MHRA Submission: The Role of Initial Company Administrator

The UK has left the EU, and the transition period after Brexit comes to an end this year. From 1 January 2021, for medicines authorized in Great Britain, Marketing Authorization Holder (MAH), will be required to submit pharmacovigilance data to the MHRA, according to GB requirements.

MHRA will require following submissions via the new MHRA Gateway or/ICSR Submissions portal.

• All pharmaceutical companies involved in making medicines regulatory submissions and vigilance activities
• All medicines clinical trial sponsors wishing to make clinical trial submissions (Initial Applications, Substantial Amendments, End of Trial Notifications and Developmental Safety Update Reports (DSURs)) to the Agency
• E-cigarette producers
• Brokers of medicinal products·

The first person in an organization who completes the registration process will become the initial company administrator.

Factors to be considered for initial company administrator-

1. 👉Smaller Organizations- a company administrator may also be responsible for making submissions or managing a team who will make submissions. It is recommended that each organization has more than one company administrator.

2. 👉Larger Organizations – may have different teams or departments who will be doing submission via MHRA Submission Portal like regulatory affairs, pharmacovigilance units, clinical trials teams etc. MAH need to carefully consider who is best in organizations for initial company administrator. This person will be responsible for adding further company administrators.

 A difference between Company Administrator and User

 👮A company Administrator: -

• A company administrator has the ability to add, edit and disable other users.
• A company administrator will also be able to see records of submissions made by users.
• A company administrator also has the ability to register multiple companies under their account.
• The initial company administrator will have the same permissions as any subsequent company administrators. However, they will be responsible for completing the user access steps for the organization and setting up the first set of additional company administrators and users.
• There are no limits to the number of company administrators

 👷A User:

• A user cannot add other users and can only make submissions for the organization they are registered to.
• A user will not see records of submissions made by other users.
• They can be added to multiple legal entities if required.

Note: if adding more than 5 users at a time, the changes will be made but you will be redirected to the homepage rather than the “user maintenance” page. To confirm that your new users have been added, simply navigate back to the “user maintenance” page.

Source: MHRA- www. gov. uk

Read More

How to gain access for performing submissions to the MHRA from 1 January 2021

 

The following groups will need to take access to MHRA Submissions in order to start submissions from 1 January 2021:

• All pharmaceutical companies involved in making medicines regulatory submissions and vigilance activities
• All medicines clinical trial sponsors wishing to make clinical trial submissions (Initial Applications, Substantial Amendments, End of Trial Notifications and Developmental Safety Update Reports (DSURs)) to the Agency
• E-cigarette producers
• Brokers of medicinal products

Gaining access to MHRA submission can be divided into three parts –

• User registration – the end to end process for adding an initial company administrator
• Add a new user – add an internal colleague as a user or company administrator
• Add a new external user – add a third-party consultant/consultancy as a user or company administrator

Prerequisite points💬 –

• The first Person In any organization who completes the registration process will become the first responsible administrator. Hence it is advisable that right person with appropriate consensus/permission becomes company administrator (registering as company administrator without permission could cause unnecessary confusion and delay to the company’s operational activities.
• Access of 5-digit company number(s) if any organization has previously submitted to the MHRA. (If you have not submitted to the MHRA, please email reference.data@mhra.gov.uk as you will need to register as a new company prior to beginning this process).
• All third-party consultants/consultancies have their own 5-digit company number and have registered for MHRA Submissions using that number.         

New Users

New users can straightway reach to MHRA account request page via the following link-

https://mhrabpm.appiancloud.com/suite/plugins/servlet/registration

Source: MHRA- www.gov.uk

Read More

Marketing Authorization Holders (MAH) should know these 10 things from BREXIT- MHRA Guidance on Pharmacovigilance Procedures

 MHRA has published updated guidance on pharmacovigilance procedures on 01 September 2020 and new rules will be effective from January 2021 (post-Brexit transition period comes to an end this year).

