CONDUCT OF INSPECTIONS OF PHARMACEUTICAL MANUFACTURERS SOP no. GMP-034/03

Transcription

1 1 of 6 SOP no. GMP-034/03 Jerusalem CONDUCT OF INSPECTIONS OF PHARMACEUTICAL MANUFACTURERS SOP no. GMP-034/03 Name Position Date Signature Dr. Mimi Kaplan Director, Institute for Standardization & Control of Michael Carmi GMP Inspector Dr. Rami Kariv Head of GMP Inspectorate Sara Covrigaro Director, Quality Assurance UNAUTHORIZED COPY

2 2 of 6 SOP no. GMP-034/03 Introduction (the Institute) GMP Inspection Unit is responsible for enforcing the rules of good manufacturing practice (GMP) in Israeli Pharmaceutical manufacturing companies of medicinal products and active pharmaceutical ingredients (API). Its key enforcement tool is on site inspections. The aim of the inspections is to evaluate compliance of the quality system and infrastructure with internationally accepted GMP standards (the reference document being the PIC/S GMP manual). These inspections also examine the compliance of the medicinal products manufactured at the site with the terms of their Israeli registration and quality specifications, as well as the strength and purity of the products required to protect the public health of the consumers. Inspections are divided into preliminary inspections required for approval of a new production line or manufacturing plant, the periodic inspections of licensed plants, and ad hoc Inspections to investigate the suspicion of a major infringement of GMP standards (such as in the case of a product recall, a complaint, or report regarding a major unexpected side effect). The spectrum of manufacturers regulated by the Inspection Unit covers manufacturers of medicinal products, manufacturers of biologicals, medical gas plants and API manufacturers. Inspected plants also divide between those who manufacture for export and are consequently inspected by overseas health authorities and those who manufacture only for the local market and are therefore regulated only by Israel's Ministry of Health. The Inspection Unit is also responsible for inspections of plants which manufacture only for export (if there are such) and for overseas plants of Israeli manufacturers manufacturing products registered exclusively in Israel. 1. Scope 1.1 This SOP sets out a uniform procedure for carrying out inspections in the range of plants falling under Inspection Unit oversight. 1.2 The SOP shall be followed by all Institute inspectors and specialists who carry out GMP inspections. 2. Applicable Documents 2.1 Compilation of Community Procedures on Inspections and Exchange of Information, EMEA/INS/GMP/03/REV SOP for Preparing for a GMP Inspection, GMP SOP for Writing a GMP Inspection Report, GMP SOP for Follow-Up of Corrective actions taken by Manufacturing Plants, GMP SOP for Information Confidentiality, GMP- 031.

3 3 of 6 SOP no. GMP-034/ SOP for Sampling during a GMP Inspection, GMP Definitions 3.1 PIC/S, Pharmaceutical Inspection Corporation Scheme the international professional association of GMP inspectors. 4. Responsibilities 4.1 It is the responsibility of the National GMP Inspector to appoint the members of an inspection team and to ensure that they follow this SOP during inspections. 4.2 It is the responsibility of GMP Inspectors and specialists carrying out an inspection to follow this SOP. 5. Methods 5.1 The Head of the GMP Inspectorate shall appoint the members of each inspection team One inspector shall be appointed to head the team (should the team number more than one inspector) Institute specialists will join the team as necessary, for example For biologicals a biological products specialist; A microbiologist from the microbiology laboratory; A laboratory specialist from the Institute analytical laboratory. 5.2 One of the team inspectors will arrange the inspection date with the manufacturer and carry out the preparatory steps set out in GMP-049, the SOP for Preparing for a GMP Inspection. 5.3 Conduct of Inspectors during a Plant Inspection The inspectors represent a government authority. They must dress accordingly and behave with courtesy The inspectors will follow local patterns of conduct and eating. In plants which provide lunch for their staff, inspectors shall eat together with plant staff In all other cases inspectors shall pay for their meals; In inspections of remote plants in Israel, where the inspection lasts several days and inspectors stay in a nearby hotel, the inspected manufacturer shall not pay for the inspectors' hospitality. 5.4 Inspectors shall act according to Institute procedures for the confidential handling of information. All information discovered by or passed to the inspectors is confidential and shall not be disclosed to any outside person or body. Inspectors shall neither carry with

