Sunset Clause

Under Article 23a of Directive 2001/83EC, as inserted by Article 1(22) of Directive 2004/27EC, the marketing authorisation (MA) holder is required to notify the competent authority (MHRA in the UK) of the date of actual marketing of the medicinal product, taking account of the various presentations authorised, and to notify the competent authority if the product ceases to be placed on the market either temporarily or permanently.

MHRA documents and guidance
We have issued the following documents and guidance on the "Sunset Clause":
› MHRA policy statement: Interpretation of Article 23a and Article 24 (4-6) of Directive 2001/83EC – the so-called "Sunset Clause" - published 15 January 2007 (23Kb)
› New rules on the notification of the date a product is placed or ceases to be placed on the market (Article 23a of Directive 2004/27/EC): the "Sunset Clause" - published 20 December 2005

One-off exercise to establish the marketing status of all medicinal products on the UK market - 25 April 2008
The MHRA has undertaken a one-off exercise to establish the marketing status of all medicinal products on the UK market, whether they have purely national authorisations, or were authorised under the decentralised or mutual recognition procedures. Herbal medicinal products with a full MA were included, but other categories of herbal medicines, homeopathic products and parallel imported/distributed products were outside the scope of this exercise. Products authorised under the centralised procedure are the responsibility of the EMEA/European Commission and their marketing status did not have to be notified to the MHRA under this exercise.

We have issued instructions on how to comply with this exercise which should have been completed by marketing authorisation holders (MAHs) by 12 July 2008. We issued a CD to each MA holder with details of each MA they hold on an Excel spreadsheets for completion and return by email or return of the CD. A detailed explanation of how to comply with this exercise was sent to each MA holder.

MAHs intending to apply for an exemption on public health grounds in respect of a product that has not been on the market in the UK since 30 October 2005 could do so at the same time as they completed and returned the spreadsheet, but may also do so at a later date, as long as this is at least two months before the date on which the MA will become invalid. You do not need to send any data supporting your application for a public health exemption, but you will need to have any such information available to submit should we ask you to do so. You may use the proforma we developed for you to use with the CD we send you for the one-off exercise. A copy is available to download below for information:
› Request for public health exemption from invalidation of a marketing authorisation (53Kb)

Proposals for conducting this exercise have been discussed and agreed with the trade associations (ABPI, BIA, BGMA, PAGB and the Herbal Forum).

We would be grateful for prompt responses to this exercise which will enable us to:

• update MHRA records
• avoid the possibility that products with invalidated MAs are unwittingly placed back on the market by MA holders
• reduce confusion and unnecessary future correspondence about the status of individual MAs.

Until we launch this exercise, you should continue to notify (first placing on the market and temporary interruptions in supply) by e-mail to: sunsetclause@mhra.gsi.gov.uk

The questions and answers below now provide additional information about the Sunset Clause and this one-off exercise.

Important information about the Sunset Clause and marketing authorisations for herbal products

Following a meeting between MHRA and representatives of the Herbal Forum on 19 May the MHRA wishes to highlight one additional circumstance in which it would be reasonable for a company to make a request for public health exemption for certain herbal products with MAs that are not currently on the market .

The MHRA initiated discussion with the Herbal Forum on 19 May about preparations for an MHRA programme, for implementation over a number of years, in which the regulatory status of existing herbal MAs would be reviewed to see whether a proportion may more appropriately come within the category of traditional herbal registration (THR). The main focus of this exercise will be on those products which around the early 1990s following review by the Committee on Review of Medicines, were given a marketing authorisation with a traditional use indication and any subsequent "piggy back" versions of these products. Full guidance on this programme will be discussed with the Herbal Forum and then posted on the MHRA website.

There may be certain herbal products with an existing MA that are not currently on the market which companies consider it may be feasible to return to the market under the THR scheme. Where a company considers there is a realistic possibility that they may want to move a currently non marketed herbal MA into THR status we would invite the company to request the public health exemption and to annotate the relevant form in the Sunset Clause exercise with the following words:

"We plan to have discussion with the MHRA about the regulatory status of this product as part of the MHRA programme to review the regulatory status of herbal products with an MA."

