SoftwareCPR Warning Letter Excerpts - All 12/13/2016 - Page 1s3-us-east-2.amazonaws.com/mlfpcontent/wp-content/... · 2018. 11. 16. · SoftwareCPR Warning Letter Excerpts - All 12/13/2016

SoftwareCPR Warning Letter Excerpts - All 12/13/2016 - Page 1

11/8/2016 Sekisui Medical Co., Ltd.Sekisui Medical Co., Ltd. Product: drug manufacturing facility Date:11/8/2016 1. Failure to maintain complete data derived from all laboratory tests conducted to ensure compliancewith established API specifications and standards. Our investigator found that you failed to maintain complete data from all laboratory analyses, and thatyou relied on the incomplete information to determine whether your drugs met establishedspecifications. For example: a. Numerous data files were found in the recycle bin folder on the computer connected to gaschromatography instruments GC-4 and GC-6. Specifically, our investigator found deleted data forresidual solvent testing for (b)(4) lot (b)(4) in the recycle bin. Your records show that you retested the lotwithout documented justification or an investigation. You retained only the final test result. b. During the inspection our investigator requested residual solvent release test data for two of yourAPI, (b)(4) and (b)(4). You were unable to retrieve this data. Any data created as part of a CGMP record must be retained so that it can be evaluated by the qualityunit as part of release criteria and maintained for CGMP purposes. We acknowledge that you commit to revising your SOP for archiving data. Your response is inadequatebecause it does not explain your failure to maintain complete records prior to the inspection. You alsodid not address validation of the systems you use to archive your data. 2. Failure to prevent unauthorized access or changes to data, and failure to provide adequate controlsto prevent omission of data. Our investigator observed that your laboratory systems lacked controls to prevent deletion of andalterations to electronic raw data. You do not have adequate controls for seven of (b)(4) highperformance liquid chromatography (HPLC) systems and one of (b)(4) gas chromatography systems.For example, the audit trail on HPLC 15 did not record the (b)(4) batch (b)(4) assay. Your recordsindicate that the assay was performed on March 3, 2014, but your audit trail shows no assaysperformed between February 28 and March 4, 2014. Moreover, your analyst demonstrated to ourinvestigator that he could change the data, including injection time and date, without the changes beingcaptured in the audit trail, prior to printing the results. We acknowledge that you have committed to upgrading your analytical systems to be compliant withCGMP requirements. However, procuring new instruments, installing new and upgraded dataacquisition software, and enabling various features on software are not sufficient alone. These steps willbe effective only if you implement appropriate procedures and systems to ensure that your quality unitreviews all production and control data and associated audit trails as part of the batch release process.Data Integrity RemediationYour quality system does not adequately ensure the accuracy and integrity of data to support the safety,effectiveness, and quality of the drugs you manufacture. We strongly recommend that you retain aqualified consultant to assist in your remediation. In response to this letter, provide the following. A. A comprehensive investigation into the extent of the inaccuracies in data records and reporting.Your investigation should include:A detailed investigation protocol and methodology; a summary of all laboratories, manufacturingoperations, and systems to be covered by the assessment; and a justification for any part of youroperation that you propose to exclude.Interviews of current and former employees to identify the nature, scope, and root cause of data


inaccuracies. We recommend that these interviews be conducted by a qualified third party.An assessment of the extent of data integrity deficiencies at your facility. Identify omissions, alterations,deletions, record destruction, non-contemporaneous record completion, and other deficiencies.Describe all parts of your facility’s operations in which you discovered data integrity lapses.A comprehensive retrospective evaluation of the nature of the testing data integrity deficiencies. Werecommend that a qualified third party with specific expertise in the area where potential breaches wereidentified should evaluate all data integrity lapses. B. A current risk assessment of the potential effects of the observed failures on the quality of yourdrugs. Your assessment should include analysesof the risks to patients caused by the release of drugsaffected by a lapse of data integrity, and risks posed by ongoing operations. C. A management strategy for your firm that includes the details of your global corrective action andpreventive action plan. Your strategy should include:A detailed corrective action plan that describes how you intend to ensure the reliability andcompleteness of all of the data you generate, including analytical data, manufacturing records, and alldata submitted to FDA.A comprehensive description of the root causes of your data integrity lapses, including evidence that thescope and depth of the current action plan is commensurate with the findings of the investigation andrisk assessment. Indicate whether individuals responsible for data integrity lapses remain able toinfluence CGMP-related or drug application data at your firm.Interim measures describing the actions you have taken or will take to protect patients and to ensurethe quality of your drugs, such as notifying your customers, recalling product, conducting additionaltesting, adding lots to your stability programs to assure stability, drug application actions, and enhancedcomplaint monitoring.Long-term measures describing any remediation efforts and enhancements to procedures, processes,methods, controls, systems, management oversight, and human resources (e.g., training, staffingimprovements) designed to ensure the integrity of your company’s data.A status report for any of the above activities already underway or completed. FDA District: CDRH

8/3/2016 Spiegelberg Gmbh & Co. KGSpiegelberg Gmbh & Co. KG Product: intercranial pressure monitoring products Date: 8/3/2016 This inspection revealed that these devices are adulterated within the meaning of section 501(h) of theAct, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for, theirmanufacture, packing, storage, or installation are not in conformity with the current good manufacturingpractice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations(CFR), Part 820.Failure to ensure that when computers or automated data processing systems are used as part ofproduction or the quality system, the manufacturer shall validate computer software for its intended useaccording to an established protocol, as required by 21 CFR 820.70(i). For example: your firm uses(b)(4) use. We reviewed your firm's response and conclude that it is not adequate. The response indicates yourfirm will follow the guidance of "Off-The-Shelf Software Use in Medical Devices" (b)(4), and ifnecessary, perform a validation. However, your firm did not provide sufficient details describing itscorrective actions for assessment. FDA District: CDRH

8/2/2016 Adamson Analytical Laboratories, Inc.Adamson Analytical Laboratories, Inc. Product: finished pharmaceuticals Date: 8/2/2016 This warning letter summarizes significant violations of current good manufacturing practice (CGMP)


regulations for finished pharmaceuticals, 21 CFR parts 210 and 211, and significant deviations fromCGMP for active pharmaceutical ingredients (API). Your firm failed to exercise appropriate controls over computer or related systems to assure that onlyauthorized personnel institute changes in master production and control records, or other records (21CFR 211.68(b)). Specifically, your high performance liquid chromatography (HPLC) and gas chromatography (GC) dataacquisition systems did not have sufficient controls to prevent deletion or alteration of raw data files.During the inspection, our investigators observed that your laboratory personnel use a shared passwordto access the HPLC (b)(4) computer system and that your GC (b)(4) computer system requires nopassword for access. In addition, multiple instruments had no audit trail function to record information about each analyticaltest, such as:type of injectiondate and timeidentity of analystreason for action taken (for example, modifying a record)This is a repeat observation from our February 7, 2013, inspection. In 2013, you committed toaugmenting the security of your computer systems within six months. However, based on our 2015inspection, it appears that you have not made appropriate corrective actions such as installing audittrails and ensuring that analysts have unique user names and passwords for your computerizedsystems. It is essential that your firm keep track of all changes made to your electronic data. The use of audittrails for computerized analytical instrumentation helps to ensure that all additions, deletions, ormodifications of information in your electronic records are authorized. It also allows you to verify thequality and integrity of the electronic data your contract testing laboratory generates for your customers. We acknowledge your commitment to install and configure appropriate electronic controls to ensurethat access to your computerized systems and data is restricted to authorized personnel with accessrights specified for each individual. However, your response is inadequate as you did not provide anaction plan describing the interim security measures in place prior to your installation of electroniccontrols. Your response also lacked details regarding the type of electronic controls to be installed, andyou did not describe how you will evaluate the effectiveness of these computerized system changes. FDA District: Los Angeles District

6/1/2016 86 Harriet Ave. Corporation DBA GeneralDevices86 Harriet Ave. Corporation DBA General Devices. Product: Carepoint EMS WorkStation/GEMS Series 4000, ElM- lOS Prep-Check, EIM-107-20APrep-Check Plus, Rosetta-Lt, and Rosetta-Rx Date: 6/1/2016 This inspection revealed that these devices are adulterated within the meaning of section 501(h) of theAct, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for, theirmanufacture, packing, storage, or installation are not in conformity with the current good manufacturingpractice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations(CFR), Part 820.Failure to adequately establish design change procedures, as required by 21 CFR 820.30(i). Forexample: A. Unsigned SOP titled "Change Notification System," dated 8/16/94, does not require that designchanges be verified or validated prior to implementation.


B. There is a lack of a documented software validation for releasing the following Carepoint.exeversions for resolving issues from one customer site, which include, but are not limited to: • #10089, dated 5/21/14: The unit kept alarming for an incoming ECG, but the ECG did not appear onthe screen.• #9169, dated 12/11/13: The unit continued to alarm audibly after a 12 Lead ECG came in.• #8429, dated 05/21/13: The unit kept having audible alarms for an incoming 12 Lead ECG, but the12 Lead ECG did not show up on the screen after the user selected View 12-Lead ECG. C. Issue Ticket# 9808, dated 4/2/14, indicated that the audio between an iPad and Carepoint EMSWorkStation, Serial No. 0464, was not working. The unit's (b)(4) program was upgraded to version1.01.26 to resolve the issue. There is a lack of documented software validation for the (b)(4) release. We reviewed your firm's written responses; however, the adequacy of your firm's responses cannot bedetermined at this time. We acknowledge that your firm's initial response, dated June 29, 2015, statedthat your firm will conduct an in-house audit of the firm'squality system and initiate corrective actionswhich were expected to be completed within 90 days "from receipt of official report." In yoursubsequent response, dated September 11, 2015, your firm outlined its implementation of correctiveactions to address each of the noted observationsin the Form FDA 483. However, the response did notprovide any supporting documentation to demonstrate how your firm corrected each deficiency. FDA District: New Jersey District

5/27/2016 Zimmer Biomet Holding, Inc.Zimmer Biomet Holding, Inc. Product: iAssist Knee System Date: 5/27/2016 8. Failure to submit a Report of Correction or Removal for a medical device correction or removalinitiated to reduce a risk to health or to remedy a violation of the Act caused by the device, which maypresent a risk to health, as required by 21 CFR 806.10. For example: a. Your firm initiated a correction in November 2007 and May 26, 2008, for the Orthosoft KneeUniversal CAS Software 2.3.2, due to a complaint relating to Right/Left knee Selection issues,Extension/Flexion Gap Assessment issues, and the SKS incorrect offset parameter value. Your firmconducted a correction or removal of these devices; however, no report was filed to FDA within 10working days of initiating this correction. b. Your firm initiated a removal in June 2008, of Sesamoid Plasty CAS workstation/base and columnassemblies 52 1.025 in the field, because the workstation could potentially collapse and fall on a user ifan attempt was made to fold the workstation without first removing the camera and arm. Your firmconducted a removal of these devices; however, no report was filed to FDA within 10 working days ofinitiating this removal. c. Your firm initiated a removal in 2008, of Unicondylar Digitizer 108.098 instruments from the field, dueto feedback received from surgeon that the newly modified software application was incompatible withthe Unicondylar Digitizer instrument, causing large off-scale errors. Your firm conducted a removal ofthese devices; however, no report was filed to FDA within 10 working days of initiating this removal. d. Your firm initiated a correction in July and August 2008, for the Magnetic Offset Paddle 108.117, dueto a complaint relating to Anterior Cortex Digitization, Implant Tolerance Interpretation Issues, andSoftware Issues. Your firm conducted a correction of these devices; however, no report was filed toFDA within 10 working days of initiating this correction. e. Your firm initiated a removal in October 2010, of NDI P7 Position Sensors, because the cameracomponents of the sensor could potentially malfunction, resulting in an interruption of the CAS system,and causing the display of positional data to stop during surgery. Your firm conducted a removal of


these devices; however, no report was filed to FDA within 10 working days of initiating this removal. f. Your firm initiated a correction in December 2011 for the Orthosoft Knee Universal CAS Software2.3.2, due to a complaint that the software can malfunction, resulting in stalling during the preoperativecalibration of the Universal Holding Platform, which in tum causes a delay in surgery or the need tocomplete the surgery using a conventional surgical technique. Your firm conducted a correction of thesedevices; however, no report was filed to FDA within 10 working days of initiating this correction. Your firm's response did not address this deficiency.FDA District: CDRH

5/16/2016 BBT Biotech GmbhBBT Biotech Gmbh. Product: pharmaceutical manufacturing facilities Date: 5/16/2016 Failure to exercise sufficient controls over computerized systems to prevent unauthorized access orchanges to data, and to provide adequate controls to prevent omission of data. Our investigator found that your (b)(4) system used for (b)(4) and (b)(4) testing lacked access controlsand audit trail capabilities. For example, all employees had administrator privileges and shared one username, so actions could not be attributed or traced to specific individuals. This exposed your electronicdata to manipulation and/or deletion without traceability. Our investigator also noted that your firm copied raw data to a CD (b)(4), and then deleted the data fromthe (b)(4) system to free space on the hard drive. Files copied to the CD were selected manually; theselection process was not supervised. Without audit trail capabilities or supervised file selection, therewas no assurance that all raw data files were copied to the CD before they were permanently deletedfrom the system. We acknowledge your commitment to hire a third-party expert to install audit trails and other controls toensure that data cannot be deleted from this electronic system. However, your response wasinadequate. Simply preventing data deletion is not sufficient. You did not show how these steps willensure that your firm retains and evaluates all data, including laboratory data, created as part of aCGMP record prior to release of your API. In your response to this letter, investigate your retention and review of CGMP data and provide theresults. Focus on your firm’s review and retention of laboratory raw data. In addition, provide yourinterim plan for reviewing and retaining data while your firm is in the process of implementing accesscontrols and audit trail capabilities. 

