Counterfeit Viagra & Cialis seizure
A large seizure of these popular lifestyle drugs has been reported in the Czech Republic. It is not clear how the counterfeit products were identified. It makes you wonder if any have actually gone through the system and ended up in the legitimate supply chain.
FDA Flu Vaccines
A good brief overview of the process of influenza vaccine production by the FDA. Interestingly the article states that the FDA actually release the vaccines into the US market. This mirrors some of the UK animal vaccine products that are released to market by the VMD and not the QP (although each batch does require QP certification prior to VMD release).
UK Class 2 recall
A recall of buprenorphine tablets due to a potential printing error with the carton supplier. This is a good example of when carton suppliers print the batch number as opposed to printing on-line in the high speed packaging lines. It is also a good opportunity to review the on line packaging controls that may have prevented this error. I'm guess that a blob detector was used to detect the presence of ink within the space for the batch number. A more complex optical character verification system may have prevented this error.
Poland's human tissue legislation not good enough
The EC has taken Poland to court as their transposition of EU directives surrounding the quality & safety of human tissues. I wonder where this leaves the QP's responsibility? If for example a UK IMP QP was certifying ATMPs manufactured in Poland.....
ATMPs on the radar
Only the 3rd ATMP application to the CAT and the 1st to include non-clinical data and eludes to more ATMP applications on the horizon. It is worth mentioning that a new MIA has established as part of ATMP manufacturing in a hospital setting. The MIA is termed 'MeAT'
FDA recall (Budesonide)
More sterility assurance issues with compounders in the States. This time a bottle of budesonide has been contaminated with fungal spores.
Medical Device Safety
The EC has introduced more measures to improve the safety of medical devices. This appears to focus the attention on the oversight of the Notifying Bodies. Yet more work for the MHRA.......
Happy Reading!
Friday 27 September 2013
Friday 20 September 2013
Friday's Round Up
More Indian woes for Ranbaxy
The FDA have issued an import alert on another Ranbaxy site within India.
Modified Release Technologies
A good overview of the methods for modifying the release characteristics of APIs and how PAT can be used to control the manufacture of these complex formulations.
Generic Xeloda
Teva has received FDA approval for generic capecitabine. This drug is a good example of a pro-drug whereby the drug is converted into 5-FU only in the presence of specific enzymes overexpressed in specific tumours. Oral oncology treatments are enabling more patients to be treated at home and enables cancer to be viewed more as a chronic disease state.
Risperdal Consta Recall
J&J have issued a recall of one batch due to the presence of a mould within vials during QC testing. This suspension of microspheres is administered IM to provide sustained release of active over 14 days for schizophrenic treatment.
Clinical trial data
An interesting report from the Guardian that discuses the publication of all clinical trial data following a parliamentary report.
More UK manufacturing investment
More good news for UK Pharma.
US compounding legislation
US Congress have release draft legislation for the control over pharmaceutical compounding following the NECC disaster in 2012. The proposed text makes for some interesting reading. It makes me wonder if this may eventually impact the compounding activities in the UK.
10 Rules of GMP
Tim Sandle's 10 rules of GMP for use as a training aid.
Bydureon Recall
A recall of one batch of Bydureon due to underfilled vials. This highlighted the fact that my
knowledge of final volume checking within high speed filling lines is lacking. I would guess this can be performed on 100% of vials via checkweighers, automatic particulate camera detectors and/or visible inspection.....I'd better look this up
New Arrival
Baby Sean arrived this week and has added a new challenge to QP studying!
The FDA have issued an import alert on another Ranbaxy site within India.
Modified Release Technologies
A good overview of the methods for modifying the release characteristics of APIs and how PAT can be used to control the manufacture of these complex formulations.
Generic Xeloda
Teva has received FDA approval for generic capecitabine. This drug is a good example of a pro-drug whereby the drug is converted into 5-FU only in the presence of specific enzymes overexpressed in specific tumours. Oral oncology treatments are enabling more patients to be treated at home and enables cancer to be viewed more as a chronic disease state.
Risperdal Consta Recall
J&J have issued a recall of one batch due to the presence of a mould within vials during QC testing. This suspension of microspheres is administered IM to provide sustained release of active over 14 days for schizophrenic treatment.
Clinical trial data
An interesting report from the Guardian that discuses the publication of all clinical trial data following a parliamentary report.
More UK manufacturing investment
More good news for UK Pharma.
