Month: April 2015
In an EDQM paper published in March 2015 the topic production of WFI by means of membrane-based technologies is discussed again and not excluded any more. Read more about WFI from membrane-based technologies.
In an EDQM paper published in Pharmeuropa in March 2015 the topic production of WFI (water for injections) by means of membrane technologies (reverse osmosis coupled with other suitable techniques) is discussed again and not excluded any more. So far distillation is the only permitted procedure for the production of WFI in Europe. It was already pointed out in the paper on the revision of Annex 1 published in February that alternative procedures for the manufacture of WFI might become possible.
The first part of the new document describes the history of the long lasting discussion of the question whether other procedures than distillation should be allowed for the production of WFI. In the end this led to the creation of a new monograph of highly purified water (HPW). This is water with WFI quality produced by means of membrane-based technologies. But its possible applications were very restricted.
Now it looks as though the Ph. Eur. Water for Pharmaceutical Use (WAT) Working Party has concluded that there is evidence to support a revision of the WFI monograph in the European Pharmacopoeia (0169). As reasons for this change are indicated for example advances in the “non-distillation technology” and improvements in the design of the water-production systems as well as an advanced process control. But it is acknowledged that the design and maintenance of any water-production system plays an important role in ensuring the security of the produced water. The manufacturer is responsible for compliance with GMP requirements. Presumably, existing guidance documents must be complemented for this by the appropriate stakeholders. Furthermore, quality assurance and monitoring should extend to storage and distribution processes for WFI.
As a result the highly purified water monograph (1927) would be made redundant and be deleted. Furthermore, the inclusion of water for dialysis in the WFI monograph could also be contemplated.
The draft monograph is available on the EDQM webpage for free, after registration. The main change reads:
WFI is produced either by [..destillation, . ].or
by reverse osmosis, which may be single-pass or double-pass, coupled with other suitable techniques such as deionisation and/or ultrafiltration.
Correct operation monitoring and maintenance of the system are essential.
The EDQM already organised a special webinar on April 22nd where this topic has been discussed.
The original document mentioned above discusses the alternative production methods for WFI.
Indian generic drugmaker Wockhardt Ltd said on Tuesday it would recall some drugs manufactured at its two plants in India before the U.S. Food and Drug Administration (FDA) banned those sites due to quality concerns.
The FDA banned U.S. exports from Wockhardt’s Waluj and Chikalthana plants in central India in 2013, citing manufacturing quality lapses.
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Just recently a so called “inspection tracker” was launched by Health Canada. Now, the agency offers an additional database which contains 3,821 inspections (per March 2015) which have been performed since 2012 – many of them outside Canada, e.g. in Europe or Asia. The information is available in an online database. The use of the database is very easy and search results are excellent.
By using the database even inspections in progress can be displayed. This is a service no other agency can provide. The database also offers further information about past inspections at the same production site. No further search is necessary because the information about past inspections will be displayed in the search result for a given production site. The rating of the inspection is also provided, and in case of GMP non compliance a detailed and very structured information about the findings is provided. The quality of information about the outcome of the inspection available from the database is outstanding. Again, no other agency worldwide is able not only to list the observations but also link them to the concrete GMP regulation paragraph in a structured and numbered table.
The database also provides information about past and present non-compliance situations. However, it also shows when a company is currently licensed by Health Canada, as the company possibly improved its GMP status and was licensed again.
The database allows three different options to search for information. The first option contains 1,301 Inspections (per March 2015) from the past three years performed in Canada. A second option allows to access the non-compliance information. Currently 52 production sites with non compliance statements are listed in the database (some of the sites received their license again after re-inspection). The third option offers access to 2,520 inspections (per March 2015) performed outside of Canada.
To access the database please visit Health Canada Drug & Health product Inspections Webpage
The “Industry Coalition” gives practical advice for the control of elemental impurities in active substances and excipients
The requirements of the “Guideline for Elemental Impurities ICH Q3D” published in December of last year mean a considerable expense for the affected pharmaceutical companies and drug manufacturers in terms of laboratory and personnel upgrading (see also our news about “ICH Q3D – Elemental Impurities” of 07 January 2015). In addition, the deadlines for the implementation of this guideline are quite tight. (June 2016 for newly approved drugs and December 2017 for already approved drugs, see our news “CHMP adopts ICH Q3D Guideline as “Scientific Guideline” of 21 January 2015).