1. General Approach to the operation of pharmacovigilance

This document outlines the submission requirements of pharmacovigilance data from 01 January 2021. There will be some different requirements for products placed on the market in the UK with respect to Great Britain (England, Wales and Scotland) and Northern Ireland. Products placed on the market in Northern Ireland will need to be in line with EU legislation and follow EU requirements.

The Marketing Authorization Holder (MAH)  of products authorized in Great Britain need to follow pharmacovigilance data submission requirements as per MHRA.

•          UK and non-UK Individual Case Safety Reports (ICSRs)
•          Periodic Safety Update Reports (PSURs)
•          Risk Management Plans (RMPs)
•          Post-Authorization Safety Studies (PASS) protocols and final study report

The Good Vigilance Practices (GVP) modules will remain in force but MHRA will publish a guidance note on the exceptions and modifications to the EU guidance on good vigilance practices in due course.

For medicines authorized to be sold or supplied in Northern Ireland information will need to be submitted according to EU requirements.

For medicines which are the subject of a UK MA covering both Great Britain and Northern Ireland, information will need to be submitted in accordance with requirements for both Great Britain and the EU, as appropriate.

MHRA may ask historical data for assessment purpose.

2. Actions for submitting and receiving ICSRs

Submission of all UK ICSRs (serious and non-serious) and serious ICSRs from other countries via the new MHRA Gateway or/ICSR Submissions portal which have been developed.

MAH can register on the MHRA-Gateway and/or ICSR Submissions portal to enable configuration for their systems prior to 1 January 2021.

For products placed on the market in Northern Ireland MAH will need to submit ICSRs according to EU requirements to the Eudravigilance database.

 3. Signal detection

MHRA will not require MAH to conduct signal detection against MHRA database. MAH also obliged to notify MHRA of signals arising from any data source. From 1 January 2021 this also includes standalone signal notifications submitted by MAH to the EMA that are relevant to MAH products as well as signals raised by the EMA.

For products placed on the NI market, MAH additionally needs to report to the EMA those safety signals that are considered to meet the definition of an emerging safety issue (see GVP-Module IX Signal Management).

From 1 January 2021 the MHRA will carry out assessment of signals and issue decisions for both signals identified by the MHRA and those highlighted internationally.

Notify MHRA about emerging safety issues within 3 working days after establishing that a signal or a safety issue from any source meets the definition of an emerging safety issue.    

 4. Risk Management Plans (RMPs)

The MHRA will continue to accept EU versions of the RMP. On scenario where specific request made by MHRA then information to be included this may need to be provided in a specific annex.

For CAPs the current approved version of the RMP should be included in the initiating sequence as part of the conversion process.

RMPs and updates to RMPs for products authorized to be sold or supplied in the UK should be submitted to the MHRA, via the appropriate variation procedure.

5. Periodic Safety Update Reports (PSURs)

5.1 PSURs submitted after 1 January 2021

The MHRA will continue to accept EU versions of the PSUR, but where the MHRA has made a specific request for information or where there is UK-specific information relevant to the benefit/ risk assessment this should be included in a specific annex.

MHRA may develop their own submission requirements and develop a list of UK reference dates, but until this happens the EU reference date (EURD) list should be followed and PSURs, with submission dates after 1 January 2021, should be submitted to the UK at the same time as submission to the EU.

All PSURs, for products which are the subject of a UK MA, with the same active/combination, should be submitted as part of the same procedure. The content and format will remain the same as currently required in the EU, and the expectation is that the same PSUR will be submitted to the MHRA as to the EU.

Unless the marketing authorization specifies differently, PSURs for actives/combinations not currently on the EURD list and therefore not subject to the single assessment process should be submitted to the MHRA, at least six monthly during the first 2 years following placing on the market, once a year for the following 2 years and every 3 years after that.