5/12/2016 Tai Heng Industry Co., Ltd.Tai Heng Industry Co., Ltd. Product: pharmaceutical manufacturing facilities Date: 5/12/2016Failure to prevent unauthorized access or changes to data, and to provide adequate controls to preventmanipulation and omission of data. During the inspection, an FDA investigator discovered a lack of basic laboratory controls to preventchanges to your firm’s electronically stored data and paper records. Your firm relied on incompleterecords to evaluate the quality of your drugs and to determine whether your drugs conformed withestablished specifications and standards. Our investigator found that your firm routinely re-tested samples without justification, and deletedanalytical data. We observed systemic data manipulation across your facility, including actions taken bymultiple analysts and on multiple pieces of testing equipment.


Specifically, your Quality Control (QC) analysts used administrator privileges and passwords tomanipulate your high performance liquid chromatography (HPLC) computer clock to alter the recordedchronology of laboratory testing events. FDA District Office: CDRH

5/5/2016 F.P. Rubinstein Y Cia SRLF.P. Rubinstein Y Cia SRL Product: laser powered surgical instruments Date: 5/5/2016This inspection revealed that these devices are adulterated within the meaning of section 501(h) of theAct, 21 U.S.C. § 351 (h), in that the methods used in, or the facilities or controls used for, theirmanufacture, packing, storage, or installation are not in conformity with the current good manufacturingpractice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations(CFR), Part 820. These violations include, but are not limited to, the following : 3. Failure to establish and maintain procedures for validating the device design, as required by 21CFR 820.30(g). For example: a. Your firm has not performed software validation (b)(4). These programs are used in the Starlightlaser product family. b. The software validation for (b)(4) is inadequate, in that the (b)(4). This message occurs when eitherthe maximum voltage (6V) is exceeded, or the actual voltage is higher than the reference voltageassociated with the intensity selected by the operator.6. Failure to validate computer software for its intended use according to an established protocol,when computers or automated data processing systems are used as part of production or the qualitysystem, as required by 21 CFR 820.70(i). For example, your firm has not validated the followingsoftware used in its quality system: a. (b)(4), used for complaint handling;b. (b)(4), used for complaint handling by your firm's sales force; andc. (b)(4), used for data analysis.8. Failure to establish and maintain procedures to ensure that all purchased or otherwise receivedproduct and services conform to specified requirements, as required by 21 CFR 820.50. For example: a. Your firm has not documented the qualifications of its suppliers, consultants, or contractors. b. Your firm's approved supplier list does not include three contractors/consultants used for softwaredevelopment and internal audits.FDA District: Center for Devices and Radiological Health

4/11/2016 Polydrug Laboratories Pvt. Ltd. CorporateOfficeRecipient:Polydrug Laboratories Pvt. Ltd. Corporate Office Product:Pharmeceuticals Date: 4/11/2016Failure of computerized systems to have sufficient controls to prevent unauthorized access or changesto data. Your firm’s computer system for entering test results and storing certificates of analysis (CoA), whichdocument whether a drug meets specifications, does not have sufficient controls to preventunauthorized changes to a CoA after quality unit approval.Your firm’s computer system for entering test results and storing certificates of analysis (CoA), which


document whether a drug meets specifications, does not have sufficient controls to preventunauthorized changes to a CoA after quality unit approval. During the inspection, our investigator reviewed (b)(4) CoA stored on computer #16, all of which wereapproved by the quality unit. A manager demonstrated for our investigator how results on an alreadyfinalized CoA could be manipulated after the formal quality unit approval. Also, the quality unit’selectronic signatures on these CoA were uncontrolled images of signatures rather than certificate-basedelectronic signatures. Your response states that your firm plans to implement an enterprise resource planning system. Yourresponse is inadequate because you did not provide sufficient detail about how this system will preventunauthorized access or data manipulation, nor did you indicate your timeframe for installing andvalidating the system. In addition, you failed to review and confirm authenticity of CoA data for productsyou have already released under the deficient conditions described above. FDA District: CDRH 

3/22/2016 FDA Guidance Genetic Tests for HeritableMarkersFDA "Guidance on Pharmacogenetic Tests and Genetic Tests for Heritable Markers" is at the linkprovided. Section III.D addresses Software and Validation of Instrumentation. In addition to referring tothe general software submission guidance it specifically states: "If applicable, you should describe howcomputational concerns such as probe saturation level, background correction, normalization, etc., areaddressed by the software."

3/16/2016 FDA Inspection Observation Summary for2015.FDA issued "2015 Annual FDA Medical Device Quality System Data Inspections, FDA Form 483Observations, and Warning Letter Citations". The full report is at the link provided. This report identifies numbers of observations and inspections by country as well as obervations byQuality subsystem. FDA noted that the number of Foreign inspection has increased. Production andProcess Controls and CAPA continue to be the most frequently cited. The most frequent Design Control citiations were Design Validation by a large margin then DesignChanges followed by Design Verification with a much lower number related to other elements of DesignControl.

2/16/2016 mplants International Ltd.mplants International Ltd. Product: orthopedic implants Date: 2/16/2016 This inspection revealed that these devices are adulterated within the meaning of section 501(h) of theAct, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for, theirmanufacture, packing, storage, or installation are not in conformity with the current good manufacturingpractice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations(CFR), Part 820.Failure to establish and maintain adequate procedures to ensure that the design input requirements aredocumented, as required by 21 CFR 820.30(c). For example, your firm’s design history file (DHF) doesnot include all design inputs for the Ring Lok Hip system. Specifically:The DHF includes computer aided design (CAD) testing for range of motion; however, there is nodesign input documented for range of motion.FDA District: CDRH


1/29/2016 pca Laboratories Ltd.pca Laboratories Ltd.. Product: pharmaceutical manufacturing facilities Date: 1/29/20161. Failure to have computerized systems with sufficient controls to prevent unauthorized access orchanges to data. During the inspection, FDA investigators discovered a lack of basic laboratory controls to preventchanges to your firm’s electronically stored data. Your firm relied on incomplete records to evaluate thequality of your drugs and to determine whether your drugs conformed with established specificationsand standards. Our investigators found that your firm routinely re-tested samples without justification, and deletedanalytical data. We observed systemic data manipulation across your facility, including actions taken bymultiple analysts, on multiple pieces of testing equipment, and for multiple drugs. You are responsiblefor determining the causes of these deviations, for preventing recurrence, and for preventing otherdeviations from CGMP. During the inspection, our investigators examined the computerized instrumentation and systems youused to conduct chromatographic analyses of your drugs and found that laboratory analysts had PCadministrator access that they utilized to manipulate raw data and test results. We found that controlson your computerized chromatographic instrumentation were not adequate to prevent analysts frommanipulating processing parameters in order to obtain passing results. We also found that yourcomputerized systems lacked controls to prevent the back-dating of test data. For example, we reviewed the (b)(4) API 12-month (b)(4) Commercial Stability assay test for residualsolvent by gas chromatography (GC). For batch #(b)(4) US-DMF ((b)(4)), you reported an (b)(4)% resultfor (b)(4) residual solvent (specification (b)(4)-(b)(4)%) obtained on July 18, 2013. We documented that the original peak had been integrated inconsistently. Standards and samples hadbeen processed using different integration parameters with no documented reason; there were nocontrols in the software to prevent analysts from manipulating integration settings in order to obtainpassing results that you relied on to evaluate the quality of this product. When our investigator askedyou to reprocess the chromatograms using appropriate integration parameters, an out-of-specification(OOS) value of (b)(4)% was obtained.. In the (b)(4) stability interval assay test of the same API, batch#(b)(4) US-DMF ((b)(4)), you reported an (b)(4)% result for (b)(4) residual solvent (specification:(b)(4)-(b)(4)%) obtained on June 12, 2013. We again found that the original sample peaks had beenre-reintegrated inconsistently. There were no controls in the software to prevent the inappropriatemanipulation of integration parameters. When our investigator asked you to reprocess thechromatograms using appropriate integration parameters, the result was an OOS value of (b)(4)%. For the same test, we found that on and after June 18, 2013, the date and time of the chromatographicinjections for the (b)(4) stability test appear to have been set back to June 12, 2013. The data wasreprocessed to obtain a passing result, upon which you relied to evaluate the quality of this drug. In addition to these examples of computerized systems that permitted inappropriate manipulation ofintegration parameters and backdating, our investigators also found several instances of computerizeddata systems that failed to prevent the deletion of original injections. For example, our investigatorsreviewed the GC audit trail for (b)(4) (finished API batch #(b)(4)) and found that the original sampleinjection for related substance was on June 4, 2013 at (b)(4). This injection was aborted with nojustification and the computerized system that your laboratory used to capture raw data did not retainthe original results. The sample was re-injected at (b)(4)., which automatically deleted the originalsample result. Passing results from the re-injection were reported for individual and total impurities. Youused these incomplete results to evaluate the quality of this drug.


The High Performance Liquid Chromatography (HPLC) audit trail for (b)(4) (finished API batch #(b)(4))shows that the first sample injection for aliquot #2 assay test was on May 28, 2013 at (b)(4). Thisinjection result was deleted without justification. The sample was re-injected at (b)(4). A passing assayresult was reported from the re-injection. As with the GC system discussed above, the electronicsystem your laboratory used to capture HPLC results lacked sufficient controls to prevent the deletion ofdata without justification, and failed to retain the original data. You relied on these incomplete results toevaluate the quality of this drug. These practices appear to be commonplace in your analytical laboratory. During the inspection, ourinvestigators spoke with an analyst who reported that “…if we find a failure, we set back the date/timesetting and re-integrate to achieve passing results…” The analyst explained that deleting, overwriting,changing integration parameters, and altering PC date and time settings were done for raw materials,in-process testing, and finished API drugs. In your response you stated that the stand-alone chromatographic instruments in the Quality Controland Stability laboratories are no longer under full control of individual analysts and have been connectedto a network-based laboratory system. You also acknowledged that you did not identify all instances ofdata manipulation that may have led to inaccurate conclusions regarding product quality. However, yourresponse still lacks a comprehensive assessment and retrospective review of data generated from all ofyour computerized laboratory systems. This includes but is not limited to a risk assessment thatevaluates all potentially-affected test data.2. Failure to adequately investigate and resolve critical deviations. Our inspection documented that your firm’s quality unit was aware of the lack of controls in yourcomputerized systems to prevent the manipulation and deletion of quality-related data. Your site’ssenior management failed to take sufficient corrective action and prevent the recurrence of theseproblems. For example, an anonymous email dated August 5, 2013 notified your quality managementabout data falsification and manipulation in your laboratory. This email stated: “…[t]here is no control ofdata in the department…Falsification is going on…Take action as early as possible..." Although youinvestigated your GC and HPLC equipment, the multi-part investigation that you opened on August 10,2013 (CD/RTM/QA/001/2013) was incomplete and did not resolve the underlying problems of datafalsification and manipulation. Phase I: GC InvestigationYour GC Investigation was limited to review of audit trails for batches analyzed on GCs #052 and #202between January and August, 2013. Although your investigation found multiple examples of deficientdata management and retention practices, you concluded that none of the deviations were consideredcritical. You also concluded that there was no product or patient risk associated with these deviations.You closed this phase of the investigation on November 27, 2013, without implementing effectivecorrective actions and preventive actions. Our investigator reviewed the same data and audit trail records that you included in your owninvestigation. In the limited time available during the inspection, our investigator found seriousdeficiencies and questionable data management practices that your own four-month investigation didnot identify, including:altering time and date settings of computerized equipment using the software administrator’s access

1/5/2016 DiamoDentDiamoDent. Product: class II dental prosthetic permanent and temporary implants and abutments Date: 1/5/2016This inspection revealed that these devices are adulterated within the meaning of section 501(h) of theAct, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for, theirmanufacture, 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. .ailure to adequately validate software used as part of production and quality systems for its intendeduse according to an established protocol, as required by 21 CFR 820.70(i). Specifically, you did notvalidate any software programs of your (b)(4) machines used to manufacture all your devices. Per youremployee, there are hundreds of tooling programs to make hundreds of different device parts asspecified in your product catalogue. Examples include, but are not limited to, software and toolingprograms for the following devices: Cement-On Post HEXED, TiteFit (Part no. 13347), Cement-On Post4mm COLLAR, 4.5mm PROFILE (Part no. 13040) and Implant Analog Aluminum (Part no. 11013-01). We reviewed your response and conclude that it is not adequate since you did not provide completedocumentation of your corrections and not enough details of your proposed corrections were submittedfor our review, such as the scope of the software validation and which devices are covered under thesoftware validation. We understand that you are implementing your “Process Validation” SOP-25, Rev.B and planned to complete software validation by October 30, 2015. In response to this Warning Letter,you should provide us with an update of these activities, including details of specific devicesinvolved.FDA District Office: Los Angeles District

