Scientific advice for licence applicants

 

Voluntary parallel scientific advice with NICE and the MHRA

NICE and the MHRA have been in discussion about the possibility of running voluntary parallel scientific advice in relation to clinical trial programmes, and have agreed to undertake a small pilot commencing March 2010. Companies who are interested in being considered for this pilot should already have experience of MHRA and NICE scientific advice procedures for other products, and should contact Ian Hudson at MHRA - ian.hudson@mhra.gsi.gov.uk - or Carole Longson/Seren Phillips at NICE.

Advice given by MHRA will be based on the questions and documentation submitted and cannot account for future changes and developments in scientific knowledge or regulatory requirements.

A broader scope for Scientific Advice Meetings - 22 August 2006 (32Kb)


When can advice be sought?
Scientific advice can be requested during any stage of the initial development of the medicinal product (before submission of a marketing authorisation application), and also during the pre-submission period for a variation to an existing marketing authorisation.

Meetings can also be held with the MHRA to discuss pharmacovigilance, advertising, proposal changes to labelling or package leaflets or post-authorisations regulatory advice relating to a product range.

What advice can be requested?
Scientific advice can be requested whether or not existing guidelines are in place. In cases where a company chooses to deviate from guidance available, it is particularly important for companies to seek scientific advice from MHRA.

The question(s) posed to MHRA by the company has/have to be as precise and clear as possible.

Such question(s) should address specific scientific issues concerning:

• quality aspects (eg the chemical, pharmaceutical and biological testing necessary to demonstrate the quality of a medicinal product)
• non-clinical aspects (eg the toxicological and pharmacological testing necessary to demonstrate the safety of a medicinal product)
• clinical aspects (eg endpoints, trial duration, target population, choice of comparator etc.)
• pharmacovigilance plans and post authorisation safety study protocols
• regulatory advice other than scientific advice, which is in connection with
• changes to dates for renewal of one or more marketing authorisations relating to a product range
• an application for variation or renewal
• amendments to the time periods for submitting periodic safety update reports (PSURs)
• in connection with a referral pursuant of Article 30, 31 or 36 of the 2001 Directive
• a procedure referred to in Article 35(2) of the 2001 Directive
• advice prior to publication of advertising for a medicinal product
• changes to labelling of packaging leaflets for medicinal products or a product range.

It is preferable that the questions are prospective and concern the future development of a medicinal product.

Submitting requests for advice
An initial request for a scientific advice meeting should made using the Request for scientifc advice form:

Request for scientific advice form

The initial request should indicate the therapeutic area, the scope of advice being sought (quality, safety, clinical, pharmacovigilance, advertising, labels and leaflets), and the likely number of company staff expected to attend. A draft of the proposed questions should also be sent. After initial receipt of a request for a meeting a date will be set. This will always be as soon as is mutually agreeable but companies are advised to contact the MHRA well in advance of their preferred meeting dates.

Following agreement by the MHRA to provide advice, the complete request should be delivered to the MHRA no less than ten working days before the agreed date of the meeting. One electronic copy of the full documentation should be submitted. The questions should be submitted in Word format (although the other items need not be). The MHRA contact person will advise the company about how many full paper copies need to be submitted.

Confirmation of receipt and acceptance
Confirmation of time, location, attendees, security, arrangement and presentation facilities will all be made by MHRA. The MHRA Finance Section will be notified to issue an invoice

In exceptional cases, for example if the scope of advice sought is not considered to be in line with the original request, or if the documentation is incomplete the meeting may have to be postponed or cancelled. No fee would be payable in such circumstances.

Structure of advice requests
The request should made using the Request for scientifc advice form:

Request for scientific advice form

Questions and company's position
The questions should address specific scientific issues. The company's position and justification(s), together with cross-references to the relevant appendices should follow each question. The final list of questions must also be available in a Word format. In case this is not possible, please contact the meeting organiser to discuss other electronic formats/options.

Appendices
The appendices, if relevant, may include:

• background information
• information relating to the questions (e.g. relevant study protocols)
• content of previous scientific advice received (national EU Authorities, other relevant international authorities)
• relevant guidelines (other than CHMP guidance documents).

