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Expiration Dating and Stability Testing of Solid Oral Dosage Form Drugs Containing Iron

  Expiration Dating and Stability Testing of Solid Oral Dosage Form Drugs Containing Iron To meet the requirements of the iron regulations, manufacturers and packagers must determine an appropriate expiration date for the drug products in unit-dose packages. Accelerated stability testing may be impractical because drug products containing iron, especially multivitamin products, often do not perform well under the artificially stressful conditions of accelerated studies. As a result, real-time stability testing may be the only method to determine an appropriate expiration date. However, the final iron regulations were published only six months before they were to take effect; therefore, there may be insufficient time for some manufacturers of solid oral drug products containing 30 mg or more of iron per dosage unit to perform real-time stability testing on their products. To minimize the burden faced by those manufacturers who have made good faith efforts to comply with
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CLEANING VALIDATION (ACCEPTANCE CRITERIA)

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)

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