12/31/2015 Zhejiang Hisun Pharmaceutical Co., Ltd.Zhejiang Hisun Pharmaceutical Co., Ltd.. Product: pharmaceutical manufacturing facilities Date: 12/31/2015We identified significant deviations from current good manufacturing practice (CGMP) for themanufacture of active pharmaceutical ingredients (API). These deviations cause your drugs to be adulterated within the meaning of Section 501(a)(2)(B) of theFederal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(B), in that the methods used in,or the facilities or controls used for, their manufacture, processing, packing, or holding do not conformto, or are not operated or administered in conformity with, CGMP. Our investigators observed specific deviations during the inspection, including, but not limited to, thefollowing.1. Failure to prevent unauthorized access or changes to data, and to provide adequate controls toprevent manipulation and omission of data. During the inspection, FDA investigators discovered a lack of basic laboratory controls to preventchanges to your firm’s electronically stored data and paper records. Your firm relied on incompleterecords to evaluate the quality of your drugs and to determine whether your drugs conformed withestablished specifications and standards. Our investigators found that your firm routinely re-tested samples without justification and deletedanalytical data. We observed systemic data manipulation across your facility, including actions taken bymultiple analysts, on multiple pieces of testing equipment, and for multiple drugs. You are responsiblefor determining the causes of these deviations, for preventing recurrence, and for preventing otherdeviations from CGMP. a. During the inspection, we reviewed the electronic log for high performance liquid chromatography(HPLC) system #36 and determined that the audit trail was disabled on February 6, 2014. One of youranalysts executed 80 HPLC injections for assay and impurity tests of validation stability batches (b)(4)of (b)(4) API. Because the audit trail was disabled, neither your quality unit nor your laboratory staff coulddemonstrate that records for these batches included complete and unaltered data. All supporting rawdata was discarded, including sample solution dilutions and balance weight printouts. Sample analyses


were not recorded in the instrument use logbook. Test results were deleted from the hard drive and allsupporting chromatograms were discarded. Audit trail functions were re-enabled on February 8, 2014,and the same analyses were repeated. You submitted the February 8th test results to the FDA in March2014 in support of Drug Master File (DMF) (b)(4). During the inspection, we asked the analyst who generated the data submitted to the FDA whether audittrails could be disabled. The analyst stated that another employee, who was no longer with thecompany, had disabled the audit trails. Your firm could not explain why the audit trail was disabled orwhy the original data was deleted, nor could you demonstrate whether the original results were withinspecification. In your response, you assumed that the original raw data was deleted because a system suitabilityfailure invalidated the data. You acknowledged that the data should not have been invalidated withoutan investigation of the laboratory event. However, your response is inadequate. There is no evidence tosupport invalidation of the original data on the grounds of a system suitability failure because your firmdeleted all of the original records associated with these analyses.c. While reviewing the audit trail on HPLC system #28, we determined that one of your analystsperformed trial HPLC injections during assay and impurities testing for batches of (b)(4) API ((b)(4) and(b)(4)). These trial injections were performed on May 4-6, 2014. The data for the sample set wasdeleted from the system. Testing was not recorded in the instrument use logbook. All supportingelectronic raw data was discarded. Testing results for these batches were then recorded on May 7,2014, when the analyses were repeated using HPLC system #32. During our inspection, one of your analysts provided the original analyses worksheets to review.According to this analyst, tests were repeated because of poor column efficiency. The analyst neitherinitiated an investigation of the laboratory event nor documented the original analyses in the instrumentuse logbook. The analyst did not respond when we asked why the initial chromatograms were deleted. However, in your written response, you claimed that this analyst later recalled deleting the data(chromatogram) because column inefficiency may have invalidated the data. Your quality unit mustreview all pertinent analytical data when making batch release decisions. When analysts deletenonconforming test results, the quality unit is presented with incomplete and inaccurate informationabout the quality of the products. Your response does not demonstrate how your laboratory proceduresprevent the deletion of data or how the quality unit ensures that the records relied upon for batchrelease and other quality review decisions are complete and accurate. Our concerns about deletion of data are heightened by the significant number of customer complaintsfor subpotency and out-of-specification (OOS) impurity levels from 2012-2014. We observed datadeletion in your laboratory related to assay and impurity levels during this time period. During theinspection, we asked to review your lab’s raw analytical data of the lots associated with four of the 61complaints. However, you were unable to provide the raw data because it had been deleted. Withoutraw test data for the lots associated with these complaints, your firm could not adequately investigatethe complaints, nor could you expand your investigation to determine whether other lots were affectedby the same problems or take corrective actions, such as recalling drugs if appropriate. We acknowledge your commitment to hire a third-party consultant, set up user access restrictions, andupgrade computerized systems with audit trails. However, simply activating audit trail functions andinstituting password controls are insufficient to correct the broad data manipulation and deletionproblems observed at your facility and to prevent their recurrence. Your management is responsible for the assuring that the scope and extent of the third party audit isadequate, including a full evaluation of sophisticated electronic systems and their potential formanipulation. Your management is also responsible for fully documenting and preserving records.FDA District Office: CDRH


12/23/2015 Cadila Healthcare LimitedCadila Healthcare Limited. Product: pharmaceutical manufacturing facilities Date: 12/23/2015Our investigators observed specific violations during the inspection, including, but not limited to thefollowing.Your firm failed to exercise sufficient controls over computerized systems to prevent unauthorizedaccess or changes to data. a. Your firm failed to adequately control the use of computerized systems in the quality controllaboratory. Our inspection team found that the laboratory manager had the ability to delete data from theKarl Fischer Tiamo software. During our limited review of your Karl Fischer data, we found that one filehad been deleted. However, because the audit trail function for the Karl Fischer Tiamo software was notactivated, and because eight different analysts share a single username and password, you wereunable to demonstrate who performed each operation on this instrument system. You do not have arecord of the acquisition of all data, nor do you have records of changes to or modifications of suchdata. FDA District Office: CDRH

12/17/2015 Sun Pharmaceuticals Industries Ltd..Sun Pharmaceuticals Industries Ltd.. Product: pharmaceutical manufacturing facilities Date: 12/17/2015Our investigators observed specific violations during the inspection, including, but not limited to thefollowing.6. Your firm failed to establish appropriate controls over computers and related systems to assure thatchanges in master production and control records or other records are instituted only by authorizedpersonnel (21 CFR 211. 68(b)). You lacked audit trails or other sufficient controls to facilitate traceability of the individuals who accesseach of the programmable logic controller (PLC) levels or Man-Machine Interface (MMI) equipment.You had no way to verify that individuals have not changed, adjusted, or modified equipment operationparameters. Access to production equipment used in parenteral manufacturing and solid (b)(4) dosage forms used apassword shared by four or five individuals to gain access to each individual piece of equipment andaccess level. During our inspection, your Executive Production and QA manager confirmed that thepassword was shared. Neither your operators nor your supervisors had individual passwords. During our inspection, firm officials also confirmed that you had not established or documented a controlprogram to describe the roles and responsibilities of production equipment system administrators.There was also no record documenting the individuals who have access to the production equipment orthe manner in which individual personnel access production equipment. In your response, you indicated that you have performed a comprehensive review of the PLCs andmanufacturing equipment associated with the production of parenteral and solid (b)(4) dosage forms toassess your access controls and traceability to individual operators. You suggested that traceability tothe individual operator could be determined through a hybrid system using the batch manufacturingrecord and equipment logbook. However, because you used shared login credentials that did not permitidentification of a specific person using the shared login, you have not shown how your hybrid systemcould link specific actions to a specific operator.


In your response, you also stated that you will conduct a retrospective risk assessment to evaluate theeffects of your deficient computerized system controls on the quality of the products manufacturedusing this automated equipment. However, you did not indicated the timeframe for your review, yourcriteria for evaluating the effects of these deficiencies on your products, or any actions needed forproducts within expiry. Finally, in your response, you indicated that you planned to (b)(4). Your response is inadequatebecause you did not indicate what controls you will implement in the interim to assure that onlyauthorized personnel change your production or other records. In response to the letter, provide your retrospective review and risk assessment of lots manufacturedusing equipment with shared passwords. Explain how you will identify which operators or personnelperformed and recorded specific activities, your criteria for evaluating how manufacturing and quality ofyour products has been affected by your deficient controls, and any actions needed to assure thequality, safety, and efficacy of products within expirry. FDA District Office: CDRH

11/5/2015 Dr. Reddy’s Laboratories Ltd.Dr. Reddy’s Laboratories Ltd. Product: pharmaceutical manufacturing facilities Date: 11/5/2015At Dr. Reddy’s Laboratories Limited CTO Units VI and V facilities, we identified significant deviationsfrom current good manufacturing practice (CGMP) for the manufacture of active pharmaceuticalingredients (APIs). At Dr. Reddy’s Laboratories Limited Unit-VII facility, we found significant violationsof CGMP regulations for finished pharmaceuticals, Title 21, Code of Federal Regulations, Parts 210 and211. These deviations and violations cause your APIs and finished drug products to be adulterated within themeaning of Section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (the FD&C Act), 21U.S.C. 351(a)(2)(B). The methods used in, or the facilities or controls used for, their manufacture,processing, packing, or holding do not conform to, or are not operated or administered in conformitywith, CGMP. We reviewed your firm’s responses of December 15, 2014, February 19, 2015, and March 27, 2015. We note that they lack sufficient corrective actions. We received your additional correspondence ofJanuary 31, April 9, May 13, May 21, July 14, and September 14, 2015. Our investigators observed specific deviations and violations during the inspection, including, but notlimited to, the following.2. Failure to prevent unauthorized access or changes to data, and to provide adequate controls toprevent omission of data. During the inspection we found the following examples of uncontrolled access to electronic systemsused to generate data in your Product Development Laboratory (PD Lab). a. Your HPLC systems are configured so that no passwords are required to log in. Credentials areunverified. Anyone who accesses the system can use software administrator privileges, which meansthat there is no electronic or procedural control to prevent manipulation of data. b. Your HPLC system had no access controls to prevent alteration or deletion of data. Furthermore,your HPLC software lacked an audit trail feature to document all activities related to thechromatographic analysis. Because of this failure, neither your quality unit nor your laboratory staffcould demonstrate that HPLC records included complete and unaltered data. They were also unable toverify that there had been no alterations or deletions.


c. One of your analysts stated that another, unknown individual had logged into the system using theanalyst’s credentials. This unknown individual performed injections and deletions without the analyst’sknowledge. FDA District Office: CDRH

9/30/2015 Merge Healthcare, Inc.Merge Healthcare, Inc.) Product: software used in clinical settings to manage patient data Date: 9/30/2015inspections revealed that your firm's devices are adulterated within the meaning of section 501 (h) ofthe Act, 21 U.S.C. § 351 (h), in that the methods used in, or the facilities or controls used for, theirmanufacture, packing, storage, or installation are not in conformity with the current good manufacturingpractice requirements of the Quality System (QS) regulation found at Title 21, Code of FederalRegulations (CFR), Part 820.Failure to adequately establish procedures for design validation, as required by 21 CFR 820.30(g).Specifically, QS-57532 (Rev. 2.0, ?WI-Customer Validation Process?) allows for devices that have notyet fully completed design validation, including software validation, to be shipped to end users forclinical use on patients in a ?Limited Availability? basis for the purpose of collecting additional feedbackprior to the completion of design validation activities. Further, the Merge HEMO V10.0 was shipped to(b)(4) end users for clinical use in cardiac catheterization procedure labs as part of the firm?s designvalidation plan as a ?Limited Availability? release; these devices had not been fully validated.Additionally, document number HEMO-6830 (Rev. 1.0, ?Customer Validation Plan Merge Hemo 10.0)describes the customer validation process conducted at the two end user facilities during the?Pre-Release/Limited Availability? release timelines where it is indicated the software will be used in a?production environment,? i.e. for patient use. We have reviewed your response dated August 12, 2015. We acknowledge your commitment toupdating your design validation procedure. However, your response is inadequate in that you have notprovided an updated procedure for review, nor have you provided a timeframe for implementation ofyour new design validation process. It is also unclear whether other in-progress design projects may beaffected by your elimination of the ?Limited Availability? release, including whether any of your devicesare currently being utilized by end users prior to completion of design validation. FDA District Office: Minneapolis District

9/28/2015 Unimark Remedies LtdUnimark Remedies Ltd Product: active pharmaceutical ingredients Date: 9/28/2015Failure to prevent unauthorized access or changes to data and to provide adequate controls to preventomission of data. Your laboratory systems lacked access controls to prevent raw data from being deleted or altered. Forexample: a. During the inspection, we noted that you had no unique usernames, passwords, or user accesslevels for analysts on multiple laboratory systems. All laboratory employees were granted full privilegesto the computer systems. They could delete or alter chromatograms, methods, integration parameters,and data acquisition date and time stamps. You used data generated by these unprotected anduncontrolled systems to evaluate API quality. b. Multiple instruments had no audit trail functions to record data changes. We acknowledge your commitment to take corrective actions and preventive actions to ensure that yourlaboratory instruments and systems are fully compliant by January 15, 2015. In response to this letter,provide a copy of your system qualification to demonstrate that your electronic data systems prevent


deletion and alteration of electronic data. Describe steps you will take (e.g., installing better systems orsoftware) if your qualification efforts determine that the current system infrastructure does not assureadequate data integrity. Explain the archival process your firm has implemented to address theseissues and how you will evaluate the effectiveness of these corrections. Provide a detailed summary ofthe steps taken to train your personnel on the proper use of computerized systems. Failure to maintain complete data derived from all testing, and to ensure compliance with establishedspecifications and standards. Because you discarded necessary chromatographic information such as integration parameters andinjection sequences from test records, you relied on incomplete records to evaluate the quality of yourAPIs and to determine whether your APIs conformed with established specifications and standards. For example: a. During the inspection, the investigator found no procedures for manual integration or review ofelectronic and printed analytical data for (b)(4) stability samples. Electronic integration parameters werenot saved or recorded manually. When the next samples were analyzed, the previous parameters wereoverwritten during the subsequent analyses. b. We found that some analytical testing data was inadequately maintained and reviewed. i. Your HPLC 14 computer files included raw data for undocumented (b)(4) stability samples analyzedon December 30, 2013, but no indication of where these samples came from and why they were tested.ii. In a data file folder created on May 22, 2013, 23 chromatograms were identified as stability samplesfor (b)(4) lots (b)(4), and (b)(4). Results were not documented. More importantly, the acquisition datewas July 7, 2013, more than six weeks after the samples were run. iii. (b)(4) lots (b)(4) and (b)(4) were not in your stability study records at the time of inspection.Additionally, there were no log notes of any samples from the three lots removed from the stabilitychamber. You responded that ?the probable reason for this inconsistency in data acquisition was due to somemalfunction in the computer system at the time of data acquisition.? Your response is inadequatebecause you have provided neither evidence to support this conclusion, nor a retrospective review ofthe effects your incomplete analytical data records may have had on your evaluation of API quality. In response to this letter, provide your revised procedures and describe steps you have taken to retrainemployees to ensure retention of complete electronic raw data for all laboratory instrumentation andequipment. Also, provide a detailed description of the responsibilities of your quality control laboratorymanagement, and quality assurance unit for performing analytical data review and assuring integrity(including reconcilability) of all data generated by your laboratory. FDA District Office: CDRH