US compounding legislation
US Congress have release draft legislation for the control over pharmaceutical compounding following the NECC disaster in 2012. The proposed text makes for some interesting reading. It makes me wonder if this may eventually impact the compounding activities in the UK.
10 Rules of GMP
Tim Sandle's 10 rules of GMP for use as a training aid.
Bydureon Recall
A recall of one batch of Bydureon due to underfilled vials. This highlighted the fact that my
knowledge of final volume checking within high speed filling lines is lacking. I would guess this can be performed on 100% of vials via checkweighers, automatic particulate camera detectors and/or visible inspection.....I'd better look this up
New Arrival
Baby Sean arrived this week and has added a new challenge to QP studying!
Friday 13 September 2013
Friday's Round Up
Putting QbD into practice
Lilly have provided an good insight into their implementation of QbD within their manufacturing processes. continuous manufacturing has been well established for years in food and medical device industries so it is about time the Pharma industry caught up.
Eye Drop recall (FDA)
A recall following mould being discovered within sterile eye drops. There are concerns that the preservative fails to protect the product during its in-use shelf life. This should prompt you to check the preservative efficacy testing methods and limits for different dosage forms. It is also worth thinking about possible causes for the lack of efficacy of the preservative such as; increased bioburden of raw materials; change in primary container plastic causing preservative adsorption; pH change of formulation; container integrity fail etc
Motrin Recall (FDA)
A recall of an infant oral formulation due to a risk of particulate contamination in the API.
Micro website
A useful website for your microbiology revision. There is a popular forum for which to post your questions.
Monoclonal Antibody Stability
This website is a good resource for the stability of monoclonals when compounded into ready to administer formulations. It is useful to know how your MAbs are being used within 'specials' compounders and their take on stability studies. It is also a good opportunity to compare the ICH stability requirements versus the information within this website.
PQG QP seminar
A reminder of the PQG QP seminar on 16th October. These seminars are an excellent introduction to QP training, scenarios and the all important networking. I'll be attending so hopefully I'll see you there!
Happy Reading!
Lilly have provided an good insight into their implementation of QbD within their manufacturing processes. continuous manufacturing has been well established for years in food and medical device industries so it is about time the Pharma industry caught up.
Eye Drop recall (FDA)
A recall following mould being discovered within sterile eye drops. There are concerns that the preservative fails to protect the product during its in-use shelf life. This should prompt you to check the preservative efficacy testing methods and limits for different dosage forms. It is also worth thinking about possible causes for the lack of efficacy of the preservative such as; increased bioburden of raw materials; change in primary container plastic causing preservative adsorption; pH change of formulation; container integrity fail etc
Motrin Recall (FDA)
A recall of an infant oral formulation due to a risk of particulate contamination in the API.
Micro website
A useful website for your microbiology revision. There is a popular forum for which to post your questions.
Monoclonal Antibody Stability
This website is a good resource for the stability of monoclonals when compounded into ready to administer formulations. It is useful to know how your MAbs are being used within 'specials' compounders and their take on stability studies. It is also a good opportunity to compare the ICH stability requirements versus the information within this website.
PQG QP seminar
A reminder of the PQG QP seminar on 16th October. These seminars are an excellent introduction to QP training, scenarios and the all important networking. I'll be attending so hopefully I'll see you there!
Happy Reading!
Thursday 12 September 2013
Off label Use
I came across an interesting example of off-label use this week. 'Off label' use is where a product with a marketing authorisation is being used outside of it's licensed indication, administration route or dosage requirements. Off label use is frequently used within both human and veterinary medicine where there is a need to meet specific requirements of a patient where existing treatment is unsuitable or ineffective.
There are numerous examples of off-label use within the UK. A recent, well publicised example is the use of Avastin in the treatment of wet macular degeneration in place of the more expensive Leucentis that is actually licensed for this indication. Another common example is the use of Viagra in the treatment of pulmonary hypotension in young children. Rare examples include the use of Pridel (lithium) in the treatment of thyrotoxicosis.
The example uncovered this week was the use of a drug licensed for IV use but actually administered via the intrathecal route (IT). The vial was reconstituted within an aseptic facility to produce the final IT syringe ready for administration. One of the first things that came to my mind was the risk of endotoxin. From your microbiology revision you should be aware that the BP endotoxin limits for IV and IT administration is different. Products licensed for IV administration have a limit of 5 EU/kg/hr whereas IT products have a limit of 0.2 EU/kg/hr.
