The Rise of Orphan Drugs

Approvals for Orphan drugs have been on the increase within both the USA and EU ever since legislation was introduced in an attempt to stimulate research into rare diseases.  The 1983 Orphan Drug Act and EU Regulation 141/2000 provided a new product class to which pharmaceutical companies can apply for marketing authorisations.  Both the EMA and FDA has seen a sustained increase in applications.  Approximately 30% of all applications for new molecular entities within the USA are for Orphan drugs and the EMA has seen a 40% increase over the past few years.

What is an Orphan Drug?

For a drug to be classified as an orphan drug the disease it is being used to treat must be designated an orphan disease.  Within the EU an orphan disease is one which affects less than 1 in 2000 patients per year and this disease must be registered with the EMA in order to gain orphan status.  This application (or sponsorship) is submitted by a corporate body, an individual researcher or a combination of both.  The sponsorship details both the orphan disease and a proposed treatment and once granted by the committee of orphan medicinal products (COMP) the sponsorship lasts for 10 years.  Within that 10 year period is it normally assumed that an application for a marketing authorisation will be submitted.  Interestingly only the holder of the orphan designation (sponsorship) can be named as the MA holder on the MAA for the treatment specified within the orphan designation.  An example of an orphan designation can be found here.

There are also a number of incentives available for pharmaceutical companies to invest in the development of orphan drugs.  These include tax relief, reduced MA application fees and most importantly product exclusivity for 10 years.  Many of these drugs, such as enzyme replacement therapies are designed to be a chronic treatment thereby requiring the patient to be treated for life.  This will obviously help companies offset the reduced size of the target population.  

With England the frequently quoted limit for new treatments to obtain NICE approval was typically £30k per patient per year.  With Orphan drugs there is no such limit as QALYs and the other pharmacoeconomic tools are harder to relate to rare diseases.  Cerezyme is a good example of this.  Within England the cost per patient per year is ~£140k.  In the States orphan treatments are now approaching $1m per patient per year for gene therapy drug Glybera.

Prior to the relevant orphan drug legislation there was little incentives for pharmaceutical companies to invest into treatments for rare diseases.  The traditional search for the next ‘blockbuster’ drug helped to drive the pharmaceutical industry into hunting for larger and larger markets such as cardiology and infectious diseases.  The shift away from blockbuster treatments to more personalised therapies has enabled clinical trials to be performed more efficiently by reducing subject numbers and stratifying trial subjects to known responders.  Clinical trials for orphan drugs may include as few as 10-20 patients and this will often form part of the marketing authorisation application. 

An MA to match

As the number of clinical trial subject can be very low the EMA can issue a conditional or exceptional circumstance MA for orphan drugs.  A conditional MA is issued on the basis that a full dossier will be submitted in the future covering long term safety & efficacy data.  Once submitted and approved the conditional MA then reverts to the traditional MA model.  Exceptional circumstance Mas are issued when a full dossier is unlikely to be issued in the future due to the small patient numbers involved.  The MA therefore becomes conditional on the MA holder performing long term safety studies and an annual assessment by the COMP.  The legal basis for exceptional circumstance MA is EU regulation 726/2004 and the EMA website provides a good overview.  The exceptional circumstance MA can therefore allow pharmaceutical companies to get their novel product to market sooner and without the costs associated with large phase 2 and 3 clinical trials.  It must be noted that the three pillars of marketing authorisations (safety, quality & efficacy) still apply to both conditional and exceptional circumstance MAs.   

Summary

The rise in marketing applications for orphan drugs can be attributed to a number of factors such as legislative developments, business incentives and the advancement of new technologies within the pharmaceutical industry.  From a trainee QP’s perspective this post does not offer a great deal of information to help with your viva.  However, being aware of how the pharmaceutical industry is changing is important to show an awareness of the bigger picture.  

The exceptional circumstance and conditional marketing authorisations would provide an additional layer to your law and admin knowledge. 

The Application Form

One of the most important pieces of the QP training jigsaw is the QP application form.  This and the Sponsor's form provide the professional body with documented evidence of the candidate's experience and is the first part of the assessment process.  The aim of the application form is to show the assessors that you have covered all the relevant knowledge & experience you need to act as a QP.  The assessors will compare your application form to the study guide to ensure all the requirements have been met.


The QP application form is analogous to a job application.  The application form is used to show you have the required skills and experience for the job and is primarily used to get you an interview.  The QP application should be treated in the same way - it is your ticket to being called for the viva.  Therefore it should be thoroughly checked for omissions and errors before submitting.  Your sponsor will play an important role here as they will need to countersign your application form.   Guidance for completing the application form for both applicants & sponsors can be found here and is definitely worth a read before making a start on your form. 

Tips for completing your QP application form 

     1.  Start early

Ideally you should start competing your application form as soon as possible.  Large sections of the application form cover personal details & employment history.  Most of these data can be lifted straight from your CV.  Even something as simple as this can take a lot of time so be prepared and plan your time effectively.  You can then build your application form over time as you gain experience from work, visits or training courses.

