Inspections, Compliance, Enforcement, and Criminal Investigations

Verichem Laboratories, Inc. 2/4/15

  

Department of Health and Human Services logoDepartment of Health and Human Services

Public Health Service
Food and Drug Administration
 
New England District Office
One Montvale Avenue, 4th floor
Stoneham, MA 02180
Phone 781.587.7500
Fax 781.587.7556
 
 
WARNING LETTER
 
CMS 446069
 
 
UNITED PARCEL SERVICE
OVERNIGHT DELIVERY
 
February 4, 2015
 
Anthony J. DiMonte
President
Verichem Laboratories Inc.
90 Narragansett Ave
Providence, RI 02907-3358
  
 
Dear Mr. DiMonte:
 
During an inspection of your firm located in Providence, Rhode Island on October 14 through November 14, 2014 investigator(s) from the United States Food and Drug Administration (FDA) determined that your firm manufactures clinical chemistry reference materials for in vitro diagnostic (IVD) use: calibrators (Class 2 devices) and calibration verifiers (Class 1 devices).  Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. 321(h), these products are devices because they are intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or are intended to affect the structure or function of the body.
 
This inspection revealed that these devices are adulterated within the meaning of section 501(h) of the Act (21 U.S.C. § 351(h)), in that the methods used in, or the facilities or controls used for, their manufacture, packing, storage, or installation are not in conformity with the Current Good Manufacturing Practice (CGMP) requirements of the Quality System (QS) regulation found at Title 21, Code of Federal Regulations (CFR), Part 820. 
 
We received a response from Anthony DiMonte, President dated December 8, 2014 concerning our investigator’s observations noted on the Form FDA 483, List of Inspectional Observations that was issued to you. We address this response below, in relation to each of the noted violations. 
 
Violations include, but are not limited to, the following:
 
1.    Failure to establish and maintain procedures for validating device design. [21 CFR 820.30(g)]
 
For example:
  • You failed to validate the BR2 Bilirubin Calibrator (list #9459), which included a change from (b)(4) to (b)(4) source material.
  • You failed to conduct stability tests for the BR2 Bilirubin Calibrator (list #9459, which has a 15 month expiration date).
  • You failed to conduct stability tests and performance validations on all products affected (and at least 14 other products) when cap design of 5 mL Amber Vial (list 4050) was changed from a threaded cap to a crimped cap. Additionally, your firm received Complaint CG010 dated 5/10/12 which revealed JAS Ammonia Ethanol Control lots manufactured with crimped caps resulted in elevated ammonia levels. Your investigation report states that the firm was aware of a leaching problem with the cap change.  
  • Stability testing for the Bilirubin Standard Kit (list # 9450) is inadequate, in that there is no statistical rationale for testing one vial from each of 5 activity levels.  
We have reviewed your response and have concluded that it is inadequate. Please provide documentation to verify when the CAPAs have been completed. A follow up inspection will be required to assure that corrections are adequate. 
 
2.    Failure to adequately maintain device master records. [21 CFR 820.181]
 
For example:
  • Specifications for vials (List #4050 and 4075) and stoppers (List #4700 and 4701) used for bilirubin products and JAS Ammonia/Ethanol products, do not state the material composition of each.
  • There are 2 different specification revisions for both Rev A and Rev B for the JAS Ethanol Calibrator 100 mg/dL (List #9662) and for Rev D of for Bilirubin Standard Level E (list 9455). 
    • Rev A has versions dated 7/21/05 and 10/16/09. The 2009 version includes a chemical component that is not included in the 2005 version.
    • Rev B has versions that are dated 3/2/06 and 6/3/11. The 2006 document included 2 chemical components that are not included in the 2011 version. The 2011 version includes 4 chemical components that are not included in the 2006 version
    • Rev D has versions that are dated 1/17/11 and 12/10/09 and they contain different packaging components (vials, stoppers and caps). 
 
We have reviewed your response and have concluded that it is inadequate. Please provide documentation to verify when the CAPAs have been completed. A follow up inspection will be required to assure that corrections are adequate. 
 
