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Where are you now? Intelligence Services > Blend Uniformity > Related Warning Letters

Blend Uniformity Related Warning Letters

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PDF PDF file (462 KB)
Opti-Med Controlled Release Labs, Inc., 2002-01-09
"We consider process validation to be an evaluation of the process to determine the optimum parameters to assure blend uniformity by testing a larger number of samples taken at various times during the blending operation from several locations in the blender."
  "Your response indicates you believe analysis of a single ingredient (copper) from the vitamin pre-mix is adequate to validate the blend uniformity for Cenogen OB Capsules....."
  "You question the need for Blend Uniformity Analysis (BUA). Your Folic Acid containing drugs are subject to the USP monograph that calls for content uniformity testing of Folic Acid Tablets. The requirements of 21 CFR 211.110 call for appropriate sampling of in-process and finished drugs to assure uniformity of the batch....."

PDF PDF file (355 KB)
Cardinal Laboratories, 2001-09-19
"Your firm has not performed blend uniformity studies for the veterinary drug products, as well as the human drug products to assure compliance."

PDF PDF file (366 KB)
Purepac Pharmaceutical Company, 2001-04-09
"The Quality Unit released batches of Phentermine Hydrochloride 37.5 mg Tablets, which failed in-process specifications for blend uniformity. Out-of-specification results, were invalidated due to sampling error, without adequate justification."

PDF PDF file (155 KB)
Stason Pharmaceuticals, Inc., 2000-09-26
"Failure to perform investigations into unexplained discrepancies of a batch or any of its components to meet specifications [211.192]. For example: you did not investigate Out of Specification (OOS) results obtained during blend uniformity testing of the final blend."

PDF PDF file (143 KB)
DuPont Pharmaceutical Co., Inc., 2000-06-15
"Your firm's investigation into this incident led to the conclusion that the blend was not uniform and a decision was made to discard the last two pails from the compression operation."
  "A high degree of variability was reported in blend uniformity results. Your firm's investigation reached the conclusion that the tool used to collect the blend uniformity samples was not appropriate. The validation was approved based on this conclusion even though no further evaluation of the sampling tool was made to confirm that it was the cause of the problem."

PDF PDF file (604 KB)
Hoffmann-La Roche, Inc., 1999-12-17
"This product has exhibited blend uniformity or blend assay failures."

PDF PDF file (262 KB)
Catalytica, Inc., 1999-10-29
"The inspection noted that review of process validation summaries lacked assay specifications for inprocess blend uniformity samples. The firm's acceptance criterion is a relative standard deviation (RSD) not exceeding 6.0% for each active ingredient, but there is no assay criterion such as 90-110%. A relative standard deviation could be met although some or all samples were outside a 90-110% assay range; this, in turn would be objectionable without further testing or investigation."

PDF PDF file (506 KB)
Watson Laboratories, Inc., 1999-01-11
"Although process validation was performed, the protocols failed to include: a) Validated and consistent sampling techniques or procedures when collecting granulation samples for blend uniformity testing; b) Adequate procedures for evaluating failed blend uniformity testing of samples collected from blenders or drums."
  "Your firm's investigations into multiple, out-of-specification blend uniformity test results consistently fail to identify the cause of the test failure, fail to determine whether the granulation blend is truly uniform, and fail to solve the problem to potentially improve blend uniformity. Virtually all blend uniformity failures are attributed to poor sampling technique since active ingredient is 'finer' in particle size than the other materials in the granulation."

PDF PDF file (329 KB)
S. S. S./Pfeiffer Company, 1998-03-30
"This was the first lot of this product manufactured at this location. This lot failed in-process blend uniformity testing. These results were confirmed by retesting. Finished product release testing of Segment 3 failed content uniformity also. The analytical method was changed and a retest using ten additional samples gave acceptable results....."
  "The in-process blend uniformity failures were not investigated."

PDF PDF file (421 KB)
Purepac Pharmaceutical Co., 1997-11-26
"Diclofenac Sodium, was retested due to a high blend uniformity result. The sample retest yielded an out of specification result. Resampling at 12 locations yielded in specification results. Initial results were attributed to sampling and analyst errors, without supporting documentation. This lot was used in support of validation for this product."

PDF PDF file (211 KB)
Jacobus Pharmaceutical Co. , Inc., 1997-10-01
"Samples taken to demonstrate blend uniformity during the manufacture of Dapsone 25 mg Tablets were not of an appropriate size. The total tablet weight as shown on the batch record is 91.7 mg. Samples taken to demonstrate blend uniformity were 30 grams. Generally, an appropriate sample size would be 1 to 3 times the dosage weight."

PDF PDF file (277 KB)
Ortho-McNeil Pharmaceuticals, 1997-04-21
"Deficiencies were noted with validation batches of several low dose products, in that there was no justification for samples sizes taken to evaluate blend uniformity. These samples were not representative of unit dose weights."

PDF PDF file (497 KB)
G & W Laboratories, Inc., 1997-02-12
"We disagree with your position that product uniformity is demonstrated by content uniformity in the finished product. Passing content uniformity result for a sampling of finished product is not an indication of blend uniformity. Samples taken from the mixing vessel are taken to demonstrate blend uniformity and they should approximate the size of the dosage unit. Inprocess blend sampling and testing is an important part of validation. Your response does not address our concern that blend samples taken during validation are not representative of the dosage unit."

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