| Public Health Service Food and Drug Administration |
Waterview Corporate Center |
Department of Health and Human ServicesTelephone (973) 331-4906
July 29, 2011
WARNING LETTER
CERTIFIED MAIL
RETURN RECEIPT REQUESTED
11-NWJ- 21
Mr. Gilbert Buchalter
President
Pharmaceutical Innovations, Inc.
897 Frelinghuysen Avenue
Newark, NJ 07114
Dear Mr. Buchalter:
During an inspection of your firm located in Newark, New Jersey,on April 14, 2011 through May 5, 2011, investigators from the United States Food and Drug Administration (FDA) determined that your firm manufacturers Ultra Phonic Conductivity Gel, Sonic Generic Ultrasound Transmission Gel, Ultra Phonic Fontanelle Scanning Pad, and Ultra Phonic Focus Conforming Gel Pad. 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.
At the close of the inspection, FDA Investigators discussed with you objectionable conditions observed during the inspection. A Form FDA-483 was issued to you.
The FDA inspection revealed that your 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 you that was dated June 10, 2011 concerning our investigator's observations noted on the Form FDA 483, List of addition, Inspectional Observations. 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 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). Specifically, your Ultra Phonic Conductivity Gel, lot # 100110, was released to the market as a sterile product; however, your firm failed to establish and maintain documented procedures for final inspection and testing activities in order to verify that the specified sterility requirements for the Ultra Phonic Conductivity Gel were met.
We reviewed your response and conclude that it is not adequate, because there was no reference to any sterility testing being performed for Lot 100110, Ultra Phonic Conductivity Gel, prior to release. In addition, your response does not discuss the specific requirements for forming the basis of final inspection and test for your Ultra Phonic Conductivity Gel in order to verify all designated release characteristics were met for your device's intended use.
2. Failure to establish and maintain procedures to ensure that equipment is routinely calibrated, inspected, checked, and maintained as required by 21 CFR 820.72. Specifically, your firm has failed to ensure that your (b)(4) dryheat sterilizers were routinely calibrated, inspected, checked, and maintained prior to use. These dry heat sterilizers are used to sterilize your 20 ml Ultra Phonic Conductivity Gel which is sold by your firm as a sterile product.
We reviewed your response and conclude that it is not adequate because there is no indication that your (b)(4) dryheat sterilizers are routinely calibrated, inspected, checked, and maintained prior to use. Your firm has failed to include provisions for remedial action in order to reestablish the limits and to evaluate whether there could be any adverse effect on your device's quality.
3. Failure to identify the action(s) needed to correct and prevent recurrence of nonconforming product and other quality problems as required by 21 CFR 820.100(a)(3). Specifically, your firm failed to open a Corrective Action Preventive Action (CAPA) for Medical Device Report (MDR) complaint 742 that documents NICU babies with positive cultures for Pseudomonas. The hospital's investigation led to culturing your ultrasound 8 oz bottles and 5 liter gel which tested positive for the Pseudomonas organism. Your firm's investigation concluded that your product was improperly used without identifying the actions needed to prevent recurrence of a nonconformity or potential nonconformity.
We reviewed your response and conclude that it is not adequate because your firm's investigation concluded that your product was improperly used without your firm identifying any corrective or preventative actions to prevent recurrence of a nonconformity or potential nonconformity. In addition, there is no documentation included in your response concerning any failure analysis or laboratory testing of the ultrasound gel that was listed in the MDR report, including a complete description of the methodology used for the testing by the hospital and your contract laboratory. Furthermore, no laboratory test results were provided in your response confirming negative results for the Pseudomonas organism in your ultrasound gel product.
4. Failure to maintain Device Master Records (DMR's) as required by 21 CFR 820.181. Specifically, your firm's Device Master Record for the Ultra Phonic Fontanelle Scanning Pad fails to include, or refer to the location of, the following information: device specifications including appropriate drawings, composition, formulation, component specifications; production process specifications including production methods, production procedures, and production environment specifications; quality assurance procedures and specifications including acceptance criteria and the quality assurance equipment to be used; packaging and labeling specifications, including methods and processes used.
We reviewed your response and concluded that it is not adequate because the DMR collected during the inspection for your Ultra Phonic Fontanelle Scanning Pad was not adequately maintained as per 21 CFR § 820.181. No documentation was included in your response to indicate that this violation was adequately corrected.
5. Failure to maintain Device History Records to ensure each batch, lot, or unit is maintained to demonstrate that the device is manufactured in accordance with DMR as required by 21 CFR 820.184. Specifically, the primary identification label and labeling used for each production unit was missing for your Ultra Phonic Conductivity Gel control # 021010 and 080810. This violation was documented during a previous inspection.
