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U.S. Department of Health and Human Services

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Enforcement Actions

Millar Instruments, Inc. 5/7/12

  

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

Public Health Service
Food and Drug Administration
 Dallas District
4040 North Central Expressway
Dallas, Texas 75204-3128 

 

May 7, 2012
 
Ref: 2012-DAL-WL-22
WARNING LETTER
 
UPS OVERNIGHT MAIL
 
Huntley D. Millar
Chief Executive Officer
Millar Instruments, Inc.
6001-A Gulf Freeway
Houston, TX 77023
 
Dear Mr. Millar:
 
During an inspection of your firm located in Houston, Texas on January 24, 2012 through February 2, 2012, investigators from the United States Food and Drug Administration (FDA) determined that your firm manufactures reusable and disposable pressure transducer catheters, to include but not limited to urological Mikro-Tip Model SUPC-780S Transducer, cardiovascular Mikro-Tip Model SPC-370S Transducer, Mikro-Cath Sterile Transducer and intracranial Model VPM-10M Transducer. 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 any 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 requirements of the Quality System regulation found at Title 21, Code of Federal Regulations (CFR), Part 820. 
 
We received a response from Fatma Ali, Director RA/QA, dated February 22, 2012, concerning our investigators’ observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, that was issued to your firm. We address this response below, in relation to each of the noted violations. These violations include, but are not limited to, the following:
 
1.    Failure to validate with a high degree of assurance and approve according to established procedures, a process whose results cannot be fully verified by subsequent inspection and test, as required by 21 CFR 820.75(a).
 
For example:  Your firm has not validated to a high degree of assurance all processes involved in the manufacture of your re-usable and disposable cardiac, intracranial and urological catheters. 
 
  1. Your (b)(4) process validation conducted to prepare the re-usable urological and cardiac catheter surfaces for (b)(4) adherence was inadequate in that it did not:
 
(1) Include a protocol specifying how you were going to conduct the validation.
(2) Include pre-determined acceptance criteria.
(3) Include worst case testing of different size catheters.
(4) State which catheter models were tested or represented.
(5) Include testing of catheters to verify if the intended use could be consistently met.
 
  1. Your verification/validation of your (b)(4) process which is conducted to prepare the re-usable and disposable cardiac, intracranial and urological catheter surfaces for (b)(4) adherence was inadequate in that it did not:
 
(1) Include testing of catheters to ensure the intended use was consistently met.
(2) Identify the variables such as exposure time, (b)(4) and material type.
(3) Include worst case scenario testing of different models of catheters.
 
We reviewed your firm’s response and concluded that it is not adequate. Your response stated that at the time of the FDA inspection, your firm did not produce sufficient evidence that the processes mentioned were validated. Your response stated that Engineering Project files EPF-20030901 and EPF-20030107 demonstrated that the (b)(4) processes were effective; however, you did not provide the referenced documents with your response for our review. 
 
Your response further stated that your firm’s past focus was on verification of product design which included process verification rather than process validation.   Your proposed actions were to validate the equipment identified in the observation and to investigate all other equipment to ensure adequate validation and/or verification. In addition, your response stated that Process Validation SOP-2632 will be reviewed and evaluated for adequacy.   Although you referenced CAPA # CA FDA 1201 in your response, you did not provide the CAPA or any other supporting documentation for your proposed corrective and preventive actions.
 
2.    Failure to establish and maintain procedures for finished device acceptance to ensure that each production run, lot, or batch of finished devices meets acceptance criteria, as required by 21 CFR 820.80(d).
 
For example:  Your firm uses non-validated test methods, which you developed in-house, to verify if critical in-process and final device testing specifications are met for your re-usable and disposable cardiac, intracranial and urological catheters.
 
  1. Non-validated test methods include:
(1) (b)(4) test for final product testing of re-usable catheter devices. 
(2) (b)(4) test for final product testing of re-usable catheters. 
(3) (b)(4) test for final product testing of re-usable catheters
(4) (b)(4) test for final product testing of re-usable catheters.
(5) (b)(4) test for final product testing of re-usable catheters. 
(6) (b)(4) test for final product testing of re-usable catheters. 
(7) (b)(4) test system for in-process and final product testing of disposable catheters.
 
