Departmentof Health and Human Services PublicHealth Service 550 West Jackson Blvd., 15th Floor
Chicago, Illinois 60661
elephone: 312-353-5863
September 24, 2002
WARNING LETTER
CHI-25-02
CERTIFIED MAIL
RETURN RECEIPT REQUESTED
Mr. Miles D. White
Chairman & CEO
Abbott Laboratories, Inc.,
One Abbott Park Road, Bldg AP6
Abbott Park, IL 60064
Dear Mr. White:
An inspection of Abbott?s pharmaceutical manufacturing operations in BuildingAP- 16,located at Abbott Park, IL, was conducted from June 18 through July 24,2002,: Theinspection covered the production of [redacted]. During the inspection,our investigators documented significant violations of current Good ManufacturingPractice (cGMP) regulations listed Title 21, Code of Federal Regulations (CFR),in your firm?s production of [redacted]. These violations cause this productto be adulterated within the 501(a)(2)(B) of the Federal Food, Drug, and CosmeticAct (the Act).
1. Failure to conduct a thorough investigation when a batch or any of its components fail to meet specifications [21 CFR 211.192]. For example:
During the production of [redacted] lot#79298AF00, black, magnetic particulateswere observed in the granulation. The corrective action taken was to reconditionthe granulation by [redacted] that were expected to eliminate the particles.No validation study was performed to establish that this procedure would successfullyeliminate all of the particles.
During processing, lot #79298AF00 was stored in containers numbered from 1-153. After finding metal particulate contamination in tablets held in container #153, your firm?s investigation covered the tablets held in container# 152 only. No additional inspection of tablets held in containers #l-151 was conducted
During the production of Erythrocin Stearate Tablets, lot #81420AF00, a metalparticle was observed on the surface of one tablet held in container was heldin a total of nine containers numbered from 1 to 9. After the remaining tabletsheld in container #9 were destroyed, your firm visually the tablets held incontainer #8 and no re-examination of the tablets held in containers #1-7 wasperformed.
2. Failure to have adequate written procedures for procedures and process controlto assure that drug products have the identity, strength, quality and puritythey purport or are represented to possess [21 CFR 211.100(a)]. For example:
[redacted] tablet lot #79298AF00 was one of the batches included in the process validation study for this product. This lot was not produced using the manufacturing process discussed in the validation study protocol. Lot #79298AF00 was subjected to several reconditioning steps, due to particulate contamination, that were not listed in the master batch record. Some of the actions taken with respect to this lot, such as the hand pouring of the granules from a drum and [redacted] were steps that were performed for the production of the two additional [redacted] lots used in the validation study.
The master batch manufacturing instructions for the production of [redacted] differ from the procedures used in manufacturing the batches produced in the validation study. The drying process for the tablet granulation component used in the validation batches used a different type of dryer and different time and temperature parameters from the procedures directed in the master batch manufacturing.
3, Failure to clean, maintain and sanitize, at appropriate intervals, equipment and utensils used in the manufacture, processing, packing, or holding of a drug product [21 CFR 211.67(a)]. For example:
Your firm determined that black particles found in tablet granulations was due to the disintegration of the mill?s drive damper and grease seals. Your firm also determined that metal particles clinging to the surface of one tablet was due to the tablet press turret rubbing the upper guard, caused by a worn Neoprene mounting pad. In both examples, there was no established schedule for inspecting or replacing these parts.
At the conclusion of the inspection, our investigators issued the FDA 483, List of Inspectional Observations, to Kay E. Peel, Vice President, Quality Assurance, PPD. A copy of the FDA 483 is enclosed.
This letter and the FDA 483 are not intended to be an all-inclusive list ofdeficiencies at your facility. It is your responsibility to ensure that thedrug products you manufacture are in compliance with the Act and the regulationspromulgated under it. Federal agencies are routinely advised of Warning Lettersissued so that they may take this information into account when consideringthe award of government contracts.
You should take prompt action to correct deficiencies at your facility. Failureto implement corrective measures may result in further regulatory action withoutnotice. These actions may include seizure of your products or injunction.
You should notify this office in writing, within 15 working days of receipt of this letter, of the specific steps you have taken to correct the deficiencies at your firm and prevent their recurrence. Your reply should be directed to the attention of George F. Bailey.
We have received Ms. Peel?s written response, dated August 6, 2002, regarding inspectional observations on the FDA 483. We note that, in response to FDA 483 item #2, Abbott has committed to running three additional validation batches of [redacted] and that a target date for completion of this activity is scheduled for October 31, 2002. Please notify this office when you have completed the additional validation batches. With regard to that commitment and the other corrective steps Ms. Peel indict underway or have been completed, we will consider your FDA 483 response in conjunction with any response to p Warning Letter and will determine the acceptability of your responses during a subsequent follow-up inspection.
Sincerely,
/s/
Arlyn H. Baumgarten
District Director
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