8/12/2015 Hoya Corporation (PENTAX Life CareDivision)Hoya Corporation (PENTAX Life Care Division) Product: endoscopes and endoscope accessories. Date: 8/12/2015inspections revealed that your firm's devices are adulterated within the meaning of section 501 (h) ofthe Act, 21 U.S.C. § 351 (h), in that the methods used in, or the facilities or controls used for, theirmanufacture, packing, storage, or installation are not in conformity with the current good manufacturingpractice requirements of the Quality System (QS) regulation found at Title 21, Code of FederalRegulations (CFR), Part 820.Failure to establish and maintain procedures for implementing corrective and preventive action, asrequired by 21 CFR 820.100(a). For example: FDA District Office: CDRH


8/7/2015 Cardiac Designs, Inc.Mylan. Product: ECG Check Application and ECG Check Wireless Lead Cardiac Monitor Date: 8/7/20151. Failure to establish and maintain design validation procedures to ensure that devices conform todefined user needs and intended uses and shall include testing of production units under actual orsimulated use conditions, as required by 21 CFR 820.30(g). 1. Your firm?s ?Design Validations? procedure Revision 1 dated May 22, 2015, states software shouldbe tested according to a test plan and requires the results of this software validation to be maintained inthe design history file (DHF). Your firm does not have any records demonstrating the ECG CheckApplication software was validated.2. Failure to establish procedures for receiving, reviewing, and evaluating complaints by a formallydesignated unit, as required by 21 CFR 820.198. a. Your ?Customer Requirements and Complaints? procedure revision 2 dated August 24, 2014, isinadequate. Your firm is currently using a contractor to receive and initially document allcommunications; however, your complaint handling procedure does not address this practice. Further,your procedure does not address how you will receive, review, and verify complaints are beingforwarded from your contract complaint handling company, to conduct the complaint investigations. b. Your ?Customer Requirements and Complaints? procedure revisions 1 and 2, dated May 22, 2013and August 24, 2014, respectively; require all complaints be documented on your ?Customer ComplaintReport Form?. However, your complaint log showed your firm received at least 87 complaints betweenApril 4, 2014 and June 15, 2015 and these complaints were not documented on your ?CustomerComplaint Report Form?. Further, there are no records showing these complaints were reviewed todetermine if an investigation was necessary or if they were evaluated to determine if they werereportable events as defined in 21 CFR 803. c. On December 16, 2014, your firm received a complaint indicating a possible failure of your ECGCheck Monitor and software to detect an abnormal heart condition. There is no record this complaintwas evaluated to determine if it was reportable under 21 CFR 803. In addition, there is no record for thiscomplaint demonstrating the nature and details of the complaint, whether the device failed to meetspecifications, or the relationship of the device to the event.FDA District Office: Dallas district

8/6/2015 MylanMylan. Product: pharmaceutical manufacturing facility Date: 8/6/2015Your firm failed to exercise appropriate controls over computer or related systems to assure that onlyauthorized personnel can change master production and control records, or other records (21 CFR211.68(b)). Your Siemens computer-based BMS and NVPMS do not require passwords to access the network andservers. Your contractors? access is uncontrolled. Responsibilities for system administrators areundefined. This violation is recurrent. On September 9, 2013, we cited your firm in Warning Letter 320-13-26 forfailure to exercise appropriate controls over computer or related systemsFDA District Office: CDRH


7/13/2015 Mahendra ChemicalsMahendra Chemicals.. Product: pharmaceutical manufacturing facility Date: 7/13/2015Failure to prevent unauthorized access or changes to data, and to provide adequate controls to preventomission of data. Your laboratory systems lacked access controls to prevent raw data from being deleted or altered. Forexample, a) There is no assurance that you maintain complete electronic raw data for your GasChromatography (GC) instrument. FDA investigators observed multiple copies of raw data files in therecycle bin connected to the GC instrument QC-04 even in the presence of ?Do Not Delete Any Data?notes posted on two laboratory workstation computer monitors. b) Employees were allowed uncontrolled access to operating systems and data acquisition softwaretracking residual solvent, and test and moisture content. Our investigators noted that there was nopassword functionality to log into the operating system or the data acquisition software for the GC, theHigh Performance Liquid Chromatography (HPLC) instrument QC-17, or the Karl Fischer (KF) TitratorQC-13. c) HPLC SpinChrome and GC Lab Station data acquisition software lacked active audit trail functionsto record changes in data, including original results, who made changes, and when. In your response, you state that your laboratory GC, HPLC and KF systems are nowpassword-protected and that you have begun drafting analytical software password procedures for theGC, HPLC and KF laboratory instruments. However, your response does not state whether everyanalyst will have their own user identification and password. You also mention plans to install avalidated computer system. However, you did not provide a detailed corrective action and preventiveaction (CAPA) plan or conduct a review of the reliability of your historical data to ensure the quality ofyour products distributed to the U.S. market. Inadequate controls of your computerized analytical systems raise questions about the authenticity andreliability of your data and the quality of your APIs. It is essential that your firm implements controls toprevent data omissions or alterations. It is critical that these controls record changes to existing data,such as the individuals making changes, the dates, and the reason for changes. FDA District Office: CDRH

5/27/2015 VUAB Pharma a.s.VUAB Pharma a.s.. Product: pharmaceutical manufacturing facility Date: 5/27/2015ailure to prevent unauthorized access or changes to data and to provide adequate controls preventingdata omissions. Our inspection noted that your firm did not retain complete raw data from testing performed to assurethe quality of (b)(4), API. Specifically, our inspection revealed your firm did not properly maintain aback-up of HPLC chromatograms that form the basis of your product release decisions. Our inspectionrevealed discrepancies between the printed chromatograms and the operational qualification protocolfor the High Performance Liquid Chromatography (HPLC) system, which is intended to demonstratecorrect operation of the HPLC. These discrepancies included injection sequences and values tocalculate relative standard deviation (RSD). While investigating these discrepancies, our investigator requested the original electronic raw data.Your quality unit, after consulting with the Information Technology (IT) department, stated they were


unable to retrieve the original electronic raw data because back-up discs were unreadable. Your qualityunit then stated that back-up disks have been unreadable since at least 2013. Your HPLC system isused to test (b)(4), API for batch release. However, without complete, accurate, reliable, or retrievableraw data about the HPLC system?s qualification, you lacked complete assurance that the system wasoperating as intended. You also failed to have proper controls in place to prevent unauthorized manipulation of yourlaboratory?s raw electronic data. Our inspection revealed your HPLC system did not have accesscontrols to prevent alteration or deletion of data. Your HPLC software lacked an audit trail recording anychanges to the data, including: previous entries, who made changes, and when changes were made.During the inspection, we also noted that all laboratory employees shared a common log-in andpassword to access the system. This lack of control over the integrity of your data raises questions about your analytical data?sauthenticity and reliability, and about the quality of your APIs. We note that the September 2008 FDAinspection uncovered concerns over your handling of raw analytical data, including discrepanciesbetween laboratory notebooks and printed chromatograms. Your response states you are qualifying a new HPLC system which allows operator-specific passwordsand has audit trial and back-up functions. Your response also states you will implement a newelectronic back-up system in your QC chemistry department.However, your response lacks sufficient detail about systems and controls you will implement. Simplyactivating audit trail functions and instituting password controls is inadequate. In addition, you failed toreview historical data to ensure the quality of your products distributed to the US market.In your response to this letter, provide a comprehensive corrective action plan for computer systemcontrols over all laboratory and manufacturing instrumentation and equipment. This response shouldinclude but not be limited to: Information regarding changes in the reliability of your information technology infrastructure, includingbut not limited to improved computer systems, systems validation, revised procedures, and appropriateretraining of employees that will be implemented immediately to ensure your firm creates and retainscomplete and accurate electronic raw data. Your firm's procedure for the establishment, issuance, and control of passwords used to access youranalytical instrumentation. All access levels for computerized systems should be clearly defined anddocumented in a written procedure.A detailed summary of the steps taken to train your personnel on the proper use of computerizedsystems.FDA District Office: CDRH

4/30/2015 Soft Computer Consultants, Inc.Soft Computer Consultants, Inc. Product: Class I/II software systems Date: 4/30/20151. Failure to adequately establish procedures for CAPA as required by 21 CFR 820.100(a). Specifically,A. Product Change Controls (PCCs) which are corrective and preventive actions for handling softwarecoding defects do not always include investigating the cause of all nonconformities relating to product,processes and the quality system, and identifying action(s) needed to correct and prevent recurrence ofnonconforming product and other quality problems. For example;i. PCC-54168 dated 4/25/14 was a CAPA for investigating a software defect in (b)(4) for clients usingthe Results Reporting interfaces to send results to an (b)(4) or (b)(4)system. The defect was that the interface fails to send the abnormal flags for Reference Lab testresults. This affects the flag that indicates the result is abnormal. Caregivers, who rely on the abnormalflag rather than the results may come to an incorrect conclusion. The PCC- 54168 identified a softwarecoding error as the assignable cause of this problem. Your firm also identified that the softwareinterface between your software and other software was not fully tested. A mandatory software Hot Fix


was created due to the severity of the failure mode. The mandatory Hot Fix led to a correction andremoval (1058332-10/13/2014-002- C). This PCC did not include the following:a. An analysis to determine if other software products manufactured have had similar failure modes dueto lack of testing of software interfaces.b. Software testing that was created for verifying this corrective action was not included in the repositoryof tests known as (b)(4) tests as required by your (b)(4) Testing Procedure, SOP TST_P005, to allowthese tests to be run for future software changes.http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2015/ucm448655.htm 2/86/3/2015 2015 > Soft Computer Consultants, Inc. 4/30/15ii. PCC-52730 dated 12/31/13 was a CAPA for investigating a software defect in (b)(4) version (b)(4)when used with (b)(4) version (b)(4). The problem was that when an isolate is resulted without aSNOWMED code, the isolate information in the downstream system may be incomplete or missing. Asa result, there is a potential for the delay or omission of patient treatment updates. Your firm identified asoftware error as the assignable cause of this problem. Your firm also identified that the softwareinterface between the (b)(4) system and (b)(4) was not fully tested which would have identified thesoftware defect. A mandatory software Hot Fix was created due to the severity of the failure mode. Themandatory Hot Fix led to a correction and removal (1058332-10/13/2014-001-C). This PCC did notinclude the following:a. An analysis to determine if other software products manufactured have had similar failure modes dueto lack of testing of software interfaces.2. Failure to adequately establish procedures to ensure that all purchased or otherwise received productand services conform to specified requirements as required by 21 CFR820.50. Specifically,A. Quality contracts for the design contractors ((b)(4) & the (b)(4)) who perform design of software donot include a provision that the design contractors agree to notify your firm of changes in the productcode or service so that your firm may determine whether the changes may affect the quality of theproduct provided.B. According to the VP of Administration and the VP of Genetics and Anatomic Pathology (AP) who areboth responsible for conducting supplier audits of the contractors in (b)(4) and in the (b) (4), the supplieraudits of the facilities are reportedly to be conducted (b)(4). The supplier audits are divided into twocategories Administrative and Technical. Administrative audits covered reviewing the Quality contract,verifying employee training and experiences are suitable at the respective contract facilities. Technicalaudits include auditing design projects, adherence to design control requirements, and adherence tostandard operating procedures. Review of the documents provided identified the following:i. There is no documented evidence that Technical supplier audits for the (b)(4) contract facility wereconducted for 2012 and 2013. The Technical supplier audit conducted for September 2014 for the(b)(4) facility has not been reviewed or approved as required by your Conducting External Quality AuditsProcedure, SOP AUD_P003.ii. There are no corresponding Quality Audit Plans as required by SOP for any Technical supplier auditsfor the (b)(4) contracting facility for 2012, 2013, or 2014.3. Failure to establish and maintain procedures for design change, as required by 21 CFR 820.30(i).Specifically,A. The software changes made by your firm and the (b)(4) and (b)(4) contractors are not assessed byyour firm to confirm that the design changes meet their intended use and conform to all of yourrequirements including all verification and validation activities. The following are examples:i. The Hot Fixes used to correct design defects for (b)(6) that were part of the correction and removalsubmitted to FDA on or about 12/10/14. The software changes were made by the (b)(4) contractor.ii. The Hot Fixes used to correct design defects for (b)(6) that were part of the correction and removalsubmitted to FDA on or about 11/4/14. A portion of the software changes were made by the (b)(4)contractor.iii. The Hot Fixes used to correct design defects for (b)(6) that were part of the correction and removalsubmitted to FDA on or about 2/17/14. The software changes were made by your firm.B. User requirements (design inputs) are not required by either your firm or any of your contractingorganizations for any software custom scripts created that can be used as part of a software Hot Fix


(software correction made to a customer). Hot fixes are used as an emergency or high priority changethat needs to be made when the client or your firm cannot wait for the normal patch process for anyproduct manufactured by your firm.For example, the Hot Fix utility used to identify the design defects for (b)(6) did not includedocumentation of user requirements (design inputs) for the Hot Fix utility 1.18021.1. This Hot Fix utilityfor the (b)(4) software was used to identify defective records in the customer's database and was a partof the correction and removal submitted to FDA on or about 12/11/14. Your Hot Fix Process, SOPG01D072, does not include any requirements for documenting design inputs forhttp://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2015/ucm448655.htm 5/86/3/2015 2015 > Soft Computer Consultants, Inc. 4/30/15custom scripts.4. Failure to establish and maintain procedures for design review as required by 21 CFR 820.30(e).Specifically,There was no evidence to demonstrate that the Release notes for Hot Fix utility 1.18021.1 used toidentify defective records in the customer's database for software package (b)(4) were reviewed andapproved. Under section 5.2d of your Release Note Processing Workflow Procedure, G04S1082, theproduct specialist or designee is required to review the release notes and place them in the publishedstatus prior to going live (release). This Hot Fix utility was part of a correction and removal submitted toFDA on or about 12/11/14. The Release notes are provided to the customer or your personnel for allsoftware changes. FDA District Office: Florida District

