Focus Group on Pharmaceutical Enzymes

The Focus Group on Pharmaceutical Enzymes is a new focus group of the Special Interest Group (SIG) Analytical Sciences and Pharmaceutical Quality, involved in the support of scientific questions regarding Pharmaceutical Enzymes and their standardization. It cooperates very closely with the FIP International Commission on Pharmaceutical Enzymes. In the future it will develop more  close contacts worldwide between pharmaceutical scientists and pharmacists within its focus.


The FIP International Commission on Pharmaceutical Enzymes was founded in 1960 by Prof. Ruyssen, also first President and Director of the Laboratory of General Biochemistry and Physical Pharmacy of the Ghent University in Belgium, Vice-president of FIP and President of its Scientific Session.  He was succeeded (also in his function at the Ghent university) by Prof. Em. Lauwers and by Prof. Jo Demeester.


Members and expert consultants are recruited from pharmaceutical companies, universities, institutes, control  laboratories etc. The commission improves assay methods and has guidelines for the preparation of pharmaceutical enzyme reference materials, calculates the potency in terms of FIP Biological Reference Preparations (BRP’s)  using a unitage expressed in International ”FIP  units”. The pharmaceutical enzymes covered are hydrolases, acting on complex substrates.

The European Directorate for the Quality of Medicines (EDQM) of the Council of Europe has adopted the FIP methods for its pharmaceutical enzyme monographies in its handbook, the  European Pharmacopeia.


The Centre of Standards (CFS) of the FIP Commission on Pharmaceutical Enzymes, located at Ghent University, Laboratory of General Biochemistry and Physical Pharmacy,  Harelbekestraat 72, B-9000 Ghent, Belgium has a coordination function in organizing collaborative enzyme assays between academic, industrial and national pharmaceutical control laboratories and in distributing FIP enzyme standards. Enzymes are known to have a limited stability. A major challenge is the optimization and regular control of the stability of the reference standards. The EDQM has a mutual agreement with the CFS for the provision of BRP pharmaceutical enzymes, substrates and activators.


For more information please contact Jo Demeester (Jo.Demeester@ugent.be), coordinator of this group and member of the FIP board. He and his staff will give support to scientific questions regarding pharmaceutical enzymes.


FIP International Commission on Pharmaceutical Enzymes - History

In 1960, during the General Assembly of the FIP at Copenhagen, a scientific symposium on enzymes used in pharmacy was organized. The available assays to measure the enzymatic activity as described in the different pharmacopoeias were often obsolete or inadequate. To cope with this unsatisfactory situation, the Council of the FIP appealed to Prof. R. Ruyssen (Director of the Laboratory of General Biochemistry and Physical Pharmacy, University of Ghent, Belgium) to form a Commission to study these problems and to formulate proposals for better assay and control methods for pharmaceutical enzymes. Prof. R. Ruyssen acted as Vice-president of the FIP (1955-1960) and as President of its Scientific Section (1958-1962). He was founder and first chairman of the International Commission on Pharmaceutical Enzymes of the FIP (1960-1975). Prof. Dr. Pharm. R. Ruyssen, born in 1901, died in 1979 after a very active life.
Prof. dr. A. Lauwers  succeeded Prof. Ruyssen from 1975 -1997 as Director of the Laboratory of General Biochemistry and Physical Pharmacy, University of Ghent, Belgium and as President of the International Commission on Pharmaceutical Enzymes FIP; since 2003 he is Honorary President of the Commission.


Since 1994 Prof. Jo Demeester is the Director of the International Centre for Standards of the International Pharmaceutical Federation (FIP) and since 1997 Director of the Laboratory of General Biochemistry and Physical Pharmacy, University of Ghent, Belgium and President of the International Commission on Pharmaceutical Enzymes (of FIP); he is also enzyme expert in the Group on Biological Products of the European Pharmacopeia.


Activities of the the International Commission on Pharmaceutical Enzymes of FIP.
Enzyme activity is determined by the quantity of substrate transformed or product formed per unit time. The measured reaction rates are depending on kinetic mechanisms, the affinity of the enzymes for their substrates and on a number of experimental conditions such as temperature, pH, ionic strength, and the presence or absence of inhibitors or activators. It is only under the conditions specified in the prescribed assay procedures that enzyme units are defined.


Assay accuracy and reproducibility are the most stringent requirements for the determination of enzyme potencies in pharmaceutical formulations. Furthermore, the unit value must correspond to an enzyme activity the physician can relate to. Expression of activity in units based on molar concentration changes per time unit is only possible when the substrate molar concentration, the reaction mechanism, and the resulting rate equation are known. For pharmaceutical enzymes this is impossible in most cases. The biological substrates  (proteins, polysaccharides, bacteria, oil emulsions) often have a molecular complexity and the fact that the potential number of bonds susceptible to  attack by  the enzyme is not always known, makes the development of suited methods and  Good Standardization Practices necessary. The International Commission on Enzymes of FIP (gathering experts of pharmaceutical companies, universities, institutes, control  laboratories) also improves assay methods and has guidelines for the preparation of pharmaceutical enzyme reference materials, calculates the potency in terms of FIP Biological Reference Preparations (BRP’s) using a unitage expressed in International ”FIP units”.


The Centre of Standards of the FIP Commission on Pharmaceutical Enzymes, located at Ghent University, Laboratory of General Biochemistry and Physical Pharmacy, Harelbekestraat 72, B-9000 Ghent, Belgium has a coordination function in organizing collaborative enzyme assays between academic, industrial and national pharmaceutical control laboratories and in distributing FIP enzyme standards. Enzymes are known to havea limited stability. A major challenge is the optimization and regular control of the stability of the reference standards.


The relationship with the EDQM of the Council of Europe, responsible for the European Pharmacopoeia (Ph. Eur.) increased since the first agreement in 1978. FIP assay procedures and standards were adopted for several enzyme systems and the results acquired a legal status in all European countries. There is a mutual agreement between Ph. Eur. and the FIP Centre for Standards about the establishment and support for the Biological Reference Preparations (enzymes, substrates and activators) for most pharmaceutical enzymes described in the monographs (all enzymes belong to the class of hydrolases: pancreatic lipase, amylase, protease, hyaluronidase etc.).


Besides those enzymes, the FIP Centre for Standards also provides BRP’s and assay methods for other pharmaceutical enzymes such as microbial lipases (also taken over by the Food and Chemicals Codex, FCC), lysozyme, papain etc.
An important related activity of the Laboratory of General Biochemistry and Physical Pharmacy (where the Centre for Standards is housed) is the provision of scientific support and training for people in academia, industry, control laboratories etc.