Wockhardt 483
Following on from my previous post regarding the multi product recall of Wockhardt products. This informative warning letter really opens your eyes to the observed actions within the factory. You have to ask where the QP oversight was and how these issues were not picked up during routine self inspection
GSK trial data issues
Yet more problems for GSK's China operations. In addition to the well publicised bribery case issues have now been raised with clinical trial activity within China. Namely the lack of pre-clinical data before products were given to human subjects.
Fresenius 483
Another revealing warning letter regarding an Indian manufacturing site. The attempt at hiding documents by stuffing them into pockets is a particular highlight. As with all these warning letters it is useful to get into the habit of using them as possible scenarios and how you would tackle them as a QP
TOC for Cleaning Validation
A useful 30min presentation/webinar on the benefits of using TOC for cleaning validation. You'll need to submit details to access the presentation (there is no confirmation email so you can put any email in the box)
Top 20 Orphan Products
As mentioned previously orphan drugs are rarely out of the news. Here is a great list showing the potential behind these lucrative drugs.
One for the Coffee Connoisseurs
Hence the reason copious amounts of coffee are available during DBA courses!
Happy Reading!
Friday 26 July 2013
Friday 19 July 2013
Friday's Round Up
API Importation Flow Chart
A good overview of the written confirmation requirements of API imports and a useful flowchart which outlines the process
CEP Update
The EDQM has updated the CEP certificate with regards to the listing of manufacturing sites. From the 15th July the CEP certificate will carry details of all manufacturing sites involved in the manufacture of the API. This includes sites performing packaging, micronisation, sterilisation & QC.
Diovan Data Fabrication
Genentech Data Issues
Yet more reports of falsified data relating to drug development. Repeated reports should be making you think of potential viva scenario questions relating to this and how you would tackle it.
Certificates of Medicinal Products
I came across the term CMPs for the first time this weeks. CMPs are issued by the EMA to confirm the marketing authorisation status and the GMP status of the manufacturing site. The appear to be primarily used for export to 3rd countries to support regulatory approval within that 3rd country.
Supplement Recall (FDA)
A recall for supplements containing medicinal active ingredient sildenafil. A good example of how API supply chains are being compromised but will the FMD prevent this from happening in the UK?
Orphan Updates
Orphan drugs are rarely out of the news. The EMA has updated its guidance on orphan applications and sponsorship transfer. This document provides a good overview of the expectations of the EMA for orphan applications.
Insects in vials (FDA 483)
More issues highlighted by the FDA relating to an Indian & New York CMO. Insects within vials is certainly something I haven't come across before. When you read about deficiency reports such as this it is good to get into the habit for thinking through your response if this was a potential QP scenario.
FDA guidance on Technical Agreements
The FDA provide a good guideline on the requirements of TAs and scenarios where TAs have been deficient.
Lucentis & Avastin Equal in Efficacy
A study by the UK government to determine if these two treatments are equally effective for macular degeneration. This is likely to further the debate between the NHS & pharma where use of a drug off-label (Avastin) instead of the approval licensed product (Lucentis) has been justified on cost despite questions over the legality of this approach.
Happy reading!
A good overview of the written confirmation requirements of API imports and a useful flowchart which outlines the process
CEP Update
The EDQM has updated the CEP certificate with regards to the listing of manufacturing sites. From the 15th July the CEP certificate will carry details of all manufacturing sites involved in the manufacture of the API. This includes sites performing packaging, micronisation, sterilisation & QC.
Diovan Data Fabrication
Genentech Data Issues
Yet more reports of falsified data relating to drug development. Repeated reports should be making you think of potential viva scenario questions relating to this and how you would tackle it.
Certificates of Medicinal Products
I came across the term CMPs for the first time this weeks. CMPs are issued by the EMA to confirm the marketing authorisation status and the GMP status of the manufacturing site. The appear to be primarily used for export to 3rd countries to support regulatory approval within that 3rd country.
