Validation Guide Sartopore® 2 Cartridges, MaxiCaps ...

1 Validation Guide sartopore 2 Cartridges, MaxiCaps , MidiCaps and Capsules| 3 1. Introduction cGMP Quality Assurance from Sartorius Quality Assurance Prevention of Contamination Complete Traceability Sartorius Drug Master File DMF 5967 Quality Management System 62. Technical Specifications Type and Part Number Overview Standard Cartridges Mini Cartridges MaxiCaps MidiCaps Capsules 150|300 Filter Material Mechanism of Filtration Pore Size Combinations Materials of Construction Fiber Release Test Methods for the Quality Assurance of Sartorius sartopore 2 Filter Cartridges and Capsules Dimensions Standard Cartridges Mini Cartridges MaxiCaps Total Height MidiCaps Capsules 150|300 Cartridges MaxiCaps MidiCaps Capsules 150|300 Maximum Back Pressure for Cartridges, MaxiCaps .

2 MidiCaps and Capsules 150|300 Wetting the Filters for Integrity Testing Rinse-Up Required for Particle Removal Sterilization Integrity Test Limits Standard Cartridges Mini Cartridges, MaxiCaps , MidiCaps and Capsules 150|300 193. Flow Rates sartopore 2 with m Final Membrane sartopore 2 with m Final Membrane sartopore 2 with m Final Membrane 284. Chemical Stability sartopore 2 335. Integrity Test Limits Basis for the Determination of Integrity Test Values Bacteria Retention Test Diffusion Test Limits for sartopore 2 Filter Elements, m Standard Cartridges and MaxiCaps (10"|250 mm) m Mini Cartridges and MidiCaps m ( m2| ft2) Diffusion Test Limits for sartopore 2 Filter Elements, m Standard Cartridges and MaxiCaps (10"|250 mm) m Standard Cartridges (5"|157 mm) m Mini Cartridges and MidiCaps ( m2| ft2) m Mini Cartridges and MidiCaps ( m2| ft2) m Mini Cartridges and MidiCaps ( m2| ft2)

3 M Capsules 300 ( m2| ft2) m Capsules 150 ( m2| ft2) m Diffusion Test Limits for sartopore 2 Filter Elements, m Standard Cartridges and MaxiCaps (10"|250 mm) m Standard Cartridges (5"|157 mm) m Mini Cartridges and MidiCaps ( m2| ft2) m Mini Cartridges and MidiCaps ( m2| ft2) m Mini Cartridges and MidiCaps ( m2| ft2) m Capsules 300 ( m2| ft2) m Capsules 150 ( m2| ft2) m Manual Determination of Maximal Allowable Pressure Drop sartopore 2 Filter Elements with m Final Membrane sartopore 2 Filter Elements with m Final Membrane sartopore 2 Filter Elements with m Final Membrane 726.

4 Mycoplasma Retention Introduction Purpose Test Methods Qualification of the Monitoring Filters Test Set-up Test Procedure Test Results sartopore 2 (10"|250 mm) m Discussion 757. Thermal Stability Steam Sterilization of Cartridges Effects on Water Flow Rates Effects on Diffusion Values Effects on Bubble Point Values Bacteria Challenge Test Values 83 Table of Contents4 | Autoclaving of MaxiCaps , MidiCaps and Capsules Effects on Water Flow Rates Effects on Diffusion Values Effects on Bubble Point Values Bacteria Challenge Test Values 918. Testing According to USP Particle Content of the Filtrate sartopore 2 Filter Elements with m Final Membrane sartopore 2 Filter Elements with m Final Membrane Determination of Oxidizable Substances of the Filtrate Standard Cartridges Mini Cartridges MaxiCaps MidiCaps Capsules Determination of pH Values and Conductivity of the Filtrate Standard Cartridges Mini Cartridges MaxiCaps MidiCaps Capsules Determination of Chloride.

5 Sulfate and Ammonia in the Filtrate Determination of Chloride Determination of Sulfate Determination of Ammonia Biocompatibility 1229. Endotoxin Testing 126| 5 Pharmaceutical products, such as injectable and infusion solutions or those which come in contact with open wounds, must conform to exactly defined quality standards. The desired quality of the final product can only be obtained when the entire production process is adequately safeguarded against contamination. Final product quality meeting the standards of the respective pharmacopeias can be achieved by using membrane filter technology at critical points where particles or microbes could contaminate a product or must be separated from it.

6 Heat-stable final products can be sterilized practically and effectively by autoclaving. This process, however, does not remove particles or dead micro organisms which may release pyrogens. Therefore, a prior membrane filtration run is required by cGMP regulations (Current Good Manufac-turing Practice of the US Food and Drug Administration) to ensure that particles and microbes are removed. Solutions containing heat-labile products, such as anti biotics, can be cold sterilized by membrane filtration immediately before aseptic filling. Microbe retentive filtration (bacteria retentive according to the European Pharmacopeia 6) or sterile filtration (sterilization by filtration in conformance with the current USP), respectively, is an important process step in the manufacture of sterile pharmaceutical products.

7 When sterilizing filters are used in the manufacture of pharmaceu-ticals, the aseptic process must be validated, taking all aspects of the product and the production process into consi deration. sartopore 2, pleated membrane filter elements with a heteroge-neous membrane, reliably fulfills the product-specific requirements which have to be imposed on a sterilizing grade filter. Validation is indispensable for guaranteeing the safety of pharmaceuticals, and is a logical supplement and significant part of the cGMP regulations which have been in force for quite some time. Guidelines for Validation are given in the US Code of Federal Regulations Title 21 and the current USP.

8 In addition, guidelines have been established jointly by the Committee for Laboratories and Official Drug Product Inspection Services and the Department of Industrial Pharmacists of the Feder-ation Internationale Pharmaceu-tique ( ), which is the European counterpart of the FDA. The term Validation is defined by the guidelines as follows: Validation , as used in these guidelines, comprises the systematic testing of essential production steps and equipment in the R & D and production departments, including testing and inspection of pharmaceutical products with the goal of ensuring that the finished products can be manufactured reliably and repro-ducibly and in the desired quality in keeping with the established production and quality control procedures.

9 We have compiled this Validation Guide so users of sartopore 2 Filter Cartridges, MaxiCaps , MidiCaps and Capsules can plan, implement and document their own Validation Introduction6 | Prevention of ContaminationSartopore 2 Filter Cartridges and MaxiCaps are sealed in protective plastics bags in a controlled production area. During production sartopore 2 Filter Cartridges and MaxiCaps are dried to reliably prevent microbial growth, and thus rule out the possibility of pyrogen synthesis during shipping and 2 MidiCaps and Capsules sizes 4 and 5 are sealed in steam permeable protective plastic bags in a controlled production area.

10 Following this step they are heat treated with steam to reliably prevent microbial growth, and thus rule out the possibility of pyrogen synthesis during shipping and Complete TraceabilityThe pore size, type and lot number are printed on the label of the protective plastic bag and on the label of the box in which the Cartridge or Capsule is packed. In addition, these specifications are imprinted on the outer cage of each Filter Cartridge or on the housing of each Capsule. The traceable lot number allows convenient retrieval of all data complied on the materials used, production steps and QC cGMP Quality Assurance from SartoriusConsistent high quality of Sartorius Membrane Filters, Capsules (ready-to-connect filtration units) and Filter Cartridges is assured by careful selection of the raw materials, well-planned and validated production technologies and an exceptionally efficient Quality Assurance Department, all of which results in high batch-to-batch reproducibility.