SITE MASTER FILE For MHRA

Transcription

1 ABC CO., LTD. For MHRA Prepared by Date Approved by Date Verified by Date Document No.: SMF, Version No: 01, Effective Date: 09/05/06

2 Document No.: SMF Version No.: 01 Effective Date: 09/05/06 Page 2 of 25 C.1 GENERAL INFORMATION C.1.1 C.1.2 C.1.3 was established in XXXX and located at (address). The site is a manufacturer and packer of XXX. The facility consists of XXX. Licences Held: The Company is licensed by Thai FDA under GMP Certificate No. XXX with a valid date from XXX to XXX to manufacture of XXX. Other manufacturing activities carried out on the site. C In addition to the manufacture of XXX the factory makes and packs XXX products. C does not produce the followings: Wound dressings Surgical sutures Drug substances Other chemicals Cosmetic and toilet preparations Household cleaning products or disinfectants Agricultural, horticultural and pesticides products C Other activities at the site e.g. Marketing, Warehousing, Research. C.1.4 Name and Address of site Address Bangkok 10110, Thailand Contact persons: Mr XXX Telephone : XXX Facsimile : XXX Telephone : XXX (after hours) C.1.5 Type of actual products manufactured. C See Annex A for a list of manufactured and repacked products. C The company does not make, pack, repack or store the active ingredients for any toxic or hazardous substances including all classes of antibiotics, hormones and cytotoxics. C The company does not manufacture, pack or repack any veterinary products. C The proposed product is XXX tablets. The product license holder is XXX. (Provide UK Product Licence number of all medicinal products which are manufactured on the site for export to the UK)

3 Document No.: SMF Version No.: 01 Effective Date: 09/05/06 Page 3 of 25 C.1.6 C.1.7 C.1.8 A short description of the site. C See Annex B for a map at a scale of 1:300,000. (Provide a map at a scale not smaller than 1:300,000 for an area of at least 15 km radius from the site. Mark the site upon it.) C The site is located in a light industrial area. There are XXX buildings at the site. The first building is XXX. The second building is XXX. C The south is XXX. The north is XXX. The east is XXX. The west is XXX. C See drawing of the site at a scale 1:100 in Annex C. (Provide drawing(s) of the site at a scale not smaller than 1:100. Indicate upon it the area(s) concerned with medicinal products.) C See photographs which illustrate different views of the exterior of the factory, and its surroundings in Annex D. (Provide not less than four photographs which illustrate different views of the exterior of the factory, and its surroundings.) C The main building is approximately XX years. Number of employees. C Production = XXX C Quality Control = XXX C Quality Assurance = XXX C Storage and Distribution = XXX C Technical & Engineering Support Services = XXX C Total of the above = XXX Use of outside scientific, analytical or other technical assistance in relation to manufacture and analysis C If manufacture, part-manufacture or product analysis is carried out on products for export to the United Kingdom at several sites, one set of information should be supplied for EACH site. C Name and address of the company. C Telephone No. C Fax No. C Brief outline of the activity being undertaken. C.1.9 Quality Management System C Quality Policy XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX C Quality Assurance function is responsible for XXX. C Describe the elements of the QA system e.g. 1) organisational structure, responsibilities, procedures, processes; 2) specifications, test methods, and other quality related data collection.

4 Document No.: SMF Version No.: 01 Effective Date: 09/05/06 Page 4 of 25 C C C C C Self inspection program is XXX. The Thai FDA audits the facility XXX. The results are reviewed by XXX to demonstrate the adequacy of the quality system. The processes are as follows: 1) Review of XXX 2) Review of XXX 3) Review of XXX The standard ISO is used to assess and audit the quality assurance system within the company, and by the company to assess its suppliers. Suppliers of critical starting materials and packing materials are assessed by XXX.

