ISPE NJ Chapter Tour Demo of Aseptic Filling Line Tour-Demo of - PowerPoint PPT Presentation

ISPE NJ Chapter Tour Demo of Aseptic Filling Line Tour-Demo of Aseptic Filling Line with Validation Workshop Dragutin Stoicovici Director of Quality Assurance Director of Quality Assurance February 16, 2011 www.cozzoli.com Dragutin Stoicovici, Dir. of QA

Technology Review h l i • Pharmaceutical, Cosmetics, Biotech Products • Aseptic Packaging • Clean Room Clean Room • cGMP Dragutin Stoicovici, Dir. of QA

Requirements i • Equipment Requirements • FDA/USDA Expectations p • cGMP Requirements • Validation • Validation Dragutin Stoicovici, Dir. of QA

Terminology i l • Endotoxin – a toxin produced within a microorganism • Pyrogen – a substance that produces fever. P b h d f Endotoxins are pyrogens. • Log Reduction – reduction of Endotoxin or L R d ti d ti f E d t i Biological indicator (1Log=10 times less, 2Log=100 3Log=1000 2Log 100, 3Log 1000…) ) Dragutin Stoicovici, Dir. of QA

Terminology i l • Aseptic Core – area requires special A i C i i l gowning • Washroom – vials washed and W h i l h d d delivered for sterilization (oven or tunnel) tunnel) • Fill Room – vials are filled with drug product and then closed product and then closed Dragutin Stoicovici, Dir. of QA

Aseptic Fill Line i ill i • Vial Washer – class 10000/100000 • Sterilizer, Depyrogenation Tunnel py g • Filler – class 100 • Closing: Plugger Capper Stoppering • Closing: Plugger, Capper, Stoppering • Crimping – class 10000 Dragutin Stoicovici, Dir. of QA

Containers i • vials • bottles • ampules • syringes • syringes • IV type bags • Special… Dragutin Stoicovici, Dir. of QA

Product d • Liquid – flammability, density, viscosity, suspension… • Powder – humidity, static charge, particle shape and size p p • Tablets Dragutin Stoicovici, Dir. of QA

Washing Equipment hi i Vials, Bottles, Ampules, Stoppers • Batch • Automatic Dragutin Stoicovici, Dir. of QA

Filling Equipment illi i Liquid, Powder • Semiautomatic • Mid Range – Intermittent • High Speed – Continuous • Inline • Rotary Rotary Dragutin Stoicovici, Dir. of QA

Liquid Filling Methods i id illi h d • Piston Pump • Diaphragm Pumps • Peristaltic Pump • Micro Fillers (IVEK) Mi Fill (IVEK) • Time Pressure Dragutin Stoicovici, Dir. of QA

Closing Equipment l i i Ampules, Stoppering, Plugging, Capping • Semiautomatic • Intermittent • Continuous C i Dragutin Stoicovici, Dir. of QA

Monoblock Equipment bl k i Ampules, Stoppering, Plugging, Capping • Fill, Seal Ampules • Fill, Plug, Cap • Fill, Stopper Dragutin Stoicovici, Dir. of QA

Ancillary Equipment ill i Ampules, Stoppering, Plugging, Capping • Unscramblers • Conveyors • Bottle Trayers Dragutin Stoicovici, Dir. of QA

Before you start… Ri k B Risk Based Approach d A h Dragutin Stoicovici, Dir. of QA

http://www.youtube.com/watch?v=IFFvATEW6dM h // b / h? IFF ATEW6dM VIDEO VIDEO Dragutin Stoicovici, Dir. of QA

Vhat is Validation? “E “Establishing documented evidence bli hi d d id which provides a high degree of assurance that a specific process will consistently produce a product meeting y p p g its pre-determined specifications and quality attributes ” quality attributes. Dragutin Stoicovici, Dir. of QA

