URS for the Replacement Old Sachet Filling & Sealing Machine with New Filling & Sealing Machine for ORS Section

URS for the Replacement Old Sachet Filling & Sealing Machine with New Filling & Sealing Machine for ORS Section

TABLE OF CONTENTS:

• Approval
• Table of contents
• Objective
• Scope
• Purpose
• Reference Guidelines
• Contractual Status
• Abbreviations
• System Description
• Process Description
• Technical Data
• Building Construction
• Manufacturing Equipment
• Risk factors
• Required document

 Objective

To define the instruction and requirements for the expansion and Replacement of U-flex multitrack Filling & Sealing Machine for ORS Section.

To start the task according to the QMS approach with handling through the Change Control for the Expansion and Development of existing facility.

Designing of Machine with suitable layouts in accordance with suitable working to meet the regulatory and cGMP requirements.

Classification of area with respect to requirement of controlled classes.

To identify the required miscellaneous item to be used for the ORS sections and keep ready the URS (User Requirement Specification) of same.

To define the procedure for procurement of equipment/ instruments with raising the Purchase Order (PO).

To define a procedure for the Area qualification/ Equipment qualifications including the DQ, IQ, OQ and PQ.

To provide the necessary utilities to ORS Section as required for the equipment/instrument and other support.

To define a brief idea for the implementation of ORS Section with complying with the regulatory norms and local regulatory requirements.

Scope

This URS will be applicable to define the procedure for the instituting Multitrack U-flex filling & sealing Machine & Manufacturing for ORS Section including the following general area which shall be covered under the scope of this URS

Area layout for Man-material movement, Area Classification and utility detail.

Procurement process of manufacturing equipments/instruments.

Facility qualification

Equipment/Instrument Qualification

Document requirement including Standard Operating Procedures and Qualification

Purpose

The purpose of this URS is to define a procedure for the development of a manufacturing Machine for the ORS section.

Reference Guidelines

The facility shall be adopted in accordance to the current valid and recognized version of the technical regulations. The following regulations are to be considered:

USP:

• <797> Clean room guidelines
• <1231> Water for Pharmaceutical Purposes

WHO Annex-6

• WHO good manufacturing practices for sterile products
• ISO-14644-1: Cleanroom and Associated Controlled Environments
• Schedule M (1A): Requirements for Manufacturing of Parenteral and ophthalmic preparation

Contractual Status

This document and its Annexure are the obligatory basis for the equipment characteristics, required services and documentation. Changes in the specified parameters must be approved and documented.

The supplier is responsible that the delivered / installed equipment operates consistently as specified throughout the entire operating parameters. The supplier is additionally obligated to inform the purchaser in the case of detected inaccuracies in specifications and drawings.

System Description

PROJECT PLAN:

Manufacturing Machine (ORS): This is what we required for the preparation of sterile respules/eye drops/sterile water for injection, filtration with bacterial retention filter and filled in container through aseptic processing, in a well-equipped with a systematic working flow and controlled environment to safely and accurately handle the manufacturing & filling process to avoid any viable or non-viable contamination. Generally the Facility perform in clean area  which is build up  in a manner to avoid any unwanted extraneous particle or micro-organism in the final product & all the required parameter temperature, humidity, differential should be controlled.

General requirement for manufacturing process:

Utility for machine operation Power Consumption: 26 kW to 28 kW main Supply: 440 VAC/3 Phase/50Hz.

Product to be packed like any Pharma powder

Pouches with given below dimension (length=90mm and width =70 mm)

Compressed Air Max-6 CFM @ 6 pressure bar

Process Description

Uflex Automatic Form Fill & Seal Multi Track Machine is user friendly packing system to pack and seal product in preformed pouch like Four Side Seal Pouch. made-up of heat sealable laminated film.

The machine is suitable to pack products like Pharmaceutical Products.

This machine is provided with the Mechanically operated sealing system driven by Servo Motor.  All the product contact parts are made up of food grade SS316L.

The machine operation cycle is actuated by Push Button. All machine operations can be customized by individual timer.

