Inspections, Compliance, Enforcement, and Criminal Investigations
Lyne Laboratories, Inc. 17-Jan-08
Department of Health and Human Services
Public Health Service
New England District
VIA CERTIFIED MAIL
January 17, 2008
Mr. Stephen Tarallo
Lyne Laboratories, Inc.
10 Burke Drive
Brockton, MA 02041
Dear Mr. Tarallo:
An inspection of your drug manufacturing facility located at 10 Burke Drive, Brockton, MA, conducted by a Food and Drug Administration (FDA) investigator on September 20 through October 5, 2007, found significant deviations from FDA's current good manufacturing practice (CGMP) regulations for finished pharmaceuticals, Title 21, Code of Federal Regulations (CFR) Part 211. These CGMP deviations were listed on an Inspection Observations (FDA-483) form issued to your firm at the close of the inspection. Failure to conform to the CGMP regulations cause products manufactured by your facility to be adulterated within the meaning of Section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. 351(a)(2)(B). Our investigator found the following significant deviations from the CGMPs for finished pharmaceuticals:
1. Failure to thoroughly review the failure of a batch or any of its components to meet any of its specifications whether or not the batch has been thoroughly distributed as required by 21 CFR § 211.192. For example, Lyne Laboratories has not completed an investigation into the chemical composition and potential patient risk for particulate matter found in Calcitriol Injection. Your firm continues to observe the presence of visible particulates in your sterile injectable product after 100% visual inspection. Your firm is responsible for the labeling, finished product testing and release of the Calcitriol product and is therefore responsible for investigation of any product failures or discrepancies.
We acknowledge that this issue was previously brought to your attention during an inspection of your facility in December 2005. Your FDA-483 response dated November 6, 2007, indicates that this investigation is still ongoing. Please provide documentation of these results as soon as possible.
2. Failure to establish adequate laboratory controls, including scientifically sound and appropriate test procedures designed to assure that drug product components and drug products conform to appropriate standards of identity, strength, quality and purity [21 CFR § 211.160(b)]. Your quality control criteria are inadequate to ensure the removal of all ampoules with visible particulates or charring in the neck during the inspection process. Your firm continues to find visible particulates after 100% visual inspection of the ampoules. We acknowledge your written response dated November 6, 2007, in which you commit to revise the specifications for acceptance. However, your inspectional process still has not been validated to show that the 100% visual inspection performed at your facility on the Calcitriol product will result in the removal of all defective ampoules. This validation is required by 21 CFR211.160(b).
In response to this Warning Letter, please submit the validation data that demonstrates your inspection testing is effective in removing ampoules with visible particulates.
The issues and violations identified above are not intended to be an all-inclusive statement of violations that exist at your facility. You are responsible for investigating and determining the causes of violations identified above and for preventing their recurrence or the occurrence of other violations. We acknowledge the efforts of the contract manufacturer, Pierre Fabre, to improve its manufacturing process and examination procedures. However, your firm has overall responsibility for resolving the remaining issues with this process and these procedures. It is your responsibility to ensure that all products manufactured by your firm are in compliance with all requirements of federal law and FDA regulations.
You should take prompt action to correct the violations cited in this letter. Failure to promptly correct these violations may result in regulatory action without further notice, including, without limitation, seizure and/or injunction. Other federal agencies may take this Warning Letter into account when considering the award of contracts. Additionally, FDA may withhold approval of requests for export certificates, or approval of new drug applications listing your facility as a manufacturer until the above violations are corrected. Are inspection maybe necessary.
Within 15 working days of receipt of this letter please notify this office in writing of the specific steps you have taken to correct violations. Include an explanation of each step being taken to prevent the recurrence of similar violations as well as copies of related documentation. If you cannot complete corrective action within fifteen working days, state the reason for the delay and the time within which you will complete the correction. If you no longer manufacture or market any products, your response should so indicate, including the reasons for, and the date on which you ceased production.
We acknowledge your written responses to the FDA-483 dated November 6, 2007. Your responses to items 2-5 in the FDA-483 appear adequate. We will verify these promised corrective actions at the next inspection of your facility. However, as discussed above, with respect to item 1 in the FDA-483, the response is unsatisfactory since your firm has still not confirmed the identity of the particulates being found and, consequently, no reliable assessment of the risk of these particles to the patient has been performed. In addition, your inspectional process still has not been validated to show that the 100% inspection will result in the removal of all defective ampoules.
Your reply should be directed to the Food and Drug Administration, One Montvale Avenue, 4th floor, Stoneham, MA 02180, Attention Karen N. Archdeacon, Compliance Officer.
Michael R. Kravchuk
Acting District Director
New England District
Cc: Mr. Robert Crisafi
Chairman of the Board
10 Burke Drive
Brockton, MA 02301-5505