Inspections, Compliance, Enforcement, and Criminal Investigations
Accumed, Inc. 09-Nov-01
DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Food and Drug Adminstration
Waterview Corporate Center
10 Waterview Blvd., 3rd Floor
Parsippany, NJ 07054
Telephone (973) 526-6004
November 9, 2001
WARNING LETTER - AMENDED FRONT PAGE
RETURN RECEIPT REQUESTED
FILE NO.: 02-NWJ-08
Burgise F.Palkhiwala, President
2572 Brunswick Pike
Lawrenceville, New Jersey 08648
Dear Mr. Palkhiwala:
On September 19 through September 28, 2001, the US Food and Drug Administration conducted an inspection of your facility located at 2572 Brunswick Pike, Lawrenceville, New Jersey. During the Inspection our investigators documented significant deviations horn the Current Good Manufacturing Practices Regulations (cGMPs) Title 21, Code of Federal Regulations, Part 210 and 211, in conjunction with your firm?s manufacture of Over-the-Counter (OTC)drug products.
The inspection revealed that drug products manufactured at your facility are adulterated within the meaning of Section 501(a)(2)(B)of me Federal Food, Drug, and Cosmetic Act (the Act), in that the methods used h or the facilities or controls used for their manufacture, processing packing or holding do not conform with cGMPs, to assure that such drug products meet the requirements of the Act The deviations were presented to you on a FDA-483, List of Inspection Observation, at the close of the inspection on September 28, 2001.
The significant observation are as follows:
1. Failure to perform an investigation into Out-Of-Specification (OOS) test results.
Your firm failed to follow Standard Operating Procedure (SOP) G-15-I Out of Specification Investigations, which requires an investigation into any results that are outside of the accepted specification. For example:
a. The Certified of Analysis (COA) dated April 24, 2001, for the product Infant Gas Relief Drops Lot #1251, showed the presence of Pseudomonas aeruginosa. [redacted] A second sample was then sent to the contract laboratory, which the results showed no P. aeruginosa The original failing result was disregarded and product lot was released on May 7, 2001. No investigation was conducted to invalidate the failing result.
b. The COA for Purified Water Lot#10982 dated June 20, 2001, showed an aerobic plate count result of 266 cfu/mL [redacted]. The purified water was used in the manufacture of Accudryl Gel Lot #1348. The product was released on June 20, 2001. No investigation was performed.
c. The COA for Purified Water Lot #10891 dated June 27, 2001, showed a Total Fungi count results of 78 cfu/mL [redacted]. The purified water was used in the Manufacture of Suprema Liquid Antacid. The product was released on June 27, 2001. No investigation was performed.
2. No assurance that the drug products, labeled as USP, meet all USP specifications.
For example, your firm uses an in-house analytical method for the product Sennosides Tablets USP that has not been proven to be equivalent or better than the USP method. There is no data to demonstrate that the raw material and finished drug product tested using the in-house method will meet all specifications outlined in the USP monograph.
3. The qualification for raw materials is incomplete in that your firm does not verify the data reported on the COA from the supplier, such as percent impurities and percent actives. For example, Acetaminophen raw material Lot #90981 was received and used in the manufacture of Accunol Children?s Suspension Lot #0054. Related substances and organic volatile impurities on COA were not verified.
4. Failure to adequately calibrate the laboratory equipment For example, the dilation of the dissolution apparatus does not evaluate parameters such as shaft wobble and shaft centering. The calibration procedure is incomplete in that it does not have specifications for these a is no written procedure for the calibration of the [redacted].
5. The analytical methods used during stability testing are inadequate in that the methods have not been proven stability indicating. For example:
a. Them is no data to demonstrate that the analytical test method for Accunol children Elixir (Acetaminophen) used to establish expiration dating can accurately measure the active in the presence of degradants and impurities.
b. No data to show that the analytical test method for Accufrin Nasal Spray (oxymetazoline hydrochloride) can separate the active ingredient from the degradants. The analytical testing procedure does not require testing of degradants and impurities for stability monitoring.
6. Method validation for the product Sennosides is inadequate in that the data does not assess all variables, such as different mobile phase concentrations and analysts, to demonstrate that the method can sustain variances.
We acknowledge your corrective action of voluntarily recalling the product Infant Gas Relief Drops Lot #1251. We received your response letter dated October 12, 2001 regarding the inspectional observations noted on the FDA-483. We recommend you conduct a comprehensive evaluation of your facility to determine cGMP compliance.
We will review the implementation and the adequacy of your corrective actions during our follow-up inspection of your firm. The above identification of violations is not intended to be an all-inclusive list of deficiencies at your facility. It is your responsibility to assure adherence with each requirement of the Good Manufacturing Practices Regulations. Federal agencies are advised of the issuance of all Warning Letters about drugs and devices so that they may take this information into account when considering the award of contracts. You should take prompt action to correct these deviations. Failure to promptly correct these deviations may result in regulatory action without further notice. This includes seizure and/or injunction.
You should notify this office in writing within 15 working days of receipt of this letter, of any additional corrective actions, including an explanation of each step being taken to prevent the recurrence of similar conditions, If corrective action cannot be completed within 15 working days, state the reason for the delay and the timeframe within which corrections will be completed. Your reply should be sent to the Food and Drug Administration New Jersey District Office, 10 Waterview Blvd, 3rd Floor, Parsippany, New Jersey 07054, Attention Andrew Ciaccia, Compliance Officer.Very truly yours,
Douglas L Ellsworth
New Jersey District Office