Deb Sedor, former Director of Quality Assurance at J&J, and Managing Expert for YourEncore’s Quality Center of Excellence, is one of YourEncore’s premier subject matter experts in GLP Analysis, collaborating with clients to improve and innovate their GxP procedures and Quality Compliance best practices. In this Expert Q&A session, Deb provides valuable insights into opportunities in GLP/GCLP and helping companies with their inspection readiness .
How do you feel that Preclinical studies have changed over the years in terms of compliance?
Years ago, if you had a rate-limiting issue during development, you would likely not go forward with the drug. Projects nowadays have enough science and technology support to be able to go forward, making the more frequent studies more complex.
Historically, preclinical studies were run within a pharmaceutical company by the in-house employees, including a toxicologist and multiple technicians. The activities that supported the preclinical study were extremely well-regulated and controlled. Over the years, preclinical studies and clinical trials have become more complex, and there are more steps taken to ensure compliance throughout the study. Most companies follow an outsourcing model, which adds inherent risk to the development process.
That difference in experience when managing and understanding all the components of these studies, impacts compliance since it inherently distributes the responsibility into several different areas, rather than within one controlled unit.
The current community of experts who have gone into consulting have helped smaller companies stay in compliance with FDA regulations and OECD guidelines, as they usually lack the historical experience of how preclinical studies need to be performed.
What is the most common observation you have when helping companies be Inspection ready?
Companies must be ready to produce the data and documentation to completely reconstruct the preclinical study. Some company stakeholders do not understand the importance of being able to retrieve, compile, and explain the data, but this reconstruction is crucial to the survival of a project.
More complex systems are used within the toxicology or the preclinical arena, along with the SEND initiative, where the government requires that some of the data be put into a standard CDISC. Agencies have used this method for a few years in the clinical world, standardizing the data for re-analysis.
In Europe, the regulatory bodies issue GLP Certificates to facilities which have successfully passed an inspection. The FDA does not issue such certification; therefore, companies are obligated to provide evidence that the facilities cited in their submission have been audited for GLP compliance. If the European reviewer has a question about the GMP compliance status of facility in the United States, the reviewer can request that an audit be performed by the foreign regulatory body to assess the GLP compliance status of the facility.
Do you think the TransCelerate common Preclinical protocol template will help companies be more efficient and effective?
Overall, the template will help companies be more efficient and effective if they use the protocol guidance when a need arises. In a way, the template is publicizing a tool that has been part of the regular battery of protocol templates for many years. Coming from someone like myself who reviews protocols and tries to connect the dots, it should make other people’s lives a bit easier, especially with preclinical studies becoming more complex.
The usage of this template is primarily driven by large Pharma, where these protocol templates could be used by their virtual associates and virtual companies. With the complexities of studies changing and outsourcing models preventing consistent in-house expertise, the TransCelerate system will be helpful. The template promotes secure data sharing and comparison, leading to growing understanding between different teams and different technologies. For example, once the preclinical toxicology studies move into the more complex technology, the template model will be much easier to fully integrate throughout the process. If you change users’ behavior now, it will be a smoother transition in the future.
I think the template is good overall, but I hope data quality remains paramount. Each team has grown over time, from one study director controlling all components, to now having all sorts of roles: toxicologist, protocol scientist, head lab tech, animal tech, etc. Even with more moving pieces, any sort of “hands-off” management concerns me the study’s data quality could suffer. Each role just needs to make sure their contributions are complete and align with the other members of the team before marking any section complete.
The FDA believes the proposed rule on GLP for non-clinical studies (24 Aug 2016) requires a complete Quality Management System (QMS). Do you feel companies are making good progress towards the development of a GLP QMS? Do you have advice for these companies?
First off, most companies start out with a GMP QA representative, so the mindset is in the GMP QA world instead of GLP. As a start, this is okay, as you need a lot of CMC data to go into your submission documents. Eventually though, they’ll bring in the clinical stakeholder and a GLP QA expert, or a clinical person who understands enough GLP context to get them to the next level.
When you look at the GLPs that have been in place for a long time, and you look at what steps make up a QMS, I think that the original GLPs are inclusive of all the information needed. It should be noted that any company that already has a mature GLP organization is that they already have a QMS, they just need to give it an official title. If a company does not have a comprehensive GLP organization or complete QMS, they are not truly meeting all the expectations of the regulations.
What do you think is the greatest opportunity for companies in GLP and GCLP?
The greatest opportunity for companies themselves in GLP or a GCLP world is more standardization and efficiency in their projects. This leads to completing projects right the first time and submitting full reports to the proper health authorities. In a GCLP world, people need to understand that Clinical QA experts may not have the right context if they have never worked in a laboratory or provided oversight to the full operation. Overall, it is much better to have a GLP person who knows GCP, but the best possible option is to have scientists who understand medicine, laboratory, and clinical aspects to the project. Bottom line, if they have never been in a lab, they won’t be able to understand what the GCLPs really mean; if they have never been in the GCP world, they won’t be able to understand the privacy and the impact of all of GCP factors.
If needed, teams should utilize outsourced experience for quality systems and GLP, especially in the GCLP, just as they do on their science and drug development. This can also help a company understand their use of this advanced science as biomarkers and endpoints in the clinical trial, ensuring that their teams need to reach a new level of collaboration and internal review to match the quality with the labs that are supporting them.