Euro Roundup: EU extends scope of guideline on clinical trials with genetically modified human cells

RoundupsRoundups | 11 November 2021 |  By 

The European Union has extended the scope of its good practice guideline on the assessment of the genetically modified organism (GMO)-related aspects of clinical trials that study human cells. Officials have revised the text to cover human cells genetically modified without viral vectors and genome edited cells.
Developers cannot use the document to determine whether cells that are genetically modified without the use of viral vectors are classified as GMOs, with officials referring readers to a separate set of frequently asked questions rather than tackle that question in the guidance. Instead, the text focuses on the environmental risks and manufacturing requirements of cells genetically modified without the use of viral vectors and how they differ from other GMOs.
The EU sees the “presence of residual infectious viral vector particles in the finished product that could be released in the environment” as one of the primary risks associated with many genetically modified human cell therapies. As such, officials have concluded that, “If viral vectors are not used, risks to the environment can be considered negligible” because, “There is no known pathology associated with non-viral vectors.”
That conclusion means most of the section on manufacturing requirements focuses on ensuring that genetically modified cells are free of residual infectious viral particles. Officials have added a short section describing the production of human cells genetically modified without the use of a viral vector.
“The manufacturing activities with cells modified without a viral vector can be carried out under BSL-1 or BSL-2 conditions depending on the specific circumstances. For example, in case of an established cell-line, BSL-1 would in most cases be considered appropriate. However, in case of cells for autologous treatments, if risks regarding the presence of pathogenic viruses cannot be excluded, BSL-2 should be considered,” the guidance states.
Officials released the revised guidance alongside an updated application form for genetically modified human cells. The new form features a section about human cells genetically modified without the use of a viral vector that asks what transfer system was used and requests a short description of the modifications made to the cells.
EU Guidance, Application Form
Commission revises mandate of working group on pharmaceuticals in the environment
The European Commission has revised the mandate of an ad-hoc working group that is looking at the EU’s strategic approach on pharmaceuticals in the environment, tasking the experts with drafting a concept paper on the regulatory framework.
Since the formation of the working group in March 2020, the EU has set out actions to address the environmental impact of the pharmaceutical industry in a strategy document covering the industry. The creation of the strategy document led the Commission to reassess the role of the working group, prompting it to add another task to its workload.
Officials want the working group to create a concept paper that outlines expert views and is “solutions oriented to bring the necessary support in the revision” of the 2001 EU pharmaceutical legislation that is now being updated. The request covers considerations on the “main elements and business processes that may need to be reflected in the regulatory framework” with regard to two areas of activity.
First, the Commission has asked for views on “strengthening the environmental risk assessment requirements and conditions of use for medicines.” Second, the Commission wants the working group to consult with the European Medicines Agency’s (EMA) Good Manufacturing and Distribution Practices Inspectors working group on “greener pharmaceuticals with respect to antimicrobial resistance.”
The Commission has given the working group until January 2022 to develop a “mature draft” and until March 2022 to prepare the concept paper. In light of the extra work, the Commission has extended the mandate of the working group by one year, meaning it will now be in place until March 2024.
EU Decision
EMA seeks feedback on enrichment biomarkers for diabetes prevention clinical trials
EMA is seeking feedback on the use of islet autoantibodies (AAs) as enrichment biomarkers for type 1 diabetes prevention clinical trials. The consultation covers a draft qualification opinion issued by EMA in response to a filing by the Critical Path Institute’s Type 1 Diabetes Consortium (T1DC).
T1DC’s new drug development tool submission centers on the use of islet AAs, proteins produced by the immune system that are associated with type 1 diabetes, alongside other patient features to optimize the selection of participants in clinical trials of interventions designed to prevent or delay the disease. EMA voiced support for the proposed context-of-use (COU) statement in a draft opinion.
“The proposed COU is overall agreed,” EMA wrote. “There have been significant failures in late-stage development of therapies in new-onset T1D. These failures have been attributed in part to a high degree of heterogeneity in the patient population and a current inability to quantitatively describe the contributions of specific sources of variability to such heterogeneity.”
While offering support for the COU, EMA also highlighted a practical problem, noting that in clinical trial recruitment “often the only parameter known is family history, which could limit the utility of this new screening/enriching tool unless mass screening efforts are taking place.” The applicant said partnerships with pre-existing trial networks such as TrialNet and INNODIA involved in screening could mitigate the problem. EMA supports the proposal.
The draft opinion also covered the adequacy of the data sources used to support the proposed COU. “The data sources are judged largely relevant, consistent with the recommendation during the QA procedure. From a modeling perspective, this approach is endorsed, and the 3 data sources seem adequate,” EMA concluded.
EMA is accepting feedback until 14 December.
Draft Opinion
EMA starts requiring registration of new sites for centrally authorized medicinal products
EMA has begun requiring the registration of new sites and organizations for centrally authorized medicinal products in Organisation Management Service (OMS) prior to the submission of associated regulatory submissions such as the transfer of the marketing authorization.
In an update to post-authorization procedural advice for users of the centralized procedure, EMA said registration became mandatory on 1 November and referred readers to a question and answer document on the topic that it published last month.
EMA used the notice to “emphasize the importance of these site/organization registrations in OMS prior to pre- and post-authorization submissions, in order to avoid any delay in the start of these procedures, as this would constitute a validation blocking issue.”
EMA Guidance
EMA starts evaluating Moderna’s COVID-19 vaccine for use in kids aged 6 to 11
EMA has begun reviewing an application to extend the use of Moderna’s COVID-19 vaccine Spikevax to children aged 6 to 11 years. The agency expects to take around two months to deliver an opinion.
Moderna received authorization to provide Spikevax for use in children aged 12 to 17 in the EU in July. The new submission includes data from an ongoing clinical study involving children aged 6 to 11 to seek authorization for use in younger children.
The global move into younger populations has run into setbacks. The US FDA is taking longer than expected to decide whether to authorize Spikevax in adolescents amid reports of myocarditis after vaccination. Those reports have also led some EU countries to favor Pfizer’s rival mRNA vaccine in younger people.
EMA Notice


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