A Call for Croatian Translators

This week saw the EC advertise for Croatian translators via Twitter.  Now you may be thinking how this relates to a QP training blog?

On the 1st of July this year Croatia will become the 28th member of the European Union.    As a QP you are expected to have a 'comprehensive knowledge of all EU and national legislation relating to the manufacture, storage & supply of medicines...' as defined by the QP study guide.  In order to have this knowledge you first need to know which countries are legally bound to this legislation and which countries are likely to join in the near future.

The EC Europa website gives a useful overview of the status of the EU member states and importantly those countries that are in the process of applying for membership.  In order to get to the first step in the process the country has to meet strict conditions for membership including incorporation of the 35 policy chapters of the EU, including chapter 28 (consumer & health protection) that covers EU legislation on medicines.

Potential countries are grouped into 3 categories depending on their current status.  The first category is for Potential Candidates and are invited to formally begin application proceedings only when they are ready.  As countries progress through their application they then become a Candidate Country and finally an Acceding Country once EU membership terms have been agreed.

Current Status of EU enlargement:

Category	Country
Acceding Country	Croatia (Entry 1st July 2013)
Candidate Countries	Macedonia, Iceland, Montenegro, Serbia, Turkey
Potential Candidates	Albania, Bosnia, Kosovo

Montenegro and Iceland are the 2 candidate countries where negotiations have been ongoing for a number of years.  These countries are the most likely to become acceding countries over the next few years. 

Relevance to the QP viva?

Having knowledge on the countries that are nearing EU membership (particularly the acceding countries) will help in your preparation for the common 'round the world' supply chain questions and scenarios.  These typically involve importation of APIs, intermediates or final products into the EU via a number of 3rd countries. 

Taking Croatia as an example, from 1st July 2013 it goes from a 3rd country to a Member State.  Therefore if you viva is coming up soon there is a high chance that the assessors will include Croatia in their supply chain scenario.  If you fail to recognise that Croatia is a 3rd country before 1st July 2013 then it is highly likely that your answers regarding importation will be incorrect and will obviously not go down well with the assessors. Having an awareness of upcoming additions to the EU shows the assessors that you understand the structure of the EU & have an appreciation of how the continuously evolving landscape within Europe affects your role as a QP.

The table below highlights some factors relevant to QPs regarding the inclusion of Croatia into the EU:

	Croatia (pre 1st July)	Croatia (post 1st July)
Legal Status	3rd Country	Member State
Finished product import Croatia into UK	Testing on import required	No testing on import required
API import Croatia into UK	Written confirmation would have been required	No restriction
QC Testing location	Importation Testing not permitted	Importation testing allowed
Retention Sample	Cannot be stored here	Can be stored here
IMP comparator sourcing	Unlikely to be sourced (equivalent EU GMP to be determined)	Likely to be sourced (EU GMP incorporated into local law)

  

Summary

As I've mentioned previously it's important to maintain up-to-date regarding the relevant legislative & GMP updates in preparation for your viva and throughout your QP career.  I would also recommend to include the structure of the EU (including EEA, EFTA etc) as well as upcoming changes as part of your update strategy leading up to your viva.  Including this RSS feed into your updates folder is highly recommended.

Friday's Round Up

USA on API white list

From next week the USA will be on the EU's white list regarding written confirmation of API imports from 3rd countries.  The USA now joins Australia, Japan & Switzerland on the white list.

Class 1 recall – Ambisome Injection

Potential lack of sterility assurance was the typically vague term used by the DMRC in describing the reason behind this recall.  Unfortunately no further information is provided  but it is worth considering the possible causes such as primary container defects, media fill results, PV complaints….  Ambisome is a critical product so a recall indicates the severity of the problem.

Aspirin tablet recall (FDA)

An example of segregation/line clearance error during packaging.  The aspirin bottle actually contained paracetamol tablets.  This should immediately draw your attention to the potential extent of the problem – ie where have the aspirin tablets gone? (in the paracetamol labelled container perhaps?  which would have the greatest risk to patients? - this is where your medicinal chemistry should help in your assessment!)

WHO guideline on QRM

These guidelines build on Q9 and provides more detailed information regarding the implementation of QRM.

EMA Q&A – Annex 1 bioburden

EMA clarifies the point at which bioburden testing should be performed (immediately prior to filtration) and bioburden limit (10cfu/100ml).  This is part of the ongoing GMP Q&A section of the EMA website that gets updated periodically but without much fanfare.

