GENERAL INFORMATION Quality system information sheet3ec13e32-8dde-408f-a42c-47b74ed5d0ab/Quality...

GENERAL INFORMATION

Quality system information sheet

This document was prepared by Purolite Corporation in February, 2017.

Prepared by: Doina Florea – Quality & Regulatory Manager

Cosmin Catanas – Quality Assurance Engineer

1 Quality System Information PSI-01-QSIS-Rev. 01 / February 2017

Issue Date: February 2017

Quality System Information Sheet

Dear valued customer,

This document is designed to provide Purolite customers, sponsors, clinical investigators and institutional review boards answers to frequently asked questions regarding Purolite and our Quality Systems. Readers will learn about the systems that are in place, supporting documentation, control measures, continual training, manufacturing procedures, and other processes and measures that ensure the quality and consistency of Purolite products and operations. The guidelines followed by Purolite demonstrate our commit to regulatory guidelines (including GMP), as well as the needs of our customers.

Customers may write to us if additional information is required.

Additionally, customers are welcome to visit our facility for auditing purposes.

We look forward to working with you.

Doina Florea Quality and Regulatory Manager



Table of Contents

COMPANY PROFILE ............................................................................................................................................................... 3

PARENT COMPANY ..........................................................................................................................................................................3 MANUFACTURING SITE .....................................................................................................................................................................3 MANUFACTURING ACTIVITIES ON SITE ..................................................................................................................................................3 BUSINESS INFORMATION ..................................................................................................................................................................4

QUALITY MANAGEMENT SYSTEM ......................................................................................................................................... 4

QUALITY POLICY .............................................................................................................................................................................4 PUROLITE SRL MANAGEMENT ...........................................................................................................................................................4 QUALITY MANAGEMENT SYSTEM COMPLIES..........................................................................................................................................5 QUALITY MANAGEMENT SYSTEM RESPONSIBLE .......................................................................................................................................5 QUALITY MANAGEMENT SYSTEM DOCUMENTATION ................................................................................................................................5 INTERNAL AUDITS / SELF INSPECTIONS .................................................................................................................................................6 CHANGE CONTROL ..........................................................................................................................................................................6 DEVIATION CONTROL .......................................................................................................................................................................6 CORRECTIVE / PREVENTIVE ACTIONS (CAPA) .......................................................................................................................................6 COMPLAINTS AND RECALLS ...............................................................................................................................................................6

PERSONNEL AND TRAINING .................................................................................................................................................. 7

SITE PERSONNEL INFORMATION ..........................................................................................................................................................7 PERSONNEL TRAINING ......................................................................................................................................................................7 PERSONNEL HYGIENE .......................................................................................................................................................................7

BUILDINGS AND FACILITIES ................................................................................................................................................... 8

DESIGN AND CONSTRUCTION .............................................................................................................................................................8 AIR, HANDLING AND ENVIRONMENT ....................................................................................................................................................8 WATER SYSTEM ..............................................................................................................................................................................9 EQUIPMENT ..................................................................................................................................................................................9 PEST CONTROL ...............................................................................................................................................................................9

MATERIALS MANAGEMENT .................................................................................................................................................. 9

PRODUCT MANUFACTURING .............................................................................................................................................. 10

DOCUMENTATION ........................................................................................................................................................................10 MANUFACTURING PROCESS.............................................................................................................................................................10 PACKAGING AND LABELLING ............................................................................................................................................................10 STORAGE ....................................................................................................................................................................................10

LABORATORY CONTROL ...................................................................................................................................................... 11

TESTING ACTIVITIES .......................................................................................................................................................................11 OOS (OUT OF SPECIFICATION) HANDLING ..........................................................................................................................................11 STABILITY STUDIES ........................................................................................................................................................................11

PRODUCT RELEASE .............................................................................................................................................................. 12

PRODUCT QUALITY REVIEW ................................................................................................................................................ 12

PERTINENT DOCUMENTS .................................................................................................................................................... 13