5 Document No.: SMF Version No.: 01 Effective Date: 09/05/06 Page 5 of 25 C.2 PERSONNEL C.2.1 Organogram of is attached as Annex F. C.2.2 The qualifications, experience and responsibilities of key personnel are as follows: 1) Position Mr XXX Education: XXX 1999 Present position position Responsible for XXX. 2) Position Mr XXX Education: XXX 2004 Present position position Responsible for XXX. C.2.3 Training C Training needs are identified XXX by XXX. C GMP training is conducted by XXX. The scopes are XXX. C Training is conducted both in-house and external for XXX. Efficacy of the training is assessed by XXX. C Retraining needs are identified by XXX. C XXX department is responsible to keep training records for each staff member in a training file. C.2.4 Health requirements for personnel engaged in production C XXX is responsible for checking health of employees. C There is a pre-employment medical examination for every employee. C There is an annual medical examination for employees depending on nature of their work. C Factory staff are required to report their sickness or contact with sick people before working in a critical area. C Factory staff in C shall report back after illness to their supervisor. C Those who work in sterile areas subject to additional monitoring. C.2.5 Personnel hygiene requirements including clothing C Washing, changing and rest areas are provided. C Staff are required to wear clean working garments in manufacturing and packing areas. Dressing in the areas is XXX, XXX, XXX and XXX. C A clear instruction of dressing is described in SOP XXX.

6 Document No.: SMF Version No.: 01 Effective Date: 09/05/06 Page 6 of 25 C.3 PREMISES AND EQUIPMENT C.3.1 A site plan showing the manufacturing area and packing area is attached as Annex G. C.3.2 The building is XXX brick with XXX roof. Internal walls are smooth and washable. Floors in manufacturing and packaging areas are epoxy-coated surface. Ceilings are XXX. Washing bay area is located XXX is used for washing of XXX. C.3.3 Ventilation System C Air supplies are filtered to comply with Class 100,000. Temperature and humidity is degree C, 50 60% RH. Pressure differentials and air change rate is XXX. Recirculation is XX%. C Filter design and efficacy Bag 99% eff. Hepa % C Filters are replaced every X years or when the total final statistic pressure reaches the setting limit. C DOP is introduced at XXX, XXX and XXX. C The HVAC systems are revalidated every X years. C.3.4 Area of the handling of highly toxic hazardous and sansitizing materials is shown in Annex H. C.3.5 Purified Water system C A schematic drawing of the purified water system is attached as Annex I. C Process water is provided to production areas by a XXX with capacity of XX m 3 per hour. C Construction materials of the vessels and pipework are XXX. C Filters in the system are XXX. C The temperature of purified water is XX o C. C The specification of the water produced a) chemical b) conductivity c) microbiological C Sampling points and frequency of sampling. C.3.6 Maintenance and servicing of the Air handling and Water system C The planned preventive maintenance programme of Air handing system is XXX. The planned preventive maintenance programme of Water system is XXX. C The maintenance procedures and reporting forms are described in SOP XXX. The documents record type, frequency of services/checks, details of service, repairs and modifications. C The maintenance routines that could affect product quality are clearly identified. C The reports are made known to the users.

7 Document No.: SMF Version No.: 01 Effective Date: 09/05/06 Page 7 of 25 C.3.7 Major production and laboratory equipment C Equipment and machinery are constructed of AISI grade 316 stainless steel for product contact equipment. C Other materials that have product contact are manufactured of XXX and XXX. They are suitably validated. C Equipment is designed with ease of cleaning. C Major production equipment is XXX, XXX, XXX and XXX. (If the equipment has additional devices, these should be recorded e.g. automatic weighing machines with printer; a labeller incorporating a bar code reader for the label; a lot number and expiry date over printer; a freeze drier equipped with a steam sterilisation facility.) C Major laboratory equipment is XXX, XXX and XXX. C Equipment in the microbiology laboratory is XXX, XXX and XXX. C Computers and microprocessors used in the factory are XXX and XXX. C.3.8 Maintenance and servicing of equipment C Engineering department is responsible for maintenance program. Some equipment has outside contract servicing. C Procedures and contractual details for outside work are detailed in SOP XXX. C The maintenance routines which could affect product quality are clearly identified. C The records are kept of type and frequency of service, details of service repairs and modifications. C The reports are made known to the users. C.3.9 Qualification, validation and calibration C The Company's general policy, and protocols for qualification, prospective and retrospective validation are XXX. C Revalidation policy is XXX. C Process validation begins with protocol preparation then XXX. C The system for the release for sale or supply of development and validation batches is XXX. C The arrangements for computer validation, including software validation are XXX. C Equipment calibration policy is XXX. Records are kept at XXX. C.3.10 Sanitation C Manufacturing and packing areas and equipment are cleaned according to approved cleaning procedures. The concentration, method and frequency are included. C The cleaning agents are changed from time to time. C The cleaning procedure is validated by direct surface sampling (swab method) and indirect sampling (use of rinse solutions). Visual examination, chemical residue and microbial contamination are the methods of evaluating the effectiveness of cleaning.

