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10 BioPharm International eBook December 2019 www.biopharminternational.com 483 forms issued has increased du r ing t his t ime per iod, while the number of observations has declined. The number of VAI and OAI observations issued has also fallen since 2017. O ve r t h i s p e r io d, t he r e h a s b e e n a d e c r e a s e i n d o m e s t i c inspections, and a positive cor- relation was found between the number of domestic inspections conduc te d a nd t he nu mb e r of VAI/OAI observations issued. The highest number of observations were related to Subpar t I –labo - rator y cont rols a nd Subpa r t J – r e c o r d s a n d r e p o r t s , S u b p a r t F – produc t ion a nd process con- trols, Subpart B –organization and personnel, and Subpart D–equip- ment. Increased inspection of labo - rator y controls (Subpart I) may a l s o r e s u lt i n i nc r e a s e d go o d document practices, records and reports observations (Subpart J) based on the positive correlation obser ved. It is also notewor thy t hat t he re wa s a n i nc re a s e i n packag ing and labeling control (Subpart G) observations in 2018. Note: This article was prepared b y the authors in their pe rsonal capacities. The opinions expressed are the authors' ow n and do not ref lect the view of their employer, gove r nme nt, or any age nc y w ith which they are affiliated. REFERENCES 1. M. Hamburg, Justification of Estimates for Appropriations Committees Fiscal Year 2016, US Department of Health and Human Sciences, FDA (2015). 2. FDA, Integration of FDA Facility Evaluation and Inspection Program for Human Drugs: A Concept of Operations (June 6, 2017). 3. FDA, Transparency Initiative: Draft Proposals for Public Comment to Increase Transparency by Promoting Greater Access to the Agency's Compliance and Enforcement, FDA Data Transparency Task Force, US Department of Health and Human Services (2011). 4. Code of Federal Regulations, Title 21: Part 210, 211: Food and Drugs, Current Good Manufacturing Practices. 5. J. Freeman, T. Young, Correlation coefficient: Association Between Two Continuous Variables, Scope Tutorial, (2009). 6. D. Hodgson, F. Maini, et al., Under the Spotlight: Data Integrity in Life Sciences, (Deloitte, London, UK 2017). BP Regulatory Sourcebook FDA Inspections Figure 6. Summary statistics. Mean 380.4 Mean 191.8 Mean 324.2 Mean 123 Standard Error 14.99867 Standard Error 20.82162 Standard Error 14.57875 Standard Error 5.949789912 Median 379 Median 161 Median 313 Median 127 Standard Deviation 33.53804 Standard Deviation 46.55857 Standard Deviation 32.59908 Standard Deviation 13.3041347 Sample Variance 1124.8 Sample Variance 2167.7 Sample Variance 1062.7 Sample Variance 177 Kurtosis -1.14213 Kurtosis -3.06251 Kurtosis -0.35406 Kurtosis 3.699224361 Skewness 0.119981 Skewness 0.643347 Skewness 0.454282 Skewness -1.883361658 Range 85 Range 94 Range 85 Range 32 Minimum 339 Minimum 155 Minimum 285 Minimum 100 Maximum 424 Maximum 249 Maximum 370 Maximum 132 Sum 1902 Sum 959 Sum 1621 Sum 615 Mean 417.6 Mean 38.6 Mean 41.8 Mean 520.6 Mean 506 Standard Error 21.18868 Standard Error 3.854867 Standard Error 1.067708 Standard Error 19.95645259 Standard Error 16.28803 Median 415 Median 39 Median 42 Median 526 Median 495 Standard Deviation 47.37932 Standard Deviation 8.619745 Standard Deviation 2.387467 Standard Deviation 44.62398458 Standard Deviation 36.42115 Sample Variance 2244.8 Sample Variance 74.3 Sample Variance 5.7 Sample Variance 1991.3 Sample Variance 1326.5 Kurtosis 1.767949 Kurtosis -0.62246 Kurtosis -1.11727 Kurtosis 0.059894877 Kurtosis -1.54527 Skewness 1.098318 Skewness 0.566635 Skewness 0.205753 Skewness -0.425902662 Skewness 0.375057 Range 126 Range 21 Range 6 Range 118 Range 90 Minimum 367 Minimum 30 Minimum 39 Minimum 457 Minimum 464 Maximum 493 Maximum 51 Maximum 45 Maximum 575 Maximum 554 Sum 2088 Sum 193 Sum 209 Sum 2603 Sum 2530 21 CFR 221.100-115 21 CFR 221.63-72 21 CFR 221.80-94 21 CFR 211. 