Supplement Recall (FDA)
A recall for supplements containing medicinal active ingredient sildenafil. A good example of how API supply chains are being compromised but will the FMD prevent this from happening in the UK?
Orphan Updates
Orphan drugs are rarely out of the news. The EMA has updated its guidance on orphan applications and sponsorship transfer. This document provides a good overview of the expectations of the EMA for orphan applications.
Insects in vials (FDA 483)
More issues highlighted by the FDA relating to an Indian & New York CMO. Insects within vials is certainly something I haven't come across before. When you read about deficiency reports such as this it is good to get into the habit for thinking through your response if this was a potential QP scenario.
FDA guidance on Technical Agreements
The FDA provide a good guideline on the requirements of TAs and scenarios where TAs have been deficient.
Lucentis & Avastin Equal in Efficacy
A study by the UK government to determine if these two treatments are equally effective for macular degeneration. This is likely to further the debate between the NHS & pharma where use of a drug off-label (Avastin) instead of the approval licensed product (Lucentis) has been justified on cost despite questions over the legality of this approach.
Happy reading!
Saturday 13 July 2013
GMP Principles in Principalities
Following on from my previous post on the entry of Croatia to the EU this post aims to give an overview of how the small principalities within Europe are integrated within the EU. As a trainee QP you will need to know how the EU operates and importantly know sufficient information to enable you to provide answers to the round-the-world supply chain viva scenario questions. These scenarios often involve complex virtual supply chains throughout and outside the EU.
I'm sure many of you are aware of the EFTA & EEA countries but how would you handle a scenario question that included importing medicines from Monaco, San Marino or Andorra? This post will aim provide you with the information required to answer that potential scenario.
Monaco
Famous for its grand prix, casino and tax exiles, Monaco is a small principality on the Mediterranean coast bordered by France. It is the most densely populated country in the world with a population of ~36,000 squeezed into a land area of 2sqKm.
Monaco is not a member of the EU, EFTA or EEA and has no MRA in place with the EU. Hence it can be considered, at face-value, to be a 3rd country with regards to medicine legislation. However, since 2003 Monaco has a formal agreement with the EU regarding legislation for medicines for human & veterinary use as well as medical devices and cosmetics. The formal agreement stipulates that certain EU legislation shall apply within the principality of Monaco and includes a number of familiar EU directives.
EU directives relevant to QP that are incorporated into Monaco law:
I'm sure many of you are aware of the EFTA & EEA countries but how would you handle a scenario question that included importing medicines from Monaco, San Marino or Andorra? This post will aim provide you with the information required to answer that potential scenario.
Monaco
Famous for its grand prix, casino and tax exiles, Monaco is a small principality on the Mediterranean coast bordered by France. It is the most densely populated country in the world with a population of ~36,000 squeezed into a land area of 2sqKm.
Monaco is not a member of the EU, EFTA or EEA and has no MRA in place with the EU. Hence it can be considered, at face-value, to be a 3rd country with regards to medicine legislation. However, since 2003 Monaco has a formal agreement with the EU regarding legislation for medicines for human & veterinary use as well as medical devices and cosmetics. The formal agreement stipulates that certain EU legislation shall apply within the principality of Monaco and includes a number of familiar EU directives.
EU directives relevant to QP that are incorporated into Monaco law:
- 2001/83/EC
- 2001/82/EC
- 2001/20/EC
- 2002/98/EC (blood directive)
- 91/356/EEC (previous GMP directive, 2003/94/EC not explicitly stated)
- 91/412/EEC (Vet GMP)
It is important to remember that these agreements with Monaco do not remove the requirement for auditing any relevant site within Monaco to determine compliance with EU GMP.
Andorra & San Marino
Both the Principality of Andorra and the Republic of San Marino are 3rd countries. They are not part of the EEA or EFTA therefore access to the EU internal-market is limited. They each have bilateral agreements in place with their immediate neighbours but they do not cover any EU medicine legislation. The EU has produced a concept paper stating that inclusion of Andorra & San Marino to the EFTA and then EEA is a viable option that should be explored in order to better integrate both countries into the EU framework.