3.    Failure to establish and maintain procedures to control all required documents.  [21 CFR 820.40]
 
For example:
 
  • The 2012 Design Input Plan, Design Output Plan and Design Review for the BR2 Bilirubin Calibrator were not documented until October 2014, more than 2 years after the design of the product. 
  • An Engineering Change Request was not written for the change from threaded to crimp cap fir for the Bilirubin Mid-Range Standard Kit (List #9575) until 10/30/14. The actual change was effective 1/17/11.
 
We have reviewed your response and have concluded that it is inadequate. Provide documentation to verify when the CAPAs have been completed. A follow up inspection will be required to assure that corrections are adequate. 
 
4.    Failure to ensure that all equipment used in the manufacturing process meets specified requirements and is appropriately designed, constructed, placed and installed to facilitate maintenance, adjustment, cleaning and use. [21 CFR 820.70(g)]
 
For example:
  • The deionized (DI) water system installed in October 2013 has not been adequately installed and maintained. The DI water is used as a component in all of your in-vitro diagnostic products (calibrator and calibration verifiers) as well as for washing glassware and tubing and rinsing cuvettes.
    • There are plumbing cross connections on the DI water system that could lead to contamination of the system.
    • The (b)(4) testing is not conducted from all points of use.
    • Review of (b)(4) test results from October 13 to present results revealed that a sample collected on 3/5/14 was incubated at a temperature that exceeded the maximum temperature specification.
 
We have reviewed your response and have concluded that it is inadequate. Please provide documentation to verify when the CAPAs have been completed. A follow up inspection will be required to assure that corrections are adequate. 
 
5.    Failure to establish procedures for quality audits and conduct such audits to assure that the quality system is in compliance with the established quality system requirements and to determine the effectiveness of the quality system. [21 CFR 820.22]
 
For example:
  • Internal Audit Procedure QOP-82-02 does not include audits of all parts of the quality system; Corrective and Preventative Action (CAPA) and complaint handling are not audited.
  • For the past 5 years, the annual internal quality audit has been conducted by the Quality Assurance Supervisor, who has responsibility for many of the areas audited.
 
We have reviewed your response and have concluded that it is inadequate. Please provide documentation to verify when the CAPAs have been completed. We acknowledge that you have contracted with an outside firm to conduct quality system audits.  A follow up inspection will be required to assure that corrections are adequate. 
 
6.    Failure to maintain device history records (DHR). [21 CFR 820.184]
 
For example, there is not documentation in the DHR of the disposition for at least 15 of 380 vials produced for the BR2 Bilirubin Calibrator (List #9459 Lot K320201), released on 8/30/12.
 
We have reviewed your response and have concluded that it is inadequate. Please provide documentation to verify when the CAPAs have been completed. A follow up inspection will be required to assure that corrections are adequate. 
 
7.    Failure to establish and maintain procedures for acceptance of incoming product. [21 CFR 820.80(b)]
 
For example: 
  • There is no statistical rationale for measuring only one serum vial per lot at incoming inspection for serum vials (List #4050), for which the length of the thread overlap was determined to be significant in preventing oxygen contamination of bilirubin. Lot sizes received in 2012 through 2014 range from 791 to 6000 vials.
  • Neither of your 2 written SOPs for raw material receiving or raw material packaging test parameters specifies the quantities to test at incoming inspection.
  • If a vial fails any one of the 5 specifications for raw materials packaging test parameters, another vial is tested; the failed test is not documented. 
 
We have reviewed your response and have concluded that it is inadequate. Please provide documentation to verify when the CAPAs have been completed. A follow up inspection will be required to assure that corrections are adequate. 
 
