Posted on 06 Apr 2020

Regulatory News - April

FDA Takes Action with Indian Government to Protect Consumers From Illicit Medical Products

First Bilateral Enforcement Operation with India Stopped Approximately 500 Shipments Through International Mail. The U.S. Food and Drug Administration today announced that its first bilateral enforcement operation with the Government of India, stopped approximately 500 shipments of illicit, and potentially dangerous, unapproved prescription drugs and combination medical devices from reaching American consumers over the course of an operation that took place in January.

“With standards and regulations varying in each country, U.S. consumers face hazards when they order drugs and other FDA-regulated products from unauthorized foreign sources and receive them through the international mail system. Consumers and physicians purchasing medicines cannot be assured the products they are receiving are legitimate, safe or effective if they are obtained from outside of the FDA-regulated pharmaceutical supply chain,” said FDA Commissioner Stephen M. Hahn, M.D. “The FDA is committed to empowering patients and providing them choice, but also protecting them through collaboration with our international regulatory and law enforcement partners. It is vital that we aggressively stop illicit products from entering the country that may place patients’ health at risk, and we are pleased to call the Government of India a partner in this effort.”

More information can be found here.

FDA COVID-19 guidance

On March 18th, the US FDA issued a guidance for industry, investigators and institutional review boards conducting clinical trials during the coronavirus (COVID-19) pandemic.

The FDA recognizes that the COVID-19 pandemic may impact the conduct of clinical trials of medical products, including drugs, devices and biological products. Challenges may arise, for example, from quarantines, site closures, travel limitations, interruptions to the supply chain for the investigational product, or other considerations if site personnel or trial subjects become infected with SARS-CoV-2, the virus that causes COVID-19. These challenges may lead to difficulties in conducting the clinical trials.

The FDA is aware that protocol modifications may be required, and that there may be unavoidable protocol deviations due to COVID-19. Although the impact of COVID-19 on trials will vary depending on many factors, including the nature of disease under study, the trial design and in what region(s) the study is being conducted, the FDA outlines considerations to assist sponsors in assuring the safety of trial participants, maintaining compliance with good clinical practice and minimizing risks to trial integrity.

Considerations recommended include, among others, sponsors evaluating alternative methods for assessments, like phone contacts or virtual visits and offering additional safety monitoring for those trial participants who may no longer have access to investigational product or the investigational site. Of particular interest to medical writers are instances where efficacy endpoints are not collected, in which case the reasons for failing to obtain the efficacy assessment should be documented. Contingency measures, a listing of all participants affected by COVID-19 study disruption, and analyses and corresponding discussions addressing the impact of implemented contingency measures should be described in the appropriate sections of the corresponding clinical study report; specific information should be captured in case report forms in case of missing data.

EMA COVID-19 guidance

On March 20th, the European Commission, the European Medicines Agency (EMA) and national Head of Medicines Agencies (HMA) have published new recommendations for sponsors on how to manage the conduct of clinical trials in the context of the coronavirus disease (COVID-19) pandemic. The impact of the pandemic on European health systems and more broadly on society, will make it necessary for sponsors to adjust how they manage clinical trials and the people who participate in these trials.

The guidance provides concrete information on changes and protocol deviations which may be needed in the conduct of clinical trials to deal with extraordinary situations, e.g. if trial participants need to be in self-isolation or quarantine, access to public places (including hospitals) is limited due to the risk of spreading infections, and healthcare professionals are being reallocated. This guidance includes a harmonised set of recommendations, to ensure the utmost safety of trial participants across the European Union while preserving the quality of the data generated by the trials. It also advises how these changes should be communicated to authorities.

There is specific advice on the initiation of new clinical trials for treatments of COVID-19, and in particular on the need for large, multinational trial protocols. This is in line with the call issued on Thursday by EMA’s human medicines committee (CHMP) for robust trial methodology in clinical trials for potential COVID-19 treatments or vaccines. The guidance was agreed by the Clinical Trials Expert Group (CTEG) of the European Commission, supported by EMA, the Clinical Trials Facilitation and Coordination Group (CTFG) of HMA and the GCP Inspectors’ Working Group. It provides a harmonised approach in the conduct of trials, in order to mitigate the negative effects of the pandemic.

In the EU, clinical trials are authorised and supervised at national level. Sponsors are advised to also check whether there might be specific national legislation and guidance in place to complement or, in some cases, to take priority over this new guidance.

EMA communication: COVID-19 - Update on treatment and vaccines under development and information on chloroquine and hydroxychloroquine.

EMA the published two press releases related to COVID-19:

Please check EMA’s dedicated webpage on COVID-19 for the latest updates.

EMA Communication

The EMA and the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePPP) encourage all researchers to register their pharmaco-epidemiological studies related to Covid-19 in the EU PAS Register. They should also upload and make their study protocols public, with a description of the data collected or planned to be collected. 

