Laboratory Control System Operations in a GMP Environment. David M. Bliesner

the Centers for Drug Evaluation and Research (CDER) will sometimes post Form 483s from inspections in the website section “Frequently requested or proactively posted compliance records” https://www.fda.gov/drugs/guidance-compliance-regulatory-information/cder-foia-electronic-reading-room 2.4.4.3 New FDA initiatives? FDA has recently become very active and is spearheading numerous activities which need to be tracked and understood. 2.4.4.4 New or updated Guidance Documents? https://www.fda.gov/regulatory-information/search-fda-guidance-documents 2.4.4.5 Keeping current with the USP/NF, BP, JP, EP, etc.? Organizations are encouraged to purchase online subscriptions to the USP/NF and other pharmacopeia as appropriate. 2.4.4.6 Keeping current with industry groups such as American Chemical Society (ACS), American Association of Pharmaceutical Scientists (AAPS), Parenteral Drug Association (PDA), etc.? 2.4.5 Does the administrator, office manager, or similar support person perform or supervise keeping current with industry trends by monitoring or subscribing to: 2.4.5.1 The “Fierce” family of industry blogs (www.fiercepharma.com)? The “Fierce Family” of blogs includes FiercePharma, FiercePharma Manufacturing, FiercePharmaMarketing, and others. 2.4.5.2 PIC/S? (Pharmaceutical Inspection Convention Pharmaceutical Inspection Co-Operation Scheme) 2.4.5.3 WHO? (World Health Organization) 2.4.5.4 ICH? (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) https://www.ich.org/home.html 2.4.6 Does the administrator, office manager, or similar support person supervise administrative service personnel such as maintenance and calibration, laboratory computers, documentation section, training section, etc.? 2.5 Laboratory Chemicals, Solutions, Reagents, and Supplies 2.5.1 Is there a written procedure for receipt and storage of chemicals and reagents? 2.5.2 Are chemicals and reagents properly labeled with date of receipt, date opened, and expiration and re-test dates? 2.5.3 Are laboratory prepared reagents and solutions properly identified (e.g. chemical name or symbol, concentration, date of preparation, initials of the analyst who prepared it, and expiration date)? Unlabeled solutions are an FDA form 483 favorite citation. 2.5.4 Are records available which document preparation and standardization of volumetric solutions? 2.5.5 Is the frequency of standardization of various reagents described? Is it consistent with the current USP? 2.5.6 Are standardized reagents properly stored to assure integrity? 2.5.7 Does a procedure exist, which describes the generation/purchase, storage, and handling of reagent grade water for laboratory use? Laboratory water, when opened (exposed to air) will start to grow microbes almost immediately. Therefore, experience has shown that lab water should not be held for greater that 24 hours. If the water is used to prepare chromatographic samples, extraneous peaks resulting from the microbial contamination are possible. This means that water stored in squirt bottles needs to be changed daily. 2.5.8 Are there procedures that describe the preparation of laboratory reagents and cultures? 2.5.9 Are there procedures that describe the maintenance of laboratory reagents and cultures? 2.6 Laboratory Reference Standards and Solutions 2.6.1 Is there a written procedure for ordering and receipt of compendial reference standards and non-compendial reference standards? 2.6.2 Are the primary standards of the current lot listed in the USP, EP, or JP? 2.6.3 Is the receipt of the standards logged? 2.6.4 Are all standards labeled with name, source, lot number, and expiration date? 2.6.5 Do written procedures include provisions for prevention of contamination of primary standards? 2.6.6 Are standards stored in a secured area under environmentally controlled and monitored conditions? 2.6.7 Are procedures for assuring standard integrity available? 2.6.8 Are working or “house” standards checked against primary standards at appropriate intervals? 2.6.9 Are stock solutions appropriately identified, and is their expiration based on their true stability? 2.6.10 Do procedures exist for the certification and use of non-commercially available reference standards? 2.6.11 Do certificates of analysis exist for all reference standards and are these certificates stored as controlled documents?