EMA guidance update on ASMF submission

This provides some details on the letter of access that API manufacturer’s use to give the regulatory authority permission to review all the commercially sensitive data regarding the API manufacturing process.   The withdrawal of access letter has been given more guidance for when API manufacturer changes or the ASMF is replaced by the CEP.

Single use Technology for biotechnology manufacturing

A useful insight to the disposable systems in use for biotechnology manufacture.  These remove the need for cleaning validation, reduce contamination and saves significant time where cleaning of multi use biotech equipment can significantly reduce the available manufacturing capacity.

Pharmafile provides a nice overview of MHRA action regarding API importation (as mentioned in last week’s post)

Happy reading!

Friday's Round Up - June 14th

This is the first of my weekly round up posts.  The aim of these is to provide an overview of any news articles, stories or anecdotes I come across during the week that may be relevant to trainee QPs. 

WHO Water Guidelines
These were published last October but only found their way to my updates folder this week.  A good overview of water systems for those with limited first-hand experience in them

Ventolin Syrup Recall (MHRA)
A class 2 recall from Glaxo Wellcome due to the potential for glass particle contamination within the syrup.  As always the recalls provide a great scenario question to test out your thought process in dealing with the initial complaint/defect. 

Vecuronium Bromide Injection Recall (FDA)
Sagent Pharmaceuticals are recalling a number of batches due to an elevated impurity result from routine testing (assuming ongoing stability testing).  Again, start thinking of the questions you would need in order to provide more information if presented with this during the viva.  For example - confirm the impurity result & with OOS investigation would be one of my first things to clarify......followed closely by identifying the impurity....

Warfarin 2mg recall (FDA)
Zydus Pharmaceuticals is recalling one batch due to oversized tablets.  This product is presented in 1000 tablet bottle and is a good example of a dose critical product where both overdose and underdose can have significant clinical consequences.    

Cilest Recall
J&J adding to the baby boom!  Anyone fancy performing the reconciliation on a recall of 32 million units?!

Ph Eur monograph update proposal for Glass containers for Pharmaceutical Use
From Tim Sandle's excellent site details a proposed update to monograph 3.2.1. regarding control of production of glass containers as well as QC testing for hydrolytic resistance. 

Updated EMA Q&A on APIs
A number of questions within this document were updated in May.  There are some that are related to the QP such as the regulatory expectation of API audit contents, qualification of API auditors (questions 8, 9 & 10).  Useful information for the FMD and round-the-world related viva questions.  (Remember - GMP Part II doesn't directly apply to IMPs)

MHRA update on API imports & written confirmation
A post that will probably lead to more work for the QP.  This outlines the MHRA's plan for the July deadline for written confirmation of APIs from 3rd countries following FMD requirements. 
The interesting section is: 
'Where UK Manufacturing Authorisation Holders ("MIA Holder") have determined that their third country AS sources are at risk and have not been contacted by MHRA they should provide evidence in the submission / declaration...'

I think it is safe to assume that 'MIA holder' will be substituted with 'QP'..... !

EMA Q&A document on Israel-EU MRA
Interesting document that covers the product types included and not included.  Interestingly GMP certificates issued prior to the MRA implementation date are considered valid

Japan added to EMA's white list for API import
The list of 3rd countries now on the white list is: Australia, Switzerland & Japan.  API imports from these countries will not require written confirmation for each batch imported into EU.   USA, Israel & Brazil are currently under evaluation.

Happy reading!

Study Toolbox Part 5: Visits

This post will provide a guide to getting the most out of your visits and hosting reciprocal visits of fellow QP trainees.  Visits will form a significant part of your QP training.  For most of us our working environment will not cover all the dosage forms and relevant aspects within the study guide.  Even those trainees working for large multinational companies there will likely be areas of the study guide that they wont be able to cover within their respective company.  This is especially important for those trainees within specialist areas such as PET radiopharmaceuticals, ATMP & medicinal gases.

Tips for arranging visits:

1.  Gap analysis

A gap analysis of your current CV or draft application form against the study guide will identify areas that you are not familiar with.  Listing these will form the basis of the ideal visits that you'd like to arrange to plug these gaps.  Your sponsor should be heavily involved in this process to ensure that all areas are considered.

Coming from a NHS background I identified a number of areas I'd want to visit.  These included, water systems, high speed packaging lines, API manufacturer (biological & chemical), high speed sterile filling lines as well as RA & PV departments.