MHRA will issue the outcomes of assessments shortly after publication of the EU assessment, at the latest, in order to maintain harmonization with the submission requirements on the EURD list. submission requirements, where appropriate.

MHRA has developed their own submission portal for PSURs which will be ready for use from 1 January 2021. More detailed requirements for submission will be issued but PSURs can be submitted to the portal in PDF or Word or as part of a zip file format. PSUR submissions will not be required as part of the CTD lifecycle in the UK and should not be submitted as part of the initiating sequence in the conversion process for centrally authorized to Great Britain MAs.

A fee of £890 will be payable for the assessment of PSURs for actives/ combinations currently listed on the EURD (or future UK reference date list) which are submitted to the MHRA. There will be a reduction to £445 for each PSUR where more than one PSUR is involved in the procedure.

Following assessment, MHRA will publish the outcome of PSUR assessment procedures including any amendments to the SPC and PL wording. No further fee will be payable for the amendment of the product information as a result of the UK assessment which will generally be made by a Type IA variation.

For Great Britain-only MAs the PSUR should be submitted to the MHRA system.

For products authorized to be sold or supplied in Northern Ireland, PSURs should be submitted in line with EU requirements and submitted to the EMA via the EU PSUR repository. The outcomes from the EU procedure should be implemented.

PSURs for UK MAs covering both Great Britain and Northern Ireland will need to be submitted to both the MHRA and EMA.

 5.2 PSURs submitted before 1 January 2021

For Great Britain-only MAs where a PSUR has been submitted before 1 January 2021 but the EU single-assessment procedure has not been concluded, MHRA will assess the PSUR considering any relevant information, including any EU decision and may request further information, where appropriate, in order to conclude the assessment.

Where the PSUR is for a product authorized by a UK MA, in respect to both Great Britain and Northern Ireland the procedure will continue in line with the single-assessment procedure.

 Where the assessment has been concluded but the outcome not implemented before 1 January 2021, the MHRA will take the necessary steps to implement the outcome.

6. Post Authorisation Safety Studies (PASS)

6.1 PASS protocols and results submitted after 1 January 2021

For PASS where the study is a condition of the UK MA, prior to the start of the study the draft protocol should be submitted to the MHRA and will be assessed in line with usual practices. Where the MA extends to Northern Ireland or is an Northern Ireland only MA the draft study protocol should also be submitted to the Pharmacovigilance Risk Assessment Committee (unless the study is only to be conducted in the UK at the request of the MHRA).

 For all PASSs that are non-interventional, that are either voluntary or a condition of the MA and that involve collection of safety data from patients/healthcare professionals MAH should send the final study reports to the MHRA for assessment

MAH should submit the final study report (and abstract of study results) to the MHRA. Where the MA extends to Northern Ireland or is a Northern Ireland only MA the study report should also be submitted to the Pharmacovigilance Risk Assessment Committee (unless the study was only conducted in the UK at the request of the MHRA).

The final study report should be submitted within 12 months of the end of data collection. The fee for assessment of PASS protocols or final study reports is £8,309. Both protocols and final study reports should be submitted to us using the Type II complex variation route (classification C.I.13) with the corresponding fee.

 6.2 Ongoing issues regarding PASS protocols after 1 January 2021

For products authorized in the UK where the EU PRAC (Pharmacovigilance Risk Assessment Committee) has either endorsed a draft study protocol or made a substantial amendment to a draft protocol before 1 January 2021, MHRA will accept the draft or the amended draft study protocol but may request that further information is submitted to us within a specified time.

Where a non-interventional PASS has been proposed or imposed but the draft protocol has not been endorsed prior to 1 January 2021, any information required by the PRAC, together with any information required by the MHRA regarding the protocol must be submitted directly to the MHRA. This must happen even if the information was submitted via the EU procedure prior to 1 January 2021. The MHRA will then assess the information in line with the usual procedures.

