Q&A: MSD UK answers your questions about the Sinemet shortage

MSD UK, the manufacturers of Parkinson's drug Sinemet joined our discussion forum for a Q&A session on the shortage of the drug.

The event took place between 13 July and 17 August 2010. Highlights of the session are below.

Transcript of the event

Message from MSD UK

Dr Paul Robinson, Medical Director, MSD UK: Thank you for posting your questions regarding Sinemet and Sinemet CR, MSD's medicines for Parkinson's disease.

As Medical Director of MSD UK, I am very concerned to hear about the problems some patients are facing and appreciate this opportunity to provide more information about the situation.

First and foremost, on behalf of the company, I want to reassure everyone affected that we sincerely regret the inconvenience or distress this interruption has caused, and I apologise for it. We know and understand how difficult it is for any patient who may not be able to receive their usual medication. We are working hard to restore supply as soon as possible.

With regards to the questions many of you have posted onto the Parkinson’s UK online forum, as well as answering each question individually, I thought it might be useful to provide some background information around this supply shortage, which will hopefully prevent any undue repetition in my answers:

Global supply

MSD has been managing a temporary global supply shortage of some formulations of Sinemet since the end of 2009, and is making every effort to restore supplies as soon as possible.

Currently, the extent of this supply shortage varies from country to country, and supply is being managed through an allocation system to optimise available stock. Although our supply estimates change from time to time, most dosage strengths of Sinemet are available in the UK. We expect that Sinemet CR (controlled release) will be fully available by mid-2011.

The global shortage arose as the company changed the supply source of an active ingredient used in the manufacture of Sinemet, a process that requires qualification of the new active ingredient to ensure it meets Merck standards and regulatory approvals of the source change.

I can assure you that the company is working very hard to resolve this issue. We are running a global stock allocation system in order to distribute available medicine in the meantime. This is a tightly managed process which has been determined by factors including whether generic medicines are marketed in the country, patient needs, and any contractual obligations to supply product, which is the situation in the United States and other countries around the world.

UK supply

In the UK, we have worked with the Medicines and Healthcare products Regulatory Agency (MHRA) to obtain the necessary regulatory approvals for use of the new active ingredient. We in the UK and my colleagues in other countries have had to go through these additional local steps because Sinemet was licensed prior to the formation of the European Medicines Agency and is consequently under local jurisdiction.

This work had to be done for each formulation of the medicines. It was expedited by the MHRA and we now have approval for both the immediate release and the controlled release formulations. We are grateful to the MHRA for their co-operation in this matter. Again, most doses of the Sinemet are available in the UK and we expect to receive further of Sinemet CR in second half of 2010 in the UK.

In the meantime, we have also worked with the MHRA and the Department of Health (DH) to determine the availability of generic alternatives in the UK and have maintained regular contact with them to track stock allocations.

We have also communicated with doctors, pharmacists and patient organisations to update them on the shortage. We are advising all patients that tablets containing the same active ingredient as Sinemet (e.g. generic equivalents) are available from other manufacturers. We recognise that it is difficult for any patient to be asked by their physician to change from a branded to a generic medicine. In many instances however this can be both a medically appropriate option and a common occurrence in clinical practice.

The NHS has also issued guidance on how patients can be transferred onto alternative treatments should Sinemet be unavailable. This advice is available via the National electronic Library for Medicines (NELM) website.

As with all prescription medicines, patients should seek advice from their GP during this shortage. Additionally, we are advising healthcare professionals to contact our medical information department if they require any additional information or clarity.

We hope this provides you with a greater understanding of the issue. Please be assured that MSD takes this matter very seriously and always intends to act in the best interests of patients in these difficult circumstances.

As I answer each of your questions I would ask you to remember that it is not possible for me to provide individual medical advice. Should this be required, this is a matter for you to address with your doctor.

I hope the information below goes some way to answering your questions.

Questions and answers

Anon via website: Why is there a shortage of this essential drug? I am 47 years old and have had this totally life controlling condition for 8 years. I have 2 children aged 15 and 18 and still work full-time. Without Sinemet and Sinemet CR I cannot function, get out of bed, walk, wash and dress myself, drive, work etc. Without this drug I might as well be dead. So thanks a lot MSD UK.

Dr Paul Robinson: Firstly, please let me apologise for any problems that have resulted from an interruption to the supply of your medication. My colleagues at MSD and I genuinely appreciate how upsetting and frustrating this situation can be for patients and we are trying very hard to rectify it to prevent future distress.

As I explained in my introductory message, the global shortage arose as the company changed the supply source of an active ingredient used in Sinemet, a process that requires qualification of the new active ingredient to meet Merck standards and regulatory approvals of the source change.

Anon via website: Why didn't the old method of production continue until the new method had passed its regulatory procedure?

