1. GMP REQUIREMENTS FOR THE PRODUCTION OF API (OVERVIEW OF GMP PART II)

2. State Pharmacopoeia of the Russian Federation XIV edition
For consideration:
Part II: Basic Requirements for Active Substances used as Starting Materials
Enacted in GMP EU
State Pharmacopoeia of the Russian Federation XIV edition

3. Requirements of the State Pharmacopoeia XIV, OFS.1.2.4.0002.18
“Microbiological purity”
Category
Substances, starting materials
Recommended norms
1.2
Pharmaceutical substances for production
А. Sterile medicinal products that are not subject to the sterilization
Substances must be sterile B.
Sterile medicinal products that are sterilized in the package
Sterile medicinal products, in the production of which sterilizing filtration is used to ensure sterility
Non-sterile medicinal products related to
category 2
Total number of anaerobic microorganisms-no more than 10-2 CFU in 1 g (ml)
Total yeast and moulds count – no more than 10-1 CFU in 1 g (ml)
No enterobacteria resistant to bile in 1 g(ml)
No Pseudomonas aureginosa in 1 g (ml)

4. Requirements of the State Pharmacopoeia XIV, OFS.1.2.4.0002.18
“Microbiological purity”
According to the interpretation, for substances used in the production of sterile drugs, not exposed to thermal sterilization:
requirements of category 1.2 (i.e. substances must be sterile) should be applied;
requirements 1.2 B should not be used, since sterilizing filtration is not considered to be sufficiently effective method of sterilization.  

5. Requirements of the decree by the Ministry of industry and trade of the Russian Federation as of June 14, 2013 № 916 “On approval of the good manufacturing practice rules»
284 These guidelines does not apply to the sterilization processes and manufacturing of sterile pharmaceutical substances in aseptic conditions. These processes should be performed in accordance with the principles and guidelines of GMP as laid down in Directive 2003/94/EC and interpreted in the GMP Guide including its Annex 1, and also in other normative legal acts of the Russian Federation.

6. Requirements of the decree by the Ministry of industry and trade of the Russian Federation as of June 14, 2013 № 916 “On approval of the rules of good manufacturing practice”
117 (110) Filtration alone is not considered sufficient when it is possible to conduct sterilisation in the final container. With regards to methods currently available, steam sterilisation is to be preferred. If the product cannot be sterilized in the final container, solutions or liquids can be filtered through a sterile filter of nominal pore size of 0.22 micron (or less), or through the filter with the equivalent micro-organism retaining properties into a preliminary sterilized containers (packages). Such filters can remove most of bacteria and moulds, but not all viruses or mycoplasmas. Therefore, preference should be given to complementing the filtration process with some degree of heat treatment.