4/11/2015 Quality Electrodynamics, LLCQuality Electrodynamics, LLC.. Product: cois used in conjunction with MRI scanners . Date: 4/10/2015Failure to document validation activities, as required by 21 CFR 820.75(a). Specifically, The setting (temperature and line speed) used during the validation studies for the reflow oven, which ispart of the SMT (Surface Mount Technology) line, to determine the optimum settings were notdocumented. Therefore, it is unknown if you are currently operating the reflow oven within yourvalidated parameters. Your response dated March 26, 2015 cannot be assessed at this time. The response states that youhave placed all 176 oven reflow profiles under the change control process and revised your ?Validationof Processes and Software? procedure, SOP 021; and training is ongoing. You are also working with anSMT (Surface Mount Technology) expert to aid in monitoring the process capability and control of theSMT line. Additionally, you have ordered new process monitoring equipment. Please provide an updateon the progress of these corrective actions. FDA District Office: Cincinnati District

4/6/2015 Yunnan Hande Bio-Tech. Co. Ltd.Recipient: Yunnan Hande Bio-Tech. Co. Ltd.. Product: active pharmaceutical ingredients . Date: 4/6/2015Our investigators observed specific deviations during the inspection, including, but not limited to, thefollowing: 1. Failure to prevent unauthorized access or changes to data and to provide adequate controls toprevent omission of data. You lacked controls to prevent the unauthorized manipulation of your laboratory's electronic raw data.Specifically, your infrared (IR) spectrometer did not have access controls to prevent deletion oralteration of raw data. Furthermore, the computer software for this equipment lacked active audit trail


functions to record changes to data, including information on original results, the identity of the personmaking the change, and the date of the change. Audit trails that capture such critical data about thequality of your batch production should be reviewed as part of the batch review and release process. We acknowledge your commitment to upgrade the IR software by adding full audit trail capabilities incompliance with CGMP. In your response, you also commit to obtain information about the (b)(4)archival of all data obtained on laboratory computerized systems, and to evaluate software upgrades toother instrumentation. However, your response is inadequate because you have not specified how youwill ensure the integrity of raw analytical data or maintain data before you complete your plannedcorrective actions and preventive (CAPA) actions. In response to this letter, provide your comprehensive CAPA plan for ensuring that electronic datagenerated in your manufacturing operations, including laboratory testing, cannot be deleted or altered. It essential that your firm implement controls that prevent the omission of data, and record informationabout changes to existing data, such as the date of the change, identity of person who made thechange, and an explanation or reason for the change. Any such changes should be made inaccordance with an established and appropriate procedure. Your response should address yourlaboratory equipment and any other manufacturing-related equipment that may be affected by the lackof adequate controls to prevent data manipulation FDA District Office: CDRH

3/31/2015 Hospira S.p.A.Hospira S.p.A.. Product: Hospira S.p.A. Date: 3/31/2015Your firm failed to exercise appropriate controls over computer or related systems to assure that onlyauthorized personnel institute changes in master production and control records, or other records (21CFR 211.68(b)). Specifically, your high performance liquid chromatography (HPLC) and gas chromatography (GC) dataacquisition software, TotalChrom®, did not have sufficient controls to prevent the deletion or alterationof raw data files. During the inspection, the investigator observed that the server that maintainselectronic raw data for HPLC and GC analyses (the J drive) contains a folder named ?Test,? and thatchromatographic methods, sequences, and injection data saved into this folder can be deleted byanalysts. The investigator also found that data files initially created and stored in the ?Test? folder hadbeen deleted, and that back-up files are overwritten (b)(4). In addition, because no audit trail function was enabled for the ?Test? folder, your firm was unable toverify what types of injections were made, who made them, or the date or time of deletion. The use ofaudit trails for computerized analytical instrumentation is essential to ensure the integrity and reliabilityof the electronic data generated. Your response indicates that you have added computer controls to prevent the deletion of folders andfiles in the J drive for electronic raw data. However, you provide no evidence demonstrating how yourfirm will prevent deletion of newly created folders and files in each of your computer systems. Weacknowledge your commitment to hire a third party consultant to address the inadequacies of your datasystems. However, your response is inadequate as it fails to address how you will enable and reviewaudit trail functions for all of your analytical computer systems. In response to this letter, provide specific details about the comprehensive controls in place to ensurethe integrity of electronic raw data generated by all computer systems used to support the manufactureand testing of drug products. Your response should demonstrate an understanding of your processesand the appropriate controls needed for each stage of manufacture that generates electronic raw data,as well as for your laboratories. FDA District Office: CDRH


2/27/2015 Novacyl (Thailand), Ltd.Novacyl (Thailand), Ltd. Product: active pharmaceutical ingredients (APIs) Date: 2/27/20153. Failure to prevent unauthorized access or changes to data and to provide adequate controls toprevent omission of data. The inadequate controls over access to your data raise questions about the authenticity and reliability ofyour data and the quality of the APIs you produce. Specifically, a. Your firm did not have proper controls in place to prevent the unauthorized manipulation of yourlaboratory?s raw electronic data. Your HPLC computer software lacked active audit trail functions torecord changes to analytical methods, including information on original methodology, the identity of theperson making the change, and the date of the change. In addition, your laboratory systems did nothave access controls to prevent deletion or alteration of raw data. During the inspection, your analystsdemonstrated that they were given inappropriate user permissions to delete HPLC data files. b. Moreover, the gas chromatograph (GC) computer software lacked password protection allowinguncontrolled full access to all employees. Your response states that you commit to upgrading your HPLC systems to have audit trails and yourGC system to have password protection by July 31, 2014. However, your response lacks sufficientdetail of the systems and controls you will implement. Simply turning on audit trail functions isinadequate. In addition, you failed to review historical data to ensure the quality of your productsdistributed to the US market. In response to this letter, provide specific details about the comprehensive controls in place to ensurethe integrity of electronic raw data generated by all computerized systems during the manufacture andtesting of your drugs. Your response should demonstrate an understanding of your processes and theappropriate controls needed for each stage of manufacturing and testing that generates electronic rawdata. Your response should also describe the controls and procedures you will implement to retain andarchive the raw data you generate. FDA District Office: CDRH

2/20/2015 XZeal Technologies, Inc.XZeal Technologies, Inc. Product: XZeal Dental X-Ray Unit Z70 Date: 2/20/20151. Failure to establish and maintain procedures for validating the device design, as required by 21CFR 820.30(g). For example: b. Your firm has not established and maintained documentation in support of Section 4.6 - DesignValidation of the Product - Conception and Development, PR0-04.01, Ver. 00, concerning softwarevalidation of the embedded software for the device. Specifically, you stated to our investigator that yourfirm is not responsible for the software because your firm does not manufacture it. You also stated toour investigator your firm did not know what, if any, validation activities were performed by your firm?sChinese supplier for this software. In addition, your firm?s Risk Analysis Report ? Software, Ver. 00, Technical File, does not adequatelyaccess the risk presented by the software controlling the XZeal Dental X-Ray Unit Z70 as a moderaterisk to users and patients. For example, the report indicates a ?No? to the questions: ?Could amalfunction of, or a latent design flaw in the Software Device lead to an erroneous diagnosis or a delayin delivery of appropriate medical care that would likely lead to Moderate Injury? and ?Does theSoftware Device control the delivery of potentially harmful energy that could result in death or serious


injury, such as radiation treatment systems, defibrillators and ablation generators.? Your firm?s October 7, 2014 response includes reference to assembly operational checks or functional(Black-box) testing of the XZeal Dental X-Ray Unit Z70. Adequate software validation of the XZealDental X-Ray Unit Z70 software would require more than functional testing, including but not limited to adescription of software (i.e.: Title, Manufacturer, Version Level, Release Date, etc.); control ofcapabilities of end user; reliability of functionality; maintenance and control of software versions; andadequate software hazard analysis. FDA District Office: Florida District

2/19/2015 Inovo, IncInovo, Inc Product: AccuPulse Model 6505 oxygen conserver, Bonsai Velocity oxygen conserver, Evolutionoxygen conserver, Evolution with Motion oxygen conserver, SmartDose oxygen conserver, Smart DoesMini oxygen conserver, Oxymizer Disposable oxygen conservers, and oxygen Regulators. Date: 2/19/20154. Failure to establish and maintain procedures for validating the device design, as required by 21CFR 820.30(g). Specifically, a. Your software development /validation: i. does not include written procedures covering the development/validation of the software used inyour devices; ii. documentation for your Evolution Oxygen Conserver device does not include structural testing atthe code level (use of static code checkers, independent code review, etc); and iii. software product testing procedure, Database/Software Controls IQP 030 Rev A dated 10/20/08,does not require structural testing and does not include provisions for the adequate description ofregression testing.We reviewed your firm?s responses and conclude that they are not fully adequate. a) The revisions to your software procedures and the initiation of the added testing requirements donot appear to timely relative to the criticality of this deficiency.FDA District Office: Florida District

1/30/2015 Apotex, Inc.Apotex, Inc. Product: intercranial pressure monitoring products Date: 1/30/2015Your firm failed to exercise appropriate controls over computer or related systems to assure that onlyauthorized personnel institute changes in master production and control records, or other records (21CFR 211.68(b)). QC personnel created unauthorized folders on laboratory computerized systems without appropriateoversight. Our review of the HPLC Empower III data collected in 2013-2014 in the commercial QClaboratory found a data folder entitled “WASH.” According to your management, the folder was intendedfor column wash injections using blank solvent prior to and following sample runs, although you have nostandard operating procedure (SOP) detailing this process. One of your laboratory analysts stated thatthis folder does not contain any standard or sample injection results. However, our investigator foundthat this folder contained a total of 3,353 injection results, some of which appeared to be samples. FDA District: CDRH


1/9/2015 Micro Labs LimitedMicro Labs Limited Product: pharmaceutical manufacturing facility Date: 1/9/20151. Your firm failed to ensure that laboratory records included complete data derived from all testsnecessary to assure compliance with established specifications and standards (21 CFR 211.194(a)).a) During the inspection, your management admitted that employees in both of your Quality Control(QC) laboratories had frequently conducted unauthorized ?trial? High Performance LiquidChromatography (HPLC) injections prior to additional injections that were used in the reported testresults. Although your management stated that this practice ended in February 2014, FDA investigatorsdiscovered evidence that this practice continues. The inspection found that the names assigned to eachsequenced injection were often changed during testing, obscuring the traceability of repeated injections. The data from ?trial? injections was not reviewed or considered in determining batch quality. Forexample, 1) For the related substances analysis of (b)(4) USP (b)(4) mg Tablets batch (b)(4) conducted onFebruary 25, 2013, there were three sample injections of vial 1_8, all named ?TEST,? which were runprior to the reported sample injections. The ?TEST? injection data was stored in the ?Trial? folderlocated on a personal computer (PC) with no audit trail linked to the HPLC instrument.5) The audit trail for the dissolution analysis of the 9-month long-term stability sample of (b)(4) USP(b)(4) mg Tablets batch (b)(4) conducted on March 22, 2014, showed a single manual injection that wasnot included in the official test results package. A manual ?trial? sample injection from vial position(b)(4) at 12:29 pm was injected between the Set (b)(4) and Set (b)(4) analytical sequences. Nodeviation was documented regarding the extra sample injection. In addition, the original injection dataobtained for vial position (b)(4) was overwritten and not saved. Because the original data wasoverwritten, you did not review and evaluate it as part of your batch release decision.b) The inspection also found similar unreported and unexplained sample data acquired during yourgas chromatography (GC), ultra violet (UV) spectroscopy and (b)(4) analyses. The extra GC data wasstored in the ?Trial? folder located on a PC with no audit trail linked to the GC instrumentation. Theextra UV and (b)(4) data was stored on the instrument hard drives. This unreported and unexplaineddata was not reviewed when assessing batch quality and making product disposition decisions. Forexample, 1) For the (b)(4) analysis of the 9-month long-term stability sample of (b)(4) USP (b)(4) mg Capsules((b)(4) drug product) batch (b)(4) conducted on January 10, 2014, three extra analyses that were runprior to the reported sample were found on the instrument hard drive. During the inspection, thecalculations that you performed showed that two of the extra analyses were OOS ((b)(4)% & (b)(4)%, ascompared to the specification of NMT (b)(4)%). Notably, there were no test sample weight records for the three extra (b)(4) tests. The extra sampledata was not reviewed when assessing batch quality and product stability.2. Your firm failed to exercise appropriate controls over computer or related systems to assure thatonly authorized personnel institute changes in master production and control records, or other records(21 CFR 211.68(b)). FDA investigators discovered a lack of basic laboratory controls to prevent changes to electronicallystored data. The following examples show that you lack effective control of the integrity of instrumentoutput data: a) The ten Shimadzu HPLC instruments in the QC ?commercial? laboratory were configured to sendacquired injection data to PCs without audit trails. b) There was a lack of controls to prevent substitution or overwriting of data. The (b)(4) audit traildated January 6, 2014, for HPLC MLG/QC/12/026 and the (b)(4) audit trail dated January 15, 2014, for


