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Forest Laboratories IPPC Licence Application Attachment C

Forest Laboratories IPPC Licence Application Attachment C - Management of the Installation

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Forest Laboratories IPPC Licence Application Management of the Installation

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Attachment C: MANAGEMENT OF THE INSTALLATION

C.1. SITE MANAGEMENT AND CONTROL

This attachment deals with the site management and control in relation to the operation of the activity and business in terms of product quality, process control, environment, safety, quality and training. Forest Laboratories operates under the following company policies: Quality Policy Statement: Forest Laboratories Ireland Ltd. is engaged in the manufacture and distribution of pharmaceutical products servicing the health care community in compliance with the following:

(a) The rules governing Medicinal Products in the European Community, Volume iv, Good manufacturing practice for medicinal products and any amendments/supplements therein.

(b) Current Good Manufacturing Practices Section 211, Title 21, Code of federal

regulations, The Federal Food, Drug, and Cosmetic Act, and any amendments therein.

The Standard Operating Procedures (SOPs) are described in Forest Laboratories S.O.P Manual, include all aspects of the GMP regulations designed to assure the quality, identity, strength and purity of the products manufactured by Forest Laboratories Ireland Ltd. This manual is available on request. Environmental Protection Policy: Forest Laboratories Ireland Ltd. understand the rapid changes in manufacturing technology and the regulatory requirements. Forest Laboratories aims to meet statutory requirements for environmental protection and to fully comply with the required legal standards. If and when required, Forest Laboratories will introduce appropriate environmental monitoring to ensure compliance with environmental legislation. Forest Laboratories aims to provide flexibility in their control equipment and processes to provide protection for the employee, the community and the environment. Forest Laboratories is making a commitment to maintain appropriate controls to ensure that the policy is being followed. Forest Laboratories will ensure that the wastes generated are disposed of in a safe and environmentally sound manner. Forest Laboratories is committed to continuous improvement in their operations with a view to environmental protection. It is the responsibility of each section manager for controlling the waste generated in their section. The overall co-ordination is dealt with by the Materials Manager. Safety Policy: A safety statement is available in Forest Laboratories in compliance with health and safety regulations. It is the objective of Forest Laboratories Ltd. to provide a safe and healthy working environment for all staff, contractors and members of the public who may visit the premises.

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The Management team of the company is committed to the continued development and implementation of policies for securing the health and safety of its employees. Forest Laboratories is committed to meeting its obligations under the Safety, Health and Welfare Act 2005 (S.I. No. 10 of 2005) and the Safety Health and Welfare at Work (General Application) Regulations 2007 (S.I. No. 299 of 2007). C.1.1 On-Site Management Structure

The site management structure is shown in the organistaion chart below. This indicates responsibility levels for the on-going management of the facility, site operations and personnel including: Head of Corporate Manufacturing - main responsibilities: § Responsible for the operation of the facility and implementation of site procedures in

relation to GMP, quality management and health & safety; § Overall responsibility for health & safety of the workplace; § Reporting to Forest Europe; § Ensuring all products meet corporate and regulatory requirements.

Operations Manager - main responsibilities: § Management of Manufacturing and Technical services personnel; § Ensure quality and production targets are met; § Ensure that all production staff receive adequate training to enable them to carry out

their tasks efficiently and safely; § Set up all production procedures.

Maintenance Manager - main responsibilities: § Management of Maintenance personnel § Implement and maintain a complete preventative maintenance schedule § Ensuring all ongoing maintenance checks are carried out; § Ensure the procedures for automatic, mechanical and electronic equipment

calibration, inspection and checking procedures are implemented; § Liaise with in-house staff or specialist contractors re maintenance schedules; § Ensure service records are kept on file and the maintenance history logbook is

maintained. Materials Control Manager - main responsibilities: § Management of Warehouse and shipping operators; § Responsible for the inspection and receipt of raw materials; § Inspection of the warehousing after cleaning; § Ensure the Warehousing Cleaning Logbook is maintained.

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Forest Laboratories IP

PC

Licence Application M

anagement of the Installation

3

C

EO

Forest E

urope

Ray Stafford

Head of

Corporate

Manufacturing

Frank H

ayes

Head of

European

QA

& G

CP

M

ing Ng

Financial Controller

Forest Europe

D

iarmuid B

urke

Head of

Corporate Q

C

Francis B

ates

Operations M

anager

Gary M

cAuslan

Manufacturing

&

Technical Services

Quality A

ssurance Finance

&

Adm

inistration

Quality C

ontrol M

aintenance Manager

C

olm G

allagher

Maintenance

Materials C

ontrol M

anager

Chris B

oylan

Warehouse

&

Shipping

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C.1.2 Management and Responsibility for the Operation and Control of

Abatement/Treatment Systems

Business Management System (BMS) is in operation at the facility. The BMS is a system composed of a front-end monitoring system, interconnecting communication devices, local loop digital controllers and end input and output devices.