6.3 Ongoing issues with PASS final study reports after 1 January 2021

For products authorized in the UK, where a final study report was submitted to the EMA before 1 January 2021 but no recommendation was made before that date, it may be required that the study report and abstract of the study report are submitted to the MHRA together with any further information relating to the study. In any event MAH should evaluate the impact of the results on the authorization and submit a variation application as necessary.

Where PRAC made a recommendation prior to 1 January 2021, the MHRA will implement the agreed measures in line with the agreed timetable. MAH should submit any variation to us (for converted CAPs please refer to the guidance on our website and MHRA will determine the application within the usual timeframes).

7. Safety Referrals

For procedures started but not concluded before 1 January 2021, such as where a CHMP/CMDh opinion had not been reached the MHRA will complete the assessment, where appropriate, and make a decision on the procedure based upon the information, including any decision made at EU level prior to 1 January 2021. MHRA may request further information regarding the procedure on a case-by-case basis where deemed appropriate and take the necessary steps to implement the decision.

Where the the referral has been concluded but the decision not implemented before 1 January 2021, the MHRA will take the necessary steps to implement the final decision.

8. Major Safety Reviews

From 1 January 2021, where there are concerns regarding a medicine or class of medicines that are authorized in the UK, the MHRA may conduct a major safety review to review the available data and consider what regulatory action may be needed.

In these circumstances, MHRA will publicly announce the initiation of the review, outlining the reasons for the review, the list of affected active substances and products, and the timescales for the review.

Where MAH holds a MA for an affected product, MAH will be notified of the start of and reasons for the review. List of questions will be provided that should be addressed by all MAHs along with the deadline by which the requested information should be submitted.

In the first instance, this correspondence will be done via the Qualified Person for Pharmacovigilance (QPPV) but a different or additional contact for future correspondence can be nominated.

The outcome of the review will be published. Where the recommendations include proposals for regulatory action the details of the measures to be taken including any changes to the product information will be published.

 A major safety review will incur the following fees for assessment: 

• £51,286 where one or two active ingredients or combinations of active ingredients are included
• £59,595, where three active ingredients, or combinations of active ingredients, are included
• £67,904, where four active ingredients, or combinations of active ingredients, are included
• £76,213, where five or more active ingredients, or combinations of active ingredients, are included

Where the review relates to 2 or more authorizations, the fee will be divided by the number of authorizations forming part of the review and MAH will pay that reduced fee for each relevant authorization it holds.

9. Post-authorization Measures (PAMs)

Post-authorization obligations, including specific obligations, Annex II conditions, additional pharmacovigilance activities in the RMP (MEA), legally binding measures (LEG) or recommendations, in place on 1 January 2021 will remain in place.

For converted EU MAs MHRA recommends that MAH need to use the current application forms for PAMs and submits the information to us as a post-authorization commitment, following the same principles for submission as for variations in the CAPs conversion guidance.

Where data relating to a PAM has been submitted before 1 January 2021, but the assessment has not been concluded MHRA will conclude the assessment where appropriate. For converted EU MAs a copy of the application should be included in the data submission package.

Where MAH evaluation of data supporting a MEA or LEG suggests that an update to the product information is required this should be submitted via a Type II variation application.

10. Implementation of outcomes of referrals and procedures concerning PSURs, PASS, signal assessments and PAMs

Where an amendment to the product information is required as a result of the above procedures, this will be implemented via a variation procedure. Where the the procedure has been concluded before 1 January 2021, but the variation has not been submitted, the outcome will be implemented by the same procedure as for the EU (Type IA, Type IB or Type II).

Where the variation has been submitted, but not finally processed before 1 January 2021, the variation will be concluded in line with the outcome of the procedure.

Where there has been no EU decision before 1 January 2021, MHRA will carry out assessment where appropriate and the outcomes of assessments will be published together with advice on implementation

Source: MHRA Updated guidance on pharmacovigilance procedures, Published 01 September 2020                      

Read More