2.  Networking

Once you have identified the main areas that you'd like to cover you'll need a list of appropriate contacts of people who may be able to arrange a visit.  This is where your sponsor should be able to help.  They should have a great network of contacts that you can utilise. By now you may now have built up your own network from training courses, conferences, symposiums etc, so now is the time to dig out those business cards and start emailing.

3.  Arranging a visit

One of the most important aspects of visits is knowing what you want to get out of them before you go.  Your aims should be discussed with your sponsor and your host in order to determine how long you will need to meet these.  Once you set a date for the visit begin working on an itinerary with your host.  Sometimes your host will provide an itinerary but you will need to ensure everything that you want to cover is included - if it isn't then amend the itinerary.  If necessary be specific and focus on one main topic for your visit especially if your time on site is limited.  During one visit I focused solely on the facility's water system and nothing else as I only had a half day on site.

It is always worth asking for a scenario session with the host which covers typical examples (real life if possible) that occur within their processes. 

4.  Preparing for the visit

Leading up to your visit it is important to spend some time preparing for the things you'll likely be witnessing.  try to get as much background knowledge on the subject area before you go.  Your sponsor should be able to provide you with a good overview of the subject but there are some good alternative sources available to you. Before heading to visit a high speed packaging line I searched you tube for the packaging line manufacturer (Ulhmann) and found a number of useful videos which gave me an idea of what to expect.

5.  During the Visit

Don't turn up empty handed - always bring some biscuits, sweets etc for the host and their team.  The other important thing to bring with you is a memory stick/usb drive.  Most of the trainee QPs will have numerous electronic resources which they may be willing to share.  It helps if you bring some of your own to trade!

Its important to ask as many questions as possible especially if there is a certain process or piece of equipment that is of interest to you.  I found it useful to put your auditor hat on during visits as this will help you to identify areas of risk and can lead to discussions over critical control parameters and in-process tests.  With my visit to the high speed packaging line it was useful to relate that process to the manual packaging process I was used to.  Ultimately the same controls are in place - the only significant difference was the volume and automation used in high speed lines. 

'If you don't ask, you don't get'.  If there is something you'd like to see, whether that is a SOP, deviation report etc then ask!  I was lucky enough on one visit to be able to view a complete marketing authorisation.  As my main experience has been with IMPs I had never seen a MA before and hence this was an obvious gap in my knowledge!  This was asked for in advance by me and meant that this was scheduled into the itinerary.  As a result I had the privilege to be talked through the MA contents by the company's PVQP.

6.  Visit end

Ensure you get all the contact details from both the trainee QPs and qualified QPs on site.  This will help build your network and if the trainee QP is a similar way through their training then it could be an opportunity to arrange regular telephone sessions.  Always  offer a reciprocal visit for their trainees to visit your own site. 
Once back at base you should update your application form with what you have gained from the visit.

7.  The reciprocal Visit

Arrange a reciprocal visit follows the same steps outlined above.  Even though you may think you wont have much to offer someone from 'big pharma' remember that those trainee may have only ever experienced high volume pharmaceutical manufacturing.  I have hosted a few visits of commercial pharma trainees and I think they gained something by reviewing small scale IMP manufacture and specialist equipment such as laminar cabinets & isolators. 

Hosting visits is a really good way of validating your own knowledge in your systems & processes.  It is almost like being audited especially if the visiting trainee QP is bombarding you with questions!  Make the most of this as one of these questions may crop up during your viva.  Again, include some scenario questions, real-life deviations and how they were dealt with during the visit.  It is a good opportunity to see how someone other than your sponsor tackles specific problems. 

Summary

Visits are an important part of your QP training.  You should aim to make the most of your time on site with arranging itineraries before hand and identifying the main objectives of your visit.  Witnessing first hand enables you to visualise processes, equipment and their associated noise, smell and scale - far better than any book or lecture could. 

I have been very fortunate to have been on a number of visits to commercial pharmaceutical companies.  Personally I think coming from the NHS helps for once as we are not a commcercial competitor and the NHS for many companies is a large customer and therefore are often willing to give something back.  I have to thank the following companies for hosting me (and feeding me!); Teva, Rosemont, Eisai, Guy's Hospital, Amdipharm/Mercury Pharma & Wockhardt. 

If anyone would like to visit my facility please feel free to contact me via this blog or my Linked In profile.


Study Toolbox Part 1:  The Onion
Study Toolbox Part 2:  Introduction to Mindmaps 
Study Toolbox Part 3:  Keeping up to date 
Study Toolbox Part 4:  Training Courses