Where the MHRA receives such a request for a herbal product with an MA we are likely to agree that an exemption from the effect of the Sunset Clause should be given for three years. Any further extension beyond three years would be for consideration in the light of circumstances at the time. Potentially such an extension could be made if at that point a company was actively pursuing THR status for the product.

Please note that where companies request the public health exemption for a herbal product in this way this does not create an obligation to pursue THR status for the product in question, but rather an initial intention to consider this possibility: we recognise that companies will need to consider their plans carefully in the light of guidance to be issued about the arrangements enabling herbal MAs to transfer to THR status. Equally, companies are reminded of the guidance, already issued for the Sunset Clause one-off exercise, that it is the responsibility of the applicant seeking to make use of the public health exemption to inform the MHRA if any of the exceptional circumstances should change. Therefore, if a company having claimed the public health exemption in this way for a non marketed herbal MA subsequently decides not to pursue this route it should notify the MHRA accordingly.

Questions and answers

How the provision operates
1. What is the relevant “start date” for the purpose of calculating the 3 year period under Article 24(5), when a product has been on the market previously but has not been on the market for a consecutive period of 3 years?
2. For a product to be classified as on the market what are the minimum requirements?
3. What does “on the market” mean in this context?
4. What date does the Sunset Clause clock start if a newly authorised product is not immediately placed on the market?
5. How will MHRA interpret “first placed in the distribution chain”?
6. If the MA for a product is invalidated, what happens to any parallel imported product?
7. Can a parallel import licence be granted after the MA for the original product has been invalidated under the “Sunset Clause”?

Interruptions in supply
8. Where a company notifies a temporary cessation and includes the re-supply date in the same letter, is a letter confirming re-supply still required?
9. Does MHRA need to be notified if – for whatever supply reasons - only limited supplies of a product are currently available and as a result the MAH limits the amount of product that can be supplied to patients?
10. Does a temporary cessation need to be notified if there is insufficient stock available to fill wholesale and pharmacy orders, but the patient will still get their prescription filled even if the MA Holder is out of stock for a few days?
11. Does temporary cessation need to be notified if other strengths, formulations or pack sizes are still available and therefore a prescription could be filled (and is that still the same if the other formulations cannot be used by all patients, or where only higher strengths are available)?

Public health exemptions
12. What will be the procedure for applying for a public health exemption?
13. Can a company apply for a public health exemption from invalidation of an MA in the UK if the product is not marketed here, but the MA is needed because the UK is the Reference Member State under the mutual recognition or de-centralised procedures?
14. Will this also apply if a company holds more than one duplicate licence for a product where the UK is the RMS (but the product is not launched in the UK), (there may be commercial reasons why different countries are launched on the different duplicates)?
15. Would the MHRA grant a public health exemption if the product is not marketed in the UK but is supplied for export to countries outside the EU?
16. If a product is not marketed when an application for a renewal of the MA is sent to MHRA, does this “re-set” the Sunset Clause clock?
17. What impact does a change of ownership of a non-marketed product have on the Sunset Clause clock?
18. What impact does creating a “piggy-back” MA (using an abridged, simple procedure) or duplicate MA have on the Sunset Clause clock relating to the original product?
19. Are there any special arrangements for generic companies who may hold many MAs which are not commercialised so as to take account of the changing nature of the market?
20. What will happen if the 3 year period falls during the processing of a variation application that will ultimately lead to a product being re-marketed?
21. Can a generic product company apply for a public health exemption if an MA has been granted for his product but because of intellectual property issues associated with the originator’s product, his product cannot be placed on the market until three years have elapsed?

Invalidation and cancellation
22. What happens if a company doesn’t notice that 3 years has passed since the product was last marketed and they re-market the product?
23. If a company has cancelled an MA rather than allow it to become invalid because of 3 years non-marketing, can that cancelled MA be used as a reference medicinal product for the purposes of applying at a later date for a new MA under abridged application procedures?
24. How far in advance of invalidation will MHRA accept an application to retain a non-marketed MA beyond 3 years on public health grounds?
25. Will the MHRA give notice to MA holders of impending invalidation of MAs under the Sunset Clause? 