Therefore using a product licensed for IV administration for IT administration may mean that the patient is at a potential risk of receiving upto 25 times the amount of endotoxin normally expected via this route. The risks are mitigated some degree by the fact that the volumes administered via the IT route are very small, typically in the region of 1-3ml and patients are often closely supervised following administration.
The other question is who is responsible for this off label use? Within the GPC prescribing guidelines it states that doctors are responsible for the prescribing and to ensure the efficacy & safety of the unlicensed use. Presribers are require to understand the risks associated with off label use. Would the prescribers actually be aware of the different endotoxin limits for IT vs IV administration? Would the pharmacist taking responsibility of the quality of the product know about this? In my experience I would hazard a guess that in most instances neither professional would take this into account.
A QP's perspective
As a QP are you aware of how & why your products are used off label within your markets? Having this knowledge should help you respond to any potential PV complaints surrounding off label use. Another point worth considering is the update to the PV requirements following 2010/84/EU which came into force in the UK last year via SI 2012/1916. These requirements now stipulate that any unlicensed, off label, abuse or overdose of your product needs to be captured within your PV system.
There are numerous examples of off-label use within the UK. A recent, well publicised example is the use of Avastin in the treatment of wet macular degeneration in place of the more expensive Leucentis that is actually licensed for this indication. Another common example is the use of Viagra in the treatment of pulmonary hypotension in young children. Rare examples include the use of Pridel (lithium) in the treatment of thyrotoxicosis.
The example uncovered this week was the use of a drug licensed for IV use but actually administered via the intrathecal route (IT). The vial was reconstituted within an aseptic facility to produce the final IT syringe ready for administration. One of the first things that came to my mind was the risk of endotoxin. From your microbiology revision you should be aware that the BP endotoxin limits for IV and IT administration is different. Products licensed for IV administration have a limit of 5 EU/kg/hr whereas IT products have a limit of 0.2 EU/kg/hr.
Therefore using a product licensed for IV administration for IT administration may mean that the patient is at a potential risk of receiving upto 25 times the amount of endotoxin normally expected via this route. The risks are mitigated some degree by the fact that the volumes administered via the IT route are very small, typically in the region of 1-3ml and patients are often closely supervised following administration.
The other question is who is responsible for this off label use? Within the GPC prescribing guidelines it states that doctors are responsible for the prescribing and to ensure the efficacy & safety of the unlicensed use. Presribers are require to understand the risks associated with off label use. Would the prescribers actually be aware of the different endotoxin limits for IT vs IV administration? Would the pharmacist taking responsibility of the quality of the product know about this? In my experience I would hazard a guess that in most instances neither professional would take this into account.
A QP's perspective
As a QP are you aware of how & why your products are used off label within your markets? Having this knowledge should help you respond to any potential PV complaints surrounding off label use. Another point worth considering is the update to the PV requirements following 2010/84/EU which came into force in the UK last year via SI 2012/1916. These requirements now stipulate that any unlicensed, off label, abuse or overdose of your product needs to be captured within your PV system.
Friday 6 September 2013
Friday's Round Up
Teva Ranitidine Recall
The FDA has issued a recall for 5 batches of ranitidine tablets due to raw material contamination with a Pseudomonas species. This shows that recalls can still be required for microbial contamination of non-sterile dosage forms. A good chance to review the likely sources of Pseudomonas within a solid dosage form. Purified water? Tablet coating? Is Pseudomonas an objectionable organism for oral preparations according to the BP?
Process Validation Guidelines from Asia
Draft PV guidelines have been published within the Asian area which are largely based on the FDA and EMA guidance already in circulation.
Inhaled Insulin
Phase 3 studies have shown some promising results for insulin delivery via the inhaled route. A good time to review the pros and cons of s/c protein suspensions vs powder protein for inhalation with regards stability, manufacturing, patient concordance etc
Risk of CJD found in medical devices
A report from the USA that describes patients put at risk from contaminated medical devices infecting patients with CJD. It is interesting to note that the sterilisation process utilised within the hospitals were incapable of killing the prions responsible and that there is no diagnostic test for CJD.
GSK's long term plan for China
Following on from GSK's bribery case in China the pharmaceutical giant is said to be contemplating its future presence within China. There is also rumours that GSK is poised to sell off some of its iconic consumer brands Lucozade and Ribena to focus on its core pharmaceutical business.
