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Regulatory Focus™ > News Articles > 7 > EU Regulatory Roundup: EMA Finalizes Guideline on Gene Therapies

EU Regulatory Roundup: EMA Finalizes Guideline on Gene Therapies

Posted 19 July 2018 | By Nick Paul Taylor 

EU Regulatory Roundup: EMA Finalizes Guideline on Gene Therapies

Welcome to our European Regulatory Roundup, our weekly overview of the top EU regulatory news.
UK Pauses Use of Vaginal Mesh After Independent Review Posts Early Findings
The United Kingdom has temporarily stopped using vaginally inserted surgical mesh to treat stress urinary incontinence. Officials instigated the hiatus on the recommendation of an independent group the government formed to review how the UK handles adverse events linked to drugs and medical devices.
Jeremy Hunt, then the UK health minister, ordered the review in February to gather information on the handling of hormone pregnancy test Primodos, anti-epileptic drug sodium valproate and surgical mesh. The focus on these products reflects criticisms of how early concerns about them were dealt with by the healthcare service. In the case of surgical mesh, many women felt doctors, regulators and other stakeholders failed to take their safety concerns seriously.
The ultimate goal of the review is to assess whether systemic failures in the regulatory system led to a slow response and to identify ways to improve how adverse event reports are handled. Those final findings are still to come, but Baroness Julia Cumberlege, who is chairing the review, has already identified some actions the government should take.
At Cumberlege’s request, the government has worked with the healthcare system and Medicines and Healthcare products Regulatory Agency (MHRA) to mostly — but not completely — stop the use of vaginal mesh in the treatment of stress urinary incontinence.
“Both the chief medical officer and Baroness Cumberlege agree that we should not introduce a blanket ban of the relevant procedures, and that there will need to be some exceptions within the pause, within a high vigilance program of restricted practice,” Jackie Doyle-Price, the parliamentary under-secretary for health and social care, said.
Cumberlege thinks widespread use of the vaginal mesh should only resume once six conditions are met. These conditions will limit the use of mesh to appropriately trained surgeons who frequently perform the procedure. Surgeons cleared to use the product will need to report every procedure to a national database. Cumberlege is also calling for the creation of a registry that identifies women who have the procedure and links to adverse event reports sent to MHRA, and for the establishment of facilities accredited to perform mesh procedures and manage the complications that can ensue.
The final condition is that the National Institute for Health and Care Excellence (NICE) must have published guidelines on the use of mesh to treat stress urinary incontinence. NICE plans to publish the guideline next year, although politicians are pressuring it to bring forward the release date. If NICE sticks to its current timeline, the use of surgical mesh will remain restricted for at least the next six months.
NICE reiterated its early 2019 target publication date after hearing Cumberlege’s recommendations. The health watchdog is working on a shared decision-making tool in parallel to the development of the guideline. NICE expects the tool to be ready around the same time as the guideline.
MHRA Notice, Government Update, NICE Notice
Years After Starting, EMA Finalizes Guideline on Gene Therapies
The European Medicines Agency (EMA) has finalized its guideline on gene therapies more than four years after writing the original draft. Progress on the guideline slowed after almost 30 organizations responded to a 2015 call for feedback.
EMA has now worked through the feedback, resulting in the finalization of the guideline. Like the 2015 draft, the final guideline discusses the quality, preclinical and clinical aspects of developing and manufacturing gene therapies. The titles of each section and subsection are nearly identical to those used in the draft. The changes are limited to the addition of a glossary and modifications of the text in each section.
Many of EMA’s modifications are minor changes, such as revisions to the wording and additions of references to other texts. That reflects the nature of most of the feedback EMA received from the industry, although some respondents did use the consultation to push for more significant changes.
“The guideline is not harmonized with other regions and BIO recommends that established regulatory authorities align on guidance as much as possible to facilitate global development programs. This is especially important as gene therapies are often being developed for the treatment of rare genetic diseases which by necessity typically feature trials that are inclusive of global patient populations,” BIO wrote in its feedback.
EMA knocked back the call for harmonization, noting that global initiatives focused on the modality are yet to start. Given the EU and United States have very different legal and regulatory frameworks for gene therapies, EMA thinks it is impossible to harmonize requirements through guidelines.
BIO was marginally more successful in its attempts to get EMA to take smaller steps toward harmonization. The trade group called for a section on safety pharmacology studies to be removed as, “It is not harmonized with any other regulatory region.” EMA retained the section in the final text but softened the language. The final text outlines a risk-based approach to deciding when gene therapy developers must run safety pharmacology studies. The draft stated such studies are always required.
Final Guideline, Document History
EU, Japan Expand GMP Mutual Recognition Agreement
The European Union and Japan have expanded the list of drugs covered by their good manufacturing practice (GMP) mutual recognition agreement. Regulators in the EU and Japan will now waive batch testing of sterile medicines, some biologicals and certain active pharmaceutical ingredients (API).
Japan entered into a limited mutual recognition agreement focused on lower-risk products with the EU in 2004. That agreement allowed some products to flow from Japan into the EU, and vice versa, without undergoing batch testing. The agreement also facilitated the sharing of information on inspections and product quality defects.
Since then, the EU has intensified its interest in mutual recognition, leading to agreements designed to lessen the burdens on officials at EMA and its peers. Now, the EU has returned to the agreement with Japan to increase its impact.
The revised agreement is still focused on batch testing and information sharing, but now covers more products. Notably, the products added in the 2018 revision pose more of a threat to patients if there are quality failures. Whereas the 2004 agreement covered low-risk products such as vitamins and herbal medicines, the revised pact includes sterile medicines, vaccines and immunologicals. The EU and Japan have also added the APIs of any medicine covered by the agreement to the pact.
In expanding the agreement, the EU has brought the arrangement with Japan more in line with its other mutual recognition pacts. The mutual recognition agreements the EU formed with Australia, Canada and New Zealand around the start of the century already cover biologicals.
EMA Notice
Other News:
EMA has provided an update on its review of valsartan medicines. The agency became concerned about the safety of the drugs after detecting probable human carcinogen N-nitrosodimethylamine (NMDA). Now, with national regulators recalling affected products, EMA thinks the near-term emergency has passed. The bigger, unanswered question is whether NMDA poses a longer-term threat to patients. EMA Notice
EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) has recommended restricting the use of Bayer’s prostate cancer medicine Xofigo. PRAC called for the restrictions after reviewing data linking the radiopharmaceutical to an increased risk of fractures and early death. EMA is yet to find an explanation for the increased risk of early death. PRAC Recommendation

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