In the March issue of “Pharmaceutical Technology Europe”, an article of the “Industry Coalition” has been published with the title “Implementation of ICH Q3D Elemental Impurities Guideline: Challenges and Opportunities“, which is intended to support the efffected companies with a number of pragmatic pieces of advice in the implementation of these requirements.
The “Industry Coalition” (exact name: “Coalition for Rational Implementation of Elemental Impurities Requirements”) is a consortium of economic/industrial associations (members include IPEC Europe, IPEC Americas, The Generic Pharmaceutical Association GPhA, etc.) and has been in existence since 2011. The aim of the coalition is to provide information regarding elemental impurities. To this end, the Coalition has developed a standardised procedure (standardised information request) according to which specific information can be requested through the use of a form. More information about the “Industry Coalition”, their goals and projects can be found in a Position Paper which appeared in “Pharmaceutical Technology Europe” in November 2012.
The Guideline ICH Q3D calls upon drug manufacturer to conduct a risk assessment as part of a strategy for the control of element impurities, but without specifying which aspects need to be considered in such an assessment. Here, the article of the “Industry Coalition” provides helpful hints; it is described how, for example, production equipment (various types of steel), processing aids (activated carbon, silica gel, etc.), inorganic reagents, solvents, packaging materials and closure systems are to be included in the risk assessment. A detailed section is dedicated to the subject of excipients, regarding which the assessment of risks is often particularly difficult in terms of element impurities, due to the unclear origin or the complex composition of the excipients.
The approaches described by the “Coalition” may be useful for many companies in their efforts to meet the requirements of the Guideline ICH Q3D. In this context, the document which has recently been published by the EMA entitled “Elemental impurities in marketed products. Recommendations for implementation” should also be considered……………..http://www.gmp-compliance.org/enews_04794_The-%22Industry-Coalition%22-gives-practical-advice-for-the-control-of-elemental-impurities-in-active-substances-and-excipients_9343,9263,9300,S-QSB_n.html
Data Integrity – Again Import Alert issued for Indian company IPCA…http://www.gmp-compliance.org/enews_04789_Data-Integrity—Again-Import-Alert-issued-for-Indian-company-IPCA_9193,S-QSB_n.html
Data Integrity has become one of the most important GMP compliance issues in past two years. This has enormous consequences for the concerned companies but also for companies and authorities in EU and US. It was the US FDA that has first experienced huge data integrity problems in companies worldwide. Many sites in India have been found to violate GMP requirements by Data Integrity issues. Tests have been repeated and original data have been deleted. This is called “testing into compliance”. At the Webpage of the US FDA IPCA products are listed which are impacted by the Import Alert. Two facilities from IPCA have been found to be out of GMP compliance: One in Pithampur (Madhya Pradesh) and one in Piparia (Silvassa) (see also report by FiercePharma).
Products manufactured at those facilities might cause high risks to patients. The quality of the products can not be specified because the original test data were simply deleted. The company IPCA was already known for not meeting the GMP requirements. Already in July 2014 IPCA halts US shipment from the Ratlam plant after FDA found massive GMP violations. As a consequence the Canadian Authority (Health Canada) has banned a huge list of APIs and medicinal products from their market as well. Now they have informed the Bombay Stock Exchange about their problems (see message regarding Import Alert issues by IPCA)
But what are the consequences for companies and authorities in Europe and the US? Authorities might be asked why the same facilities that have been found to be involved in the falsification of data are still allowed to supply to EU patients. For example IPCA is still listed with a GMP certificate for the concerned facilities in EudraGMDP. And EU and US companies need to check very carefully which supplier, partners and own sites they have in India. Quite a few companies have been found to delete data and to perform testing into compliance. FDA has started to check whether companies have checked their suppliers for data integrity. The MHRA has put this on the agenda for their inspections as well.
With the new biocidal products regulation from 2013 in-situ generated ozone now also falls into the scope of this directive. Ozone generation systems with a biocide application (such as disinfection of pharma water) thus require an approval after the transitional period expires in the September 2017. The ozone registration group is active for this purpose. Read more about the Ozonization of Pharmaceutical Water and the Biocidal Products Regulation.
With the new biocidal products regulation from 2013 in-situ generated ozone now also falls into the scope of this regulation. Ozone generation systems with a biocide application (such as disinfection of pharma water) thus require an approval after the transitional period expires in the September 2017. We already reported about the impact of the new Biocidal Products Regulation – please see the GMP News “Pharmaceutical Water: Uncertainty caused by the New Biocidal Products Regulation” from 21 May 2014.
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