As the biopharmaceutical industry increasingly turns its focus to discovering and delivering targeted, personalized medications, the companion diagnostics field is rapidly advancing. By 2015, the worldwide companion diagnostics market will be worth $3.45 billion, according to London-based market research firm Visiongain. The involvement of central laboratories in the companion diagnostics space is also growing, as they increasingly play a role as partners with, and facilitators between, biopharma and diagnostic companies.
In September 2012 at the Clinical Business Expo in Boston, MA, Covance gave a presentation on the role of the central laboratory as a partner in the co-development and regulatory approval processes for a targeted therapeutic with a companion diagnostic. The presentation highlighted how central laboratories help sponsors develop and collect data for companion diagnostic testing. In addition, key success factors for personalized medicine partnerships were addressed, including best practices and how to avoid complications that can make such partnerships challenging.
Companion diagnostics are emerging as a key part of personalized medicine. The official definition of a companion diagnostic test is an in vitro diagnostic device (IVD) or test that is intended to assure that a specific therapeutic drug or biological product is used in accordance with its label to achieve approved safety and effectiveness. Essentially, it is a test that must be administered to a patient to determine whether or not a drug is going to be efficacious, or if treatment could result in an adverse event.
Involvement of a central laboratory as a facilitator between biopharma and diagnostics companies can have several benefits. For instance, central laboratories have an intimate understanding of the drug development process and practical experience developing and deploying biomarker tests.
Covance was recently contacted by both a pharmaceutical company and an IVD manufacturer to help with the development of two different companion diagnostic tests. The following two partnership examples are fundamentally very different; however, both yielded similar lessons and best practices to consider for future partnerships.
Central Laboratory/Pharma Companion Diagnostics Partnership
The first partnership example was a prospective study, where Covance tested patients at enrollment into the protocol. A pharmaceutical company contacted Covance Central Laboratory Services to perform testing of a companion diagnostic they needed to pair with a therapeutic drug they developed for non-small cell lung carcinoma.
The target for the therapeutic drug was a protein in a signal transduction pathway. Mutations in the gene coding for this protein could have an adverse effect on the drug’s efficacy. Therefore, the assay Covance was asked to perform was designed to detect specific mutations in that gene. The samples tested were formalin fixed, paraffin embedded, tumor biopsy tissues obtained from each patient; DNA was extracted from each of these samples for the actual testing.
In this particular case, the pharma company was working directly with the medical device partner (the manufacturer of the test) to design the test kit. This kit came to Covance labeled as Investigational Use Only (IUO) and would eventually be submitted to the FDA. The medical device manufacturer was responsible for training Covance personnel on the study requirements. However, all of the data analyzed by Covance was sent back to the pharmaceutical client, not the device manufacturer. In addition, it was a global study, entirely in Asia with Chinese samples analyzed inChinaand other samples from two different countries in Southeast Asia analyzed in the U.S.
An additional requirement for this project was to test the circulating tumor DNA in plasma. Covance had to validate a new procedure and develop its own protocol for the DNA extraction. Testing the tumor tissue was done in real-time, while testing the circulating DNA was done at the end of the study. In the end, all testing was performed on time at both testing sites.
From the standpoint of the study, we demonstrated our scientific expertise through the successful design and implementation of the application for testing circulating tumor DNA in plasma, plus satisfied the requirements of the client by providing results on their required number of patients on time.
Central Laboratory/IVD Companion Diagnostics Partnership
This second partnership example was a retrospective study, where Covance tested patients at the conclusion of the protocol. An IVD company contacted Covance Central Laboratory Services to assist with the clinical evaluation of a companion diagnostics test they were developing for a pharmaceutical client’s malignant melanoma drug. Specifically, the IVD company asked Covance to perform testing for their premarket approval (PMA) submission to the FDA.
The IVD manufacturer provided Covance with the test kits, instrumentation and equipment, training of Covance’s lab personnel, and all patient samples (multiple slides per patient). One of the challenges Covance encountered through this process was with sample tracking, since the samples had to be handled by three different sections within Covance (Anatomic Pathology, Medical Affairs, and the Genomics Laboratory).
To effectively handle sample tracking, Covance’s Specimen Management team built a database to keep track of everything, including re-labeling slides with our own set of accession numbers prior to distribution to Anatomic Pathology. All aspects of the processing and testing of these samples were extensively documented. After testing, all of the results were entered into the client’s database. In the end, there was a tremendous amount of labor in terms of record keeping and specimen tracking.
Ultimately, the outcome was extremely successful, as we tested all the samples sent to us, while meeting all deadlines and requirements. The data resulting from this study has been submitted to the FDA by the manufacturer.
Lessons Learned/Best Practices
Through these partnerships with both a biopharma and IVD company, Covance Central Laboratory Services has learned some of the following best practices in regards to the co-development and regulatory approval process of companion diagnostics.
For one, rapid turnaround time is absolutely critical since. For varying reasons, patients need to be enrolled quickly into the particular study. In some cases the patients may be in the end-stage of their disease. In addition, there is tremendous competition for these patients, which are a precious resource for clinical studies. Second, central laboratories need to have understanding and expertise in companion diagnostics because we may be required to develop new testing protocols. Third, communication is key when you are working on either side. This is especially true when it comes to expectations of sample handling requirements, reporting of results, and deadlines.
Central laboratories also have the ability to help develop and standardize global collection and storage procedures. For example, in China, the current limitations on exporting whole blood, tissue, or any other DNA-containing biological samples from China, requires that any molecular diagnostic testing be performed in China. This is driving biopharma clients to use central labs with wholly owned facilities in China, rather than local labs where the quality and experience in running global trials may not yet be at the required level. Overall, this is helping to ensure more seamless data delivery.
Central laboratories play a critical role in helping pharmaceutical companies and the IVD industry align the diagnostic test with the therapy. Ensuring appropriate sample handling, rapid turnaround time, high standards and quality of testing, and accurate reporting of results, are all critical services that Covance Central Laboratory Services delivers on a daily basis. The end goal in mind is always to help patients by targeting patient populations that will most likely benefit from the drug, and to spare those who will not from inappropriate treatment.
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Ted Schutzbank, Ph.D., is Associate Director of Genomics for Covance. Prior to joining Covance in 2008, Ted worked in various leadership roles in molecular diagnostics/molecular pathology and the IVD industry. Ted received his Postdoctoral Fellow from State University of New York at Stoneybrook; his Ph.D. in microbiology from Columbia University; his M.S. in Bacteriology from Iowa State University; and his B.A. in biology from Temple University, Pennsylvania. Ted is board certified in medical and public health virology by the American Board of Medical Microbiology and has been published in numerous peer-reviewed journals.