GxP-Compliant Calibration Learning from the Warning Letters - PowerPoint PPT Presentation

GxP-Compliant Calibration Learning from the Warning Letters

Vaisala in Brief  We serve customers in controlled environments in life science, power transmission, and other targeted industrial applications.  Over 80 years of expertise providing a range of innovative instrumentation and measurement products and services. 2 Restricted

Vaisala in Life Sciences Our Offering Measurement instrumentation, continuous monitoring systems and validation systems for regulated or highly controlled life science environments. Our Goal is to Help Customers • Reduce their risk of lost or adulterated product • Reduce their risk of failing to meet GxP regulations and/or guidelines 3 Restricted

Webinar Team Speaker: Guest Speaker: Chat Manager: Paul Daniel Heather Wade Janice Bennett Vaisala Heather Wade Group Vaisala Sr. GxP Regulatory Expert Metrology Consultant Marketing Manager 4 Restricted

GxP-Compliant Calibration Learning from the Warning Letters

Agenda  Brief Review of GxP Calibration Regulations  Basic Regulatory Process  Real FDA Warning Letters issued for Calibration failures 6 11/04/2020 Restricted

What are GxP “Life Science” Industries?  Usually described by the products:  Pharmaceuticals  Medical Devices  Biologics  Tissue (Blood and Organs)  Nutraceuticals  Cosmetics  Veterinary Products 7 11/04/2020 Restricted

What are our GxP “Life Science” Regulations?  USA  21 CFR Part 211: cGMP for Finished Pharmaceuticals  21 CFR Part 820: Quality System Regulation (Devices)  Multiple Countries (USA, Canada, Japan, Europe)  ICH Topic Q7: Guidance on GMP for APIs  International (over 50 countries)  PIC/s: Guide to GMP for Medicinal Products - Part I 8 11/04/2020 Restricted

Regulations: FDA – 21 CFR Part 211  cGMP for Finished Pharmaceuticals  211.68(a): Automatic, mechanical, and electronic equipment – Automatic, mechanical, or electronic equipment or other types of equipment, including computers, or related systems that will perform a function satisfactorily, may be used in the manufacture, processing, packing, and holding of a drug product. If such equipment is so used, it shall be routinely calibrated , inspected, or checked according to a written program designed to assure proper performance. Written records of those calibration checks and inspections shall be maintained.  211.160 (b)(4): Laboratory Controls – General Requirements – The calibration of instruments, apparatus, gauges, and recording devices at suitable intervals in accordance with an established written program containing specific directions, schedules, limits for accuracy and precision, and provisions for remedial action in the event accuracy and/or precision limits are not met. Instruments, apparatus, gauges, and recording devices not meeting established specifications shall not be used.  211.194 (d): Laboratory Records Complete records shall be maintained of the periodic calibration of laboratory instruments, apparatus, gauges, – and recording devices required by § 211.160(b)(4). Restricted

Regulations: FDA – 21 CFR Part 820  Quality System Regulation (Devices)  820.72(a): Control of Inspection, Measuring, and Test Equipment – Control of inspection, measuring, and test equipment. Each manufacturer shall ensure that all inspection, measuring, and test equipment, including mechanical, automated, or electronic inspection and test equipment, is suitable for its intended purposes and is capable of producing valid results. Each manufacturer shall establish and maintain procedures to ensure that equipment is routinely calibrated , inspected, checked, and maintained. The procedures shall include provisions for handling, preservation, and storage of equipment, so that its accuracy and fitness for use are maintained. These activities shall be documented.  820.72(b): Calibration – (b) Calibration procedures shall include specific directions and limits for accuracy and precision. When accuracy and precision limits are not met, there shall be provisions for remedial action to reestablish the limits and to evaluate whether there was any adverse effect on the device’s quality. These activities shall be documented. – (b)(1) Calibration Standards: Calibration standards used for inspection, measuring, and test equipment shall be traceable to national or international standards. If national or international standards are not practical or available, the manufacturer shall use an independent reproducible standard. If no applicable standard exists, the manufacturer shall establish and maintain an in-house standard. – (b)(2) Calibration Records: The equipment identification, calibration dates, the individual performing each calibration , and the next calibration date shall be documented. These records shall be displayed on or near each piece of equipment or shall be readily available to the personnel using such equipment and to the individuals responsible for calibrating the equipment. Restricted