ANNEX 1 – REGISTRATION CERTIFICATE, NATIONAL TRADE REGISTRY........................................................................................................13 ANNEX 2 – CORPORATE ORGANIZATION TABLE ....................................................................................................................................14 ANNEX 3 – QUALITY POLICY ............................................................................................................................................................15 ANNEX 4 – ISO 9001:2008 CERTIFICATE .........................................................................................................................................16 ANNEX 5 – U.S. F. D. A. INSPECTION REPORT FOR 21 CFR 20.64(D)(3) .................................................................................................19 ANNEX 6 – GMP CERTIFICATE ........................................................................................................................................................20 ANNEX 7 – PUROLITE ROMANIA ORGANIZATIONAL CHART ......................................................................................................................22



Company Profile

Parent company Company Name: Purolite Corporation

President Steve Brodie

Vice-President Don Brodie

Headquarters: 150 Monument Road, Bala Cynwyd, PA, USA, 19004

Telephone: +1 610 668 9090

General Fax: +1 610 668 8139

Customer Service Fax: +1 800 260 1065

E-mail: [email protected]

Web-site: www.purolite.com

Manufacturing site Company Name: Purolite SRL

Site Address: Str. Aleea Uzinei Nr. 11, 505 700 Victoria, Jud. Brasov, Romania

Telephone: +40 268 243 004 to 243 010

Fax: +40 268 243 002 and 243 003

GPS Coordinates: Latitude: 45° 40’ North Longitude: 25° East

Registration Certificate: CUI: 6039433 / 11.08.1994 Annex 1

DUNS Number: 565718892

Facility size: 30880 m2

E-mail: [email protected]

Web-site: www.purolite.com

Manufacturing activities on site

Industrial manufacturing activities on the site:

Purolite SRL is manufacturing ONLY Ion Exchange Resins and Adsorbents. (see www.purolite.com for full list)

Pharmaceutical manufacturing activities on the site:

The plant is manufacturing ONLY bulk Active Pharmaceutical Ingredients and Excipients and Special Polymers.

Active Pharmaceutical Ingredients and Excipients manufactured by Purolite SRL:

Purolite® C100MRNS – Sodium Polystyrene Sulfonate

Purolite® C100CaMRNS – Calcium Polystyrene Sulfonate

Purolite® A430MR – Cholestyramine

Purolite® C115KMR – Polacrilin Potassium

Purolite® C115HMR – Polymethacylic Acid

mailto:[email protected]

http://www.purolite.com/






Business information Business Organization: Corporate organisation chart Annex 2

Annual Turnover:

2016: 174.763.727 lei

2015: 169.871.447 lei

2014: 157.946.936 lei

Pharma products: 5%

Number of years in business

Starting from 1985, over 31 years. The Purolite business started from 1985, over 31 years. Pharmaceutical production started over 25 years ago. Purolite SRL production started from 1995, over 22 years, and pharma production, over 13 years.

Quality Management System

Quality policy Purolite SRL ensures that the Quality Policy (Annex 3) is communicated and understood within the organization.

Purolite SRL management Name Position Contact

Arvind Verulkar Plant General Manager T: +40 268 243 004 to 010 F: +40 268 243 002 and 003 [email protected]

Cornel Mezei Plant Manager T: +40 268 243 004 to 010 F: +40 268 243 002 and 003 [email protected]

Dan Petrascu Production Manager T: +40 268 243 004 to 010 F: +40 268 243 002 and 003 [email protected]

Doina Florea Quality and Regulatory Manager T: +40 268 243 004 to 010 F: +40 268 243 002 and 003 [email protected]

Cristina Samoila Quality Control Manager T: +40 268 243 004 to 010 F: +40 268 243 002 and 003 [email protected]








Quality Management System compliance Purolite SRL is operating a Quality Management System, which complies with the requirements of:

• BS EN ISO 9001:2008 – Quality Management systems – Requirements;

Certification Authority: British Standard Institute (BSI UK)

Original registration date: 23.07.1992

Last inspection date: December 2016 (re-assessment twice per year)

Certificate no.: FM 21074 Annex 4

• FDA Guide – cGMP – ICH Q7A Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients

Inspection Authority: US FDA

Other inspections: 2004, 2009, 2013

Last inspection date: February 2016

FEI: 3004201705 Annex 5

• Part II of EU Good Manufacturing Practice: Basic Requirements for Active Substances used as Starting Materials

Certification Authority: National Agency of Medicines and Medical Devices

Certified from: 2009

Last inspection date: July 2015

Certificate no.: 039/2015/RO Annex 6

Quality management system responsible Name Position Reporting to:

Doina Florea Quality and Regulatory Manager General Manager

Quality management system documentation − All QMS documents are controlled by document number, revision number and date;

− There is a system in place to assure that only the current version of document is being used;

− All production documents are reviewed and approved by Quality Unit;

− Revised documents and records are retained six (6) years.



Internal audits / Self inspections − Regular internal audits / self-inspections are performed each year for all Purolite processes;

− Internal audits / self-inspections are performed per Audit Schedule;

− All internal audits findings and corrective actions are documented;

− Management is notified about audit findings.

Change control − There is a documented system in place for change control capable to evaluate and handle

all changes; − All changes are approved by the Quality Unit; − Whenever applicable, authorities and customers are notified about changes that could

impact the product quality.

Deviation control − There is a documented system in place for deviation handling, which includes deviation

reporting, recording, investigation, corrective and preventive action taken, etc.; − All deviations are approved by the Quality Unit.

Corrective / Preventive actions (CAPA) − There is a procedure for documenting and implementing corrective and preventive action;

− All CAPA records are kept;

− The efficiency of CAPAs is verified.

Complaints and recalls − Customer complaints handling is performed as per written documented procedure;

− All complaints are investigated;

− Complaints are analysed for trends on a routine basis;

− Corrective actions coming from complaints are completed and documented.



Personnel and training

Site personnel information Department Number of employees

Administration: ~29

Production: ~212

Quality (QC+QA): ~25

Total: ~266

Number of shifts: 2 / 12 h

Working days / week: 7

Part-time employees: 0

Organisational Chart: Annex 7

Personnel training − All personnel involved in Pharma production are knowledgeable of pharmaceutical

industry requirements; − All personnel have job descriptions and the education, training and experience to enable

them to perform their assigned jobs; − There is a training program in place approved by the Quality Unit;

− Records of training are completed for all personnel;

− All personnel involved in Pharma production receive monthly documented GMP training;

− All involved personnel are retrained when procedures are revised;

− The training records for each individual are maintained by the HR Department.

Personnel hygiene − Smoking, eating, drinking, chewing and storage of food is forbidden on the manufacturing

site, there are specially designed areas separated from the manufacturing areas; − All personnel engaged in manufacturing, processing and packing of Pharma products wear the

appropriate Personal Protective Clothing and Equipment (PPCE) as per written procedure; − All personnel who have an apparent illness or open lesions are reporting immediately to

their supervisor; − Medical checks are done for all Purolite SRL employees once per year, records are kept.



Buildings and facilities

Design and construction − All access to the Pharma manufacturing area is restricted by card access;

− Pharma manufacturing areas are separated from non-pharma areas; − Pharmaceuticals are manufactured in four (4) independent and separate manufacturing lines,

meeting the requirements of Clean Room Class 100 000; There are dedicated lines for APIs and excipients.

There are defined areas for: • Receipt, identification, sampling, and quarantine of incoming materials; • Production operations; • Laboratory operations; • Packaging & sampling of Pharma products; • Quarantine before release or rejection of Pharmaceutical products; • Rejected materials.

Purolite SRL is manufacturing only Ion Exchange Resins; NONE of the following are manufactured or handled within or near the production facility:

• Penicillin, cephalosporin, beta-lactam or other antibiotics; • Steroid, hormone products or derivatives; • Biological materials; • Cytotoxic or antineoplastic agents; • Herbicides, pesticides or rodenticides; • Agrochemicals; • Other potent, toxic, hazardous or sensitizing products.

Air, handling and environment − Air handling systems (HVAC system) are in place for all manufacturing lines;

− Air quality is ensured; • Humidity; • Temperature; • Airflow; • Airborne particulate; • Pressure differential.