MSD UK: We did build supply inventory from our original supplier and we are manufacturing using supply from our new supplier. However, the process of identifying, qualifying, and obtaining necessary regulatory approvals that are required to establish a new supply source for an active ingredient is complex and takes time.

Anon via website: If MSD have received approval for new ingredient why is there this delay?

MSD UK: Supplying new product to meet current global demand takes time and depends on many factors, including meeting patient needs in countries where no alternatives are available and rebuilding stock levels. Manufacturing of Sinemet has continued, and the product is being packaged and shipped to countries as regulatory approvals are obtained in the individual countries.

Panda692: Please you could clarify the reason that the ingredient supply was changed. I think this fact is pivotal. For example, was the change a sudden unavoidable requirement that did not allow enough time to manage the situation before a shortage developed?

MSD UK: MSD's global supply process can be affected by several factors, including changing manufacturing needs to support our current product and pipeline portfolio, decisions made by our suppliers about their business, and local regulatory requirements. Identifying, qualifying, and obtaining necessary regulatory approvals are all activities required in establishing a new supply source for an active ingredient and it is a complex global process that takes time.

For Sinemet, MSD changed the manufacturing supply source as a result of a decision by our supplier about their business. As you can appreciate, because MSD is bound by a confidentiality clause with its supplier, we are not able to provide further details of our contractual arrangements.

Anon via website: What are the contractual obligations that apply in USA and other countries that don’t appear to be the case in the UK?

MSD UK: In the US and Canada, the product was marketed by BMS, and in other countries, MSD has contracts with the local government.

lindylanka: When did Merck first know that there would be a supply problem?

MSD UK: MSD has been managing a temporary global supply shortage of some formulations of Sinemet since the end of 2009, and since that time has been making every effort to restore supplies as soon as possible.

jazz: Why were contingency plans not put into place?

MSD UK: Again, MSD is managing a temporary global supply shortage of some formulations of Sinemet and quickly put into place an allocation system to optimise available supply. We have worked with health authorities to ensure that all requirements continue to be met with urgency as part of managing the issue. We also initially communicated with doctors, pharmacists and patient organisations about the shortage and advised them of alternative measures to help alleviate the problem.

Production did continue, however the company needed to implement an allocation plan to ensure that patients in countries where there are no alternatives continued to obtain treatment. The global shortage arose as the company changed the supply source of an active ingredient used in Sinemet, a process that requires qualification of the new active ingredient to meet Merck standards and regulatory approvals of the source change.

We are actively managing supply levels in the UK, and globally, in an effort to minimise the impact of these supply shortages and to ensure that patients in countries where there are no generics can obtain alternative therapy.

SF: Can you be more precise about when distribution will restart? (2011 is a whole year long). It would then give us a chance to plan our future medication and make decisions about whether we need to use an alternative.

MSD UK: Most of the Sinemet immediate release range is available in the UK. We expect further supplies of the Sinemet CR range by the second half of 2010 in the UK.

With regards to whether or not patients should consider using generic alternatives to Sinemet, I would advise that you discuss this with your doctor, who is best placed to provide you with guidance.

Anon via website: During the time that there will be a shortage of Sinemet, how will the distribution be managed? Will all available medication be distributed until it has all been used, or will there be a monthly/weekly cap so that there will be an even shortage across all months?

MSD UK: Our experience over the past 9 months has demonstrated that the allocation system, for the most part, has been effective in optimising available supply in the UK and managing new supplies of Sinemet that are being manufactured, packaged and shipped to the UK. We are shipping more supplies of Sinemet to the UK and will do our best to meet patients' needs as soon as we can.

While we can not provide exact tablet numbers, we believe we can meet full demand for Sinemet in the UK by the second half of 2010 based on the information we hold of patient needs and current market factors, such as the availability of generic equivalents.

Again, manufacturing of both Sinemet and Sinemet CR has continued, and new supplies are being packaged and shipped to the countries as regulatory approvals are obtained in the individual countries. In the UK, we are shipping more supplies of Sinemet and will do our best to meet patients' needs as soon as we can.

jazz: Why does this not affect manufacture and availability of generic co-careldopa?

MSD UK: As you can appreciate, we can only speak with certainty about the manufacturing and availability of Sinemet.

lindylanka: Can Merck give an indication of just how bad the shortage is, both here in the UK, and globally?

MSD UK: I am very conscious of the impact any supply shortage, no matter how isolated, can have on any patient who is unable to fill their prescription.

With regards to the global situation, a number of countries are affected, albeit to different extents, depending on a number of factors. Currently, much of the Sinemet range is available in most countries. The Sinemet CR range is expected to be fully re-supplied by mid 2011 in most countries. Again, we are working very hard to rectify this problem and to ensure full stock levels are returned as soon as possible.

Anon via website: Why and who made the decision not to inform users of the upcoming shortage? This has caused deep concern, distress and upset to people who use this medication. This could have been handled by placing a short note of explanation in the medicine boxes as you do with the statutory medicine leaflet.

