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[CASE STUDY]

Biosimilar Development

Utilising Clinical Data Management, Statistical Programming, Pharmacovigilance and Medical Writing Services for Successful EMA Approval

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Study Introduction

Quanticate supported a biopharmaceutical company across the full remit of clinical data services for the development of a new biosimilar. The Sponsor was seeking a provider that could offer full service support across the biometric functions and wanted to benefit from the efficiencies gained by centralizing their Clinical Data Management (CDM), Statistical Programming, Medical Writing (MW) and Pharmacovigilance (PV) activities to a single service provider.

The clinical studies Quanticate worked on were part of a development programme aiming to license a biosimilar for the treatment of a series of inflammatory conditions. The series of studies actively tested the proposed biosimilar in healthy volunteers and patients with rheumatoid arthritis (RA). However, extension of use for other inflammatory conditions such as psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, plaque psoriasis and juvenile idiopathic arthritis was subsequently sought. The Statistical Programming and PV teams provided support for a further 2‑3 clinical studies in the clinical development programme.

Each of the studies presented their own unique challenges which were resolved by Quanticate and resulted in the approval of the proposed biosimilar by the European Medicines Agency (EMA).

Humira Biosimilar

Clinical Data Management

Quanticate provided CDM services across the Phase 3 studies. Some of the challenges faced by the CDM team are detailed below.

Challenges

During the interim analysis (IA) of the OLE study, the Statistical Programming team noticed that there were a lot of site data entry issues. Investigation into these issues revealed that the clinical site had made changes to the data after the database had been locked for the IA data cut‑off. Due to the data issues encountered from the clinical site, once the IA had been performed, the Sponsor requested that Quanticate create a ʽData Entry Key Remindersʼ document to be distributed to all the clinical sites to ensure that they entered data correctly going forward in order to improve data quality.

Solution

The CDM team updated the ʽEdit Checkʼ document to capture all the issues that were identified during the IA. The CDM team also created a ‘Data Entry Key Reminders’ document which illustrated all the live examples/scenarios that the sites needed to be aware of.

Outcome

The solutions detailed above were implemented and resulted in a successful database lock for the final analysis without any issues. This was because the sites were able to rectify their mistakes using the guidance provided to them by Quanticate. All issues identified during the first and second IA were resolved. The Sponsor was very happy with the approach taken by Quanticate and were appreciative of the CDM team's input into solving the issues. There are also other ways of improving a site’s data integrity via Data Quality Oversight (DQO) and centralized statistical monitoring, both of which Quanticate can support.

Statistical Programming

Quanticate provided Statistical Programming support to the Sponsor for the Phase 1 and Phase 3 studies. Support for the Phase 1 studies was requested as PK analysis in biosimilar studies is a standard requirement to demonstrate the effectiveness of the potential biosimilar vs. the existing approved drug.

Challenges

Being a virtual company, the Sponsor needed a reliable provider that could support with all relevant functions, and Quanticate had all the necessary expertise, including several consultant statisticians with a vast and proven record of experience within the immunology therapeutic area that the Sponsor was planning to conduct the studies in. In addition, Quanticate also had PK specialists and who had worked on other biosimilar studies as biosimilar development has specific considerations for clinical study design, e.g., there is no requirement to conduct Phase 2 studies.

Solution

Quanticate's centralized approach proved to be the key element that enhanced our capability to be efficiently reactive to the challenges occurring during the clinical development programme. Every issue was dealt with in a way that considered any potential effect on other functions not directly impacted by the issue itself (e.g., what impact could a reporting issue have on the MW work and timelines?). This ultimately led to an increased efficiency (the solution applied minimized work/re-work time across all impacted functions) and to a higher quality of the final deliverables.

Outcome

Being able to easily discuss matters at hand with the study team largely improved the reaction time, so that any problem could be identified, analysed, discussed and solved quicker than it would have been possible had the various functional teams come from different vendors. There was a great team spirit with the aspiration to provide high quality results to the Sponsor and a great partnership that was testified by the continuous flow of requests to support the submission process.

Pharmacovigilance

Quanticate provided PV support on the Phase 1 and Phase 3 studies.

Challenges

It was expected that the Sponsor's proposed biosimilar would have a similar safety profile to that of the existing drug when administered to the patient population under study. The Sponsor required a full range of PV services and a comparative approach in order to determine whether the safety profile of their proposed biosimilar was similar to that of the existing drug.Quanticate held the responsibility for the processing and follow-up of all serious adverse events (SAEs) and pregnancy cases collected during the studies in Quanticate's safety database; expedited reporting of Suspected Unexpected Serious Adverse Reactions (SUSARs), generation and reporting of Development Safety Update Reports (DSURs) and performing ongoing reconciliation with the data collected in the clinical database.A particular challenge faced was the migration of the safety data following completion of the Phase 3 studies. In order to commercialize the proposed biosimilar, the Sponsor announced a partnership with a large pharmaceutical company. As a result of this, the Sponsor required all its PV case data records for the proposed biosimilar to be transferred from Quanticate’s safety database to their Partner's safety database.

Solution

The Quanticate PV team prepared a detailed Safety Monitoring Plan (SMP) defining the roles, responsibilities, procedures and processes for both the Quanticate PV team and the Sponsor. In addition, the Quanticate PV team set‑up the Sponsor’s database within Quanticate’s safety system configured to meet the specific requirements for the proposed biosimilar studies.In response to the data migration project, and after confirmation from the Sponsor's Partner regarding successful transfer of the sample cases in to their Argus safety database, Quanticate exported XML files in ICH E2B(R2) file format of all the cases and provided these to the Partner, together with all case source documents and related non‑E2B data listings. This was completed within agreed timelines and to stipulated quality expectations.

Outcome

The Quanticate PV team were able to deliver high‑quality work and the required support for data migration within the agreed timelines while maintaining data privacy and compliance. Quanticate provided a flexible solution to the ever‑changing demands of running a busy clinical development programme. The Sponsor provided positive feedback about the work completed.

Medical Writing

Quanticate’s medical writers provided support on the Phase 1 study, the Phase 3 studies and the EMA submission which was successfully accepted.

Challenges

The Sponsor outsourced all their MW requirements due to a lack of in‑house MW resource. The outsourced work included the preparation of protocols and protocol amendments, investigator brochure (IB) and IB updates, clinical study reports (CSRs) and Submission Documents.

Solution

Quanticate provided a Lead MW as a point of contact to ensure consistency of delivery. The Lead MW was assigned at the start of the clinical programme in 2012. Other MW resource was provided to support the Lead MW as required during periods of high need or tight timelines (e.g. EMA submission).

Outcome

A positive response was received from the EMA leading to marketing approval. Quanticate built an experienced team of MWs who developed expertise with the product and therapy area and so were able to prepare high quality documents efficiently and with limited oversight.

Wider Support

In addition to supporting the Sponsor with their development of a biosimilar, Quanticate has also supported the client with their development of a second biosimilar (for oncology).

Conclusion

Quanticate worked extensively with the Sponsor from the start of their clinical programme and after several years of support and a good relationship, the Sponsor was able to achieve their goal of having their proposed biosimilar successfully approved by the EMA. Following successful EMA approval, the Sponsor is planning submissions in other regions.