Procedures and fees
26. When will MHRA have the capacity to receive Sunset Clause notifications electronically via the Sentinel portal?
27. If an MA becomes invalid under the Sunset Clause, will companies get a refund on their service fee for the remainder of the year?
28. What happens if a variation application has been submitted for a non-marketed product but this has not been approved by the time the 3 years of non-marketing has elapsed?
29. What fees are payable for the one-off exercise in 2008 and in the future?
30. What was the “one-off exercise”?
31. What happened where discrepancies were identified between information held by MHRA and information on company databases (eg in relation to the spreadsheet issued by MHRA for the purposes of the one-off exercise)?

How the provision operates

1. What is the relevant “start date” for the purpose of calculating the 3 year period under Article 24(5), when a product has been on the market previously but has not been on the market for a consecutive period of 3 years?
The MHRA will take as the “start date” for the purposes of calculating the 3 year period, the date that the marketing authorisation (MA) holder ceases to place the product on the market – that is, the date he enters the last batch into the supply chain. Although this may mean that at the end of the 3 year period some product remains in the supply chain despite the invalidation of the MA, this is not an unusual scenario – for example when MA holders cancel MAs but do not recall remaining stock already in the supply chain.

2. For a product to be classified as on the market what are the minimum requirements?
There must be at least one pack of one of the presentations included in an MA on the market somewhere in the UK.

3. What does “on the market” mean in this context?
In this context “on the market” normally means within the distribution chain beyond the control of the MA holder and before receipt by the patient.

4. What date does the Sunset Clause clock start if a newly authorised product is not immediately placed on the market?
The relevant date is the date the MA was granted. It is therefore important that MA holders comply with Article 23(a) first paragraph which states that the MA holder must inform the competent authority of the date of actual marketing of the product in the UK, taking account of the various presentations authorised.

5. How will MHRA interpret “first placed in the distribution chain”?
The MHRA takes the view that a product first enters the distribution chain when it leaves the control of the MA holder’s company. For example, if a product passes from the manufacturing division of a company to the wholesale dealing or distribution division of the same company, there has been no transfer and no placing on the market. The placing on the market occurs when the product passes into the control of another company (e.g a wholesale dealer, distributor or a pharmacy).

6. If the MA for a product is invalidated, what happens to any parallel imported product?
Unless the original product is withdrawn from the market for safety reasons, the parallel imported product can remain on the market after the MA for the original product has been invalidated. If the original product has been removed from the market for safety reasons, the MHRA will contact the parallel importer to advise that he may no longer import that product.

7. Can a parallel import licence be granted after the MA for the original product has been invalidated under the “Sunset Clause”?
Yes.

Interruptions in supply

8. Where a company notifies a temporary cessation and includes the re-supply date in the same letter, is a letter confirming re-supply still required?
No - we would fill in both dates when we receive the notification unless the date of re-supply changes in which case we will need a further notification.

9. Does MHRA need to be notified if – for whatever supply reasons - only limited supplies of a product are currently available and as a result the MAH limits the amount of product that can be supplied to patients?
As Article 23a of Directive 2001/83/EC only requires MA holders to report if a product “ceases to be placed on the market”, shortages or deliveries of limited supplies do not need to be notified to the MHRA. However, please note that the Department of Health (DH) also has an interest in the availability of products for supply to the NHS, and you may need to inform them about any shortages in supply. Their guidelines on medicines shortages and discontinuations can be found on the DH website at www.dh.gov.uk/medicinesupply

MA holders should also bear in mind their obligations under Article 81 of Directive 2001/83EC which provides that the MA holder and distributors have an obligation to ensure appropriate and continued supplies of a medicinal product to pharmacies and persons authorised to supply medicinal products so that the needs of patients in the Member State in question are covered. Failure by a MA holder to comply with this obligation is a criminal offence, unless the MA holder took all reasonable precautions and exercised all due diligence to avoid such a failure.

10. Does a temporary cessation need to be notified if there is insufficient stock available to fill wholesale and pharmacy orders, but the patient will still get their prescription filled even if the MA Holder is out of stock for a few days?
No - although the company will need to consider whether there is sufficient stock to allow the company to meet their obligations under the Best Practice Guidelines (available at: www.dh.gov.uk/medicinesupply) in place with the DH in relation to supply to the NHS. This would be for DH to answer, rather than the MHRA.

