Poor Documentation and Lab Controls Top 2014 Form 483 Observations

Lax procedural documentation in quality control units topped the list of reasons why drugmakers received Form 483s in fiscal 2014, its ninth consecutive year at the top, while poor laboratory controls jumped to second place from fourth in the annual rankings of inspection observations.

The data come from the FDA’s annual statistical report released today of 2,855 domestic and foreign drug inspections it scheduled to conduct from Oct. 1, 2013, through Sept. 30, 2014. During this period, the FDA issued 645 Form 483s to drugmakers, down from 690 in the previous fiscal year and 787 in 2012.

The top 10 observations in drug 483s were:

1. Responsibilities and procedures for quality control units aren’t in writing or fully followed (cited in 145 forms, down from 155 in 2013);
2. Laboratory controls aren’t scientifically sound or appropriate (109, up from 99);
3. Failure to thoroughly review a batch failure and whether it was already distributed (94, down from 131);
4. No written procedures for production and process controls (87, down from 106);
5. Written procedures aren’t established for cleaning and maintenance of equipment (72, down from 77);
6. Procedures to prevent microbiological contamination of sterile drug products aren’t established, written or followed. Compounding pharmacies are typically cited for this observation (72, down from 76);
7. Testing and release of drug products doesn’t include appropriate laboratory determination of conformance to specifications for the active ingredient (64, down from 66);
8. Equipment and utensils aren’t cleaned or maintained (63, down from 71);
9. Routine equipment maintenance isn’t performed according to a written program (54, down from 56); and
10. No written testing program to assess stability (51, down from 62)

The top 10 observations largely reflect those on the 2013 list, with some key differences. Notably, the ninth observation of not performing routine equipment maintenance was 12th last year. It bumped manufacturing processes validation to 11th on the current list.

One expert was surprised the observation on not performing routine equipment maintenance made the list at all.

When a firm has an effective internal quality audit program, this is something that should be easily caught in less than 10 minutes in the lab or on the factory floor, John Avellanet, managing director and principal at the consulting firm Cerulean Associates, says. Avellanet attributes the observation’s high rank to calibration, inspection and checking procedures that are either poorly written or not practical.

Avellanet adds that lax procedural documentation continues to top the charts because of poorly written or impractical standard operating procedures and inadequate training.

The FDA also released the top 10 Form 483s for biologics manufacturers, some of which focused on blood banks. The observations include failure to perform a thorough investigation of discrepancies in specifications (21 citations, down from 44), failure to submit a biological product deviation report on time (20, up from 18), not maintaining records (16, down from 18), failing to take detailed production records (16, down from 26), not using supplies or reagents per the manufacturer’s instructions (10, up from 7), failure to make available written procedures for use by personnel where procedures are performed (8, up from two), failing to review lot or unit records before release (8, no change).

The observations were culled from 146 issued 483s, down from 2013’s total of 191.

To view the FDA’s statistics report, visit www.fda.gov/ICECI/Inspections/ucm424098.htm. — Robert King