4 4 of 6 SOP no. GMP-034/03 them written or printed materials relating to other plants, nor disclose any information relating to another company The inspectors task is not only to expose deficiencies. They must answer any professional queries put to them, while as far as a possible abstain from offering advice. 5.5 Inspections shall start with an opening session, at which plant staff set out the structure of the company and its key officials and the inspectors set out the inspection program At this opening session The inspectors shall identify themselves and describe their jobs; The inspectors shall state which documents they need to study once they have completed their preliminary tour of the site. 5.6 There will be a preliminary tour of the site to allow the inspectors to get a general orientation of the site. It can take several forms, either following the flow of materials from storage to final product or following the flow of staff around the plant or any other form that suits the inspectors This preliminary tour should be no more than a quick overview: in general no detailed inspection should be done at this stage. 5.7 Over the course of the inspection the inspectors shall review all procedures, production and laboratory records, validations and any other record or documentation relating to production and control of the production process. 5.8 The inspection shall also include detailed tours of all production facilities, laboratories, stores, technical systems and the plant s record and documentation centre The following specific issues shall be investigated, inter alia: The suitability of the facility for its purpose, including the orderliness of its layout and cleanliness; The production equipment its calibration and cleanliness, preventive maintenance, daily maintenance records Whether production records are fully maintained and in real time Critical systems: air-conditioning, water, clean compressed air, sewage and drainage, any other relevant systems. 5.9 Inspectors shall talk to the staffers who actually carry out the work and not make do with general answers from the quality assurance manager or production manager Samples may be taken during the inspection as the inspectors see fit. In taking samples inspectors shall follow SOP GMP-032. Details of the samples shall be entered on form GMP-032A and the samples taken for examination to the Institute laboratories.

5 5 of 6 SOP no. GMP-034/ Issues that the inspectors believe will figure as deficient in the final inspection report should be talked over with plant staff before the inspectors final meeting with them, in order to give plant representatives the chance to clarify matters incorrectly understood On overseas inspections, where plant procedures and records are written in a language the inspectors do not know, it is the responsibility of the manufacturer to provide the inspectors a written or oral translation into English or Hebrew The inspectors shall ask plant representatives to furnish them copies of documents they wish to take away for further examination or as evidence of a deficiency they have found The plant shall mark and sign the photocopied documents according to its usual internal practice The documents shall be collected into a file, which the inspectors shall take with them at the end of the inspection The documents taken away shall be bound together and kept at the Institute at least until the next inspection The inspection shall conclude with a final session between inspectors and plant representatives. Should the inspectors see fit and the manufacturer agree each day s inspection can also be concluded with such a session The final session shall cover (at least) A detailed listing of the findings and deficiencies found by the inspectors during the course of their inspection; Should a major deficiency come to light during the course of the inspection, representing a grave risk to public health, the inspectors shall take immediate steps to eliminate the risk Post-inspection activities The inspectors shall summarize their findings in an Inspection Report, following SOP GMP-037. The Report shall be sent to the manufacturer within 45 working days The inspectors shall maintain regular oversight over improvements introduced by the manufacturer (see SOP for Monitoring Corrective Measures in a Plant after Inspection). 6. Inspection Documentation 6.1 All inspections shall be recorded in notebooks issued to the inspectors by the Institute quality assurance department. 6.2 The notebook pages shall be pre-numbered.

6 6 of 6 SOP no. GMP-034/ Inspectors shall enter on the first page of each notebook their name, the name and address of the plant under inspection and the date of the inspection. 6.4 No page shall be torn out of a notebook. 6.5 Any deletion or correction in a notebook shall be done in a way that leaves the original text readable. 6.6 Do not write in a notebook in pencil. 6.7 Inspectors shall record all their observations in their notebooks, not just the deficiencies found. 6.8 The Inspectors could record their findings on a mobile computer. At the end of the inspection the file will be printed, signed and added to the notebook. 6.9 Inspection notebooks and the final inspection report shall be kept for at least ten years and then sent to the state archives, in accordance with the State Archivist s instructions All documents removed from a plant shall be kept in the GMP Inspection Unit s offices at least until the next inspection and shall be used to prepare for that inspection Documents removed from a plant may be shredded only after the inspectors have been given up-to-date documents at the next inspection At the time of shredding, care must be taken not to shred from the earlier inspection file the records made by the inspectors during their inspection (notebooks and final report).