  1. Your qualification of the (b)(4) test equipment for in-process testing of reusable and returned catheter devices was inadequate to ensure the repeatability and reproducibility of the test method in that the qualification was a comparison study between the functionality of your (b)(4) system and your non-validated (b)(4) system.
  2. Your validation of the in-process (b)(4) test for reusable urology and cardiovascular catheters was inadequate to ensure the repeatability and reproducibility of the test method. Your validation of the drift test did not:
(1) Include a protocol.
(2) Include pre-determined acceptance criteria.
(3) Include worst case testing of different models of catheters.
(4) State which catheter models were tested or represented.
(5) Document the actual processing of any catheters through the (b)(4).
(6) Identify the variables, such as (b)(4) of the (b)(4) and (b)(4) of the (b)(4).
(7) Identify the test equipment which includes (b)(4), and multiple chart records.
(8) Address re-testing of a catheter through the same process after it fails the test, as allowed by your test procedure. 
 
We reviewed your firm’s response and concluded that it is not adequate. Your response said the tests referenced above were either determined by the supplier or based on (b)(4), however, you did not provide for our review the supporting documentation that include data to support these test methods are valid for testing re-usable and disposable cardiac, intracranial and urological catheters. 
 
Your response stated that the test methods used were initially developed prior to 1979 and were documented in engineering notebooks and memos, that at that time formal protocols were not required, and that the test methods were refined and by 1992 closely resembled the test methods used today. Your proposed actions were to validate the test equipment mentioned in the observation using formal protocols and systematic methods following your Protocol and Report Writing procedure. In addition, your response stated that your firm will review all other test equipment within manufacturing and QA processes and identify the need for validation as appropriate. Although you referenced CAPA # CA FDA 1202 in your response, you did not provide the referenced CAPA or any other supporting documentation for your proposed corrective and preventive actions.
 
3.    Failure to establish and maintain procedures to ensure that device history records for each batch, lot, or unit are maintained to demonstrate that the device is manufactured in accordance with the device master record, as required by 21 CFR 820.184.
 
For example: 
  1. Your device history records failed to document the critical manufacturing steps, (b)(4) treatments, that are used during production to ensure appropriate (b)(4) bondage of your reusable and disposable catheters and sensor housings. Your device history records also lack the actual time the catheter and sensor housing is exposed to the (b)(4) treatments, even though you have required production time parameters for these treatments. 
  1. You fail to maintain the original results (in units of (b)(4)) for converted test results (in units of (b)(4)) that you document in the device history records for the (b)(4), and (b)(4) tests.
 
We reviewed your firm’s response and concluded that it is not adequate. Your response stated that the (b)(4) steps were included in the device history record under a signoff that covers multiple steps, and the practice of having multiple operations represented by one signature was established many years ago by Millar. Your response stated that it would be difficult to complete the catheter assembly in the absence of (b)(4) steps, and that at the time your firm determined the process was verifiable and individual signoff steps were not required. Your proposed actions were to identify the (b)(4) and (b)(4) steps in the reusable products device history records and add appropriate signoffs, to include a duration sign off for the production parameter of time. For disposable products with shorter (b)(4) times, your response stated that you planned to automate the time portion of the process such that the operator-dependent factor is removed, and a specific signoff for the zapping step would be added to the respective device history records, and training to this revision would be conducted. Your response stated that you would review manufacturing steps and evaluate critical steps to ensure that there are appropriate process step segregations and signoffs in the device history records, and your design control procedure would be reviewed for possible clarification of requirements for documenting critical step sign offs in the device master record/device history record, and training on this revision would be conducted. Although you referenced CAPA # CA FDA 1204 in your response, you did not provide the referenced CAPA or any other supporting documentation for your proposed corrective and preventive actions. 
 
4.    Failure to establish and maintain procedures to control environmental conditions, as required by 21 CFR 820.70(c).
 
For example:  Your firm’s Cleanroom Operating Condition procedure states no food or drink is allowed in an Environmentally Controlled Room. However, your environmentally controlled anti-chamber gowning area, which leads into the sterile production area for disposable cardiac catheters, has a large water dispenser and paper cups for drinking available for employee use on the “clean” side. 
 