My sponsor left his application form till the end of his training thinking it would not take long to complete.  In the end it took him over 2 months to finish the application form!  At this stage of your training you want to be spending all your effort on revising not completing your application form     

     2.  GAP analysis

When populating your application form have the latest version of the study guide open.  Perform a gap analysis of your current application form content verses the content required by the study guide.  Your sponsor should be willing and able to do this for you.  Once you know the areas that require further work you can tailor your training program to meet these objectives.
 

After my initial gap analysis I typed out all the missing sections in red.  Once each section was completed I simply changed the font to black and moved on to the next section.  Using a different colour font helped me to prioritise those sections of the study guide.


     3.  Be specific

After a while you can lose the will to live whilst completing the endless sections of the application form.  It therefore becomes easy to write generic statements in an attempt to rush the process.  The assessors reading your application form will be looking for details of what you actually did.

For example: which statement would best demonstrate to the assessor your knowledge on supplier audits? 
 - Perform supplier audits
 - Performing a supplier audit on a media manufacturer who supplies my organisation.  The audit included a  review of the supplier's ISO9001 certified QMS, media manufacturing processes & facilities.

     4.  Know your dosage form

The contents of your application form will dictate some of the lines of questioning from the assessors.  This will be particularly important when it comes to your specified dosage form.  You obviously wont be expected to know every dosage form but you'd better know all the ones you put down on your form - especially those other dosage forms on your MIA license. 

Summary

The application form is a critical part of your application process and will provide the assessor's a first impression of you and your potential to be a QP.  Completing the form takes time and I would highly recommend starting as soon as possible.

Thanks to my sponsor for help with this article and for reviewing my own application form!

Study Toolbox Part 4: Training Courses

This 4th post in the Study Toolbox series will provide an overview of the training courses available to help you on your long road to eligibility. 

One of my previous posts gave a brief overview of the QP Study Guide which provides a general syllabus that all prospective QPs are expected to have a detailed understanding of.  There is a wealth of topics within the Study Guide and the breadth of topics can be overwhelming at first glance.  This may be of particular relevance for trainee QPs from either small scale manufacturing operations (like me) or from those from relatively niche areas such as  PET radiopharmaceutical or medical gas manufacture.

So how can you demonstrate you have the required knowledge & experience in all 11 sections of the Study Guide?   The training providers listed below will provide this but they are not compulsory or expected to be on your application form.

Commercial Training Providers

Training courses are one way of gaining sufficient knowledge.  The main commercial training providers offer modules based on each of the 11 sections of the Study Guide.  These courses not only provide comprehensive training but also provide a fantastic opportunity for networking with other trainee QPs.  This is especially important for identifying potential study partners and arranging reciprocal visits.  (I'll aim to cover visits in a future post).

NSF-DBA

The David Begg Associates courses have been running for a number of years now and are viewed by many to be the gold standard with regards to QP training packages.  The full course is linked with the University of Strathclyde and offers candidates the opportunity to gain a post graduate certificate, diploma or MSc.  The modules run over 21 months but you can pick and choose the modules to fit in with your own requirements or knowledge gaps.

Each module lasts between 4 to 5 days in Durham or York Marriott hotel conference centres.  Lecture notes for each module are substantial and include not only the slides but a very useful overview of each lecture in an easy to read format that compliments the slides really well.  The week long course is broken up into lectures and practical group work.  Written exams are held for those students aiming to complete the post graduate university course.

Is there a downside?   At circa. £3-4k per module the cost my be prohibitive for some companies or individuals who are self-funding (like me).  Also the length of the course means added expense of hotel & travel.  DBA offer special rates for the Marriott hotel at circa. £100 per night and will obviously provide a great platform to continue the networking into the early hours!   

DBA does offer a generous 50% discount for NHS employees which then brings it the price down in line with other providers.  To qualify for the discount you'll need a confirmation letter from your employer and DBA will then invoice you with the discount included.

DBA also offer a free annual QP training day for prospective students and their sponsors.  The date for this year is May 14th and I'll be heading up for the day.  It might be worth contacting DBA directly to enquire for last minute availability.

RSSL

RSSL specialise in scientific analysis, consultancy, product development and training for the pharmaceutical and food sectors.  Their popular QP training packages offer the similar layout to DBA by offering 11 stand alone modules the reflect the Study Guide.  There is no university collaboration so post graduate qualifications are not available to run in parallel with the QP course.

RSSL has its advantages over DBA.  The training is held within Reading and typically over 2 days meaning less impact to your work and family duties and may not require nights away from home for those based around London.   The costs per module is more accessible at circa £1.5k.  The shorter duration of the module means more of a focus on the relevant details required for your QP training.  The notes are more succinct than DBA but do not provide the excellent text overview for each lecture.   

Inspired Pharma

Inspired Pharma offer an alternative platform with their QP training.  They provide online tutor-facilitated courses on the Study Guide topics.  This allows you to fit the training in and around your busy work/life schedule without the need to spend 3-5 days on a residential course.  There is not a great deal of information on their website regarding the costs of these courses but I would suggest emailing them for further information.