We reviewed your response and concluded that it is not adequate because there was no indication that you will be including any primary identification label and labeling with your Device History Records.
6. Failure to perform design validation under defined operating conditions on initial production units, lots, or batches to ensure that devices conform to defined user needs and intended uses as required by 21 CFR 820.30(g). Specifically, there was no design validation performed for your Ultra Phonic Fontanelle Scanning Pad in order to ensure that it conforms to defined user needs and intended uses. The product labeling indicates that the intended use of your Ultra Phonic Fontanell Scanning Pad is for the ultrasound of neonates on their skin and skull. Your firm has failed to perform testing of your finished devices for performance under actual conditions of use or simulated use conditions in the actual or simulated environment in which the device is expected to be used.
We reviewed your response and concluded that it is not adequate because your firm will not perform design validation for your Ultra Phonic Fontanelle Scanning Pad in order to ensure that it conforms to defined user needs and intended uses.
7. Failure to establish and maintain procedures for changes to a specification, method, process, or procedure where the changes shall be verified or, where appropriate validated according to 21 CFR 820.75 as required by 21 CFR 820.70(b). Specifically, your batch record log for your Ultra Phonic Conductivity Gel 36-1000 documents different formulas were used for lots # 010101, 011201, and 041401. Your firm has failed to review and evaluate the process changes for your Ultra Phonic Conductivity Gel and perform revalidation where appropriate.
We reviewed your response and concluded that it is not adequate because no documentation was provided to show that you had verified the changes made to the formula did not influence the validated process for your Ultra Phonic Conductivity Gel.
8. Failure to establish and maintain procedures to control product that does not conform to specified requirements as required by 21 CFR 820.90(a). Specifically, operating procedure QOP-4.10.4-1, Final Inspection and Testing, requires a nonconformity report to be prepared for nonconforming product in order to identify and correct reoccurring problems. Your firm failed to generate a nonconforming report for lot # 052610, Fontanelle Scanning Pads, where 24 units of finished product were rejected without an investigation into the root cause of the nonconformities.
We reviewed your response and concluded that it is not adequate because your firm has failed to implement procedure QOP-4.1 0.4-1 which requires a nonconformity report to be prepared for nonconforming product. In addition, your firm is required under 21 CFR 820.90(a) to evaluate a nonconformance that includes a determination of the need for an investigation and notification of the persons or organizations responsible for the nonconformance, where the evaluation and the investigation would need to be documented.
9. Failure to establish and maintain procedures to ensure that all purchased or otherwise received product and services conform to specified requirements as required by 21 CFR 820.50. Specifically, your firm has no written agreements with the suppliers of raw materials and the laboratories used to do finished product testing, such as microbial testing of your sterile Ultra Phonic Conductivity Gel packets. In addition, your firm has failed to provide your testing facilities with any microbial testing requirements specific to your finished devices. Furthermore, your firm does not conduct any audits of your suppliers and laboratory testing facilities in order to ensure that all purchased or otherwise received product and services conform to your specified requirements.
We reviewed your response and concluded that it is not adequate because your firm has not provided any documentation to support that you have established and maintained procedures to ensure that all purchased or otherwise received product and services conform to your specified requirements. Purchasing must be carried out under adequate controls, including the assessment and selection of suppliers, contractors, and consultants in order to ensure that only acceptable products and services are received. The specifications for the finished device cannot be met unless the individual parts of the finished device meet specifications.
10. Failure to maintain legible records for review and copying at the manufacturing establishment or other location that is reasonably accessible to employees of FDA designated to perform inspections as required by 21 CFR 820.180. Specifically, all documents and procedures provided to employees of FDA for the manufacture of your Fontanelle Scanning Pads or the Ultra Phonic Conductivity Gel were written over with a black marking pen and were made illegible. These records contained the specifications and formulations for your Ultra Phonic Conductivity Gel.
We reviewed your response and concluded that it is not adequate because you cannot remove information from records that are required to be maintained by 21 CFR 820. This includes specifications and formulations for the manufacture of your Fontanelle Scanning Pads and Ultra Phonic Conductivity Gel.
You 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 FDA 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.
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 violations, or similar violations, from occurring again. Include documentation of the corrective action 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: Robert J. Maffei, Compliance Officer, U.S. Food and Drug Administration, 10 Waterview Boulevard, 3rd Floor, Parsippany, New Jersey, 07054. If you have any questions about the content of this letter, please contact Mr. Maffei at 973-331-4906.
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 violations noted in this letter and in the 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 violations, and take prompt actions to correct the violations and to bring your products into compliance.
Sincerely yours,
/s/
Diana Amador-Toro
District Director
New Jersey District Office
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