8.    Failure to maintain complaint files. [21 CFR 820.198]
 
For example:
  • The Quality Assurance Supervisor, who is responsible for evaluating and investigating all complaints, does not review the Technical Calls Log.  
  • At least 3 potential complaints in the Technical Calls Log did not result in investigations or any follow-up.
    • 1/29/14 call reporting low Urea Nitrogen recovery.
    • 8/15/11 call reporting an Ammonia Iron Standard, Level 1 failure
    • 6/28/11 call reported a leaking/cracked vial from List # 9450, lot G302406
 
We have reviewed your response and have concluded that it is inadequate. Please provide documentation to verify when the CAPAs have been completed. A follow up inspection will be required to assure that corrections are adequate. 
 
9.    Failure to establish and maintain procedures that describe the methods for authorizing the receipt from and dispatch to storage areas and stock rooms. [21 CFR 820.150(b)]
 
For example: 
  • SOP#139 Procedure for Handling Retention Samples was not followed for products removed from the Sample Retention Freezer; there is no documentation indicating use or discard of products removed from the freezer from 7/28/11 through 1/1/14.
  • SOP#106 Handling and Disposal of Extra of Expired Bulk Products does not include the Retention Sample Freezer in the list of areas where product is stored.
 
We have reviewed your response and have concluded that it is inadequate. Please provide documentation to verify when the CAPAs have been completed. A follow-up inspection will be required to assure that corrections are adequate. 
 
You should take prompt action to correct the violation(s) addressed in this letter. Failure to promptly correct these violation(s) may result in regulatory action being initiated by the Food and Drug Administration without further notice. These actions include, but are not limited to, seizure, injunction, and/or civil money penalties. Also, federal agencies are advised of the issuance of all Warning Letters about devices so that they may take this information into account when considering the award of contracts. Additionally, premarket approval applications for Class III devices to which the Quality System regulation deviations are reasonably related will not be approved until the violations have been corrected. Requests for Certificates to Foreign Governments will not be granted until the violations related to the subject devices have been corrected.
 
We are requesting that you submit to this office on the schedule below, certification by an outside expert consultant that he/she has conducted an audit of your establishment's manufacturing and quality assurance systems relative to the requirements of the device QS regulation (21 CFR, Part 820). You should also submit a copy of the consultant's report, and certification by your establishment's Chief Executive Officer (if other than yourself) that he or she has reviewed the consultant's report and that your establishment has initiated or completed all corrections called for in the report. The initial certifications of audit and corrections and subsequent certifications of updated audits and corrections (if required) should be submitted to this office by the following dates:
  • Initial certifications by consultant and establishment – (07/30/2015)
  • Subsequent certifications – (7/30/2016 and 7/30/2017)
Please notify this office in writing within fifteen (15) working days from the date you receive this letter of the specific steps you have taken to correct the noted violations, including an explanation of how you plan to prevent these violation(s), or similar violation(s), from occurring again. Include documentation of the corrective action (which must address systemic problems) you have taken. If your planned corrections will occur over time, please include a timetable for implementation of those corrections. If corrective action cannot be completed within 15 working days, state the reason for the delay and the time within which the corrections will be completed.
 
Your response should be sent to: Compliance Officer Diane M. Prince. If you have any questions about the content of this letter please contact: Compliance Officer Prince at 781-587-7442.
 
Finally, you should know that this letter is not intended to be an all-inclusive list of the violation(s) at your facility. It is your responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violation(s) noted in this letter and in the Inspectional Observations, Form FDA 483 (FDA 483), issued at the closeout of the inspection may be symptomatic of serious problems in your firm’s manufacturing and quality assurance systems. You should investigate and determine the causes of the violation(s), and take prompt actions to correct the violation(s) and to bring your products into compliance. 
 
Sincerely yours,
/S/                                                           
CAPT Diane M. Prince
Acting District Director

Page Last Updated: 11/07/2016
Note: If you need help accessing information in different file formats, see Instructions for Downloading Viewers and Players.
Language Assistance Available: Español | 繁體中文 | Tiếng Việt | 한국어 | Tagalog | Русский | العربية | Kreyòl Ayisyen | Français | Polski | Português | Italiano | Deutsch | 日本語 | فارسی | English