that all documentation supporting the study really reflects what happened during the study.
ANY OTHER ADVICE YOU WOULD LIKE TO GIVE?
In my view, it’s important to keep in mind that you can only achieve compliance quality, inspection readiness if you have the right resources, right technology, and right process. An eTMF should be designed in such a way that it is going to provide the organisation with the tools and visibility that they need to be inspection-ready and compliant. The infrastructure and the framework have to be placed in the hands of the individuals who have the expertise, knowledge, understanding and capacity to define, implement and monitor TMF operations.