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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.
Admission will take place in two stages. In the first step, ozone is certified as an active ingredient and registered in the list of active substances authorised in the EU. In the second step, the ozone generation system is approved as a biocidal product. The major manufacturers of ozone generation systems have joined forces for this in the ozone registration group (ORG). It aims at relieving users of ozone systems from the registration procedure. That means the documents should be provided to the users. The access to the marketing authorisation dossier is supposed to be assured through a Letter of Access (LoA). One of the open questions seems to be resolved now: the question whether an authorisation document will be required for each ozone precurser (i.e. water, oxygen or air). As this seems to be unnecessary, only one authorisation document is currently being processed.
The question with regard to how reasonable it is to include ozone from pharmaceutical water systems in the biocidal products regulation cannot be clarified at this point. The same is true with regard to the question on who is supposed to control pharmaceutical companies and whether their ozone comes from approved ozone systems.
You can find more information on the page Ozone registration group.
GMP Handbooks with all major GMP and GDP Guidelines
Everyone involved in the GMP/GDP environment needs to use the current GMP and GDP Guidelines for reference. The ECA offers a range of booklets with all major Guidelines such as the EU GMP Guide (with all current Annexes), the new EU GDP Guideline, the FDA cGMP Guide and many more. You can order the GMP booklets here.http://www.gmp-compliance.org/eca_handbuecher.html
ECA Good Practice Guide on Validation
(1st Edition of October 2012)
This document is intended to provide support to both regulators and industry. On one hand, the guide contains the main elements of the new approach (“what to do”). On the other hand, it also serves as a supporting guide for the implementation (“how to do”). The guide contains 163 pages divided in 5 chapters and 4 annexes. The topics covered are among others:•Risk based qualification and validation legacy products
•Case study about process validation in biopharmaceutical manufacturing
•Case study about continuous process verification
•Paperback in the handy format 14,8 x 21 cm
Price*: € 149 Non ECA Members, € 99 ECA Members
Booksellers receive a 15% discount – please ask for a COUPON CODE before ordering!
If you want to use the major GMP Guidelines on your smartphone or tablet we recommend to use the free of charge GMP Web App developed by the ECA Academy
The new GMP WebApp from ECA
ECA is pleased to announce a major development: now you can have all GMP information on your smartphone or Tablet PC (e.g. iPad) – with the new free of charge ECA GMP WebApp.
The unique new WebApp provides a number of GMP features. The App, which works on all smartphones (Apple and Android), is a useful tool for all professionals in the GMP environment. To open it, just go to app.gmp-compliance.org in your browser and the WebApp opens immediately.
To use the App in a convenient way you need to add the ECA icon to the Home screen (see below).
From ECA‘s weekly GMP Newsletter you are used to get the latest trends in the GMP environment. Now you can have these news at hand and keep track of all GMP developments any time. You will always find the latest GMP News on your App.
Major GMP Guidelines
The App allows you to access the major GMP Guidelines very easily. Whenever a revised GMP Guide is published the document is available without any update of the App. So you can always check the relevant Guidelines in seconds.
If you are looking for additional GMP information, the „Search“ function is very helpful. Just enter a keyword and select a specific database – or just search in all databases. The GMP Database contains hundreds of GMP articles and more than 1.000 GMP Guidelines. You do not need to search on different websites for the information. The GMP Database provides the links to the most relevant information.
GMP Courses & Conferences
On the ECA website you can scroll a list with all currently offered courses and conferences. The new WebApp does provide that list as well. Simply go on „GMP Courses & Conferences“ to access the complete ECA course and conference programme any time. If you just want to get a list with courses and conferences in a certain area, simply use the „GMP Search“ function decsribed before. And… by the way… if you found the programme you were just looking for… you can even register by using the App.
GMP Guideline Manager
Access to more than 1.200 GMP Guidelines This function is an exclusive service for ECA Members (Company Members will get access for all employees*). After login you will have access to all GMP Guidelines from EU/EMA, FDA, ICH, PIC/S, ICH, APIC, IPEC and WHO. To log in simply use your user name and password from your ECA Membership account. ECA Members have access to two so called Webtrees. One Guideline Tree is structured according to GMP topics. The second Guideline Tree is structured according to authorities. By using the Guideline Trees you can easily access the Guideline of interest.
* Employees of all sites in the country in which the company signed up for the membership.
What GMP Changes can we still expect for 2014?
Heraclitus once said: “There is nothing permanent except change”. This statement is even true for the rather conservative GMP environment. What can we still expect for 2014? The answer to that question can be found in a work plan of EMA’s GMP/GDP Inspectors Working Group.
What are the coming plans?
- Finalising the changes planned for the Chapters 3 and 5 of the EU GMP Guide
- Finalising the revision of Chapter 8 of the EU GMP guide (with regard to product shortage notifications and specific risk management concepts)
- Agreeing, in consultation with PIC/S, whether guidance is needed on biofilms concerning Annex 1 of the EU GMP Guide
- Finalising the revision of Annex 15 of the EU GMP Guide (comparison with the new EMA process validation guideline and inclusion of necessary changes in the light of ICH Q 8-10)
- Finalising the revision of Annex 16 of the EU GMP Guide
- Finalising the revision of Annex 17 of the EU GMP Guide
- Further measures regarding the EudraGMDP database
The finalisation of the revision of Chapter 6 (Quality Control) of the EU GMP Guide is already completed (April 2014). The revised chapter will apply as of October 2014.
The following topics are also addressed in the work paper:
- Inspections under the centralised system
- Mutual Recognition Agreements (MRAs)
- Harmonisation topics
- Collaboration with the EU Commission (the collaboration should enable by the end of 2014 the publication of the GDP guidelines for APIs and the risk assessment guidelines to establish GMP for excipients)
- Collaboration with other groups (i.e. Reverse Osmosis for the production of WFI and biological indicators for monitoring and the control of sterilisation are topics addressed together with the EDQM in Strasburg)
Please also see the complete “Work plan for GMP/GDP Inspectors Working Group for 2014“.