MSD UK: I can assure you that since this issue occurred at the end of 2009 we have been in regular contact with the Medicines and Healthcare products Regulatory Agency (MHRA) and the Department of Health to discuss how best to manage supply. In addition, we have also communicated with doctors, pharmacists and patient organisations to update them on the shortage.

Information provided to patients is very carefully regulated and controlled - as such, we felt it was best to inform doctors and pharmacists of the supply situation, to enable them to communicate this to any patients affected. We are conscious however that, in some instances, this information cascade has not been effective. As such, we are now taking steps to ensure patients are kept regularly informed of the situation, through forums such as this as well as additional communications channels.

I can assure you that the company has been actively communicating since the issue arose at the end of 2009, however, as I have already mentioned, it is clear that our messages were not being cascaded to all patients.

We have communicated with doctors, pharmacists and patient organisations to update them on the shortage and advise them of alternative measures to help alleviate the problem since the issue arose at the end of 2009. In addition, we have responded to all requests for additional information as public interest increased in recent months.

Anon via website: Do the executives have any training or awareness of the true effect of missed does of a dopamine replacement?

MSD UK: On behalf of the company I do express my sympathy for your situation. We hope that you will understand our situation better from reading this exchange. You can see that most of the Sinemet range is available, and we expect further supplies of the Sinemet CR range by mid 2011. I will endeavour to keep you informed of our progress towards this goal through Parkinson's UK. In the interim, we would advise that you consult your doctor about alternative options available to you.

Please be assured that MSD takes this matter very seriously and always intends to act in the best interests of patients in these difficult circumstances.

I understand that this is very a worrying situation for any patient or carer concerned that they will not be able to access the medication. The best thing to do in this situation is to consult your husband's doctor to discuss if an alternative generic treatment might be appropriate. Most of the Sinemet immediate release range in the UK is available and that we expect further supplies of the Sinemet CR range in the second half of 2010 in the UK.

mojo: What is Merck’s response to the accusation that they are not fulfilling their statutory obligations? http://www.psnc.org.uk/pages/manufacturer_quota_schemes_.html#Background

MSD UK: We have been working closely with health authorities to ensure that the required processes governing essential medicines supply continue to be appropriately met.

Thank you for including this link as reference. That section of PSNC relates (primarily) to 'trading medicines for profit'. The Sinemet shortage is due to a global supply issue, related to a source of supply change of an active ingredient in Sinemet.

Again, please be assured that MSD takes this matter very seriously and always intends to act in the best interest of patients in these difficult circumstances.

Anon via website: Why does it seem to be only people in the UK who are experiencing problems with getting hold of Sinemet?

MSD UK: This is a temporary global supply shortage of some formulations of Sinemet. Currently, the extent of this supply shortage varies from country to country, and supply is being managed through an allocation system to optimise available stock. Although our supply estimates change from time to time, I am pleased to report that most strengths of Sinemet are available in the UK. We expect that Sinemet CR (controlled release) will be fully available by mid-2011.

Our efforts to improve the supply shortage are focused on ensuring patients in countries where there are no alternatives available are able to access treatment which may be effective in managing their condition.

This is a genuine supply shortage and not a result of any importing/exporting issue.
Any Sinemet packaging which looks different or does not have an English Patient Information Leaflet is likely to have been brought into the UK by a system called Parallel Import (PI). This is not the result of an MSD activity.

The Medicines and Healthcare products Regulatory Agency (MHRA) is responsible for granting wholesaler dealer/Parallel Import licences.

Any Sinemet which has been imported should be clearly marked as such. If patients have concerns about the packaging of their medicine they should address them to their pharmacist in the first instance.

jazz: Why is the availability so unpredictable week to week? In the past 3 weeks there has been no availability then full (normal stock levels) availability and now back to no availability.

MSD UK: Although much of the Sinemet range is available in the UK, we may still experience interruptions in the supply until such time that we are fully resupplied to full stock levels in the UK. This may result in a reduced level of certain doses from time to time. We expect to receive further supplies of Sinemet CR range in the second half of 2010.

We are working to resolve this and will continue to operate the global stock allocation system described in my letter above until normal supply is resumed in all markets. We hope this will be by mid 2011.

lindylanka: Could Parkinson's UK support the issue of the Sinemet shortage being raised in Parliament as a matter of urgency?

Parkinson's UK Campaigns team: Parkinson's UK has supported a number of members to contact their MPs, and has provided information and assistance to interested MPs and Lords to raise the issue in Parliament.

Steve Brine MP and Baroness Thornton have received responses from Health Ministers, confirming that the Department of Health has had regular discussions with the manufacturers of Sinemet and its generic alternatives since autumn 2009 and that the situation is being kept under review.

• email
• Share