Currently
Andorra and San Marino does not have any mutual recognition with regards to
pharmaceuticals. As a result movement of pharmaceuticals between the EU
and San Marino
is restricted and importation requirements as for other 3rd countries will apply.
Summary
Understanding the intricacies of the EU is a vital part of your law & admin module of the study guide. Expanding your knowledge into very specific areas & countries such as Monaco should give you more confidence during your viva supply chain scenarios.
Of the 3 countries mentioned only Monaco has implemented EU legislation regarding medicines and hence can be deemed as a 'quasi-EEA' member. Both Andorra & San Marino have not implemented any relevant EU legislation and are therefore true 3rd countries.
Summary
Understanding the intricacies of the EU is a vital part of your law & admin module of the study guide. Expanding your knowledge into very specific areas & countries such as Monaco should give you more confidence during your viva supply chain scenarios.
Of the 3 countries mentioned only Monaco has implemented EU legislation regarding medicines and hence can be deemed as a 'quasi-EEA' member. Both Andorra & San Marino have not implemented any relevant EU legislation and are therefore true 3rd countries.
Friday 12 July 2013
Friday's Round Up
A busy week for recalls and an important update to Annex 16 has now been published in draft.
Multiple Class 2 Wockhardt Product Recall (MHRA)
Multiple product recalls are rare. The previous example can be traced back to another Indian manufacturer Ranbaxy. For the recall not to state specific batch numbers means an endemic problem and I wouldn't fancy being in the Wockhardt QP's shoes this week. More information on this can be found here and here. It appears to centre on a lack of cleaning and falsification of training documents were the main reasons behind the recall.
Erythromycin Class 2 Product Recall (MHRA)
likely to be linked to the Indian CMO implicated in the Wockhardt recall but this has specific batch numbers affected.
50ml Sterile Syringe recall (BD)
MHRA field safety notices for medical devices are often overlooked area for information for trainee QPs. This recall is for sterile syringes. This is a recall that may directly affect specials manufacturing, especially those units that manufacture sterile pre-filled syringes commonly used for analgesia. As the syringe is the primary container knowing that these have been recalled due to a potential for leaks will require the specials unit to recall those syringes as this will pose a risk to sterility assurance.
Multiple Class 2 Wockhardt Product Recall (MHRA)
Multiple product recalls are rare. The previous example can be traced back to another Indian manufacturer Ranbaxy. For the recall not to state specific batch numbers means an endemic problem and I wouldn't fancy being in the Wockhardt QP's shoes this week. More information on this can be found here and here. It appears to centre on a lack of cleaning and falsification of training documents were the main reasons behind the recall.
Erythromycin Class 2 Product Recall (MHRA)
likely to be linked to the Indian CMO implicated in the Wockhardt recall but this has specific batch numbers affected.
50ml Sterile Syringe recall (BD)
MHRA field safety notices for medical devices are often overlooked area for information for trainee QPs. This recall is for sterile syringes. This is a recall that may directly affect specials manufacturing, especially those units that manufacture sterile pre-filled syringes commonly used for analgesia. As the syringe is the primary container knowing that these have been recalled due to a potential for leaks will require the specials unit to recall those syringes as this will pose a risk to sterility assurance.
There
is more emphasis on supply chain verification and increased scope for
routine duties of the QP including a formal assessment of 3rd part audit reports. QP discretion is highlighted but only if
registered specifications
are met and formal impact assessment documented. I presume there will
be a period where 2 different lists for routine QP duties are available
(annex 16 update & current code of practice) and you’ll need to know
both for your upcoming viva.
Mexico have published these presumably to be considered for inclusion
to the EU white list for API importation.
The FDA have recently published this guidance document following the heparin contamination issue during 2008.