The extent of the appendices should be limited to essential information. Extensive information, in excess of that specified in relevant summaries in the Common Technical Document, should not be included.

Face-to-face meeting
The MHRA prefers to meet face-to-face with companies but in exceptional circumstances, video-conferencing may be arranged. Telephone and tele-conference meetings are generally not considered satisfactory to discuss complex scientific and regulatory issues.

MHRA staff will have reviewed the company's documentation in advance of the meeting and either arrived at provisional advice or determined further questions and clarification to be sought at the meeting.

The company may wish to make a brief presentation but this should be kept as short as possible (usually only 10 to 15 minutes) to allow maximum time for discussion. A brief presentation of the issues (and perhaps controversies) surrounding each question may be helpful to begin the discussion. Only in exceptional circumstances should any new information, not previously presented in the briefing document, be presented.

Meetings are normally scheduled to last no more than 90 minutes.

The MHRA answers to the company's questions will be sent in writing within 30 working days of the meeting.

Notes of the meeting
The company should take notes of the meeting and a copy of these should be received by MHRA within 15 working days of the meeting. These notes will be for information only and will not be commented on; the final advice should be taken as written in the MHRA final advice letter, not the company's notes.

Written advice from the MHRA
Following the meeting with the company and receipt of the company's notes, a letter will be prepared giving the answers to each question. The advice will answer the written questions. The final scientific advice letter will be sent to the company within 30 working days of the meeting. Internal MHRA procedures will be in place to ensure quality of the final advice letters.

Follow-up/clarification
No fee will be charged for clarification of advice which, if necessary, will be dealt with by teleconference. Such clarification is limited to the advice given and does not extend to how the advice may impact on other aspects of the company's development plan or on other development strategies the company may consider in the light of the advice received.

Subsequent meetings and follow-up meetings, whether held because new questions come to light or when further development has taken place and new data may become available, will be charged at the same rate as initial meetings (subject to the scope of the advice being requested).

Binding status of advice
Companies seeking scientific advice should note that any scientific advice given is not legally binding with regard to any future application of the product concerned, neither on the part of MHRA/CHM nor on the company. Furthermore, advice cannot be taken as indicative of any future agreed position.

The answers given by MHRA are based on the questions and documentation submitted and cannot account for future changes and developments in scientific knowledge or regulatory requirements. Companies should note that the advice provided is without prejudice to applicable legislation relating to the particulars and documents which should be submitted in support of any marketing authorisation (or other) application; it is also without prejudice to any intellectual property rights of third parties.

The above statement will be included in each advice letter sent to the company.

Fees
The following fee structure applies:

Pre-application meetings		Fee £
Quality development only		2,378
Safety development only		2,378
Quality and safety development		3,308
Clinical development only		2,986
Quality and clinical development		3,917
Safety and clinical development		3,917
Quality, safety and clinical development		4,849
Discussion on development of paediatric forms and uses meeting criteria for waiver set down in schedule 5 paragraph 10 of SI 2008 No 552		No fee
Drug/device meetings
Quality development only		832
Safety development only		832
Quality and safety development		1,054
Clinical development only		1,054
Quality and clinical development		1,443
Safety and clinical development		1,443
Quality, safety and clinical development		1,831
Company discussion meetings		4,810
Pharmacovigilance advice meetings
Standard meeting		3,309
Major meeting		3,917
Post-authorisation regulatory advice meetings		2,986
Advertising advice		2,378
Advice on labels and leaflets		2,378
Reclassification advice meetings
P to GSL switch		2,986
POM to P switch		3,917

All fees become payable within 30 days following written notice from the licensing authority requiring payment of those fees..

Meetings held at the request of the MHRA will not incur charges, nor will those covered by agreed waivers.

Monies may be drawn from the 'deposit scheme' for meetings relating to variations to licences.

Contact for further information 
For further information, please contact Mrs Denise Till, telephone 020 3080 7164, email denise.till@mhra.gsi.gov.uk or Susan Delaney, telephone 020 3080 6476, email susan.delaney@mhra.gsi.gov.uk