11. Does temporary cessation need to be notified if other strengths, formulations or pack sizes are still available and therefore a prescription could be filled (and is that still the same if the other formulations cannot be used by all patients, or where only higher strengths are available)?
Yes we need notification even if other strengths and formulations on other licences are available, and even if other pack types (eg blister, bottle) are available on the same licence. We record marketing status down to the pack type level on each licence ("taking into account the various presentations authorised", Article 23a) but not down to individual pack size level.

Public health exemptions

12. What will be the procedure for applying for a public health exemption?
The MHRA has developed a pro-forma for capturing this information. This pro-forma will also be available on the MHRA website for future use.

13. Can a company apply for a public health exemption from invalidation of an MA in the UK if the product is not marketed here, but the MA is needed because the UK is the Reference Member State under the mutual recognition or de-centralised procedures?
Yes, we will consider a public health exemption from invalidation in these circumstances. This is in line with the CMD(H) advice which all Member States have agreed to apply. However, the company will have to formally request this, otherwise the MA will become invalid.

14. Will this also apply if a company holds more than one duplicate licence for a product where the UK is the RMS (but the product is not launched in the UK), (there may be commercial reasons why different countries are launched on the different duplicates)?
Yes, in these circumstances (where a product is not marketed in the UK but the UK is Reference Member State for the control of the MA – including any duplicate authorisations – and the product is placed on the market in one or more Member States) it is likely that the MHRA would take the view that a public health exemption would be appropriate so as to maintain continuity of supply of the product to the single market, but the company will have to write formally requesting this and explaining the circumstances otherwise the MA will become invalid.

15. Would the MHRA grant a public health exemption if the product is not marketed in the UK but is supplied for export to countries outside the EU?
Yes, we will consider an exemption in these circumstances but companies must apply for it otherwise the MA will become invalid. We do not require companies to submit any supporting data to justify their application, but they should have it available to submit to us if requested to do so.

16. If a product is not marketed when an application for a renewal of the MA is sent to MHRA, does this “re-set” the Sunset Clause clock?
No, issuing a renewal MA has no impact on the “Sunset Clause clock”.

17. What impact does a change of ownership of a non-marketed product have on the Sunset Clause clock?
Change of ownership does not create a new MA and so it will have no impact on the Sunset Clause clock. However, if it is envisaged that the work associated with a change of ownership will extend beyond a three year period during which the product has not been marketed, both companies will have to apply for an exemption of invalidation of the MA. The MHRA will normally grant a 2 year exemption under these circumstances to allow the change of ownership work to be concluded.

18. What impact does creating a “piggy-back” MA (using an abridged, simple procedure) or duplicate MA have on the Sunset Clause clock relating to the original product?
The “piggy-back” or duplicate MA is a new MA and will therefore re-start the Sunset Clause clock (until it is placed on the market). However, the Sunset Clause clock will continue in respect of the original MA, and will, if the product is not marketed for 3 consecutive years, result in the MA becoming invalid.

19. Are there any special arrangements for generic companies who may hold many MAs which are not commercialised so as to take account of the changing nature of the market?There are no special arrangements proposed, but companies may apply in the normal way for an exemption from invalidation of MAs that have not been commercialised for three years.

20. What will happen if the 3 year period falls during the processing of a variation application that will ultimately lead to a product being re-marketed?
The MHRA will not invalidate an MA whilst a variation application that will allow the product to be manufactured and placed on the market is being processed. In these circumstances we would consider allowing a one year public health exemption from invalidation for the product.

21. Can a generic product company apply for a public health exemption if an MA has been granted for his product but because of intellectual property issues associated with the originator’s product, his product cannot be placed on the market until three years have elapsed?
In these circumstances the MA holder will be able to apply for such an exemption (but, as with all other applications for a public health exemption, this cannot be made more than 3 months before the end of the 3 year period).

Invalidation and cancellation

22. What happens if a company doesn’t notice that 3 years has passed since the product was last marketed and they re-market the product?
The MA will have become invalid after 3 years have elapsed and the marketed product will be unlicensed. The MHRA will aim to notify companies in advance of the date on which the MA will become invalid to avoid this happening, but it is the MA holder’s responsibility to ensure that such products, without valid MAs, are not remarketed.

