Chemical Quality Control Lecture 5 PDF

Chemical Quality Control (PHCM521) Lecture 5 1 The correct QC of medicinal products manufacturer relies upon: A. Premises E. Sampling B. Personnel F. Documentation C. Materials G. Equipment D. Reference Subs...

Chemical Quality Control (PHCM521) Lecture 5 1 The correct QC of medicinal products manufacturer relies upon: A. Premises E. Sampling B. Personnel F. Documentation C. Materials G. Equipment D. Reference Substances 2  Equipment  Each item of equipment, instrument or other devices should be uniquely identified.  Regular calibration of all the instruments used is absolutely essential and a specific schedule should be established for each type of instrument.  All equipment requiring calibration should be labelled to indicate the status of calibration and the date when recalibration is due.  Laboratory equipment should undergo design, installation, operation & performance qualifications.  Only authorized personnel should operate equipment.  Records should be kept of each item of equipment. 3  Equipment  Standard operating procedure (SOPs) should be placed beside the complicated instrument.  Instruments either subjected to overloading or mishandling, giving suspect results, shown to be defective or outside specified limits, should be taken out of service and clearly labelled or marked.  Wherever possible they should not be used until they have been repaired and requalified.  When the equipment, instruments and other devices are outside the direct control of the laboratory for a certain period or have undergone major repair, the laboratory should requalify the equipment to ensure its suitability for use. 4  Equipment  In order not to delay the establishment of a laboratory, the analytical work could start with minimum requirements, and the process of procurement could be phased for three years accordingly, the requirements for the equipment are listed in three parts: 1st List of equipment to be obtained before analyst assures their duties. 2nd List of equipment to be ordered in the first year 3rd List of equipment to be in the second year In the third year, full utilization of all equipment should be achieved.  The list of equipment considered to be adequate differ between these stages. 5  Equipment  In the case of a medium-sized laboratory, specific sections are devoted to a microbiology unit and pharmacognosy/phytochemistry unit. 6  A separate instrument room (Central Instrument lab), is preferred; otherwise serious corrosion may spoil the costly instruments.  A separate log book should be maintained for each instrument which should include: 1) When the instrument was last used? 2) Who had used it? 3) The purpose for which it was used.  All the instruments should be provided with a fully stabilized electric current and housed in an air conditioned room. 7  List of equipment for central instrument lab:  Analytical balance.  pH meter.  HPLC  Double beam UV-Visible spectrophotometer.  IR spectrophotometer.  HPTLC scanner with accessories.  Gas Chromatograph (GLC).  Spectroflourimeter.  Atomic Absorption Spectrometer (AAS).  Polarograph.  Potentiometeric titrator. 8  Quality building and good quality achievement can only be expected and obtained when the steps of Development, Optimization and Validation approaches are together and at the same time well considered and regarded.  Validation is “the assurance that processes are controlled in such a way that will perform routinely in the manner in which they are planed to”.  Total Analytical Validation is a process that consists of many steps: Tools Method System validation validation validation 11/1/2022 1:26 PM AIQ Dr. Said A. Hassan System suitability 9  AIQ and analytical method validation generally ensure the quality of analysis before conducting a test; system suitability ensures the quality of analytical results immediately before or during sample analysis.  In the modern analytical methods, there should be validated soft- and hardware as well as a qualified system, where a validated analytical method using qualified systems can be developed. Finally, total validation is achieved by stabilizing system suitability. 10  Validation vs. Qualification  While the overall process is called validation, some of the steps are also referred to by qualification.  Qualification is a subset of the validation process that verifies proper module and system performance prior to the instrument being placed on-line in a regulated environment.  The term validation is used for manufacturing processes, analytical procedures, and software procedures.  The term qualification is used for instruments.  Thus, the phrase “Analytical Instrument Qualification” (AIQ) is used for the process of ensuring that an instrument is suitable for its intended application (Tools Validation). 11  The process of validation begins with validated (standardized, qualified and calibrated) tools.  The instrument qualification and calibration records are among the most frequently requested items in regulatory inspections.  Instruments are qualified according to a stepwise process: design qualification (DQ), installation qualification (IQ), operational qualification (OQ), and performance qualification (PQ).  Another way of looking at the AIQ process is sometimes referred to as a timeline approach, where a true chronological order of events takes place. 12  SOP Pre-purchase Post-purchase Routine Operation Phase Phase Phase 13  DQ phase occurs at the vendor’s site, where the instrument with software are developed, designed, and produced in a validated environment according to good laboratory practices (GLP), current good manufacturing practices (cGMP), and ISO 9000 standards.  Users should ensure that the instrument is fit for their intended use and that the manufacturer has adopted a quality system for development, manufacturing, and testing, and has adequate support for installation service, and training.  Vendor-supplied documentation and consumer audits of the vendor are usually sufficient to satisfy users’ DQ requirements.  Before purchasing, the choice qualification insures the required specifications of the actual current and future needs. 14  Depending on the function and operation of the instrument, the design qualification of a commercially available standard instruments may be omitted as the installation, operational & performance qualifications may be considered to be a sufficient indicator of its suitable design. 15  Users should study the site preparation guide from the vendor. Careful planning is required to ensure that the necessary preparations to house the new instrument in the laboratory have been completed prior to installation.  It is a common mistake to underestimate the effort and time required for site preparation.  The following are the key considerations for site preparation: Physical dimensions. Suitable operational environment. Utilities. Health and safety requirements. Electrical safety. 