Japanese Pharmacopoeia and Japanese GMP Regulations available online
On Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) website, you can download documents on GMP as well as on marketing authorisations for medicinal products. An English version of the Japanese Pharmacopoeia (JP) is also available. You will find the direct links in the News.
On Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) website, you can find in the section “Regulations and Procedures” under the heading “GMP” requirements regarding the inspection of manufacturers of medicinal products and APIs who want to introduce their products into Japan.
Now, a document was supplemented in January 2014 which describes which documents have to be submitted to the Japanese Agency within a pre-approval inspection and/ or a periodical post-approval inspection.
Go to the PMDA webpage to get more information.
There, you can also access the current Japanese Pharmacopoeia Sixteenth Edition in English.
Source: PMDA, Japan
GMP deviations and even data falsification have been identified in a number of companies in India. How is it possible that interpretation of FDA and EU authorities on one side and the Indian authority on the other side come to a completely different picture? Read more in our GMP News
GMP deviations and even data falsification have been identified in a number of companies in India. The FDA has issued numerous Warning Letters, the EU has published GMP Non Compliance Reports in its EudraGMDP database and EDQM has withdrawn various CEPs because of GMP inspection findings.
In an article published by Regulatory Focus on 28 January 2014 the question has been raised whether Indian companies have a chronic data falsification problem. The article lists 7 companies in India which have received a Warning Letter in the past months – all of them because of GMP deviations and because of “actually or potentially tampering with their data”. In addition to the 7 companies the Ranbaxy case is a story of its own. Not only one facility was found to manipulate data but several sites of the company are involved. For this reason the US FDA has issued a consent decree of permanent injunction against Ranbaxy. All manufactured products in the facilities concerned are now subject to an FDA import alert. In a press release the FDA states: “Because this company continued to violate current good manufacturing practice regulations and falsify information on drug applications, the FDA took these actions in an effort to protect consumers.” Dara Corrigan, FDA associate commissioner for regulatory affairs goes on: “The FDA continues to be committed to protecting consumers from potentially unsafe products that may be offered on the market.” On January 23, 2014 the FDA added an additional facility of Ranbaxy to the existing consent decree.
So far, the Indian Authority did not initiate the same measures like US and European counterparts. This also questions the supervision system in India. If inspections have been performed by Indian Inspectors at the concerned facilities why did they fail to make the same findings? The Drug Controller General of India, Mr. G.N. Singh, gave an interesting interpretation: According to an interview published by live mint & Wall Street Journal he said: “…it must be stated that every country has different measures and we cannot judge Ranbaxy by standards set up by the American drug regulator“. When Mr Singh was asked about the problems identified at three Ranbaxy plants he stated: “Some of those were found to be true and my office had told Ranbaxy to take corrective measures. Similar procedures will be followed in this case as well. But I do not think this is a situation which will warrant withdrawal of drugs from the domestic market. Our biggest objective is to maintain good quality of medicines and we are doing that. There are no drugs in the Indian market that are not up to the standards stated under the Drugs and Cosmetics Act.” In a final statement in the interview he also mentioned that he is “not worried about issues of quality.” In another interview with the Business Standard Press Mr Singh made an alarming statement for all customers of medicinal products and APIs in Europe and the US. “If I follow US standards, I will have to shut almost all drug facilities“. If this is the truth EU and US customers are in big trouble because products not complying to EU/US GMP standard (e.g. ICH Q7 GMP for APIs) would need to be taken from the market immediately.
This all looks like it will not fit together. How is it possible that interpretation of FDA and EU authorities on one side and the Indian authority on the other side come to a completely different picture? It can only mean that dual standards exist. This would result in two quality levels, an international and a domestic quality level. Such a policy possibly causes questions by Indian patients who have to accept a different and probably lower quality standard.
It does not look like the Indian Regulators will re-think the GMP inspection approach and the quality standard in their country. Instead of acting in his own country the Drug Controller General of India announced inspections in the US and the EU.
But what are the international implications of this strategy? European Regulators need to react as they require from the Indian Authority to issue Written Confirmations of GMP compliance. Without a Written Confirmation APIs can not enter EU market. Currently more than 200 Written Confirmations have been issued by Indian Authority. If the inspections which have been performed as a prerequisite for issuing a Written confirmation were not based on the international standard ICH Q7 (GMP for APIs) the Written Confirmations are no longer valid documents. This issue might be raised by an EU court if a substandard API in a medicinal product will cause a health risk to patients in Europe.
Characterization of the “hygroscopic” properties of active pharmaceutical ingredients.
SSCI, Inc., West Lafayette, IN, USA. firstname.lastname@example.org
The amount of water vapor taken up by an active pharmaceutical ingredient (API) as a function of relative humidity is routinely evaluated to characterize and monitor its “hygroscopicity” throughout the drug development process. In this minireview we address the necessity of going beyond the measurement of water vapor sorption isotherms to establish the various mechanisms by which solids interact with water and the important role played by the crystalline or amorphous form of the solid. Practical approaches for choosing experimental conditions under which water vapor sorption should be measured, including the pre-treatment of samples and the time allowed to reach an equilibrium state are presented. With the assistance of a flowchart, we provide a basis for the systematic examination of samples to establish the likely mechanisms of sorption and the indicators pointing toward future problems with physical and chemical instabilities. Finally, we present strategies for managing materials that might be susceptible to the detrimental effects of water vapor sorption.
(Copyright) 2008 Wiley-Liss, Inc.