Regulations: ICH Topic Q7  Guidance on GMP for APIs  Definitions: – Calibration – The demonstration that a particular instrument or device produces results within specified limits by comparison with those produced by a reference or traceable standard over an appropriate range of measurements.  Chapter 2: Quality Management Responsibilities – Quality Unit: – Making sure that effective systems are used for maintaining and calibrating critical equipment; – Production Activities: – Making sure that the necessary calibrations are performed and records kept; Restricted

Regulations: ICH Topic Q7  Guidance on GMP for APIs  Chapter 5.3: Calibration – 5.30: Control, weighing, measuring, monitoring and test equipment that is critical for assuring the quality of intermediates or APIs should be calibrated according to written procedures and an established schedule. – 5.31: Equipment calibrations should be performed using standards traceable to certified standards… – 5.32: Records of these calibrations should be maintained. – 5.33: The current calibration status of critical equipment should be known and verifiable. – 5.34: Instruments that do not meet calibration criteria should not be used. – 5.35: Deviations from approved standards of calibration on critical instruments should be investigated to determine if these could have had an impact on the quality of the intermediate(s) or API(s) manufactured using this equipment since the last successful calibration . Restricted

Regulations: ICH Topic Q7  Guidance on GMP for APIs  Chapter 6.6: Laboratory Control Records – 6.61: Complete records should be maintained for… periodic calibration of laboratory instruments, apparatus, gauges, and recording devices;  Chapter 19.3 - Equipment and Facilities – 19.30: During all phases of clinical development, including the use of small-scale facilities or laboratories to manufacture batches of APIs for use in clinical trials, procedures should be in place to ensure that equipment is calibrated , clean and suitable for its intended use.  Chapter 19.6 – Validation – 19.60: Process validation for the production of APIs for use in clinical trials is normally inappropriate, where a single API batch is produced or where process changes during API development make batch replication difficult or inexact. The combination of controls, calibration , and, where appropriate, equipment qualification assures API quality during this development phase. Restricted

Regulations: International  Guide to GMP for Medicinal Products Part I  Chapter 3: Premises - Equipment – 3.41: Measuring, weighing, recording and control equipment should be calibrated and checked at defined intervals by appropriate methods. Adequate records of such tests should be maintained.  Chapter 4 - Manufacturing Formula and Processing Instructions – 4.18(b): The Processing Instructions should include… the methods, or reference to the methods, to be used for preparing the critical equipment (e.g. cleaning, assembling, calibrating , sterilizing). 4.29: There should be written policies, procedures, protocols, reports and the associated records of actions – taken or conclusions reached, where appropriate, for… equipment assembly and calibration ; – 4.31: Logbooks should be kept for major or critical analytical testing, production equipment, and areas where product has been processed. They should be used to record… calibrations , maintenance, cleaning or repair operations, including the dates and identity of people who carried these operations out.  Chapter 6 - Quality Control - Documentation – 6.7: …the following details should be readily available to the Quality Control Department: procedures for and records of the calibration of instruments and maintenance of equipment. Restricted

ISO/IEC 17025:2017 General requirements for the competence of testing and calibration laboratories  Applicable worldwide  Top laboratory management standard  Accreditation = www.ilac.org – Mutual Recognition Arrangement (MRA) – “Accredited Once, Accepted Everywhere” Restricted

ISO/IEC 17025:2017 Equipment Calibration Requirements:  Shall be accessible  Shall have procedure(s) for handling, transport, storage, use, and planned maintenance  Shall verify equipment before placing into use  Shall be accurate for its applications  Shall be calibrated when:  The accuracy or uncertainty affects validity of data  Establishing metrological traceability of the reported results  Shall be recalibrated to maintain confidence Restricted