Top 483s of 2018 PDF

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List of Top 483 to pharma companies...

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The Top 10 FDA 483s from FY 2018 By Regina Fullin, Director of GxP Consulting at Compliance Team Commentary: In 2017, the FDA made big changes, with Program Alignment, and the changes were shown in the Top 10 483 data, with a short-term spike in the number of 483s issued in 2017. The rate of 483s issued has since normalized in 2018, as shown in the table below, which covers the major FDA program areas in FY 2016, 2017 and 2018.

Number of 483s** Issued from the System in FY 2016 vs. 2017, by Program Area Program Area

2016

2017

2018

Biologics 84 232 Bioresearch Monitoring 215 228 Devices 934 2573 Drugs 691 1923 Foods 2196 7729 Human Tissue for Transplantation 92 118 Parts 1240 and 1250 97 123 Radiological Health 32 24 Veterinary Medicine 281 544 Total** 4622 13,494

89 216 966 716 2583 97 70 26 206 4910

% Change* (2016) % Change* (2017) +6% +0% +3% +4% +17% +5% -27% -19% -27% +6%

-261% -106% -266% -269% -300% -122% -176% -92% -264% -275%

* To keep calculations consistent, the denominator in the % change calculation is the number from 2018. ** The data only represent 483s issued electronically, and totals may be greater than the sum because a single citation, applied to multiple product areas may have been counted twice.

Other changes that were noted during the Program Alignment period seem to have leveled off. For example, during the program alignment period, the FDA seemed to have changed its focus to place increased priority on employee training and complaints in the pharma program area, while changing priority on Design Validation and Device History Records on the device side. Findings for these CFR elements were an anomaly and are no longer in the Top 10. It was hypothesized earlier that this change of focus may have resulted from Program Alignment, but this new data it appears to suggest an overall greater enforcement effort in FY 2017.

Pharma Top 10 Citation 21 CFR 211.22(d)

Rank/Short Description 1. Procedures not in writing, fully followed

Long Description The responsibilities and procedures applicable to the quality control unit are not [in writing] [fully followed]. 2017 #1

Frequency 208

The Top 10 FDA 483s from FY 2018, Continued Citation

Rank/Short Description

21 CFR 211.160 (b)

2. Scientifically sound laboratory controls

21 CFR 211.192

3. Investigation of discrepancies & failures

21 CFR 211.100(a)

4. Absence of Written Procedures

21 CFR 211.67(a)

5. Cleaning / Sanitizing / Maintenance

21 CFR 211.68(b)

21 CFR 211.67(b)

6. Computer control of master formula records 7. Written procedures not established/ followed

21 CFR 211.110(a)

8. Control procedures to monitor and validate performance

21 CFR 211.68(a)

9. Calibration/ Inspection/ Checking not done

21 CFR 211.165(a)

10. Testing and release for distribution

Long Description Laboratory controls do not include the establishment of scientifically sound and appropriate [specifications] [standards] [sampling plans] [test procedures] designed to assure that [components] [drug product containers] [closures] [in-process materials] [labeling] [drug products] conform to appropriate standards of identity, strength, quality and purity. 2017 #4 There is a failure to thoroughly review [any unexplained discrepancy] [the failure of a batch or any of its components to meet any of its specifications] whether or not the batch has been already distributed. 2017 #2 There are no written procedures for production and process controls designed to assure that the drug products have the identity, strength, quality, and purity they purport or are represented to possess. 2017 #3 Equipment and utensils are not [cleaned] [maintained] [sanitized] at appropriate intervals to prevent [malfunctions] [contamination] that would alter the safety, identity, strength, quality or purity of the drug product. 2017 #7 (as part of 211.67) Appropriate controls are not exercised over computers or related systems to assure that changes in master production and control records or other records are instituted only by authorized personnel. (Not on Top 10 for last 5 years) Written procedures are not [established] [followed] for the cleaning and maintenance of equipment, including utensils, used in the manufacture, processing, packing or holding of a drug product. 2017 #7 (as part of 211.67) Control procedures are not established which [monitor the output] [validate the performance] of those manufacturing processes that may be responsible for causing variability in the characteristics of in-process material and the drug product. (Not on Top 10 for last 2 years) Routine [calibration] [inspection] [checking] of [automatic] [mechanical] [electronic] equipment is not performed according to a written program designed to assure proper performance. 2017 #8 Testing and release of drug product for distribution do not include appropriate laboratory determination of satisfactory conformance to the [final specifications] [identity and strength of each active ingredient] prior to release. (Not on 2017 Top 10, but #7 for previous years)

Frequenc y

127

107

86

81

71

64

64

60

56

The Top 10 FDA 483s from FY 2018, Continued

Devices Top 10 Citation 21 CFR 820.100(a)

21 CFR 820.198(a)

21 CFR 820.50 21 CFR 803.17 21 CFR 820.75(a)

21 CFR 820.90(a) 21 CFR 820.100(b) 21 CFR 820.22

21 CFR 820.30(i) 21 CFR 820.181

Rank/Short Description 1. Lack of or inadequate procedures 2. Lack of or inadequate complaint procedures 3. Purchasing controls, Lack of or inadequate procedures 4. Lack of Written MDR Procedures 5. Lack of or inadequate process validation 6. Nonconforming product, Lack of or inadequate procedures 7. Documentation 8. Quality audits Lack of or inadequate procedures 9. Design changes Lack of or Inadequate Procedures 10. DMR - not or inadequately maintained

Long Description Procedures for corrective and preventive action have not been [adequately] established. 2017 #1

Procedures for receiving, reviewing, and evaluating complaints by a formally designated unit have not been [adequately] established. 2017 #2 Procedures to ensure that all purchased or otherwise received product and services conform to specified requirements have not been [adequately] established. 2017 #5 Written MDR procedures have not been [developed] [maintained] [implemented]. 2017 #9 A process whose results cannot be fully verified by subsequent inspection and test has not been [adequately] validated according to established procedures. 2017 #7 Procedures have not been [adequately] established to control product that does not conform to specified requirements. 2017 #3

Frequency

354

229

142

139

138

119

Corrective and preventive action activities and/or results have not been [adequately] documented. 2017 #10

86

Procedures for quality audits have not been [adequately] established. 2017 #4

78

Procedures for design change have not been [adequately] established. (Not on Top 10 in 2017, but between #8 and #9 in previous years)

76

A device master record has not been [adequately] maintained. (Not on Top 10 in 2017, but between #9 and #10 in previous years)

63...