Regulatory News - March
EMA published an update of the scientific guideline:
Guideline on good pharmacovigilance practices (GVP): Module VII – Periodic safety update report - Explanatory note [02 Mar 2020]
ICH E9(R1) and S5(R3) to take effect in the EU by the end of July 2020.
The European Medicines Agency (EMA) adopted two International Council for Harmonisation (ICH) guidelines, the ICH E9(R1) addendum on estimands and sensitivity analysis in clinical trials, and ICH S5(R3) on reproductive toxicology, with both guidelines set to take effect on 30 July 2020.
ICH E9(R1):
The 19-page E9(R1) addendum presents a framework for defining an appropriate estimand for a clinical trial and conducting sensitivity analyses. The guideline defines an estimand as a “precise description of the treatment effect reflecting the clinical question posted by a given clinical trial objective [and] summarizes at a population level what the outcomes would be in the same patients under different treatment conditions being compared.” For estimands, the guideline lays out recommendations for handling intercurrent events as they relate to the clinical question of interest, attributes that make up an estimand and considerations for constructing the estimand. The guideline also discusses the impact of estimands on clinical trial design and conduct. “The design of a trial needs to be aligned to the estimands that reflect trial objectives. A trial design that is suitable for one estimand might not be suitable for other estimands of potential importance,” the guideline states. Additionally, the guideline discusses the impact of estimands on clinical trial analysis and provides recommendations for conducting sensitivity analyses.
ICH S5[R3]
Within the 127-page S5(R3) guideline, ICH sets recommendations for a harmonized approach to assessing nonclinical developmental and reproductive toxicity (DART) testing used to support clinical trials and drug approvals. The guideline is the third revision made to the S5 guideline since its introduction in 1993 and has been updated to include discussions on the use of exposure margins in dose level selection and risk assessment. The guideline has also been expanded to cover vaccines and biopharmaceuticals, though it does not apply to cell and gene therapies or tissue-engineered products. Within the guideline, ICH lays out a framework for assessing drugs for reproductive toxicity, including study design and evaluation; test system selection; and dose level selection, route of administration and schedule. The two annexes make up the bulk of the guideline, with Annex 1 covering in vivo study designs and Annex 2 discussing the use of qualified alternative assays to support hazard identification and risk assessment.
PRAC confirms four-week limit for use of high-strength estradiol creams.
EMA’s safety committee (PRAC) has confirmed its recommendation to limit the use of high-strength creams containing 100 micrograms/gram (0.01%) of estradiol to a single treatment period of up to 4 weeks. This follows a re-examination of its recommendation of October 2019 which was requested by one of the companies that market high-strength estradiol cream. The PRAC reviewed available data on the safety and effectiveness of high-strength estradiol-containing creams used to treat symptoms of vaginal atrophy in women who have been through menopause. Data on these creams show that in postmenopausal women who use them, the levels of estradiol in the blood were higher than normal postmenopausal levels. The PRAC concluded that absorption of estradiol into the bloodstream is of concern and could result in similar side effects to those seen with hormone replacement therapy (HRT). The side effects of HRT taken orally or used transdermally (as patches) include venous thromboembolism (formation of blood clots in the veins), stroke, endometrial cancer (cancer of the lining of the womb) and breast cancer. In addition, there are limited safety data on long term use of high-strength estradiol creams. For these reasons, the PRAC recommended that these creams should only be used for a single treatment period of a maximum of 4 weeks. The PRAC recommends that the prescribing information for these creams will be updated with the new recommendations. A warning that the medicine is to be used for a single treatment period of up to 4 weeks only will be placed on the outer and inner packaging and the size of the tube will be limited to 25 grams to prevent use for longer than recommended. The PRAC recommendations will now be sent to the CMDh to make a decision about their implementation. The CMDh is a body representing EU Member States as well as Iceland, Liechtenstein and Norway.
EMA consultation: Public statement on the use of herbal medicinal products containing estragole.
The European Medicines Agency has released for public consultation of a public statement on the use of herbal medicinal products containing estragole. In 2005, the HMPC prepared the ‘Public statement on the use of herbal medicinal products containing estragole’. There are a large number of plants and their preparations which contain estragole, sometimes in very high amounts. From the European perspective, the most interesting plants are Foeniculum vulgare Mill. (both fruit and essential oil) and Pimpinella anisum L. (fruit). Since 2005, a number of significant publications on estragole have appeared in the scientific literature. The new data has raised concerns from a toxicological point of view and this has prompted the HMPC to re-assess all available data regarding their relevance for the safe human use of herbal medicinal products containing estragole. The draft public statement is available by clicking here. Comments should be provided using this template and sent to hmpc.secretariat@ema.europa.eu by 15 May 2020.
Update from the HMA/EMA Task Force on Big Data – final report (phase two) published.
Update: In January 2020, the HMA/EMA Task Force on Big Data published its final report (phase two) containing practical recommendations on how the European medicines regulatory network could make best use of big data by evolving its approach to data use and evidence generation in support of innovation and public health.
It identifies ten priority actions and practical steps to implement them:
- HMA/EMA Joint Task Force on Big Data - Final (Phase II) report - Evolving data-driven regulation
- Summary of ten priority recommendations
The European medicines regulatory network is now considering how to implement the task force's recommendations, in consultation with the European Commission.
25th EMA anniversary Conference "From data to evidence in medicines regulation" on 22 April 2020.
As part of a programme of events to celebrate the 25th anniversary of the European Medicines Agency we are pleased to inform you of the upcoming conference "From data to evidence in medicines regulation" which will take place on 22 April 2020.
The objectives of this conference are to:
- Explore the evolution to data-driven regulation.
- Understand enablers, challenges and opportunities.
- Discuss the opportunities to contribute to future actions. “From data to evidence in medicines regulation" conference will take place at the EMA offices in Amsterdam. We anticipate space for approximately 300 experts and stakeholders and attendance will be a mixture of invitation and open call for interest.
An outline agenda and details on registration process will be published shortly.
Useful websites related to updates on the Coronavirus outbreak.
Updates, distribution, epidemiological curve of the Coronavirus outbreak and current recommendations are available at the following links: