Euro Regulatory Roundup: EMA clears mutual recognition partners to co-audit GMP inspectorates

The European Medicines Agency (EMA) has changed its joint audit program guidance to permit the involvement of its international peers as co-auditors. The revised guidance gives regulatory agencies with mutual recognition agreements (MRAs) with EMA the chance to take part in audits of the good manufacturing practice (GMP) inspectorates of national authorities.
 
Working with EMA, the Heads of Medicines Agencies (HMA) set up the audit program to monitor the implementation and equivalence of GMP inspectorates in the European Economic Area. Through the program, EMA and HMA seek to satisfy the requirements of MRAs with overseas regulatory agencies and maintain confidence in the GMP compliance systems used in Europe. Those elements make the joint audit program part of the reason foreign regulators trust GMP reports from European agencies.
 
Despite the significance of the program for the functioning of MRAs, EMA’s foreign partners have historically had limited direct involvement in the audits. The guidance adopted by EMA and HMA last year on the subject set out the rules on observers of audits but lacked provisions for MRA partners to take a more active role in the process.
 
The updated guidance released late last month changes the situation, stating “MRA partners may be invited to participate in particular [joint audit program] regular re-audits as observer or co-auditor” if they express an interest. MRA partners still cannot serve as lead auditor, a role that is reserved for European groups, but the co-auditor provision permits them to play a bigger role than in the past.
 
EMA has established rules for MRA partners that sign on as co-auditors. MRA partners will need to sign a confidentiality agreement and complete an EMA declaration of interests and curriculum vitae. Representatives of an MRA partner cannot outnumber the European auditors and must pay for their own travel, accommodation and translation costs. Partners that need translators should clarify the situation “well in advance of the audit” and agree arrangements with the lead auditor and auditee. 
 
The rules also set out the role the MRA partner will play during and after the audit, stating “in case any audit objective should be covered by the MRA partner representative alone in the framework of the MRA ... this should be preliminarily discussed with the lead auditor to confirm if EU legislation, rules, procedures or guidelines were effectively considered and impacted.” The same rule applies if an MRA partner has an “observation or opportunity for improvement.”
 
During the audit, EMA wants MRA partners to raise any concerns. In doing so, EMA wants the audit teams to reach “consensus on the results, findings and conclusions.” Once a decision is taken on-site by the audit team, MRA partners should not challenge the position.
 
EMA Guidance
 
UK government asks industry to stockpile ahead of next Brexit deadline
 
The United Kingdom’s Department of Health and Social Care (DHSC) has written to medicine suppliers to ask them to stockpile enough products to last six weeks ahead of the next big Brexit deadline at the end of the year.
 
With the UK government declining to seek an extension to trade deal negotiations, it needs to reach an agreement with the European Union to avoid a hard split at the end of the year. The transition period, which largely maintains the pre-Brexit status quo, is due to end on 31 December. In practice, the UK and EU will need to strike a deal well before then to ensure both sides have time to ratify the agreement.
 
UK and EU negotiators are yet to reach an agreement on some key issues, notably state aid rules. If the negotiators fail to find a compromise, the UK could leave the EU without a trade agreement or with a deal that is so insubstantial it still causes major disruption at the start of 2021.
 
Those concerns led DHSC to write to medicine suppliers this week. The letter is part of the UK’s push to prepare for the prospect of “reduced traffic flow” at the short straits that link the UK to the EU “in a reasonable worst-case scenario.” To mitigate the impact of that worst-case scenario, DHSC wants medicine suppliers to keep six weeks of stock on UK soil.
 
As DHSC notes, the request comes at a time when “global supply chains are under significant pressure, exacerbated by recent events with COVID-19.” DHSC made the same request the last time a potential no-deal Brexit loomed on the horizon. Back then, industry groups said a lack of cold-chain storage would prevent them from keeping enough of some products to last six weeks. DHSC is also rebuilding the stockpile it established in the run up to the previous Brexit deadline.
 
The stockpiling is advancing in parallel top efforts to ensure products continue reaching the UK. DHSC wants to reroute medicines away from potential disruption points and has contracted three logistics providers to help it urgently move medicines into the country.
 
Government Letter
 
Swissmedic shares guidance on authorization of non-conforming devices
 
The Swiss Agency for Therapeutic Products (Swissmedic) has released guidance on authorizations of non-conforming medical devices. Swissmedic created the document to explain the requirements and responsibilities associated with the regulatory pathway.
 
Typically, devices need to undergo a conformity assessment before being placed on the Swiss market. Manufacturers can skip that step “in the interests of public health or patient health and safety.” The guidance explains the options for companies that want to take advantage of the regulatory flexibility.
 
Companies can apply for authorization to sell a non-conforming device. In that situation, Swissmedic expects the device to meet the essential requirements. The applicant must inform Swissmedic of all incidents involving the device in Switzerland, as well as any recalls or other safety corrective actions. Swissmedic expects applicants to perform post-market surveillance and have a recall system.
 
The guidance also permits companies to place medical devices on the market without Swissmedic authorization. That option is open to devices that meet certain criteria, for example that they serve to avert life-threatening conditions that cannot be addressed by available conforming products.   
 
Swissmedic Notice
 
MHRA identifies areas its COVID-19 flexibilities diverge from EU policies
 
The UK Medicines and Healthcare products Regulatory Authority (MHRA) has updated its guidance on the flexibilities available to the industry during COVID-19 to highlight areas in which its position diverges from that of the EU.
 
MHRA identified nine areas of divergence from the EU. The list includes MHRA’s positions on qualified person declarations, the 30-day limit for type 1B variation replies, leaflet mock-ups and over-labelling. MHRA has not added details of how its positions differ from that of the EU to the updated guidance.
 
The UK regulator has also highlighted flexibilities that it offers that are aligned with the EU but cover the supply of “essential products that have been affected by the outbreak by factors such as travel and transportation restrictions or shortages of starting materials,” not just treatments for COVID-19
 
MHRA picked out seven flexibilities that fall into that category, including its approach to expedited assessments, GMP requirements, re-testing of imported products and audits of notified bodies and manufacturers.
 
MHRA Guidance
 
Other News:
 
Swissmedic has updated its guidance on document protection with new details about simultaneous authorizations. Swissmedic Notice