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

h l i Technology Review

• Pharmaceutical, Cosmetics, Biotech

Products

• Aseptic Packaging
• Clean Room

Clean Room

• cGMP

i Requirements

• Equipment Requirements
• FDA/USDA Expectations

p

• cGMP Requirements
• Validation
• Validation

i l Terminology

• Endotoxin – a toxin produced within a

microorganism P b h d f

• Pyrogen – a substance that produces fever.

Endotoxins are pyrogens. L R d ti d ti f E d t i

• Log Reduction – reduction of Endotoxin or

Biological indicator (1Log=10 times less, 2Log=100 3Log=1000 )

2Log 100, 3Log 1000…)

i l Terminology

A i C i i l

• Aseptic Core – area requires special

gowning W h i l h d d

• Washroom – vials washed and

delivered for sterilization (oven or tunnel) tunnel)

• Fill Room – vials are filled with drug

product and then closed

product and then closed

i ill i Aseptic Fill Line

• Vial Washer – class 10000/100000
• Sterilizer, Depyrogenation Tunnel

py g

• Filler – class 100
• Closing: Plugger Capper Stoppering
• Closing: Plugger, Capper, Stoppering
• Crimping – class 10000

i Containers

• vials
• bottles
• ampules
• syringes
• syringes
• IV type bags

• Special…

d Product

• Liquid – flammability, density,

viscosity, suspension…

• Powder – humidity, static charge,

particle shape and size p p

• Tablets

hi i Washing Equipment

Vials, Bottles, Ampules, Stoppers

• Batch
• Automatic

illi i Filling Equipment

Liquid, Powder

• Semiautomatic
• Mid Range – Intermittent
• High Speed – Continuous
• Inline
• Rotary

Rotary

i id illi h d Liquid Filling Methods

• Piston Pump
• Diaphragm Pumps
• Peristaltic Pump

Mi Fill (IVEK)

• Micro Fillers (IVEK)
• Time Pressure

l i i Closing Equipment

Ampules, Stoppering, Plugging, Capping

• Semiautomatic
• Intermittent

C i

• Continuous

bl k i Monoblock Equipment

Ampules, Stoppering, Plugging, Capping

• Fill, Seal Ampules
• Fill, Plug, Cap
• Fill, Stopper

ill i Ancillary Equipment

Ampules, Stoppering, Plugging, Capping

• Unscramblers
• Conveyors
• Bottle Trayers

Before you start…

Ri k B d A h Risk Based Approach

h // b / h? IFF ATEW6dM http://www.youtube.com/watch?v=IFFvATEW6dM

VIDEO VIDEO

Vhat is Validation?

“E bli hi d d id “Establishing documented evidence 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.

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)

Title page

Equipment Location Location Protocol

Approvals Author Blank Protocol Approval Fi l P t l A l Final Protocol Approval

Each Section Purpose Scope Scope

Certification …to the best of

executor’s knowledge executor s knowledge… If the executor is not qualified in a specific area then qualified help h ll b d shall be used.

System description Introduction Process Definition

System description …more… Process Definition

Instructions to be followed when executing the protocol and protocol and …

Responsibilities assigned

Acceptance Criteria G id d b th I t ti Guided by the Instructions and using the Method, the acceptance needs to be

• confirmed. Any deviation

will be noted and a course

• f action initiated.

• f action initiated.

Check List

This is the script for executing the This is the script for executing the

• protocol. Each item will be accepted
• r 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.

IQ Check List

• Equipment and Instrument Check list

Documentation

• Documentation
• Drawings, Schematics and

Component Identification

• Supporting Utilities

Supporting Utilities

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

PQ Check List PQ Check List

• Reference (Any relevant SOPs)
• Process Instruments
• Media Fills
• Cap Seal Integrity
• Capping Application (torque)

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.

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.

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.

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.

The End …

…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.

The end of the validation effort will come only when the equipment has reached it’s end

• f life and it’s decomission has

been completed.

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

Thank you y