Sterile compounder recall
Yet another recall issued from a US steriles compounder due to questions over contract sterility testing methods.
Free Webcast - containment strategies in high-potency manufacture
The cost of Drug Development
An interesting article where NICE is questioning Pfizer's estimate of the cost of bringing a drug to the market. The quote from the NICE chief exec sums it up nicely:
will QbD bring about a reduction in these costs?
Spanish Pharmacy Debt
Bail outs are often associated with the financial sector so this article came as a surprise to me. As a potential QP releasing product to Spain you should be aware of these policies as it may affect your market. If pharmacies do close down will there be an increase in demand? Will this increase lead to counterfeit risk? Will patients turn to the internet? Will this manifest as a change in your PV complaints from this market?
Hospira Recall
Hospira has issued a recall of Aminosyn II sterile infusion due to the presence of a human hair within the product. This should make you question the gowning requirements for aseptic filling. How would you tackle this as a potential scenario?
New Herceptin Formulation
Roche has received approval for a sub-cutaneous version of Herceptin. This will help offset the risk of patent expiry of the IV formulation for a few more years. A good time to review the administration risks of SC vs IV. It is also worth considering how the IV version is actually administered to patients. Read section 6.6 of the SPC and see for yourself! Hopefully the SC formulation will be easier to administer.
QP as leaders
A great article examining the role of leaders within the ever changing world of biotechnology. QPs should be leaders and 'change agents' not only within the quality department but throughout the entire organisation. These soft skills are an essential element to your QP training.
Happy Reading!
The FDA has issued a recall for 5 batches of ranitidine tablets due to raw material contamination with a Pseudomonas species. This shows that recalls can still be required for microbial contamination of non-sterile dosage forms. A good chance to review the likely sources of Pseudomonas within a solid dosage form. Purified water? Tablet coating? Is Pseudomonas an objectionable organism for oral preparations according to the BP?
Process Validation Guidelines from Asia
Draft PV guidelines have been published within the Asian area which are largely based on the FDA and EMA guidance already in circulation.
Inhaled Insulin
Phase 3 studies have shown some promising results for insulin delivery via the inhaled route. A good time to review the pros and cons of s/c protein suspensions vs powder protein for inhalation with regards stability, manufacturing, patient concordance etc
Risk of CJD found in medical devices
A report from the USA that describes patients put at risk from contaminated medical devices infecting patients with CJD. It is interesting to note that the sterilisation process utilised within the hospitals were incapable of killing the prions responsible and that there is no diagnostic test for CJD.
GSK's long term plan for China
Following on from GSK's bribery case in China the pharmaceutical giant is said to be contemplating its future presence within China. There is also rumours that GSK is poised to sell off some of its iconic consumer brands Lucozade and Ribena to focus on its core pharmaceutical business.
Sterile compounder recall
Yet another recall issued from a US steriles compounder due to questions over contract sterility testing methods.
Free Webcast - containment strategies in high-potency manufacture
The cost of Drug Development
An interesting article where NICE is questioning Pfizer's estimate of the cost of bringing a drug to the market. The quote from the NICE chief exec sums it up nicely:
“if it really does cost £1.2 billion to develop a new drug, the
question the pharmaceutical industry must be able to answer is this: are
you absolutely confident that it needs to?”
will QbD bring about a reduction in these costs?
Spanish Pharmacy Debt
Bail outs are often associated with the financial sector so this article came as a surprise to me. As a potential QP releasing product to Spain you should be aware of these policies as it may affect your market. If pharmacies do close down will there be an increase in demand? Will this increase lead to counterfeit risk? Will patients turn to the internet? Will this manifest as a change in your PV complaints from this market?
Hospira Recall
Hospira has issued a recall of Aminosyn II sterile infusion due to the presence of a human hair within the product. This should make you question the gowning requirements for aseptic filling. How would you tackle this as a potential scenario?
New Herceptin Formulation
Roche has received approval for a sub-cutaneous version of Herceptin. This will help offset the risk of patent expiry of the IV formulation for a few more years. A good time to review the administration risks of SC vs IV. It is also worth considering how the IV version is actually administered to patients. Read section 6.6 of the SPC and see for yourself! Hopefully the SC formulation will be easier to administer.
QP as leaders
A great article examining the role of leaders within the ever changing world of biotechnology. QPs should be leaders and 'change agents' not only within the quality department but throughout the entire organisation. These soft skills are an essential element to your QP training.
Happy Reading!
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