EMA communication: Addressing the potential impact of novel coronavirus disease (COVID-19) on medicines supply in the EU

EMA and its partners in the European medicines regulatory network are closely monitoring the potential impact of the outbreak of the novel coronavirus disease (COVID-19) on pharmaceutical supply chains into the European Union (EU). No reports of current shortages or supply disruptions of medicines marketed in the EU due to this outbreak have been received at this point. As the public health emergency develops, shortages or disruptions cannot be excluded.

The EU (EMA, the European Commission and national competent authorities in the Member States) have organised the first meeting of the EU Executive Steering Group on shortages of medicines caused by major events to discuss measures aimed at addressing the impact of the outbreak of COVID-19 on the supply of medicines in the EU. The mandate of this group is to provide strategic leadership for urgent and coordinated action within the EU in case a crisis caused by major events, such as the COVID-19 outbreak, risks impacting the supply of medicinal products for human and veterinary use.

In the context of COVID-19, the group will identify and coordinate EU-wide actions to protect patients when medicines in the EU are at risk of supply shortage, e.g. due to a temporary lockdown of manufacturing sites in areas affected by COVID-19 or travel restrictions impacting shipment. The group will also ensure that patients and healthcare professionals across the EU are kept informed in a consistent and transparent manner about the risks and the remedial actions taken.

EMA notice to stakeholders

The notice describes the legal situation at the end of the transition period for the EU and UK, separation provisions of the Withdrawal Agreement, and rules applicable to Northern Ireland as of the end of the transition period. Of particular relevance is the reporting of individual case safety reports and safety data to be included in Periodic Safety Update Reports. The notice was released on March 13th and replaces Revision 2, dated February 1st 2020.

Direct healthcare professional communications.

A marketing authorisation holder may send a direct healthcare professional communication (DHPC) to healthcare professionals to inform them of important new safety information about a medicine and any actions they should take.  The European Medicines Agency (EMA) publishes DHPCs agreed at European Union (EU) level and links to national registers of DHPCs, as of February 2020, on a dedicated webpage.

EMA’s restrictions in use of cyproterone due to meningioma risk.

EMA’s safety committee (PRAC) has recommended that medicines with daily doses of 10 mg or more of cyproterone should only be used for androgen-dependent conditions such as hirsutism (excessive hair growth), alopecia (hair loss), acne and seborrhoea (excessively oily skin) once other treatment options, including treatment with lower doses, have failed. Once higher doses have started working, the dose should be gradually reduced to the lowest effective dose. The medicines should only be used for reduction of sex drive in sexual deviations in men when other treatment options are not suitable.

There is no change in use of the medicines in men for prostate cancer.

The recommendations follow a review of the risk of the rare tumour meningioma with cyproterone. Meningioma is a rare tumour of the membranes covering the brain and spinal cord. It is usually non-malignant and is not considered to be a cancer, but due to their location in and around the brain and spinal cord, meningiomas can cause serious problems. Overall, this side effect is rare: it may affect between 1 and 10 in 10,000 people, depending on the dose and duration of treatment. The risk increases with increasing cumulative doses (the total amount of medicine a patient has taken over time).

Available data do not indicate a risk for low-dose cyproterone medicines containing 1 or 2 milligrams cyproterone in combination with ethinylestradiol or estradiol valerate and used for acne, hirsutism, contraception, or hormone replacement therapy. However, as a precaution, they should not be used in people who have or have had a meningioma. This restriction is already in place for the higher dose medicines.
Doctors should monitor patients for symptoms of meningioma, which can include changes in vision, hearing loss or ringing in the ears, loss of smell, headaches, memory loss, seizures or weakness in arms and legs. If a patient is diagnosed with meningioma, treatment with cyproterone medicines must be stopped permanently.

As part of the ongoing surveillance of the safety of the medicines, companies marketing medicines containing 10 mg or more of cyproterone will be required to carry out a study to assess doctors’ awareness of the risk of meningioma and how to avoid it.

EMA’s review of Yondelis started. 

EMA’s human medicines committee (CHMP) has started a review of the cancer medicine Yondelis (trabectedin), used to treat ovarian cancer (cancer of the ovaries) and soft-tissue sarcoma (a type of cancer that develops from the soft, supporting tissues of the body). The review started after a clinical study (OVC-3006) investigating the use of Yondelis in patients with ovarian cancer was stopped ahead of time, because an interim analysis of the results showed that, overall, patients treated with Yondelis plus pegylated liposomal doxorubicin (PLD, another cancer medicine) did not live longer than patients given PLD alone.

Although there were some differences in the types of patients enrolled in study OVC-3006 compared with those of the study on which the authorisation of Yondelis for ovarian cancer was based, study OVC-3006 also included patients for whom Yondelis would be indicated. EMA will therefore review the available data to assess whether the results from study OVC-3006 have an impact on the authorised use of Yondelis in patients with ovarian cancer.

This review does not cover the use of Yondelis for the treatment of soft-tissue sarcoma. While the review is ongoing, Yondelis can continue to be used for the treatment of both ovarian cancer and soft-tissue sarcoma, according to the authorised product information. Patients who have any questions about their treatment should speak to their doctor.

EMA published the 2019 public engagement highlights

The annual overview of the involvement of patients and healthcare professionals in the work of the European Medicines Agency (EMA) can be found here.