− Records are available for the adequacy of air handling systems;

− Clean rooms air and surfaces are sampled and tested for microbiological organisms.



Water system − Purolite uses Demineralized Water that is UV treated;

− DM Water is routinely monitored; • Physical / Chemical characteristics (on-line and off-line); • Microbial count (once in two weeks).

− Water system is validated.

Equipment − The manufacturing lines are clean and well maintained; − Cross contamination is avoided by manufacturing one product at a time on a manufacturing

line, between two product types, full cleaning procedures are applied; − Cleaning validation data is available for manufacturing lines;

− The walls, floors, ceilings, fixtures, etc. have smooth, easy-to-clean surfaces;

− There are written procedures and records for cleaning, maintenance and calibration of equipment;

− Full traceability of all key equipment used in production is ensured.

Pest control − A pest control program is in place including maps indicating locations where pest control

is performed; − External Supplier: S.C. Coral Impex S.R.L.

Materials management

− Purolite SRL is working only with qualified suppliers, as per documented procedure;

− List of approved suppliers for raw materials and packing components;

− Written specifications for all raw materials and packing components;

− Defined inspection procedure for testing of incoming materials;

− Incoming materials are received with vendor’s documentation and Certificate of Analysis;

− Prior to use in manufacturing, raw materials are tested and approved;

− First In First Out (FIFO) inventory management is used;

− Labelling and packaging materials are controlled;

− Status of materials (e.g. Quarantine, Release, Reject) is clear at all the times.

http://www.coralimpex.ro/



Product manufacturing

Documentation − All manufacturing processes are in accordance with written procedures and

work instructions; − Products are manufactured in accordance with Batch Records;

− Master Batch Records are approved by Quality Department;

− All manufacturing process steps are double-checked;

− Records for API manufacturing are retained for six (6) years.

Manufacturing process − Purolite SRL batch numbering system: XXXXL/YY/M;

XXXX - Sequential number; L - Letter representing the month of production; YY - Number representing the production year; M - Number representing Purolite’s manufacturing site –five ( 5) indicates

“Romania.”

− Manufacturing lines are marked with the name and Lot # of products that are being manufactured;

− All equipment and piping system is labelled;

− All weighing equipment is of suitable accuracy for the intended use;

− Quality Unit approves Product Specifications.

Packaging and labelling − Packaging and labelling of the final products is done as per written procedures;

− Specifications for all packaging materials and labels are established;

− Packaging area is controlled in the same way as the manufacturing area;

− Labels are controlled, access to labels is limited to authorized personnel;

− All deviations are investigated and approved by the Quality Unit.

Storage − The Purolite SRL Warehouse has adequate conditions for the storage of the

final products; − Purolite SRL Warehouse conditions are monitored for temperature and humidity;

− Monitoring records of the storage conditions are kept; − Separate storage areas are provided for quarantined, rejected, returned or

recalled products.



Laboratory Control

Testing activities − Purolite SRL laboratory is situated at the same location as the manufacturing site; − Purolite SRL laboratory is equipped to deal with all necessary testing, except

micro-testing; − All tests are carried out in accordance with written procedures;

− Calibration and maintenance program is available for all analysing equipment;

− Purolite SRL laboratory is testing the products according to approved specifications;

− Analysis methods are validated according to current regulatory requirements; − Whenever applicable, reference standards have NIST traceability and are stored

under appropriate conditions; − Test results are documented in accordance with GMP requirements;

− A Certificates of Analysis (CoA) is issued for each product batch by QC Manager; − Certificate of Analysis includes all tests performed listed, together with acceptance

limits and numerical results obtained; − Retention samples of the final product are maintained —~500 g, for six (6) years;

− Microbial testing is performed by an external supplier: IFIN-HH;

OOS (Out of Specification) handling − Written procedure is in place for OOS (Out of Specification) handling;

− All OOS results are investigated.