HPLCs MLG/QC/12/031 and MLG/QC/12/027 each showed sample injections marked with the samesmall graphic symbol. For each of these entries, you replaced the original injection sequence data withdata from a single manual injection and failed to save the original sequence data. In your response to this letter, include a chronology of Chromeleon audit trail information that shows allsingle manual sample injections that replaced data collected during HPLC testing. c) A ?File Note? dated February 10, 2014, signed by the QC Head, established that the printed dataused for batch disposition decisions from the Metrohm Titrando Instrument MLG/QC/12/048 hard drivewas not necessarily the complete data for a batch. Our inspection found that data on the instrumentwas selected for use and was not protected from change and deletion. Notably, the audit trail capabilityof this QC ?commercial? laboratory instrument was not enabled, even aftercreation of the ?File Note.? FDA District Office: CDRH

12/19/2014 Novacyl Wuxi Pharmaceutical Co., Ltd. Novacyl Wuxi Pharmaceutical Co., Ltd. . Product: pharmaceutical manufacturing facility Date: 12/19/20141. Failure to manage laboratory systems with sufficient controls to ensure conformance to establishedspecifications and prevent omission of data.Our inspection revealed serious deficiencies related to your documentation practices, including missingraw data. It is a basic responsibility of your quality unit to ensure that your firm retains the supportingraw data that demonstrates your APIs meet specifications that they are purported to possess. For example, during the inspection, our investigator found a chromatogram related to (b)(4), API in thetrash, dated October 15, 2013, which reported an additional chromatographic peak when compared tothe standard. During the inspection, your firm stated that the analyst discarded the chromatogrambecause it was present in the blank injection. However, the analyst was unable to retrieve the blankchromatogram from the system because it was overwritten by a subsequent injection. In addition, the inspection documented that your firm made changes to integration parameters for theimpurities test without appropriate documentation or justification. Your firm relied upon hand writtennotes on a chromatogram discovered in a drawer at the laboratory as the documentation for thischange. Furthermore, your firm implemented this change without an audit trail that would have capturedthe date of the change and who made the change.Other significant deficiencies noted in your laboratory system include: a) Failure to have a written procedure for manual integration despite its prevalence. b) Failure to use separate passwords for each analyst?s access to the laboratory systems. c) Use of uncontrolled worksheets for raw analytical data in your laboratory. d) Presence of many uncontrolled chromatograms, spreadsheets and notes of unknown origin foundin a drawer. The lack of controls on method performance and inadequate controls on the integrity of the datacollected raise questions as to the authenticity and reliability of your data and the quality of the APIs youproduce. Your firm?s response, dated November 06, 2013, stated that your firm will create a validation programfor all uncontrolled computer systems, create a new standard operating procedure (SOP), and retrain allanalysts performing analytical tests. However, observations found during the most recent inspectionregarding the inadequacy of your HPLC system raises questions regarding your ability to implementsustainable corrective and preventive actions, as previous commitments made to the agency were notfulfilled. Please provide specific milestones and your detailed plan on how you intend to implement theappropriate corrective actions. We will also encourage you to submit monthly reports to the agency of


your progress. As part of your response, provide a complete validation plan for your laboratory computerized systems.This plan should include an audit trail component and other appropriate controls to prevent deletion andoverwriting of data. In addition, include a retrospective review of the analytical data and batch recordsfor all of the APIs distributed that remain within expiration, along with an evaluation of data that mayhave been generated to support a drug application, including any Drug Master File. This investigationshould include a review of all APIs manufactured at your site. Furthermore, provide details of thesystemic corrective actions taken to prevent recurrence of these deficiencies. .FDA District Office: CDRH

12/18/2014 Moor Instruments Ltd.Moor Instruments Ltd. Product: Laser Doppler Blood Flow Monitor devices Date: 12/18/2014This inspection revealed that these devices are adulterated within the meaning of section 501(h) of theAct, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for, theirmanufacture, packing, storage, or installation are not in conformity with the current good manufacturingpractice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations(CFR), Part 820.Failure to establish and maintain procedures for changes to a specification, method, process, orprocedure, as required by 21 CFR 820.70(b). For example, your firm completed design change note798 to modify the moorVMS-LDF device and updated the software from version 1 to version 2. Workinstruction procedure, ?(b)(4)?, states that version 1 is uploaded onto the device during the main boardtesting operation. However, your firm did not update the work instructions to address the softwareversion change.Failure to establish and maintain procedures for quality audits and conduct such audits to assure thatthe quality system is in compliance with the established quality system requirements and to determinethe effectiveness of the quality system, as required by 21 CFR 820.22. For example, your firm?sInternal Audit Procedure does not require quality audits to be conducted by individuals who do not havedirect responsibility for the matters being audited. During the 2011 and 2012 internal audits, your firm'sQuality and Regulatory Representativeaudited matters that were under her direct responsibility,including customer complaints implemented by your firm?s Customer Feedback procedure. We reviewed your firm?s response and conclude that it is not adequate. Your firm?s response did notaddress this observation. Given the serious nature of the violations of the Act, devices, including moor VMS-LDF and moorVMS-LDF-HP Laser Doppler Blood Flow Monitor devices,manufactured by your firm are subject torefusal of admission under section 801(a) of the Act, 21 U.S.C. § 381(a), in that they appear to beadulterated. As a result, FDA is taking steps to refuse entry of these devices into the United States,known as ?detention without physical examination,? until these violations are corrected. In order toremove the devices from detention, your firm should provide a written response to this Warning Letteras described below and correct the violations described in this letter. We will notify you regarding theadequacy of your firm?s response and the need to re-inspect your firm?s facility to verify that theappropriate corrections and/or corrective actions have been made.FDA District Office: CDRH

12/9/2014 Customed Inc.Customed Inc. Product: medical devices, including convenience packs for surgical procedures Date: 1/9/2015Failure to validate the defined user needs and intended uses of the (b)(4) used as part of the qualitysystem according to an established protocol, as required by 21 CFR 820.70(i). Specifically, your firmimplemented (b)(4) to track product inventory (incoming materials, finished/released products and


quarantine items), however the software was not validated. In addition, the status of lots of finishedproducts and incoming materials in the warehouse failed to match the (b)(4) system inventory. Your firm?s response dated August 21, 2014, is not adequate. Your firm initiated CAPA (b)(4) toprepare a software validation protocol, however, you failed to initiate a corrective action to identify andaddress pertinent quality system and production software that have not been appropriately validated. Further, your firm failed to provide the executed (b)(4) validation protocol and summary report forreview. FDA District Office:San Juan Office

8/11/2014 Spacelabs Healthcare, Inc.Spacelabs Healthcare, Inc.. Product: patient monitoring devices Date: 8/11/20141. Failure to establish and maintain procedures for implementing corrective and preventive action(CAPA), as required by 21 CFR 820.100(a). a. Your firm failed to implement corrective and preventive actions needed to correct and preventidentified quality problems. Specifically, several CAPAs identify corrective actions but were closedwithout implementation of the corrective actions. For example: i. Your firm opened CAPA 31920 on July 22, 2013, to address the shipment of an outdated version ofÉlance Central software. Your firm?s root cause investigation determined the ECO did not addresswhich version of the software to scrap, and that the latest version of the software was not checked priorto shipment. Your firm identified the following corrective and preventive action plan, (b)(4) CAPA 31920was closed on September 9, 2013, even though the action plan was not implemented. ii. Your firm opened CAPA 24340 on January 29, 2013, to address ICS G2 units that were releasedwhen they were covered by a stop ship that was intended to prevent their shipment. In CAPA 24340,your firm documented that a (b)(4).? Your firm opened the follow-up CAPA 24356 on January 29, 2013,but then closed it without further corrective actions on February 1, 2013, because it was documented asa duplicate of CAPA 24340. CAPA 24340 was closed on October 2, 2013, and documented aseffective, even though your firm did not make changes to the stop/ship purge process to prevent theissue from reoccurring. b. Your firm failed to verify or validate its corrective and preventive action to ensure such action iseffective and does not adversely affect the finished device. For example, CAPA 31363 was opened onJuly 8, 2013, to address language bill of materials (BOMs), which called for a previous version of Elancesoftware to be installed on monitors instead of the latest software version. Your firm documentedseveral corrective and preventive actions including the requirement to add the software to the bill ofmaterials with the engineering change order (ECO) PR034750. Under your firm?s confirmation ofresults section, your firm states ?PR034750 has been implemented? as its verification and validation ofeffectiveness results, but your firm does not document how it verified or validated the actions to ensurethat the actions were effective. Your firm later updated its corrective actions to require the deletion ofbedside software from Elance language bill of materials. Under ?Was the plan effective?? your firmstates ?yes? without documenting activities performed for verification or validation of effectiveness. Your firm?s response is not adequate. Your response indicated your firm revised its CAPA process andis implementing a CAPA management system to support the changes. Your firm plans to providetraining to personnel on several revised procedures and to conduct a retrospective review of closedCAPAs. Your firm has not explained how its new CAPA system will ensure that follow-up CAPAs aredocumented and tracked to allow for proper processing. Your firm has not submitted an update to orimplementation plan for CAPA 24340 or your firm?s plan for verifying or validating the effectiveness ofits corrective actions for CAPA 31363. Your firm should complete the remaining corrective andpreventive actions and submit evidence of implementation. We note that these violations have been


observed previously during FDA inspections. 3. Failure to establish and maintain procedures for receiving, reviewing, and evaluating complaints bya formally designated unit, as required by 21 CFR 820.198(a). For example, your firm failed to follow itsprocedure, Complaint Handling, 1100-0012, Rev. K, which defines a complaint as ?any written,electronic, or oral communication that alleges deficiencies related to the identity, quality, durability,reliability, safety, effectiveness, or performance of a device after it is released for distribution? andrequires that a complaint be entered into an electronic database as a complaint record. Your firm failedto initiate a complaint record for service calls including, but not limited to: CA822459 on April 23, 2013;CA831398 on September 25, 2013; and CA833691 on November 4, 2013. CA822459 was for three91496 modules that would not boot up after a software change. CA831398 was for a neurology monitorwith a non-volatile random access memory failure. CA833691 was for a monitor that would not poweron. The adequacy of your firm?s response cannot be determined at this time. Your firm has enteredCA822459, CA831398, CA833691, and other service records into the complaints system. Your firmplans to complete a retrospective review of service calls to determine if they are complaints and toprovide training to field personnel regarding the revised complaint handling process. However,evidence of implementation of these corrective actions was not provided for review. We note that theseviolations have been observed previously during FDA inspections. 6. Failure to establish and maintain procedures for validating the device design to ensure that devicesconform to defined user needs and intended uses, as required by 21 CFR 820.30(g). For example, yourfirm?s software validation testing for the Qube compact monitor (part number 91390) was conductedaccording to Design Validation Plan 91390 Salish Compact Monitor,819-0011-00, Rev. A, for theEnglish and foreign language packs. There were multiple test case failures, yet your firm reported inDesign Validation Report, 816-0099-02, that ?the test results showed the product is acceptable and itmeets the user requirements for patient monitoring.? Failures include, but are not limited to: (b)(4) outof (b)(4) test case failures for Level 0 Alarm (Suite 80) in the Czech language on January 26, 2012;(b)(4) out of (b)(4) failures for Level 0 Admit Patient (ADT) (suite 78) in the Polish language on January12, 2012; and (b)(4) out of (b)(4) failures for Level 0 Alarm (Suite 80) in the Portuguese Brazilianlanguage on January 24, 2012. The Qube compact monitor device was released for general distributionon June 18, 2012. Your firm?s response is not adequate. Your firm revised Design Controls, 1100-006, to Revision F toinclude a requirement that the validation protocol define expected results and acceptance criteria,including the criteria to pass or fail an activity. Your firm plans to provide training to appropriatepersonnel on the revised procedure. Your firm plans to perform a retrospective review of its patientmonitoring design projects to confirm that change requests are accepted prior to product release anddo not include non-conformances against product requirements. Your firm did not submit a currentadequate validation for the software cited for the Qube compact monitor. Additionally, your firm shouldcomplete and submit evidence of implementation of its corrective and preventive actions.FDA District Office: Seattle District

7/7/2014 Trifarma S.p.A.Trifarma S.p.A. Product: active pharmaceutical ingredients (APIs) Date: 7/7/20141. Failure to maintain complete data derived from all testing and to ensure compliance withestablished specifications and standards pertaining to data retention and management. Your firm did not retain complete raw data from testing performed to ensure the quality of your APIs.Specifically, your firm deleted all electronic raw data supporting your high performance liquidchromatography (HPLC) testing of all API products released to the U.S. market. In addition, your firmfailed to retain basic chromatographic information such as injection sequence, instrument method orintegration method for the tests. Your firm?s lack of data control causes us to question the reliability ofyour data.


