Since March 2020, MHRA Inspectorate has not conducted on-site inspections unless they were  linked to the UK Government’s COVID-19 response or any other potential serious public health risk.

Consequently, most of the GMP certificates released by MHRA were going to expire due to impossibility to organize inspections. For this reason, the validity of the certificates has been extended initially to 2021, then to the 2022 and, recently MHRA has announced that the expiry has been further extend until the end of 2023.

On November 8^th, 2022, MHRA Inspectorate announced the resuming of the programme of international onsite GMP inspections. The decision has been taken following the successful results obtained during the pilot programme of International onsite GMP inspections started in April 2022.

After two years, UK and the world itself are gradually returning to the “normal” life and international travels are now becoming easier to be organized. In April 2022, MHRA launched a pilot program, involving GMP Inspectors, with the aim to evaluate a potential return to onsite international GMP inspections. The risk assessment that was conducted led to a favourable result for the resumption of inspections.

The inspections will be managed adopting a risk-based approach, precedence will go to the ones with the greatest impact on UK public health and patient safety. Sites will be contacted directly by the authority to arrange the inspections.

Regulatory Pharma Net (RPN) can provide support in preparation of GMP inspections by undertaking gap analysis prior to the inspection by the regulatory agency.

The ECDRP (EC Decision Reliance Procedure) is coming to an end on the 31^st December 2023 and will be replaced from the 1^st January 2024 by the IRP (International Recognition Procedure). This new procedure will be open to applicants that have already received an authorisation for the same product from one of MHRA’s specified Reference Regulators (RRs):

Australia (TGA), Canada (Health Canada), Switzerland (SwissMedic), Singapore (HSA), Japan (PMDA), United States (FDA), European Union (EMA) and Member State Competent Authorities (This includes approvals through the centralised, MRP/DCP and individual member state national routes).

The implementation of IRP will enable the MHRA to carefully consider the valuable expertise and decision-making abilities of reliable regulatory partners, ultimately resulting in improved outcomes for patients in the UK. While the MHRA will conduct a focused evaluation of IRP applications, it will also possess the necessary authority to decline applications that are deemed to have insufficiently strong evidence.

There are two recognition timetables for initial MAAs:

• Recognition A: 60-day timetable
• Recognition B: 110-day timetable

Applicants are requested to complete an eligibility form 6 weeks prior to their planned MAA submission to determine their suitability for Recognition A or B.

To be eligible for Recognition A, the RR approval must have been granted within the previous 2 years. If Major Objections are identified which cannot be resolved within 60 days, the timetable may revert to Recognition B.

To be eligible for Recognition B, the RR approval should have been granted within the previous 10 years.

If an application does not meet the criteria for Recognition A or B, it may still be submitted as a full national application if it complies with the requirements set by MHRA.

IRP can also be used for post-authorisation procedures including line extensions, variations and renewals. Generally, it is recommended that the same RR is used for IRP applications throughout an individual product lifecycle. Changes of RR during the product lifecycle should be highlighted in the post-authorisation procedure cover letter.

Regulatory Pharma Net provides full regulatory assistance during the whole product lifecycle and is ready to support companies on all regulatory needs and to guide them through any new MHRA requirement/procedure.

In recent years, drug shortages have become a growing concern in many European countries, especially in small markets. These markets, often characterized by limited population sizes or lower commercial appeal, tend to face significant challenges in maintaining a steady supply of essential medicines. Factors such as production issues, delays in drug registration, and commercial decisions contribute to these shortages. In response, the European Union has implemented regulatory measures to streamline access to medicines while ensuring their safety and efficacy. One such measure is the Mutual Recognition Procedure (MRP) Day 0.

The Mutual Recognition Procedure (MRP) Day 0 allows a marketing authorization granted in one EU member state to be recognized by others. This procedure allows harmonization between the Reference Member State (RMS) and Concerned Member States (CMS).

The new CMDh guidance “Procedural Advice on Zero day MR procedure”, issued in April 2024 provides more clarity on this procedure and helps the applicants in understanding the steps to be performed in order to prepare the submission package. Some key points are summarised below:

• The RMS and the CMS must accept to participate in the procedure before the application is submitted. The Applicant must guarantee that the product will be placed on the market in the MS.
• More CMSs could participate in the same procedure in case the requirements are the same for both countries.
• The dossier to be submitted should be in eCTD format, for dossier not in eCTD format the applicant should liaise with the CMS and follow national guidance.
• The CMS agrees to accept the assessment of the RMS without any comments or questions. This kind of procedure is finalized once the application has been accepted by the RMS and CMS. The zero-day procedure is concluded on the same day it starts.

Regulatory Pharma Net provides full regulatory assistance during the whole product lifecycle and is ready to support companies on the preparation and submission of MRP day 0 procedure.