Sandoz
helping with the baby boom! A good example of a lack of segregation
control for commercial combination product. It is worth considering the
impact of this
type of issue with regards to IMPs and comparing the risks compared with commercial
product (eg GCP risk).
A comprehensive list of who to follow in the world of global regulatory affairs.
Happy reading!
Thursday 4 July 2013
Friday's Round Up
Tuesday saw the deadline for written confirmations of APIs imported from 3rd countries not on the 'White list'. This overview provides resource for these requirements and covers potential problems with German custom officials. UK Law has yet to incorporate this requirement, as detailed here.
WHO outlines proposed Good Pharmacopoeial Practice (GPhP)
These proposed guidelines aim to promote harmonisation of pharmacopoeial monographs.
These proposed guidelines aim to promote harmonisation of pharmacopoeial monographs.
Genzyme
are recalling a batch of thymoglobuline due to stability issues. This
is an example of a company led recall as opposed to the standard ‘Drug
Alert’
response. Note these recalls do not have a statutory time limit for
action and as they are not as well distributed through primary/secondary
care they can often go unnoticed.
Fresenius
Kabi are recalling a number of batches due to presence of glass
particles within the vials. The FDA recall alert provides a good
overview of the risks
of injecting glass particles. Compare the risks to the patient if the
product were an oral liquid. You may have more to consider then just
the affect to the internal organs – think about patient compliance &
confidence in your product.
Another good overview of how bacteria adhere to surfaces and formation of biofilms.
MSD are recalling a single batch due to potential for cracked vials. As with all sterile products once you have a defect that reduces your sterility assurance level a recall is pretty much a given.
My Sponsor discovered this site recently which provides a good selection of public WHO inspection reports for a number of finished product manufacturers, API manufacturers, QC laboratories and CROs. The audits are based on relevant WHO guidelines for countries generally outside of ICH. The API manufacturer inspection reports are particularly useful and relevant now that the EMA has stated on the API written confirmation template that WHO GMP guidelines are considered equivalent to EU GMP.
Wednesday 3 July 2013
Written Confirmations – confirmed in writing?
This week saw the deadline for written confirmations for
APIs imported into the EU from 3rd countries as part of the measures included
within the falsified medicines directive (2011/62/EU). The FMD states that all APIs imported from 3rd
countries that are not on an approved list (‘White list’) require a written
confirmation from the manufacturer’s competent authority for each batch stating
the API has been manufactured according to equivalent EU GMP and that the
manufacturing site is subject to unannounced inspections. A template of the written confirmation can
be found in EU GMP Part III.
Legal Basis
As you are aware EU directives are required to be transposed
into UK law within a specific time frame.
The FMD is an update to 2001/83/EC which is transposed into UK law via
the Human Medicines Regulations 2012 (SI 2012/1916). SI 2012/1916 was active as of August 2012 and
since then no updates to this legislation have occurred (except for an update
regarding fees). As a result, SI
2012/1916 (as it stands on 2nd July) does not include the
requirement for written confirmations.
All references to API manufacture within this legal document refer to
the requirement for API GMP and quotes the GMP directive
(2003/94/EC) for guidance. The FMD does
not update 2003/94/EC therefore the UK law does not incorporate the requirements
of the FMD. As a QP in the UK one of your legal duties states; ‘….each batch has
been manufactured in accordance with these regulations…..’ (ie SI 2012/1916)
not 2001/83/EC.
A draft amendment to SI 2012/1916 is
available on the MHRA website which does incorporate the requirement for the
written confirmation (Chapter 4, Paragraph 45P) as well as the other
requirements under FMD (e.g. GDP for API).
As of today (2nd July) this draft has not been incorporated
into UK law.
Summary
The written confirmation deadline for APIs has come and
gone. As we currently stand the UK law
does not match the requirement within the falsified medicines directive with
regards to the written confirmations of imported APIs.
During this intervening time while we await
an update to SI 2012/1916 what should the UK QPs be doing - following FMD or UK Law? It might make for a good scenario question................
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