23. If a company has cancelled an MA rather than allow it to become invalid because of 3 years non-marketing, can that cancelled MA be used as a reference medicinal product for the purposes of applying at a later date for a new MA under abridged application procedures?
Yes, this would be acceptable – because under EU legislation the reference product can be either currently or previously authorised.

24. How far in advance of invalidation will MHRA accept an application to retain a non-marketed MA beyond 3 years on public health grounds.
The MHRA will accept an application no more than three months and no less than two months before the date of the invalidation. The MHRA will respond to the MA holder with a decision before the date on which the MA would become invalid.

25. Will the MHRA give notice to MA holders of impending invalidation of MAs under the Sunset Clause? 
We expect to be able to advise MA holders in advance of the date on which their MA will become invalid but the responsibility for identifying the date on which this will occur remains with the MA holder.

Procedures and fees

26. When will MHRA have the capacity to receive Sunset Clause notifications electronically via the Sentinel portal?
This facility is already available. If you wish to use this mechanism to report to the MHRA either the date a product is placed on the market (either for the first time, or after an interruption), or to notify the date a product has ceased to be placed on the market, you should usethe Portal “General Product Licence Submission Electronic Application Form”. The completion of this form requires very few fields, and should be easy for anyone trained to use the Portal forms for other submissions.

• Choose “Information update” in section 1. “This Application Concerns:”

• Make sure all relevant Authorisation Numbers are added in 2. “Authorisation Number(s)”, and importantly, that the “Add Authorisation” button is hit to drop them into the “List of Authorisations” box. This will allow an electronic “External information update” case folder to be created in Sentinel.

• Complete sections “3. Applicant” a) & b) and “4. Person Authorised for Communication” a) to d) and “Signature” a) to d)

• Use comments to describe the situation about which you are informing us.

27. If an MA becomes invalid under the Sunset Clause, will companies get a refund on their service fee for the remainder of the year?
Service fees are levied in advance and no refund is available if for part of a year an MA for a product is invalid.

28. What happens if a variation application has been submitted for a non-marketed product but this has not been approved by the time the 3 years of non-marketing has elapsed?
In these circumstances (where action rests with the MHRA or another medicines regulatory agency) and where approval of the variation can be argued as essential to allow marketing of the product, this will constitute a valid justification for keeping the MA valid until the variation can be determined and the product can be placed on the market.

29. What fees are payable for the one-off exercise in 2008 and in the future?
The MHRA has not charge a fee to MA holders for completing and returning information about the marketing status of their products under this “one-off” exercise, or for the work associated with receiving, considering and replying to applications for exemption from invalidation of the MA under this one-off exercise. Neither will we, for the time being, charge a fee for future notifications of marketing status under the “Sunset Clause” provisions or public health exemption applications. However, we will monitor the costs associated with dealing with all aspects of the Sunset Clause provisions, and we may consult in future years on the introduction of fees for elements of this work.

30. What was the “one-off exercise”?
This exercise was conducted by the MHRA to establish the marketing status of all medicinal products with a full UK MA on the UK market. It included herbal products with full MAs, MAs granted by the MHRA for products authorised under the mutual recognition or de-centralised procedures, but not those authorised under the centralised procedure (which are the responsibility of the EMEA/European Commission) or products imported under “parallel trade” rules from elsewhere in the EU.

We needed to know the marketing status of all products with a full MA in order to apply the Sunset Clause rules – which will affect products not marketed for three consecutive years from 30 October 2008 by invalidating the MA. Neither the MHRA nor the MA holder needs to take action for the MAs of such products to be invalidated – they simply become invalid after the three year period during which the product has not been on the UK market. If we did not conduct this exercise, there is a possibility that products not marketed for three years after 30 October 2008 would be placed back on the market without a valid MA.

31. What happed where discrepancies were identified between information held by MHRA and information on company databases (eg in relation to the spreadsheet issued by MHRA for the purposes of the one-off exercise)?
We expected the MA holder to inform us of any discrepancies (by separate letter) so that we could update our databases.