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EU Regulatory Roundup: MHRA relaxes GMP rules on drug imports to ease pandemic logistical challenges

Posted 02 April 2020 | By Nick Paul Taylor 

EU Regulatory Roundup: MHRA relaxes GMP rules on drug imports to ease pandemic logistical challenges

Welcome to our European Regulatory Roundup, our weekly overview of the top EU regulatory news.
MHRA Approves Adapted CPAP Device for COVID-19, Shares Design Specifications
The United Kingdom’s Medicines and Healthcare and products Regulatory Agency (MHRA) has approved an adapted Continuous Positive Airway Pressure (CPAP) device developed by organizations including the Mercedes Formula One team. MHRA also shared specifications for a rapidly manufactured CPAP system to support the work of other groups.
With the fast-rising number of COVID-19 cases in the UK likely to overwhelm ventilator capacity, the government is scrambling to add capacity for patients who need breathing support. CPAP devices, which are typically used to manage conditions such as sleep apnea, provide hospitals with one way to add extra capacity but they are in short supply, leading the UK to seek to acquire more systems while also building up its ventilator stocks. 
A team made up of engineers at University College London (UCL) and Mercedes has responded to the UK’s call for help by building an adapted CPAP device designed to enable healthcare professionals to get oxygen to the lungs of patients without using a ventilator. MHRA thinks the device may help to keep COVID-19 patients out of intensive care.
In disclosing the approval, MHRA said it provided regulatory guidance to the UCL and Mercedes engineers. Two days earlier, MHRA published a specification for a minimally clinically acceptable CPAP system for use in UK hospitals during the coronavirus crisis.
The document, which went from first draft to publication in six days, defines the characteristics a CPAP system must have to be of clinical benefit, as well as features that are desirable but should not be added if they significantly delay time to market. The essential requirements include the ability to deliver oxygen concentration in the range of 35% to 80%. Ideally, the selection of oxygen should be continuous, but MHRA will accept systems that deliver the element in increments of 5%.
MHRA published the CPAP specifications shortly after it released a similar document covering the minimum requirements for rapidly manufactured ventilator systems. The agency updated the ventilator document this week, adding a new section on biological and software safety.
MHRA Notice, Design Specifications, More
European Agencies Find no Link Between Blood Pressure Drugs and COVID-19 Outcomes
The European Medicines Agency (EMA) and national regulators have found no link between the use of blood pressure medicines and negative outcomes in COVID-19 patients. Based on the analysis, EMA and the other agencies are urging people to continue taking angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs).
With some research suggesting the interaction between SARS viruses, such as the strain behind the COVID-19 pandemic, and ACE2 is a factor in the infectivity of the pathogen, questions have been raised about whether people should continue to use ACE inhibitors and ARBs.
Over the past week, EMA, MHRA and the Danish Medicines Agency (DKMA) have separately voiced their views on the subject. EMA came out strongly in support of the continued use of ACE inhibitors and ARBs in the treatment of conditions including high blood pressure, heart failure or kidney disease.
“It is important that patients do not interrupt their treatment with ACE inhibitors or ARBs and there is no need to switch to other medicines. There is currently no evidence from clinical or epidemiological studies that establishes a link between ACE inhibitors or ARBs and the worsening of COVID-19,” EMA wrote. MHRA and DKMA expressed similar sentiments.
The flurry of notices on the subject began days before the publication of a paper in the New England Journal of Medicine that discussed the current evidence. The authors note that “select” preclinical studies have found a link between the drugs and ACE2 expression, providing the scientific basis for the concerns about the use of the medications.
However, the authors said there is insufficient data to show whether the preclinical findings translate to humans. As abrupt withdrawal of the drugs in high-risk patients “may result in clinical instability and adverse health outcomes,” the authors think the benefits of continued use of ACE inhibitors and ARBs outweigh the risks in stable patients who have, or are at risk of developing, COVID-19.
EMA Notice, MHRA Notice, DKMA Notice, NEJM Paper
MHRA Relaxes GMP Rules on Drug Imports to Ease Pandemic Logistical Challenges
MHRA has adopted “flexible approaches” to enable imports of drugs from third countries to continue entering the UK despite disruption caused by the COVID-19 pandemic. The policy takes advantage of a mechanism to allow “unexpected deviations” in analytical control methods or production processes.
Having assessed Annex 16 of the good manufacturing practices (GMP), MHRA thinks there is scope for qualified persons to apply the flexibility the regulations provide when they encounter a minor deviation in the finished product specifications. MHRA is entrusting qualified persons to make the decision on whether to permit a minor deviation, asking them to use their professional judgment to determine whether safety and efficacy are compromised.
Other aspects of MHRA’s flexible approach also rely on Annex 16. For example, MHRA thinks the annex frees qualified persons from the need to repeat all quality control tests when they receive an import from a third-country manufacturer.  
If a qualified person finds they are unable to deal with logistical challenges quickly despite taking advantage of the flexibilities provided by Annex 16, MHRA wants them to contact its staff as soon as possible. MHRA may adjust the regulatory system in light of reports from the industry. 
MHRA Notice
Swissmedic Shares Ways Sponsors can Adapt Studies to Handle COVID-19 Disruption
The Swiss Agency for Therapeutic Products (Swissmedic) has shared details of how sponsors can adapt their clinical trials in response to disruption caused by the COVID-19 pandemic.
With the pandemic, as well as measures enacted in response to it, stretching healthcare resources and making it hard for patients to visit study sites, Swissmedic has joined with a group representing Swiss ethics committees to provide guidance for sponsors affected by COVID-19. The guidance hits some of the same points as documents published by Swissmedic’s international peers.
Swissmedic is open to direct-to-patient delivery of study medication provided the drug is sent from the study site, not the manufacturer or wholesaler. Sponsors can also limit monitoring to the items that are most essential to patient safety. Details of such a change, and others permitted under the guidance, must be submitted to the lead ethics committee, although a delayed filing is acceptable. Swissmedic and the ethics committees are accepting bulk filings for several clinical trials.
Swissmedic Notice
MHRA Offers Fast-Track Approval to Device Developers to Ease Pressure on Hospitals
MHRA has opened a fast track to developers of some medical devices to help healthcare providers get the equipment they need to tackle COVID-19.
Using powers enshrined in the Medical Devices Regulations 2002, MHRA is planning to authorize the use of products that lack the CE mark companies normally need to market medical equipment in the UK. The switch to a fast track for devices related to COVID-19 has caused agencies other than MHRA to take the lead on some tasks.
The Department for Business, Energy and Industry Strategy has become the touchpoint for requests for regulatory exemptions for personal protective equipment, while the Department of Health and Social Care is handling approvals of ventilators.
MHRA Notice, More

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