We reviewed your firm’s response and concluded that it is not adequate. Your response to the FDA 483 Observations stated that you provide employees working in the environmentally controlled room (ECR) with water out of a water dispenser and conical shaped cups which are located in the environmentally controlled anti-chamber gowning room, and that the water is consumed immediately and not stored in the cups. Your response stated that the particulate counts in the anterooms are systemically monitored and the presence and use of a water dispenser with paper cups do not adversely affect the work environment in the environmentally controlled room. Your response stated that the statement in your Cleanroom Operating Condition procedure stating “no food or drink is allowed in an ECR” has been focused on not allowing employees to consume or store snacks (including candy and gum), sodas, or meals in the ECR. You said water coolers with conical shaped cups have been located in the anteroom (gowning area) for many years, and it was an oversight that the procedure did not address the water dispenser in the ante-room. Your proposed actions were to update your Cleanroom Operating Condition procedure to allow for water dispensers with conical shaped disposable paper cups to be located in the anterooms and to allow employees to consume water in the anteroom, and to provide training on the revised procedure. Your response stated that you would review your Cleanroom Operating Condition procedure in detail to verify the procedure is adequate and being followed. Although you referenced CAPA # CA FDA 1205 in your response, you did not provide the referenced CAPA or any other supporting documentation for your proposed corrective and preventive actions, to include but not limited to, documentation to support that the practice of allowing your employees to drink water in the (b)(4) anteroom does not adversely impact the quality of the (b)(4) anteroom and the adjoining (b)(4) sterile production area.  
 
5.    Failure to establish and maintain procedures to ensure sampling methods are adequate for their intended use, as required by 21 CFR 820.250(b).
 
For example:  Your firm did not follow the sampling plan of your Statistical Techniques procedure. Your procedure required a minimum sample size of (b)(4) catheters, however, your firm used (b)(4) catheters as a testing sample size for the validation update of your QA testing method for (b)(4) and (b)(4) tests, and for your (b)(4) Catheter Test System method validation.
 
We reviewed your firm’s response and concluded that it is not adequate. Your response stated that it was unclear from your procedure whether “sample size of (b)(4) meant (b)(4) devices or (b)(4) repetitions of tests. Your proposed actions were to update your Statistical Technique procedure to clarify the sampling requirements, provide training on the revised procedure, and review all sections of the procedure to ensure clarity. Although you referenced CAPA # CA FDA 1203 in your response, you did not provide the referenced CAPA or any other supporting documentation for your proposed corrective and preventive actions. 
 
6.    Failure to ensure that quality audits are conducted by individuals who do not have direct responsibility for the matters being audited, as required by 21 CFR 820.22.
 
Your firm failed to follow your internal audit procedures to ensure auditors are not responsible for the areas they have direct responsibility. For example, your Process Improvement Project Manager who was responsible for making changes to manufacturing procedures was also responsible for auditing those procedures.
 
We reviewed your firm’s response and concluded that it is not adequate. Your response stated that this was a misinterpretation of the area of responsibility as stated in the QSR, and Millar had not considered that providing feedback on a document was the same as owning the document or being responsible for the execution of the document. Your response said you would update the internal audit procedure, auditor training materials, and (b)(4) audit plan to include clear segregation of duties and to clarify the auditors’ assignment based on the documents being audited in each area. Although you referenced CAPA # CA FDA 1206 in your response, you did not provide the referenced CAPA or any other supporting documentation for your proposed corrective and preventive actions. 
 
Your firm should take prompt action to correct the violations addressed in this letter.  Failure to promptly correct these violations may result in regulatory action being initiated by the FDA without further notice.  These actions include, but are not limited to, seizure, injunction, and civil money penalties.  Also, federal agencies may be advised of the issuance of 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 violations 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.
 
Please notify this office in writing within fifteen business days from the date you receive this letter of the specific steps your firm has taken to correct the noted violations, as well as an explanation of how your firm plans to prevent these violations, or similar violations, from occurring again.  Include documentation of the corrections and/or corrective actions (including any systemic corrective actions) that your firm has taken.  If your firm’s planned corrections and/or corrective actions will occur over time, please include a timetable for implementation of those activities.  If corrections and/or corrective actions cannot be completed within fifteen business days, state the reason for the delay and the time within which these activities will be completed. Your firm’s response should be comprehensive and address all violations included in this Warning Letter.
 
Your firm’s response should be sent to the Food and Drug Administration, 4040 North Central Expressway, Suite 300, Dallas, Texas 75204, Attention: Rose M. Ashley, Compliance Officer. Refer to the unique identification number, 2012-DAL-WL-22, when replying. If you have any questions about the content of this letter please contact: Rose M. Ashley at (210) 541-9450, Ext. 1118.
 
Finally, you should know that this letter is not intended to be an all-inclusive list of the violations at your firm’s facility.  It is your firm’s responsibility to ensure compliance with applicable laws and regulations administered by FDA.  The specific violations noted in this letter and in the Inspectional Observations, FDA 483, issued at the close of the inspection may be symptomatic of serious problems in your firm’s manufacturing and quality management systems.  Your firm should investigate and determine the causes of the violations, and take prompt actions to correct the violations and bring the products into compliance. 
 
Sincerely,
/S/                                                          
Reynaldo R. Rodriguez, Jr.
District Director