The Pharma Solution

CLEANING VALIDATION (ACCEPTANCE CRITERIA) Introduction Companies must demonstrate during validation that the cleaning procedure routinely employed for a piece of equipment limits potential carryover to an acceptable level. That limit established must be calculated based on sound scientific rational. Methods of Calculating Acceptance Criteria    Acceptancecriteria using health-based data PermittedDaily Exposure (PDE) The procedure proposed in this document for determination of health based exposure limits for a residual active substance is based on the method for establishing the so-called Permitted Daily Exposure (PDE) as described in Appendix 3 of ICH Q3C (R4) “Impurities: Guideline for Residual Solvents” and Appendix 3 of VICH GL 18 on “residual solvents in new veterinary medicinal products, active substances and excipients (Revision)”. The PDE represents a substance-specific dose that is unlikely to cause an adverse effect if an individual is exposed a

PERMITTED DAILY EXPOSURE (PDE) or ACCEPTANCE DAILY EXPOSURE Introduction During the manufacture of medicinal products accidental cross contamination can result from the uncontrolled release of dust, gases, vapours, aerosols, genetic material or organisms from active substances, other starting materials, and other products being processed concurrently, as well as from residues on equipment, and from operators ’ clothing. Due to the perceived risk, certain classes of medicinal product have previously been required to be manufactured in dedicated or segregated self contained facilities including, “certain antibiotics, certain hormones, certain cytotoxics and certain highly active drugs”. Until now no official guidance is available in order to assist manufacturers to differentiate between individual products within these specified classes. METHODS FOR ESTABLISHING EXPOSURE LIMITS The Gaylor-Kodell method of risk assessment (Gaylor, D. W. and Kodell, R. L.: Linea

CLEAN ROOM MONITORING – REGULATORY STANDARDS Ø  Air Classification as per Schedule M Grade Maximum permitted number of particles / m3 equal or above at rest in operation 0.5µm 5.0µm 0.5µm 5.0µm A 3,520 29 3,500 29 B 35,200 293 3,52,000 2,930 C 3,52,000 2,930 35,20,000 29,300 D 35,20,000 29,300 not defined not defined Note:-  Grade A and B correspond to with class  100, M 3.5, ISO 5   Grade C correspond to with class 10000, M 5.5, ISO 7  Grade D correspond to with class 100000, M 6.5, ISO 8 Ø   Air Classifications by US FDA guideline on Sterile Drug Products Clean Area Classification <0.5 µm Particles/ft3 <0.5 µm Particles/mt3 Microbiological Limit cfu/ft3 cfu/m3 100 100 3,500 <1 <3 1000 1000