Campaign manufacturing of highly active pr sensitising ingredients: a comparison between the GMPs of various regulatory agencies

INTRODUCTION Highly active or sensitising ingredients (API/SI) need special rules for their production. Cross-contamination and mix-ups represent the greatest dangers related to the manufacturing of API/SI. These risks are obviously greater in campaign manufacturing (CM) and therefore this type of production can only be performed using certified procedures able to guarantee non residue between the two different processes. Nevertheless, as there is no global harmonization of GMPs, some nations require particular working conditions for manufacturing given products, while other countries require different ones. In this paper we have studied the problems related to the CM of API/SI under the different Regulatory Authorities, by analyzing and comparing their Good Manufacturing Practices (GMPs). METHODS We studied the GMPs of the different Regulatory Agencies (EMA, CFDA, COFEPRIS, FDA, Health Canada, ANVISA, CDSCO, PIC/S, and WHO) in order to assess which Authorities allow CM for the production of the following categories of drugs: hormones, immunosuppressants, cytotoxic agents, API, biological preparations, steroids, antibiotics, cephalosporins, penicillin, carbapenems, beta-lactam derivatives. RESULTS The rules of the Regulatory Agencies we studied (regarding the production of API/SI) can be divided into three types: 1) CM is permitted only where adequate technical/organisational measures are used as well as adequate cleaning measures that can guarantee the safety of the method: Health Canada, EMA, PIC/S, FDA. 2) CM is permitted for the production of certain classes of API/SI only in exceptional circumstances: CFDA, WHO, ANVISA. CFDA and WHO allow CM only for the production of “certain” API and in exceptional circumstances (without defining in the regulations which circumstances can be defined as exceptional). ANVISA allows the use of CM only in the case of serious emergencies (i.e.: war, fires, floods). 3) CM is not provided or mentioned: COFEPRIS, CDSCO. CONCLUSIONS Significant differences emerged between the GMPs Regulatory Authorities both as regards the classes of drugs that can be produced through CM and as regards the Agencies that authorize it. The pharmaceutical industry, in deciding which drugs can be produced according to the principles of CM, will have to use a Quality Risk Management and choose this production method only where the Regulatory Authority allows it and where there are procedures that can guarantee the elimination of the risk of cross-contamination.