Figure-1: Flow Diagram of Project expansion of existing manufacturing Machine

Area Selection for the Expansion – Area Layout

Area Construction – With Utility Provision

DQ of AHUs and Equipments – FAT / SAT / AHU/LAF/Mfg. / Ducting/ Installation of HEPA

AHU Installation – IQ/OQ/PQ

Area Qualification (Particle Count/ PAO Test/ Filter Integrity/ Flow Pattern/Recovery/ACPH)

DQ of Production Equipments – FAT / SAT / Equipment Installation /IQ/OQ/PQ – Equipment Qualification – Validation Activities – Ready to Work

Project Plan/Project Proposal:

With keeping the vision of expansion and upgradation of Sachet filling machine with Multitrack U-flex Machine ,the hiring of external technical support is contracted and signed with the below mentioned certified agency.

Technical Data

Area requirement:

For the expansion and upgradation of existing facility we have to keep the area ready as :Easily approachable with sufficient access area for the entrance of manufacturing equipments and  AHUs

Sufficient space is required in existing facility for the expansion and inclusion of following….

• Sampling/Dispensing Tool cleaning area
• Primary packing material/Resin Store
• Resin charging & Sampling Room
• Printed Packing Material Store
• Manufacturing Room I & II
• Filling Room
• Packing Room
• Incubation Room

Utility Requirement

U-flex Automatic Form Fill & Seal Multi Track Machine are needed the external utilities like Compressed Air.

AHU designing for the ORS Area:

   Controlled environment codition shall be maintained as per the requirement mentioned in Filling Room by the Air Handlin Units (AHU). The Air Handling Units shall be connected to the area through  insulated Galvinizing Iron ducts. To provide the air of required standard quality terminal HEPA (High Efficiency Particulate Air) filters are there in Filling room. For the control of humidity and temperature, dehumidifier and heatin/ cooling coil is there.

Visibility requirements

For the Filling Room, there should be appropriate visibility level so the activity can be performed comfortably. Not less than 500 Lux should be available in the room where the critical process are going.

Room Construction:

Building and Premises:

The civil work for the expansion of Room for the ORS Section Facility shall be done in accordance to the technical guidance .

Wall Partiotions shall be made up of Cement and Conkret thickness and roof shall be made up of same material  with smooth finish and coving on joints and corner to prevent the dust accumulation. Joints of partition should be properly sealed to prevent the air leakage.

View Glass to be provide in Area, filling to Packing area and joints of view glass should be properly sealed and smooth.

Embeeded lighting should be there with proper sealing.

Complete floor ( Filling Room, coridor and entry to all these rooms), should be epoxy coated with smooth and uniform surface) & Non sterile corridor, ,Packing hall) should be floored with Kota Stone.

Doors shall also having smooth finish and having door closure provision. Door closure should be SS(304) to avoid rusting. Door handle and push plate should be of SS(304). Door should have door seal at the bottom. All critical area airlock door should have interlocking system, so the both side door can not be opened at same time. Also biometric access is required at the main entrance of the Filling Area.

Air Controlling System:

To maitain the required lavel of air classification, Air Handing Units shall be installed.

Cemented AHU platform is required with labeled surfce for the installation of AHUs.

AHU ducting should be insulated and leakfree and connected AHU to the terminal HEPA with minimum bends. All joints are perfectly closed to prevent any kind of air leakage.

The Grill-Frame of Terminal HEPA and Return riser should be SS 316 with SS screw working. 0.3 micron EU13 HEPA is required in supply air line while 10 micron fitters are to be placed in return air.

The grills of supply line and return riser should be properly sealed with appropriate sealent like silicon gel food grade. Flters should be perfectly fit into the grills so any kind of leakage can be prevented.

Electric/Wiring and its Components

Electric switches should be modular type and electric connection to the equipment/instrument should be through the three pin plug (No open connection will be there)

Electric supply should be with proper earthing.

For Filling Area 415 Volt, 3-Phase -50 Hartz, AC suuply is required.

Close wall embeeded electric wiring to be ensured.

UPS (Unintrupted Power Supply) is required for Filling Mchine PLC

Other Utilities:

Compressed air qualification should be there for machine operation and other activity.

Risk Factors:

During expansion, renovation and reconstruction there might be some risk takes place on existing Equipments/instruments and environment.

This is defined as, the situation that may cause negative impact on the safety, quality and continuity.

Following basic risks can be arise on Equipments/instruments during the project. To overcome this risk mitigation plan have to be develop.

Required Documents:

As the activity need to be properly documented in chronological order. Thus the requirement of records/ document are shown in below Flow diagram.