8 Document No.: SMF Version No.: 01 Effective Date: 09/05/06 Page 8 of 25 C The cleaning methods are monitored routinely by chemical and microbiological methods. C Water system is cleaned by sanitization with hot water 80 o C for X hours at monthly interval. The filters of the air handling system are cleaned every XXX by XXX. Dust extraction system is cleaned by XXX.

9 Document No.: SMF Version No.: 01 Effective Date: 09/05/06 Page 9 of 25 C.4 DOCUMENTATION C.4.1 Arrangements for the preparation and revision and distribution of documentation. C Documentation system is consisted of 4 levels of documents. Level 1 Policy Level 2 Manual Level 3 SOP Level 4 Form/Records C Document control centre in QA department is responsible for preparation, revision and distribution of controlled documents. C Master documents are stored at Document control centre. C A standard format and instruction of how documents are to be prepared is described in SOP XXX. There are documents for; 1) Product/process specifications 2) Raw materials specifications 3) Packaging materials specifications 4) Standard process instructions including packaging 5) Batch records including packaging 6) Analytical methods 7) QA release procedures C Documentation is controlled by Document control centre. C All controlled documents are retained for a minimum of 5 years. C Documents are not stored electrically or microfilmed. C.4.2 Other documentation related to Product Quality The following documents are available and in use. C Equipment specifications C Specification for disposables i.e. cleaning materials C Standard operating procedures C Quality control procedures C Training procedures C Computer program specifications C Documentation control of process deviations C Calibration and test documents C Validation documents C Reconciliation of batches of raw materials, major packing components i.e. product-contact and printed materials C C.4.3 Additional documentation C In addition to the above, other documents in use are: Product complaints and Product recalls record GMP corrective action request Change control form

10 Document No.: SMF Version No.: 01 Effective Date: 09/05/06 Page 10 of 25 C.5 PRODUCTION C.5.1 All production operations follow batch record instructions and written standard operating procedures. See Annex A for a list of manufactured and repacked products. Manufacturing and Packing processes are operated as following flow charts. C.5.2 Control of starting materials, packing materials, bulk and finished products, including sampling, quarantine, release and storage. Identification of suppliers lot number with the company's lot number. Sampling plans. Status labelling eg. by using labels or by computer. Issue of materials to manufacture and package. The control of weighing. Checking methods. C Control of bulk manufacture Checks on key parameters during manufacture eg. blend times, filter integrity tests. Records of key parameters. In process checks. Records of in-process checks. Compliance with the Marketing Authorisation. C Packing Release of bulk, semi-finished products, packing materials; Confirmation of identity and line clearance checks; In process checks. C All packaged products, pending release by QA, are held in quarantine area. Upon review Batch manufacturing records and Batch packing records, they are released for sale by XXX. C XXX is responsible for release of packing materials. XXX is responsible for release of starting materials. XXX is responsible for release of bulk products. XXX is responsible for release of finished products for sale. C.5.3 Arrangements for handling reject materials and products C Reject materials and products are identified with red Failed labels and they are separated and securely kept in the controlled area.

11 Document No.: SMF Version No.: 01 Effective Date: 09/05/06 Page 11 of 25 C Rejected materials are destroyed by incineration at XXX. Rejected products are land filled by XXX Co., Ltd. in accordance to The Environment Protection Authority. List of destroyed products and materials is retained. C.5.4 See para for outline of process validation protocol.

12 Document No.: SMF Version No.: 01 Effective Date: 09/05/06 Page 12 of 25 C.6 QUALITY CONTROL C.6.1 Activities of the Quality control C The quality control laboratory has a responsibility of microbiological and chemical testing of raw materials, in-process materials, finished products, stability samples, packing components and labelling to assure that they conform to appropriate written specifications. Starting materials are tested according to product specifications including EP/BP/USP/JP (where required). C Batch documentation is reviewed by XXX and released for sale or rejected by XXX. Batch manufacturing record and batch packing record are reviewed for completeness as following points: 1) XXX 2) XXX 3) XXX 4) XXX C Authorised person in QA section is responsible for preparation or revision of the specification test methods then approved by XXX.

