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European Directorate for the Quality of Medicines (EDQM) has issued the draft guidelines on endotoxins, pyrogens and sterile products. The Pharma Europa (Ph.Eur.) which is a free online EDQM publication now seeks comments from the pharma and biotech industry on the draft guidelines. With the development of biological drugs gaining momentum, the revised draft guidelines are seen crucial for bio-pharmaceutical industry.
Endotoxins from gram-negative bacteria are the most common cause of toxic reactions resulting from contamination of pharmaceutical products with pyrogens. A new section is included for the bacterial endotoxins. It covers aspects that need to be considered when establishing an endotoxin limit for a specific substance.
In the case of pyrogens, the draft norms have highlighted monocyte-activation test as a potential replacement which avoids use of live animals. The regulator stated that the revision was in line with the European Convention for the Protection of Vertebrate Animals used for experimental and other scientific purposes. The test consists of measuring the rise in body temperature evoked in rabbits by intravenous injection of the substance to be examined.
With reference to the new norms on sterile products, there is extensive revision. These include omission of reference to GMP. In the section on sterility assurance level, the reference to exponential inactivation has been removed as membrane filtration is not a first order process. The sections on the different sterilisation processes, now insist on the same format of equipment, sterilisation cycle, cycle effectiveness and routine control. Modern concepts for validation of steam sterilisation have been added. A wider description of the equipment suitable for dry heat sterilisation has been provided. In the section on ionising radiation sterilisation, the reference to European notes for guidance has been removed.
In the section on gas sterilisation, two different types of agents are defined. These are alkylating agents and oxidising agents. In fact, the establishment of the cycle effectiveness has been described in greater detail.
Under membrane filtration, the description of the microbial challenge test has been removed as it is proposed for inclusion in the revised chapter on biological indicators. With regards to Aseptic preparation, freeze-drying under aseptic conditions is added.
The regulatory authority noted that sterility is the absence of viable micro-organisms and is therefore a critical quality attribute for a wide variety of human and veterinary preparations. The drugs are not restricted to preparations administered to normally sterile areas of the body, such as parenteral and ophthalmic preparations but also covered some irrigation and inhalation preparations, intra-mammary and intra-uterine preparations, mandating stringent norms to ensure quality standards and patient safety.
According to Kaushik Desai, Hon. General Secretary, Indian Pharmaceutical Association, the revision of norms was required as the biological drug development and manufacture is more robust. This has led to the creation of a stringent regulatory environment bringing about the need to update existing guidelines related to critical aspects to test biological. Therefore industry should take cognizance of the change and start implementing and also provide comments to those aspects of the guidelines which would be difficult to comply.
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