180-198 21 CFR 211.160-176 21 CFR 221.142-150 21 CFR 221.122-137 Subpart F--Production and Process Controls Subpart G--Packaging and Labeling Control Subpart H--Holding and Distribution Subpart I--Laboratory Controls Subpart J--Records and Reports 21 CFR 221.22-34 21 CFR 221.42-58 Subpart B--Organization and Personnel Subpart C--Buildings and Facilities Subpart D--Equipment Subpart E--Control of Components and Drug Product Containers and Closures Mean 380.4 Mean 191.8 Mean 324.2 Mean 123 Standard Error 14.99867 Standard Error 20.82162 Standard Error 14.57875 Standard Error 5.949789912 Median 379 Median 161 Median 313 Median 127 Standard Deviation 33.53804 Standard Deviation 46.55857 Standard Deviation 32.59908 Standard Deviation 13.3041347 Sample Variance 1124.8 Sample Variance 2167.7 Sample Variance 1062.7 Sample Variance 177 Kurtosis -1.14213 Kurtosis -3.06251 Kurtosis -0.35406 Kurtosis 3.699224361 Skewness 0.119981 Skewness 0.643347 Skewness 0.454282 Skewness -1.883361658 Range 85 Range 94 Range 85 Range 32 Minimum 339 Minimum 155 Minimum 285 Minimum 100 Maximum 424 Maximum 249 Maximum 370 Maximum 132 Sum 1902 Sum 959 Sum 1621 Sum 615 Mean 417.6 Mean 38.6 Mean 41.8 Mean 520.6 Mean 506 Standard Error 21.18868 Standard Error 3.854867 Standard Error 1.067708 Standard Error 19.95645259 Standard Error 16.28803 Median 415 Median 39 Median 42 Median 526 Median 495 Standard Deviation 47.37932 Standard Deviation 8.619745 Standard Deviation 2.387467 Standard Deviation 44.62398458 Standard Deviation 36.42115 Sample Variance 2244.8 Sample Variance 74.3 Sample Variance 5.7 Sample Variance 1991.3 Sample Variance 1326.5 Kurtosis 1.767949 Kurtosis -0.62246 Kurtosis -1.11727 Kurtosis 0.059894877 Kurtosis -1.54527 Skewness 1.098318 Skewness 0.566635 Skewness 0.205753 Skewness -0.425902662 Skewness 0.375057 Range 126 Range 21 Range 6 Range 118 Range 90 Minimum 367 Minimum 30 Minimum 39 Minimum 457 Minimum 464 Maximum 493 Maximum 51 Maximum 45 Maximum 575 Maximum 554 Sum 2088 Sum 193 Sum 209 Sum 2603 Sum 2530 21 CFR 221.100-115 21 CFR 221.63-72 21 CFR 221.80-94 21 CFR 211. 180-198 21 CFR 211.160-176 21 CFR 221.142-150 21 CFR 221.122-137 Subpart F--Production and Process Controls Subpart G--Packaging and Labeling Control Subpart H--Holding and Distribution Subpart I--Laboratory Controls Subpart J--Records and Reports 21 CFR 221.22-34 21 CFR 221.42-58 Subpart B--Organization and Personnel Subpart C--Buildings and Facilities Subpart D--Equipment Subpart E--Control of Components and Drug Product Containers and Closures FDA Publishes Drug Master File Guidance FDA published draft guidance on drug master files in October 2019. The new guidance revises the agency's September 1989 guidance and details the preparation and submission of drug master files (DMFs). The new guidance discusses the types of DMFs, how to submit DMFs including format and delivery, and how to report changes to DMFs. The guidance also details FDA review processes including administrative review and technical review. DMFs are submissions to FDA that provide "confidential, detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of human drug products." DMFs may also contain toxicology information and shared system risk evaluation and mitigation strategies. DMFs may be used to support new drug applications, abbreviated new drug applications, and investigational new drug applications. They may also support biologics license applications under the Public Health Service Act. DMFs themselves are not approved by FDA but the technical contents of DMFs may be reviewed in connection with the applications that reference them, according to the agency. Reference 1. FDA, Drug Master Files, Guidance for Industry, Draft Guidance (CDER, CBER, October 2019) —The Editors of BioPharm International