13 Document No.: SMF Version No.: 01 Effective Date: 09/05/06 Page 13 of 25 C.7 CONTRACT MANUFACTURE AND/OR ANALYSIS Manufacturing, packing and testing of XXX are conducted at Only XXX testing is conducted by outside contractor, XXX. XXX is the Technical contract between and XXX. GMP compliance is assessed to ensure product compliance with Marketing Authorisation.

14 Document No.: SMF Version No.: 01 Effective Date: 09/05/06 Page 14 of 25 C.8 DISTRIBUTION, COMPLAINTS AND PRODUCT RECALL C.8.1 Storage and Distribution C The company warehouse is secure. C The temperature is monitored in warehouse. C There is no product requiring refrigerated storage. C Materials are stored on pallet racking. C The status of products is controlled by both computer and status label, which indicates on each pallet. C Reject material is securely isolated in the control area. C The contract warehouse utilises road and train transport to distribute goods to customers. The company warehouse utilizes sea-freight agencies to distribute goods for export. C The picking system is configured to pick goods by lot numbers on the first-in first-out (FIFO) basis. C.8.2 Record and Distribution For the above product despatch records will be maintained. C.8.3 Complaints C XXX is responsible for logging and classifying the complaints. XXX is responsible for investigating the complaints according to a written procedure. C Written reports are prepared for each complaint. C The results of the investigations conducted are reviewed by XXX and XXX. C Records are kept for a minimum of 5 years. C.8.4 Product recalls C XXX is responsible for product recalls. C There are written procedures for Product recalls which include distribution, notification to customers, receiving of recalled products, investigation and reporting of corrective actions. C The Thai FDA and/or other affected agencies are contacted by XXX. C The Competent Authority is not involved in complaints but involved in the decision to recall. C If needed recalls can be effected below wholesale level. C There is no recall of product produced by ABC over the last two years.

15 Document No.: SMF Version No.: 01 Effective Date: 09/05/06 Page 15 of 25 C.9 SELF INSPECTION C.9.1 The Self inspection process begins with the establishment of GMP Committee which will set an audit schedule. The frequency will be based upon its importance and its previous audit history. A report is issued for review and a plan for corrective action is developed. C.9.2 Self inspection will assess whether business activities comply with the documented procedures and will determine the effectiveness of the system. C.9.3 Procedure for the self inspection system and for the follow-up actions are documented by XXX in XXX. C.9.4 The results of the self inspection are documented and brought to the attention of the personnel having responsibility for the area audited. C.9.5 There is a follow-up system controlled by XXX to ensure that those responsible for the area or activity take timely corrective action on the deficiencies found.

16 Document No.: SMF Version No.: 01 Effective Date: 09/05/06 Page 16 of 25 MANUFACTURED AND REPACKED PRODUCTS Annex A Product Name Active Ingredients Dosage Form

17 Document No.: SMF Version No.: 01 Effective Date: 09/05/06 Page 17 of 25 MAP AT A SCALE OF 1:300,000 Annex B

18 Document No.: SMF Version No.: 01 Effective Date: 09/05/06 Page 18 of 25 DRAWING OF THE SITE AT A SCALE OF 1:100 Annex C

19 Document No.: SMF Version No.: 01 Effective Date: 09/05/06 Page 19 of 25 PHOTOGRAPHS OF THE FACTORY AND ITS SURROUNDINGS Annex D/1 Front office Factory Laboratory

20 Document No.: SMF Version No.: 01 Effective Date: 09/05/06 Page 20 of 25 Annex D/2 Warehouse The back of warehouse

21 Document No.: SMF Version No.: 01 Effective Date: 09/05/06 Page 21 of 25 ORGANIZATION CHART OF QUALITY ASSURANCE DEPARTMENT Annex E

22 Document No.: SMF Version No.: 01 Effective Date: 09/05/06 Page 22 of 25 ORGANOGRAM OF ABC CO., LTD. Annex F

23 Document No.: SMF Version No.: 01 Effective Date: 09/05/06 Page 23 of 25 MANUFACTURING AND PACKING AREAS AT A SCALE OF 1:100 Annex G

24 Document No.: SMF Version No.: 01 Effective Date: 09/05/06 Page 24 of 25 AREA OF HANDLING OF HIGHLY TOXIC HAZARDOUS AND SANITIZING MATERIALS AT A SCALE OF 1:100 Annex H

25 Document No.: SMF Version No.: 01 Effective Date: 09/05/06 Page 25 of 25 WATER SYSTEM Annex I