Pharmaceutical Quality Group

Although not strictly a QP training provider, the PQG is an invaluable source of information for trainee QPs.  Membership is only £17 per year and this provides access to a wealth of documents and presentations available via their website.  For trainee QPs the PQG provide QP seminars specifically aimed at trainees and newly qualified QPs.  These full day seminars based in London provide a great introduction to QP training.  They cover the application process, requirements and legislation/GMP update session.  

My first foray into the QP training arena was attending last year's November seminar.  I found it extremely useful and a great opportunity for networking with other trainee QPs from the pharmaceutical industry.  I met a great study partner from this course and we still have weekly calls to discuss scenarios etc. 

The PQG also arrange visits to a wide range of pharmaceutical manufacturing facilities, distributors, API manufacturers.  The events page on their website gives all the visits coming up.  These are particularly good value at around £60 per visit. 

Non-Commercial Training Providers

Q3P (UCL School of Pharmacy)
 
This is the only non-commercial provider that I am aware of.  The Q3P course was initially aimed at addressing the shortage of QPs within the NHS sector.  The course is free for NHS staff and provides a similar layout to the commercial providers in following the Study Guide with 1 or 2 day modules.  Although still in its infancy the course is now enrolling its 3rd cohort.  The training has evolved since the first cohort and includes lecturers from both the pharmaceutical industry and NHS sectors as well as QP assessors. 

The Q3P course has a free open day on the 6th June 2013 for prospective students.  See their website for details.

Post Graduate University Courses

There are a number of university courses that cover some aspects of the Study Guide.  Although not specifically tailored to QP training they do offer a good grounding in the essential elements of pharmaceutical manufacturing & quality assurance.  These part time courses are designed on a modular basis and will provide the opportunity for post graduate qualifications to MSc level.  Post graduate qualifications are available with the NSF-DBA course (see above).

PIAT (Manchester University)
Industrial Pharmaceutical Sciences (Brighton University)
Pharmaceutical Technology (Bradford University)
PTQA (Leeds University)
Leeds University has now stopped supporting the PTQA course and currently there is no further information on the future of the course.

Completion of these courses would usually be expected before gaining QP trainee positions.  From there the QP trainee would often be sent on the specific commercial training courses to build on the knowledge from the post graduate course. 


Individualised Mentoring & Training

All of the courses above will provide you with a great amount of knowledge covering all aspects of the Study Guide.  However it must be noted that attendance to these course wont automatically get you through the viva.  The knowledge gained wont provide you with the detail and expertise required to structure well reasoned responses to the viva questions. 

This is where personalised training will help translate your knowledge into a well structured format to get you through the viva.  They will also offer to review your application form and provide either face-to-face or telephone training sessions tailored to suit you and your specific requirements.  The providers will also be well networked within the QP community and hence should be able to provide contacts for potential visits.

QPQuandary

This personalised training company provides coaching and mentoring to both QP trainees and sponsors.  It is run by Alex Hall who provides teaching on some of the commercial training courses including RSSL & Q3P as well as one-to-one coaching.

Alex is the RSC Chief Assessor and senior QP for Roche, but will be running QPQuandary full time in the near future. Therefore she knows what it takes to get through the viva and can provide mock vivas, application form reviews and numerous other services to help meet your training needs. In addition she provides a fantastic weekly teleconference service for groups of QP trainees from a wide range of backgrounds. For more information see the QPQuandary website for her contact details.


Other Training Sources

Self Study

Your own personal study underpins everything you learn both from your job and attendance at training courses.  There are no shortcuts.  You will have to hit the books for hour after hour to ensure all the knowledge remains at the forefront of your mind especially leading up to viva day.  Self study is acceptable for inclusion into your application form.

In House Training

Some of the larger companies (e.g. GSK) provide substantial in-house training programmes for trainee QPs that rival even the DBA course.  For those with shallower pockets in house training can be provided by your sponsor or from subject matter experts within your company.  This can be on a one-to-one basis or as part of departmental-wide training sessions. 

My own training plan

My training is underpinned by a Pharmacy degree and  post graduate diploma in the PTQA course.  I've chosen a pick n' mix selection from the training providers in order to fill in the gaps.  A gap analysis really helps identify those areas that need supplementing with training courses.  I'll be using DBA for API manufacture, roles of QP and Law & Administration courses this year.  Law & Admin and QP roles are essential as they form the majority of the fundamental modules of the Study Guide.  API manufacture is not something I have exposure to from either work experience or from my previous training courses and hence is a significant knowledge gap for me.  In addition to these I've booked a mock viva & mentoring sessions with QPQuandary as a milestone for me prior to submitting.  I've also got into the habit of self study most evenings to supplement all the above.

 Summary

There are a wide range of QP training courses available to cater for all your training requirements.  They are not compulsory for getting to the viva but will provide you with the knowledge, networking and confidence in new subject areas.   Supplementing these with one-to-one coaching sessions either from your sponsor or specialist training providers should provide the final polish for you before you enter the lions den.

I'm sure there are other providers out there.  Please add any to the comments section below.


Study Toolbox Part 1:  The Onion
Study Toolbox Part 2:  Introduction to Mindmaps 
Study Toolbox Part 3:  Keeping up to date