In addition, your laboratory management was unaware of, and therefore did not follow, the writtenprocedure detailing the review of analytical data. Furthermore, your management confirmed that thereview of analytical data did not include evaluating the system suitability parameters to ensure propercolumn performance. Your response states that your firm has been researching backup systems since July 2013 and willhave a backup system online by the third quarter of 2014. Your response also states you have begunprovisionally storing backup data on each computer, including the integration method as part of thatdata. However, you do not address the backup of the injection sequence, the instrument method oraudit trails. In addition, your response does not address how your firm will ensure that electronic filesare not deleted prematurely from local computers. In response to this letter, provide a comprehensive corrective action plan addressing the foregoingconcerns. Include information regarding system-wide changes, revised procedures, and appropriateretraining of employees that will be implemented immediately to ensure retention of complete electronicraw data for all laboratory instrumentation and equipment. 2. Failure to prevent unauthorized access or changes to data and to provide adequate controls toprevent omission of data.Your firm did not have proper controls in place to prevent the unauthorized manipulation of yourlaboratory's raw electronic data. Specifically, your laboratory systems did not have access controls toprevent deletion or alteration of raw data. The inspection noted that all laboratory employees weregranted full privileges to the computer systems. In addition, prior to January 7, 2014, HPLC and gas chromatograph (GC) computer software lackedactive audit trail functions to record changes to data, including information on original results, theidentity of the person making the change, and the date of the change. Your response statesyour Agilent GC system and HPLC systems now have audit trails, with (b)(4) moreGC systems to be upgraded by the second quarter of 2014. However, your response did not describethe audit trails for the processing of the data on your Agilent systems. Your response also states yourfirm has begun to retain electronic raw data on the local hard drive, but without proper safeguards toensure they cannot be deleted prematurely. Such safeguards will not be implemented until the thirdquarter of 2014. In response to this letter, provide your corrective action plan to prevent deletion and alteration ofelectronic data. In addition, describe with more detail your firm?s new archival process and provideassurance that it will consistently function to prevent the types of failures described above fromrecurring in the future. We also note that your firm lacked electronic raw data supporting cleaning, method and processvalidations. In response to this letter, provide a corrective action plan to review all related test methodsassociated with products distributed to the U.S. in light of the lack of supporting raw data. FDA District Office: CDRH

6/27/2014 Zynex Medical, Inc.Zynex Medical, Inc.. Product: NesWave and IF8000 electrical stimulators Date: 6/27/2014This inspection revealed that these devices are adulterated within the meaning of section 501(h) of theAct, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for, theirmanufacture, packing, storage, or installation are not in conformity with the current good manufacturingpractice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations(CFR), Part 820. These violations include, but are not limited to, the following:Failure to establish procedures for design verification as required by 21 CFR 820.30(f).


Specifically, your firm did not conduct a complete design verification of the software requirements ofyour NexWave multimode electrical stimulator. Your verification testing of the software did not includeverifications to ensure all your software requirements were met. For example, verification testing did notinclude testing of the control/reset of the treatment timer, idle shut off functionality, and the treatmentdata storage functionality. We have reviewed your response and have concluded it is inadequate. Your response states you willupdate the design control SOP and verify detailed software specifications. However, you did not includeevidence to show a comprehensive review of the verification activities of other aspects of yourNexWave device. In addition, you did not provide sufficient details of the planned corrections to yourdesign control procedures to allow for evaluation at this time.Failure to establish procedures for internal audits as required by 21 CFR 820.22. Specifically, you did not complete your scheduled internal auditing activities as required by your 2013auditing schedule. You did not conduct audits of your training, document control, managementresponsibility, CAPA, complaints, calibration, purchasing, or servicing systems during 2013. We have reviewed your response and have concluded that the adequacy of your response cannot bedetermined at this time. Your firm has committed to drafting new internal audit procedures; until youhave completed internal audits and we can review these procedures, we cannot determine theadequacy of your response. FDA District Office: Denver District Office

6/16/2014 Apotex Pharmachem India Pvt LtdApotex Inc. Product:pharmaceutical manufacturing facility Date: 6/16//2014These deviations cause your APIs to be adulterated within the meaning of section 501(a)(2)(B) of theFederal Food, Drug, and Cosmetic Act (the Act), 21 USC § 351(a)(2)(B), in that the methods used in, orthe facilities or controls used for, their manufacture, processing, packing, or holding do not conform to,or are not operated or administered in conformity with, CGMP. Our investigators observed specific deviations during the inspection, including, but not limited to, thefollowing:1. Failure to maintain complete data derived from all laboratory tests conducted to ensure compliancewith established specifications and standards.Your firm lacked accurate raw laboratory data records for API batches shipped by your firm. Theinspection revealed that batch samples were retested until acceptable results were obtained. Inaddition, your quality control (QC) laboratory failed to include complete data on QC testing sheets. Failing or otherwise atypical results were not included in the official laboratory control records, notreported, and not investigated. For example, A review of the Gas Chromatograph (GC) electronic records from July 13, 2013, for (b)(4) USP batch#(b)(4) revealed an out-of-specification (OOS) result for the limit of residual solvents that was notreported. However, the QC test data sheet included passing results obtained from samples tested onJuly 14, 2013 and July 15, 2013. The inspection documented that your firm discarded samplepreparation raw data related to the OOS results. In your response you indicate that the electronicchromatographic data and the weighing log books were available and reviewed during the inspection.However, the raw data and sample preparation information used for the calculation of the test resultsthat were found OOS or disregarded were not in fact available for review. A review of the High Performance Liquid Chromatograph (HPLC) electronic records from July 3, 2013,for (b)(4) batch #(b)(4) revealed an Out-of-Trend (OOT) result. The sample preparation raw data wasdiscarded and not reported. A QC analyst indicated that these results were discarded due to somesmall extra peaks identified in the chromatogram fingerprint and an unexpected high assay result. TheQC test data sheet reported two new results that were obtained from samples tested on July 4, 2013


and July 5, 2013, using a different HPLC instrument. A review of the Karl Fischer electronic records from November 21, 2013, for (b)(4) EP batch #(b)(4)revealed an OOS result that was not reported. The passing results reported on the data sheets weregenerated from another sample tested an hour after the initial OOS results were obtained on the sameday, November 21, 2013. 2. Failure to investigate and document out-of-specification results. Your firm?s investigation of the data from the Empower software identified instances where additionaltesting was performed but not properly documented in laboratory records. This investigation was limitedin scope to only a short timeframe, the month of August 2013, and to only one type of laboratoryinstrumentation, FDA District Office: CDRH

6/2/2014 HeartWare, IncorporatedHeartWare, Incorporated. Product:HeartWare Ventricular Assist Device (HVAD) system Date: 6/2/2014The inspection revealed that this device is 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, its 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 FederalRegulations (CFR), Part 820. Our investigators observed specific deviations during the inspection, including, but not limited to, thefollowing: Failure to validate computer software for its intended use according to an established protocol whencomputers or automated data processing systems are used as part of production or the quality system,as required by 21 CFR 820.70(i). For example, your firm did not validate software used with the (b)(4)tester prior to implementation of the new test, as required by SOP00090, ?(b)(4).? According to Section2 of SOP00090, this procedure applies to ?any software used to automate device design, testing,component acceptance [?] or to automate any other aspect of the quality system.? Section 6 of thisSOP requires software validation. The software for the (b)(4) tester was changed as part of a correctiveaction to address premature battery failure issues. The new test was implemented on July 23, 2013,before the modified software was validated in September 2013. This change was related to 238complaints and 119 MDR events. The adequacy of your firm?s responses cannot be determined at this time. Your firm indicated that itwill revise its procedures, perform training, and retrospectively conduct software validation of the batterytesters. However, without evidence of implementation of these activities, FDA cannot determineadequacy., FDA District Office: Florida District

5/22/2014 Steris Isomedix ServicesSTERIS Corporation Product:facility sterilizes medical devices Date:5/22/20141. Failure to establish and maintain adequate procedures for implementing corrective and preventiveaction, as required by 21 CFR 820.100. Your CAPA procedure, PROC-00007, Revision 19, is deficient in that it does not adequately describehow to identify, correct and prevent the recurrence of nonconforming product and other qualityproblems, including any actions necessary to mitigate such risk. For example, the investigation,NC-05731, opened on July 29, 2013 to investigate data manipulation/falsification at the inspected facilitywhere product was overdosed but was subsequently made to appear within specification, did notinclude a review of all potentially affected products. Specifically, NC-05731 excluded:


all runs that were not suspected overdosed runs. This would include all dosimeters that are readfollowing the possible manipulation of the spectrophotometer to improperly zero the instrument which isnot stored in the instrument?s audit trail. If the spectrophotometer is not properly zeroed, 8. Failure to adequately validate software used as part of production and the quality system for itsintended use according to an established protocol, as required by 21 CFR 820.70(i). Specifically,actions were not taken to ensure that computer errors would not result in the loss of dosimetry and rundose data from the Dosimetry Measurement Application (DMA) module of (b)(4). For example, a. The inspection found that 2,900 records were missing from the main table of the DMA module of(b)(4) between the time that it was installed at the Libertyville North facility on November 4, 2011 andNovember 6, 2013. Each missing record represents an attempt at creating a dosimeter record. b. Of the 2,900 missing records, 1,623 records/dosimeters (representing (b)(4) irradiation runs)contained dosimetry data and were intentionally deleted from the DMA module. These recordscontained a calculated dose when they were deleted, and 192 of the dosimeters (representing (b)(4)unique runs) were out-of-specification low (under-dosed). c. The (b)(4) and DMA systems are set up to automatically discard any dosimeter absorbancereadings outside the set operating range of (b)(4) to (b)(4) absorbance units. We have reviewed your responses to sub-points (a) through (c) and have determined that the adequacyof the responses cannot be determined at this time because your firm?s corrective actions are eitheron-going or documentation was not provided to allow for FDA review. For example, your responsesindicated that the (b)(4) software and system documentation will be remediated, and a full revalidationof the (b)(4) system will be performed; however, this is not complete. In addition, your responsesindicated a number of corrective actions to address the specific issues listed above; however, nodocumentation was included with the responses to verify these actions. FDA District Office:Chicago District

5/7/2014 Sun Pharmaceutical Industries LimitedSun Pharmaceutical Industries Limited Product: pharmaceutical manufacturing facility Date:5/7/20141. Failure to ensure that laboratory records included complete data derived from all tests necessary toensure compliance with established specifications and standards.our firm frequently performs ?unofficial testing? of samples, disregards the results, and reports resultsfrom additional tests. For example, during stability testing, your firm tested a batch sample six times andsubsequently deleted this data. Our investigators found your practice of performing initial ?trial? sample high performance liquidchromatography (HPLC) analyses prior to acquiring the ?official? analyses. The ?trial? sample resultswere subsequently discarded. ?Trial? HPLC analyses for (b)(4) USP ((b)(4)) were apparently run aspart of the 12-month long-term stability studies on batch #(b)(4) for related substances. The inspectionrevealed that on August 26, 2011, your employee ran an HPLC analysis sequence with the samplenames (b)(4) and subsequently deleted the raw data files. It was noted that the assigned names for thesequence injections indicates that your quality control staff named the samples using the last threedigits of the batch numbers to link the "trial" injections for the batches with the official assay analyses.Your Senior Quality Control (QC) Officer confirmed that these were analyses of batch samples.Furthermore, we found that on August 27, 2011, this batch was analyzed for unknown impurities andthe results were reported to be within specifications. However, the chromatographic data showed thatthe "trial" injection data for this batch failed the unknown impurities specification of (b)(4)% in multiplecases. Your Senior QC Officer confirmed that QC laboratory employees had frequently practiced the use of?trial? injections at your facility. Significantly, in addition to the example above, our inspection found


5,301 deleted chromatograms on a computer used to operate two HLPC instruments in your QClaboratory. Many of these files were ?trial? injections of batches. n addition, the inspection revealed numerous examples of deleted GC electronic raw data files on thecomputer controlling the GC instruments that were replaced with identical ?official? chromatogram filenames. The identically named GC data files that were deleted had been created at different times andcontained disparate data. Also, it appeared that data was not consistently archived to the central server. Your response is inadequate in that you did not conduct an adequate investigation into the pervasivepractice of deleting files. In the reports provided in your response, you did not identify what criteria youused to designate each type of HPLC and GC data files (e.g. blanks, standards, samples, and systemsuitability runs). The response does not identify any impurity standards used in your procedures anddoes not provide the procedures that your firm was using to conduct the ?trial? and ?unofficial? runs. Inaddition, your investigation found 47 instances of apparent trial injections of samples for which theresults were out-of?specification (OOS), and some of these batches were distributed to the U.S.market. The investigation failed to adequately examine why your analysts hid or deleted these runs.Your response only explains that your firm chose to retest samples from the implicated lots, but doesnot address the causes of the original OOS results, or justify the basis of your decision to invalidate theoriginal failing result and accept the passing retest result. Such an investigation is necessary for anyOOS event. Refer to the FDA?s guidance on OOS investigations Guidance for Industry, InvestigatingOut-of-Specification (OOS), Test Results for Pharmaceutical Production. The above examples suggest a general lack of reliability and accuracy of data generated by your firm'slaboratory, which is a serious CGMP deficiency that raises concerns about the integrity of all datagenerated by your firm. We are concerned that your laboratory allowed the practice of "trial" injectionsand deletion of both GC and HPLC files to persist without implementation of controls to prevent datamanipulation until at least September 2013. Your company?s executive management is responsible forensuring the quality, safety, and integrity of your products. Implementing adequate controls and systemsto prevent manipulation of laboratory data is at the foundation of fulfilling this critical responsibility.Our investigators also observed significant violations regarding the finished drug product manufacturingoperations at your facility, including, but not limited to, the following: 1. Your firm failed to exercise appropriate controls over computer or related systems to assure thatonly authorized personnel institute changes in master production and control records, or other records(21 CFR 211.68(b)). The investigator identified numerous deleted raw data files on computers used for your GC instrumentsin your quality control laboratory. The software (?GC Solutions?) on the computers used to control theGC instruments allowed your analysts to delete files from the computer?s hard drive with no audit trailor other adequate form of traceability in the operating system to document the deletion activity. Thesoftware as configured assigned sequential, numerical names to raw data files within the same folder. When a raw data file was deleted or moved out of the designated folder, the next file recorded into thefolder would be saved with an identical name as the deleted file. As a result, data can be manipulatedso that saved files appear to be in sequence even if they were not generated sequentially. Due to thebasic lack of audit trail and data security, an analyst could delete analytical files without traceability ofthis unacceptable practice. The inspection revealed that you stored GC raw data files in multiple folders on the hard drives in theQC laboratory. Your Senior QC Officer stated you had no written procedure describing the managementof GC raw data file storage. According to your firm's electronic data archival SOP IT-001, each QCanalyst manually transferred individual raw data files to the central server at (b)(4). Your procedure didnot address how this data transfer by QC analysts could be reliably verified, and whether propercomputerized system controls will be implemented by your company.