Stability studies − An on-going stability testing programme is in place, as per written procedure; − For each Pharma products one batch per year is added to the stability

monitoring programme; − The storage conditions and time points are:

Temperature [°C] 25 ± 2 Humidity [%RH] 60 ± 5 Time points [months] 3, 6, 9, 12, 18, 24, 36, 48 and 60

− Stability samples are stored in the similar packaging materials as the final product.

https://www.nipne.ro/



Product release

− Product release is done as per written procedure;

− Products can be released only if all steps are conforming to the requirements;

− Products are released by the Quality Unit.

Product quality review

− Product Quality Review is completed for all Pharma products as per written procedure; − Product Quality Review report is evaluated and an assessment is made of whether corrective

action or any revalidation should be undertaken.



Pertinent documents

Annex 1 – Registration certificate, National Trade Registry



Annex 2 – Corporate organization table

Purolite Corporation

Americas Asia Europe

Canada

USA

Latin America

Mexico

South America

China

Japan

Korea

Southeast Asia

Taiwan

Western Europe

Eastern Europe

Middle East

India

Australia

Africa

Purolite Romania is Purolite’s manufacturing plant in Europe, and the company’s only GMP certified production facility.

The company also has production in the USA and China for non-pharmaceutical grade products.

Purolite Ltd

Romania



Annex 3 – Quality policy



Annex 4 – ISO 9001:2008 certificate



Annex 4 – ISO 9001:2008 certificate, continued



Annex 5 – U.S. F. D. A. inspection report for 21 CFR 20.64(d)(3)



Annex 6 – GMP Certificate



Annex 6 – GMP Certificate, continued



Annex 7 – Purolite Romania organizational chart

Assistant

Drivers

Assistant

Sales Office Bucharest

Raw Materials Supervisor

Material Receivers

Plant General Manager

Purchasing Manager

Administrator Purolite SRL;

Global Operation Manager

Finance Manager

Shipping Supervisor Clerks

Storekeepers

Economists Procurement Supervisor Purchaser

R&D Engineers TS Chemists

Laboratory Technicians

R&D and TS Manager Quality & Regulatory Manager

QC Manager

Chemical Eng. Laboratory Technicians Quality Assurance

Plant Manager

Production Manager

Human Resources Manager

Receptionist Housekeepers

Security

Anion Supervisor Shift Lead

Process Op.

Instrumentation Supervisor

Electrical Forman Technicians Electricians Metrologist

Maintenance Manager

Process Engineers Project Engineers

HS&E Manager

Cation Supervisor Shift Lead

Process Op.

Specials Supervisor Shift Lead

Process Op. CR4 Operators

Specials I Supervisor Junior Supervisor

Shift Lead Process Op.

Junior Supervisor Forklift Drivers

Polymer Supervisor Shift Lead

Process Op.

Safety Officer

Secretary

Plant Cleaners

Mechanical Supervisor Mechanics Op. Utilities Storekeeper

Boiler operators

©2017Purolite All rights reserved

PSI-01-QSIS-Rev. 01/February 2017

Americas150 Monument RoadBala Cynwyd, PA 19004T +1 800.343.1500T +1 610.668.9090F +1 [email protected]

Purolite—the leading manufacturer of quality ion exchange, catalyst, adsorbent and specialty high-performance resins— is the only company that focuses 100% of its resources on the development and production of resin technology.

We’re ready to solve your process challenges. For further information on Purolite® products and services, visit Purolite.com or contact your nearest Technical Sales Office.

EuropeLlantrisant Business ParkLlantrisantWales, UKCF72 8LFT +44 1443 229334F +44 1443 [email protected]

Asia PacificRoom 707, C Section Huanglong Century PlazaNo.3 Hangda RoadHangzhou, Zhejiang, China 310007T +86 571 876 31382F +86 571 876 [email protected]

AustraliaBahrainBrazilCanadaChinaCzech RepublicFranceGermanyIndia

IndonesiaIsraelItalyJapanJordanKazakhstanKoreaMalaysiaMexico

MoroccoPolandRomaniaRussiaSingaporeSlovak Republic South AfricaSpainTaiwan

TunisiaTurkeyUKUkraineUSAUzbekistan

GENERAL INFORMATION Quality system information sheet3ec13e32-8dde-408f-a42c-47b74ed5d0ab/Quality...

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