• Selection of Outsourced agency for technical assistance – Proposal of Project and Contract Agreement
• Area selection/ Design of  Filling Area – Area Layout with drawings of Man-Material movement, Area Classification, Utility Requirements, AHU Air Supply
• To outline the requirements for development of existing facility –  User Requirement Specification for development of existing facility
• To handle the activity with QMS approach – Change Control Initiation for changes in existing facility
• Requirements of equipments/ instruments – URS of Equipments
• Procurement Process of equipments/ instruments – Purchase order
• Check the designing of ordered equipment as per PO – Design Qualification (DQ)
• Check of equipment at manufacturer’s site – Factory Acceptance Test (FAT)
• Check of equipment at our site – Site Acceptance Test (SAT)
• Area qualification – Particle Count, ACPH of Room, Flow pattern, filter Integrity test, Recovery test. Visibility Check.
• Equipment Qualification – Installation Qualification (IQ) ,Operation Qualification (OQ),Performance Qualification (PQ)

Drawings and layout of Area:

After selection of area room drawing shall be prepared which shall cover the following scope

• General area drawing with room dimensions
• Area classification
• AHU air supply
• Man-Material movement
• Utility requirement
• Drain point requirement
• Room data sheet

Change Control for the expansion and development of existing facility:

Considering QMS approach, the change control process shall be followed for the reconstruction of Existing facility. Before starting the activity change control approval is required from the Quality head & Plant head.

User’s Requirement Specification (URS) for the instruments/equipments:

URS is a normative documents which reveals the requirements/features of equipment what we want considering the safety, regulatory requirements, precise and effective controlling.  This document shall be provided to the manufacturer as specification for the ordered equipment/ instrument and on the basis of this, manufacture shall provide the Design Qualification document.

Factory Acceptance Test (FAT) and Site acceptance Test (SAT)

Before taking delivery of the filling & sealing machine user has the responsibility to verify the equipment against the Design Qualification at the site of Manufacturer of machine. This is called Factory Acceptance which should be necessarily performed for the equipment like Air handling Unit (AHU).

At the time of receiving of the equipment, again verification shall be done at the receiving site reviewing all the concerns as defined in Design Qualification. This test is to be performed to all the newly purchased equipments.

Qualification of Equipments:

Before using the equipments, qualification activity shall be performed which include…
• Installation Qualification (IQ)
• Operation Qualification (OQ)
• Performance Qualification (PQ)

Area Qualification:

After getting the AHU installed, Area qualification with respect to categorized class, shall be performed to include following considerations:

• Light intensity check of rooms for the visibility level measure met.
• Temperature of room
• Pressure differential of room
• Particle count
• Air changes per hour (ACPH)
• Air-Flow Pattern
• Filter Integrity (PAO Test)
• Recovery test of rooms

Standard Operating Procedures (SOPs):

A standard operating procedure (SOP) is a set of step-by-step instructions compiled by an organization to help workers carry out complex routine operations. SOPs aim to achieve efficiency, quality output and uniformity of performance, while reducing miscommunication and failure to comply with industry regulations. Categorization of sort of SOPs shall be as follow

Operation, Cleaning, calibration/qualification SOPs of equipments/instruments

Entry-Exit Procedure in production area, controlled area, mfg. and filling

General SOPs related to Personal hygiene/Clean room behaviour

Batch Preparation

Cleaning & maintenance of clean area

Fogging/Fumigation

Abbreviations

• ACPH :Air Changes per hour
• AHU :Air handling Unit
• CFR :Code For Regulation
• DQ :Design Qualification
• GI :Galvanizing iron
• HEPA :High Efficiency Particulate Air
• HPHV :High Pressure High Vacuum
• FAT :Factory Acceptance test
• ISO : International Organisation of Standardization
• IQ : Installation Qualification
• LAF : Laminar air flow
• PLC :Programmable Logical Control
• MOC :Material Of Construction
• OQ :Operation Qualification
• PQ :Performance Qualification
• PAO: Poly Alfa Olefin
• PLC :Programmable Logical Controller
• PO :Purchase order
• QMS :Quality Management System
• SAT :Site Acceptance test
• URS :User Requirement Specification
• UPS :Uninterrupted Power Supply
• USP : United State Pharmacopoeia
• WFI : Water For Injection