The SOP for the Operation of the BMS in Building 2 is provided. (Ref: CLO-SOP-MNT-00023).

A description of the air and sewer abatement in place at Building 1 and Building 2 is described in Attachment F - Control & Monitoring.

C.1.3 Calibration & Maintenance Systems

The maintenance department is responsible for the calibration and inspection of automatic, mechanical and electronic equipment. The calibration and maintenance procedure is as follows: § Calibration of equipment that is performed according to a specified schedule;

§ Calibration of equipment that is performed everyday when the equipment is in use.

There is an SOP in place for Preventative Maintenance (Ref: CLO-SOP-MNT-00019). Intervals for preventative maintenance of selected major equipment are detailed below. No. Description Frequency 1. Manesty Accela-cota Every 6 months 2. Fluid Bed Dryer Every 6 months 3. Manesty BB4 Tablet Press Every 6 months 4. Niro-Fielder Granulator Every 6 months 5. Frewitt Mill Every 6 months 6. Apex Y-Cone Blender Every 6 months 7. Pharmatech Y-Cone Blender Every 6 months 8. Lightning Blender Every 6 months 9. Matcon IBC Blender Every 6 months 10. Manesty Rotapress Every 6 months 11. Manesty Xpress Every 6 months 12. Matcon Blender Every 6 months 13. Pharmatech Blender Every 6 months 14. Hotpack Oven Every 6 months In addition, the SOP relating to the Equipment Calibration procedure (Ref: CLO-SOP-MNT-00001) is provided. C.1.4 Waste Control Systems

Each department is responsible for the segregation of waste. Each department has been provided with labelled bins to enable them to segregate their waste at source. All general waste and recyclables are removed from site by an EPA licenced waste management company, to be broken down into different waste streams for recycling and landfill. The waste company provides certificates for all waste. All hazardous waste (including waste from the laboratory) is packaged in UN approved packaging and removed from site by EPA licenced hazardous waste management company for treatment and/or recovery. The main types of hazardous waste generated at Building No. 1 and Building No. 2 is in relation to waste tablets and powders, laboratory materials, glass

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containing residues and solvent drums. The approved waste contractor provides certificates for all wastes. C.1.5 Spill Response Procedure

There is an SOP in place for the Cleaning of Chemical Spillages in Production (CLO-SOP-MAN-00113). This is included in Attachment J - Accident Prevention & Emergency Response. Material Safety Data Sheets (MSDS) for all raw materials are maintained on-site.

C.1.6 Quality Control Procedure – General Outline

Forest Laboratories has a Quality Policy in place. The following information has been taken from the Forest Laboratories Quality Policy. This is available upon request.

This Quality Policy incorporates the use of current GMP. Good Manufacturing Practice is that part of Quality Assurance which ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by the product specification or the relevant regulatory bodies e.g. FDA or IMB. The Quality Function consists of the Quality Assurance (QA) and Quality Control (QC) Departments. Both QA and QC are independent and responsible only to Management. The QC department is responsible for analytical testing and other laboratory activities whereas Quality Assurance oversees the formal establishment of specifications and procedures, review and monitoring of processes, inspection and sampling, compliance with standard operating procedures and GMP regulations, training of personnel in GMP and employee responsibilities. Structure & Responsibilities: Head of European QA - has overall responsibility for the quality function.

QA Manager - with responsibility for day-to-day running of the QA department. Review of batch documentation, investigation and deviation reports. Co-ordination of Change Control management and Product Complaint.

QA Technicians (Product Support) - with responsibility for QA Inspection Sampling and Analysis, Production support and checking of Test Reports. Calibration, Validation, Vendor and Database Systems.

QA Technicians (BMR Review) - Review and compile all batch files i.e. BMR, QC Results and related documentation. Quality Assurance is responsible for all matters, which individually or collectively influence the quality of a product. It is the sum total of the organised arrangements made with the object of ensuring that medicinal products are of the quality required for their intended use.

QA Responsibilities:

The QA responsibilities include the following:

1. Documentation § Maintenance of documentation control system Standard Operating

§ Procedures (SOP’s), Batch Manufacturing Records (BMR’s),

§ Protocols, Test procedures and specifications.

§ Issuance of batch manufacturing records

§ Retain of Batch Manufacturing Records and Laboratory reports

§ Deviations and investigations

§ Change Control Management

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§ Customer complaints

§ Review and submission of license applications

§ Organisation of Protocol and Validation Systems

§ Coordination of Calibration schedule

§ Stability Monitoring of products

§ Vendor Qualification

2. QA Sampling/Production Support/Checking of Test Reports.

§ Inspection, Sampling and status labelling of Raw Materials, in-process material, film

coat dispersions, Finished Product and monitoring of Purified Water system.