16  IQ is a process to establish that the instrument was received as specified & installed properly according to the design requirements in an environment suitable for its operation. It can be divided into: a) Preinstallation: Information considering proper installation, operation and maintenance should be reviewed. Site requirement, receipt of all parts & user manual are to be confirmed. b) Physical installation. Documentation describing how/who installed the instrument & serial coding of different instrument's parts should be archived. 17  On reinstallation, requalification of the equipment is required to ensure that it functions properly. IQ Instrument Identification Form 18  OQ ensures that the specific modules of the system are operating according to the defined specifications for accuracy, linearity and precision. Small or minor clear discrepancies can be overcome by following the indicated trouble-shootings.  First, fixed parameters (length, weight, height, voltage inputs, pressures) are verified against vendor-supplied specifications.  Next, secure data handling is verified.  Finally, instrument function tests are undertaken to verify that the instrument (or instrument modules) meets vendor and user specifications. 19  Instrument function tests should measure important instrument parameters according to the instrument’s intended use and environment.  In HPLC, the following types of tests might be included:  Pump: flow rate accuracy & Gradient accuracy  Injector: precision, linearity, and carryover  Detector: linearity of response, noise, drift, and wavelength accuracy.  Column oven and auto sampler temperature 20 OQ report obtained from HPLC 21  PQ is a process to demonstrate that an instrument can fulfill the requirements outlined in the user requirements.  The PQ-testing is conducted under actual running conditions (typical application in the user requirements).  However, OQ and PQ are usually performed together particularly for repeatability (linearity and precision).  In practice, a known method, with known predetermined specifications, is used to verify that all the modules are performing together to achieve their intended purpose. 22  After the qualification testing, a summary report should be written to summarize validation activities with a conclusion as to whether the instrument is suitable to be put into routine use.  The report must be reviewed and approved by quality assurance and/or management before product use.  There may be times when some test results fail to meet acceptance criteria. The nature and cause of the failure must be investigated.  The failure, the investigation, the actions to rectify the failure, and the retest must be documented in the exception log. 23  Users should get involved in the qualification process whenever possible. This provides a very good learning opportunity for users to work with the service engineer and learn more about the system’s design and functions. 24  After the instrument is qualified & placed on-line in the laboratory, it can be used to generate analytical data. A Standard Operating Procedure (SOP) has to be written for the new instrument.  SOP is a set of step-by-step instructions compiled by the organization to help workers carry out routine operations.  SOPs aim to achieve efficiency, quality output and uniformity of performance, while reducing miscommunication and failure to comply with industry regulations. 25  The operation instruction, maintenance, and calibration should be included in the SOP.  Procedures should include instructions for the safe handling, transport and storage of measuring equipment.  The frequency and tasks to be performed during maintenance should be stated in the maintenance section.  Definitions of major and minor repairs which necessitate partial or full system requalification should be included.  The tests required to calibrate the instrument, the acceptance criteria, and the frequency for each test should be included in the calibration section of the SOP. 26  The cGMP requirements dictate that the calibration of instruments should be performed at suitable intervals in accordance with an established written program.  Instruments not meeting established specifications must not be used.  Calibration is a process which compares the values indicated by a measuring instrument to the values assigned to a measurement standard.  The measurement standard must be calibrated and have a calibration certificate which indicates its measurement uncertainty. 27  Records of these calibrations should be maintained.  The current calibration status of critical equipment should be known and verifiable.  Deviations from approved standards of calibration should be investigated. 28 Schedule for calibration/inspection of some major instruments 29  Preventive maintenance is systematic inspection, detection, correction, and prevention of incipient failures, before they become actual or major failures.  Preventive maintenance is a good investment that will save valuable time and money in the long run.  Schedules and procedures should be established for the preventive maintenance of equipment.  Maintenance procedures should be established, e.g. regular servicing should be performed by a team of maintenance specialists, whether internal or external, followed by verification of performance. 30  For sustainability, a laboratory should allow a margin of 10–15% per year of the purchasing expenditure on equipment to cover the cost of maintenance.  It is not necessary to requalify an instrument when parts are replaced for minor repairs or routine maintenance or normal repair. However, when major repairs are undertaken, some subset of requalification (OQ/PQ) becomes necessary. 31  A qualification protocol should be available for review and approval before qualification begins. It provides details about:  The system  The scope and constraints of the qualification  Qualification tests  Test procedures  Acceptance criteria  The protocol should also contain an exception log to record any out- of-specification results, investigation, and problem resolution. 11/1/2022 1:26 PM Dr. Said A. Hassan 32  The instruments used in the laboratories vary significantly in the design and operation complexity.  The validation requirements should reflect the level of complexity of the instrument.  It is obvious that the amount of effort required to validate a simple pH meter will be different from that required for a fully automated dissolution system. 11/1/2022 1:26 PM Dr. Said A. Hassan 33  USP categorized instruments into three groups: A, B, and C. 1) Group A instruments (the lowest level of qualification) with user requirements is determined by visual observation; no independent qualification process is required. 2) Group B instruments with user requirements is determined according to SOP & IQ/OQ, calibration is required, and their failure is usually readily discernible. 3) Group C instruments are defined as highly method-specific, complex instruments. Full qualification is applied to instruments in this group. 11/1/2022 1:26 PM Dr. Said A. Hassan 34  USP categorized instruments into three groups: A, B, and C. 11/1/2022 1:26 PM Dr. Said A. Hassan 35