Require Documentation: - Customer Specification (May include SOP’s) -Manufacturer’s Proposal -Purchase Order- do not need the dollar amounts Purchase Order do not need the dollar amounts -Order Acknowledgement -Customer component drawings -Electrical Schematics/Drawings -All drawings provided for the equipment. An index of drawings only, All drawings provided for the equipment An index of drawings only will be acceptable. -Cut Sheets for components utilized in the manufacturer of the equipment -Material Certification for product contact and exposed parts. Material Certification for product contact and exposed parts Certification must include which parts were manufactured from the materials. -Passivation reports (where Passivation is required) -Electropolish reports (when electropolish is required) -Electropolish reports (when electropolish is required) -Bill of Material, listing component manufacturer, model no, type, etc. -Operator interface screens -Ladder Logic (where PLC is utilized) Dragutin Stoicovici, Dir. of QA

Title page Equipment Location Location Protocol Dragutin Stoicovici, Dir. of QA

Approvals Author Blank Protocol Approval Fi Final Protocol Approval l P t l A l Dragutin Stoicovici, Dir. of QA

Each Section Purpose Scope Scope Dragutin Stoicovici, Dir. of QA

Certification … to the best of executor’s knowledge executor s knowledge… If the executor is not qualified in a specific area then qualified help shall be used. h ll b d Dragutin Stoicovici, Dir. of QA

System description Process Definition Introduction Dragutin Stoicovici, Dir. of QA

System description Process Definition …more… Dragutin Stoicovici, Dir. of QA

Instructions to be followed when executing the protocol and protocol and … Dragutin Stoicovici, Dir. of QA

Responsibilities assigned Dragutin Stoicovici, Dir. of QA

Acceptance Criteria G id d b th I Guided by the Instructions t ti and using the Method, the acceptance needs to be confirmed. Any deviation will be noted and a course of action initiated. of action initiated. Dragutin Stoicovici, Dir. of QA

Check List This is the script for executing the This is the script for executing the protocol. Each item will be accepted or rejected, if there are multiple methods of verifying, then specify method, and always initial and date. Also at the bottom of each page note any comments and the persons that completed and verified sign and date completed and verified sign and date. Dragutin Stoicovici, Dir. of QA

IQ Check List -Equipment and Instrument Check list -Documentation Documentation -Drawings, Schematics and Component Identification -Supporting Utilities Supporting Utilities Dragutin Stoicovici, Dir. of QA

OQ Check List -Instrument Calibration -Operator Interface -Manual and Automatic Controls -PLC Logic and Controls PLC Logic and Controls -Alarms -Fill Weight Verification (or other critical parameters) -Capping Verification Dragutin Stoicovici, Dir. of QA

PQ Check List PQ Check List -Reference (Any relevant SOPs) -Process Instruments -Media Fills -Cap Seal Integrity -Capping Application (torque) Dragutin Stoicovici, Dir. of QA

PQ Check List PQ Check List As IQ is very generic in relation to the process, the OQ becomes more specific involving specific groups of people (operators) and SOPs, and the PQ is totally dependant of the specific process. Dragutin Stoicovici, Dir. of QA

Summary of Results Summary of Results The acceptance criteria of every section will be listed here together with the result here, together with the result. Dragutin Stoicovici, Dir. of QA

Exception Report Exception Report All Exceptions are captured in this section. This is done every time an acceptance criteria can time an acceptance criteria can not be fulfilled. Dragutin Stoicovici, Dir. of QA

Exception Report Exception Report A protocol execution is successful only after each and every one of the exceptions every one of the exceptions have been corrected. Dragutin Stoicovici, Dir. of QA

The End … Dragutin Stoicovici, Dir. of QA

…well, this is just the beginning. Once the equipment has been successfully validate, all changes shall be made under change control control. There also is a regular revalidation cycle, every 6 month revalidation cycle, every 6 month (or a year) as dictated by your SOP. Dragutin Stoicovici, Dir. of QA

The end of the validation effort will come only when the equipment has reached it’s end of life and it’s decomission has been completed. Dragutin Stoicovici, Dir. of QA

References: 21 CFR Parts 210 & 211 21 CFR Part 11 GAMP cGMP cG USP 24 <1211> - Sterility USP 24 <85> - Biological Test, Bacterial Endotoxin Tests www . fda . gov www . ispe . org p g Dragutin Stoicovici, Dir. of QA

Thank you y Dragutin Stoicovici, Dir. of QA