§ Review of Raw Material test reports from Quality Control Laboratory.

§ Review of In-process cores and coated tablets

§ Review of Rinses and Swabs

§ Conducting area clearances between production batches.

§ Carrying out AQL’s on cores and coated tablet product as required.

§ Shipping of Finished Products

§ Environmental Monitoring

3. Inspections

§ Routine self-inspections

§ Vendor audits

§ Management of external audits and inspections

QA Audits:

Quality Assurance regularly appraises the effectiveness and applicability of the Quality Assurance system, by conducting an Internal or Self-Inspection audit at suitable intervals. The programme covers the GMP units of operation on a rotational basis and identifies teams for the inspections, which consists of personnel from different departments to carry out the self-inspections. Personnel involved in the inspection verify that previous recommendations have been addressed and the team leader issues a report on all observations to all relevant personnel. The manager then makes a detailed response in a timely manner responsible for the area to the team leader and to other relevant personnel. Quality Control for Manufactured Product: The procedure of manufactured products requires QC reports and completed batch records, process deviation forms, investigations and other relevant documentation to be submitted to Quality Assurance for review. Prior to the disposition, i.e. approval / rejection of a batch, Quality Assurance will carry out the following actions:

a) Ensuring that the BMR is properly completed and that each significant step is fully documented (i.e. dates, equipment/lines used, specific identity and weights/measures of materials used, packaging materials used, labels (copies) used, identification of persons performing and supervising step) and all relevant documentation, including sampling, inspection, quarantine and investigation of any deviation (if applicable), are correctly in

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place in the batch file. The batch file should be identifiable with the Master batch manufacturing number of the product on the cover.

b) Processing / packaging deviations are investigated explained and approved.

c) All yield calculations (both theoretical and actual) are correct and acceptable.

d) Inspection sheets are complete and approved.

e) All in process, inspection and test results are acceptable.

f) All raw materials have been approved.

g) Laboratory results for conformity with specifications.

h) All discrepancies in results are investigated explained and approved.

i) After the QC results have been verified and approved the Certificate of Analysis is generated and signed by the QP.

j) Investigational Medicinal Products (IMP) are manufactured, reviewed and approved using the same systems as commercial product.

Material/Supplier Controls: Forest Laboratories has documented procedures to ensure that purchased materials conform with specified purchase requirements. The qualification procedure for supplier evaluations is based initially on carrying out a “Vendor Pre-Qualification Assessment” where regulatory/compliance standards, ability to supply materials of the required grade and quality, ability to supply relevant documentation with the materials and ability to supply cost efficient materials as required by Forest. Quality Assurance assesses suppliers of critical starting materials and packing materials - actives, excipients and containers. The following aspects are considered: 1. Equipment and Facilities

2. Methods of manufacturing, packaging, processing etc.

3. Test methods

4. Control Processes

5. Shipping of materials

6. Personnel

7. Quality Assurance System

8. Validation Program

Upon completion of a Vendor audit, Q.A. will determine whether the vendor should be approved or not approved. In the event of an active material audit consideration must be given to ICH Q9 Quality Risk Management (Annex II). The audit results are maintained on file by Q.A. Vendors are, classified into 5 status groups as follows: a) Other

b) Approved

c) Validated

d) Preferred

e) Certified

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A certified supplier has gone through all classes of the vendor programme and has built up a strong relationship with company. A Certified supplier has proven their ability to provide a quality product and as a result the least amount of testing is required on materials supplied. A reduced testing programme determines the level of testing required for each category of material supplier. Preferred supplier status means that Reduced Level II testing is applied. Validated suppliers receive Level I testing. Reduced sampling applies to suppliers with Approved status. Full testing applies to Suppliers with ‘Other’ status, on the first GI received and on successful completion tightened sampling is applied. When all of the items in Quality Control for Manufactured Product are found to be satisfactory, the status of the Batch (Approved/Rejected) is recorded in SAP by the QP along with any comments. Only QPs have user rights for the Level 2 reviews. C.2. Environmental Management System

There is no formal Environmental Management System (EMS) in place at the facility. There are plans to develop a formal EMS, which will improve Forest Laboratories Environmental performance and control site operations. The EMS will be developed once the IPPC licence has been granted. Environmental performance will be assessed as part of the proposed EMS through implementation of the company’s environmental policy and establishing a programme of environmental objectives and targets. C.3. Hours of Operation

Forest Laboratories operates a 2-shift system. The hours of operation of the production department within Forest Laboratories Ireland are as follows: Monday - Thursday 6:30 am to 11pm Friday 6:30 am to 7:30pm Normal office hours are from 9 am to 5:30 pm.

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Forest Laboratories IPPC Licence Application · The Standard Operating Procedures ... Forest...

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