We acknowledge your firm?s commitment to amend the data handling system of your GC instrumentsto implement controls that ensure that analyses performed by employees are maintained as accurate,with data integrity and traceability. In your response to this letter, describe your detailed systemicimprovements, training activities, and other actions implemented to provide evidence of theeffectiveness and sustainability of these changes.FDA District Office: Center for Drug Evaluation and Research

5/7/2014 Gold Standard Diagnostics, Inc.Gold Standard Diagnostics, Inc. Product: Gold Standard Diagnostics test kits for the detection of infectious pathogens Date:5/7/2014Quality SystemThis inspection also revealed that these devices are adulterated within the meaning of section 501(h) ofthe Act, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for, theirmanufacture, packing, storage, or installation are not in conformity with the current good manufacturingpractice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations(CFR), Part 820 1. Failure to establish procedures for design changes as required by 21 CFR 820.30(i). For example,your design and development procedure does not address software changes, or describe how they willbe defined, documented, or implemented. You do not describe the types of changes that requiresoftware verification or validation. In response to Complaint # CC0159 you made changes to theThunderbolt GUI software. You were unable to provide documentation to show the verification orvalidation of this software change when our investigator asked you for it. 2. Failure to establish requirements that must be met by suppliers as required by 21 CFR 820.50(a).For example, you have no documentation of the design responsibilities your Thunderbolt analyzersoftware supplier (supplier ?A?) must meet and there is no documentation that you or your supplierhave validated or verified the analyzer?s software; and according to your management representative,you evaluated supplier ?B? solely on years of doing business with them and executive managementknows them. Supplier ?B? provides reagents, antigens, and antigen coated plate components for yourinfectious disease devices. 3. Failure to perform a risk analysis as required by 21 CFR 820.30(g). For example, our investigatorasked you for and you were unable to produce a risk analysis for the following in vitro diagnostic kitsyou manufacture: Brucella IgM, Borrelia burgorferi B31 IgG and IgM, and Entamoeba histolytica IgG;and you failed to mitigate the risk of patient misdiagnosis in your Thunderbolt Risk Analysis. YourThunderbolt Risk Analysis Summary, RMP-0001-3 requires items (b)(4) to have control measures toreduce the probability of occurrence; however, you have assigned a (b)(4) to the general ?Operational?hazard that may lead to patient misdiagnosis and have not mitigated the hazard.FDA District Office: San Francisco District

3/6/2014 Smruthi Organics LtdUSV Limited Product: pharmaceutical manufacturing facility Date:3/6/20141. Failure to maintain complete and accurate laboratory test data generated in the course ofestablishing compliance of your APIs to established specifications and standards. a. There was no written explanation for deletion events observed on audit trails for your standaloneHPLC units. Your standard operating procedures (SOPs) did not include instructions for the retention ofelectronic raw data. In response to this letter, provide your procedures describing requirements tomaintain complete dataAudit and identify the extent of this activity in your laboratory and manufacturing operations and providean update to your investigation into this matter. .FDA District Office: CDRH


2/6/2014 USV LimitedUSV Limited Product: control laboratory testing facility Date:2/6/2014Your firm failed to exercise appropriate controls over computer or related systems to assure that onlyauthorized personnel institute changes in master production and control records, or other records (21C.F.R. §211.68(b)). Your firm failed to have adequate procedures for the use of computerized systems in the quality control(QC) laboratory. Our inspection team found that current computer users in the laboratory were able todelete data from analyses. Notably, we also found that the audit trail function for the gas chromatograph(GC) and the X-Ray Diffraction (XRD) systems was disabled at the time of the inspection. Therefore,your firm lacks records for the acquisition, or modification, of laboratory data. Moreover, greater than (b)(4) QC laboratory personnel shared (b)(4) login IDs for (b)(4) highperformance liquid chromatographs (HPLC) units. In addition, your laboratory staff shared one login IDfor the XRD unit. Analysts also shared the username and password for the Windows operating systemfor the (b)(4) GC workstations and no computer lock mechanism had been configured to preventunauthorized access to the operating systems. Additionally, there was no procedure for the backup andprotection of data on the GC standalone workstations. In your response, you indicate that your firm performs periodic back-ups of data, however your firmlacks assurance that the periodic backed up data includes all of the original data generated. Yourresponse to this deficiency does not discuss how you will ensure that data audit trails will not bedisrupted in the future and lacked a computer life cycle approach to, for example, assure routineverification of access controls in computer systems. In your response to this letter provide a comprehensive computer life cycle program to assure thatappropriate controls are always exercised over computer or related systems to comply with 21 CFR211.68. .FDA District Office: CDER

1/29/2014 ConMed CorporationConMed Corporation Product: medical devices used for open and laparoscopic surgical procedures Date:1/29/2014The inspection revealed that these devices are adulterated within the meaning of section 501(h) of theAct [21 U.S.C. § 351(h)], in that the methods used in, or the facilities or controls used for, theirmanufacture, packing, storage, or installation are not in conformity with the current good manufacturingpractice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations(CFR), Part 820. These violations include, but are not limited to, the following:Procedures for design change have not been adequately established, per 21 CFR 820.30(i). YourDesign Verification & Validation procedures, SOP #168 (Rev. 1 & 2) require an evaluation of the impactof changes to a released design on the device function and performance. However, your firm failed tofully and adequately evaluate design changes to Altrus Tissue Fusion System 5mm and 10mmHandpieces to ensure that verification and/or validation activities were complete. For example:b. Your firm failed to adequately evaluate a revision to the Altrus Tissue Fusion System ControllerSoftware which (b)(4). Specifically, after your Impact Analysis determined that the software changewould (b)(4) tests, these protocols were repeated; however, numerous deficiencies were observed withthe design verification protocols, including: i. No documentation of any (b)(4) tests to evaluate (b)(4) on the 5mm handpieces.ii. (b)(4) handpieces (5mm) tested for (b)(4) failed the (b)(4) acceptance criteria (b)(4) test points(combined total), yet the (b)(4) were not investigated and the Design Verification Report results were


marked as ?Pass?.iii. The Design Verification Reports, 5mm Handpiece (b)(4) and (b)(4) report show that the designverification tests were conducted with (b)(4), not the (b)(4).iv. The Design Verification Protocol, approved on 12/21/12 and executed on 12/24/12, shows thatmultiple tests were ?Not executed per (b)(4); however, that document, (b)(4), was not approved until2/26/13, approximately two months after the executed protocol. Furthermore, Impact Analysis (b)(4)does not include any justification for omitting certain tests (b)(4).v. Design Verification report, (b)(4), shows that your firm used data from a previous designverification study (b)(4) which showed failing results for (b)(4) handpieces tested for (b)(4) and whichstated, (b)(4).However, there was no documentation that the failing test results were addressed. c. Design verification for a software change (b)(4) was incomplete. Design control deficienciesincluded: i. No documentation of any (b)(4) tests to evaluate (b)(4).ii. The Impact Analysis record for the 10mm handpieces (b)(4) identified (b)(4) of the 10mmhandpiece that were affected by the (b)(4); however, test data showed that the (b)(4) Test for (b)(4) onlytested the (b)(4), not the specified (b)(4). The results were marked as ?Passed.?iii. (b)(4) handpieces (b)(4) tested for (b)(4) failed the (b)(4) verification acceptance criteria (b)(4)test points (combined total), yet the (b)(4) were not investigated and the Design Verification Reportresults were marked as ?Pass? on the Design Verification Report.iv. The Design Verification Report (b)(4) summarizes results from the executed Altrus HandpieceDesign Verification Protocol (b)(4) which indicated that both 5mm and 10mm handpieces were to beevaluated for (b)(4); however, there was no documentation that 10mm handpieces were subjected tothese tests.v. Portions of the Installation Qualification for the (b)(4), applicable to the configuration file were (b)(4)in the 10mm handpiece (b)(4). However, the associated Performance Qualification was not re-executed(b)(4)Acceptance activities were not documented and maintained as part of the device history record asrequired by 21 CFR 820.80(e). For example:(b)(4) device history records reviewed for Altrus (b)(4) failed to include documentation of all requiredin-process acceptance activities.FDA District Office: Denver District

12/19/2013 Baxter Healthcare Corp.Baxter Healthcare Corporation Product:elastomeric infusion pumps and specialty medical devices Date:12/19/2013This inspection revealed that these devices are adulterated within the meaning of section 501(h) of theAct, 21 U.S.C. § 321(h), in that the methods used in, or the facilities or controls used for, theirmanufacture, packing, storage, or installation are not in conformity with the current good manufacturingpractice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations(CFR), Part 820. These violations include, but are not limited to, the following:7. Failure to validate for its intended use according to an established protocol software used as part ofproduction and the quality system, as required by 21 CFR § 820.70(i). A. There is no protocol and documentation of validation for (b)(4) used in (b)(4) prior to 2011 in yourExpiration (Shelf-life) Testing Program. We reviewed your firm?s response and conclude that it is notadequate. B. Compounding formulation for (b)(4), (b)(4), (b)(4) and (b)(4) used for all infusion pump bladdersand reservoirs were changed and programmed into the (b)(4) equipment. There is no documentedvalidation conducted for changes to the software. We reviewed your firm?s response and concluded that it is not adequate. For item 7A above, your firmdid not address conducting software validation for the software used for (b)(4). For 7B above, your firm


stated that the software will be revalidated. However, your firm has not validated the newly programmed?(b)(4)? software. .FDA District Office: Los Angelesr District

11/25/2013 SAN UP S.ASAN UP S.A. Product: piston and ultrasonic nebulizers Date:11/25/2013Our inspection revealed that your firm?s piston and ultrasonic nebulizer devices are misbranded undersection 502(t)(2) of the Act, 21 U.S.C. § 352(t)(2), in that your firm failed or refused to furnish materialor information respecting the device that is required by or under section 519 of the Act, 21 U.S.C. §360i, and 21 CFR Part 803 - Medical Device Reporting. These violations include, but are not limited to,the following:Failure to validate computer software for its intended use according to an established protocol, asrequired by 21 CFR 820.70(i). For example, your firm uses (b)(4) to generate, store, and disseminatestandard operating procedures, forms, and other records. (b)(4) is also used by your firm to generateand store Device History Records (DHRs) and other quality system data. During the inspection, yourfirm indicated that the procedure titled, ?Validacion del software utilizado en el sistema de calidad,GC-E-07-49, Rev. 00,? dated March 14, 2011, states that validation is concentrated on software anddocuments used in the quality system since there is no software used in your firm?s manufacturingequipment. However, your firm could not produce any evidence to demonstrate that the softwareprograms were validated for their intended use.FDA District Office: CDRH

11/25/2013 Wockhardt LtdWockhardt Limited Product: pharmaceutical manufacturing facilities Date:11/25/2013Investigators from the U.S. Food and Drug Administration (FDA) identified significant violations ofcurrent good manufacturing practice (CGMP) regulations for finished pharmaceuticals, Title 21, Code ofFederal Regulations, Parts 210 and 211. These violations cause your drug products to be adulteratedwithin the meaning of Section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (the Act), 21U.S.C. 351(a)(2)(B), in that the methods used in, or the facilities or controls used for, their manufacture,processing, packing, or holding do not conform to, or are not operated or administered in conformitywith, CGMP. We have conducted a detailed review of your firm?s responses and note that they lack sufficientcorrective actions. We also acknowledge receipt of your firm's additional correspondence dated October 2, 2013. Our investigators observed specific violations during the inspection, including, but not limited to, thefollowingYour firm failed to exercise appropriate controls over computer or related systems to assure that onlyauthorized personnel institute changes in master production and control records, or other records (21CFR 211.68(b)). Chikalthana Facility (FEI 3002808503): The inspection documented that all of your QC laboratory computerized instruments ((b)(4) HPLCs)were found to be stand-alone, and laboratory personnel demonstrated that they can delete electronicraw data files from the local hard drive. Your firm deleted multiple HPLC data files acquired in 2013allegedly to clear up hard drive space without creating back-ups. Your QC management confirmed thatthere is no audit trail or other traceability in the operating system to document the deletion activity.Furthermore, your analysts do not have unique user names and passwords for the computer andlaboratory information systems; your QC analysts use a single shared user identifier and password to


access and manipulate multiple stand-alone systems. Waluj Facility (FEI 3004540156): The (b)(4) HPLC systems in operation at the Waluj facility are also stand-alone, and during ourinspection, an employee demonstrated to the investigator that data can be deleted through the localhard drive of the data acquisition system. As with the Chikalthana facility, all Waluj facility employeesuse a shared password to access the operating system. During the inspection, your firm?smanagement informed our investigator that (b)(4) back-ups of data are performed. However, we areconcerned that your system and procedures permit deletion of HPLC files and that (b)(4) backed updata may not represent all the original data generated. You are responsible not only for having controls to prevent alteration or loss of the data, but also forrecording any changes made to existing data, which should include the date of change, identity of theperson who made the change, and an explanation or reason for the change. In response to this letter, provide your evaluation of all laboratory equipment that may be affected by thelack of adequate controls to prevent data manipulation. In addition, address the root cause of yourquality unit's failure to control and detect the manipulation or alteration of laboratory documents anddescribe actions to prevent recurrence. In response to this letter, provide your procedures to manage allcomputerized data and how the data will be used, retained and stored to ensure its integrity.FDA District Office: CDRH

11/22/2013 23andMe, Inc23andMe, Inc Product: Saliva Collection Kit and Personal Genome Service Date:11/22/2013The Food and Drug Administration (FDA) is sending you this letter because you are marketing the23andMe Saliva Collection Kit and Personal Genome Service (PGS) without marketing clearance orapproval in violation of the Federal Food, Drug and Cosmetic Act (the FD&C Act). This product is a device within the meaning of section 201(h) of the FD&C Act, 21 U.S.C. 321(h),because it is intended for use in the diagnosis of disease or other conditions or in the cure, mitigation,treatment, or prevention of disease, or is intended to affect the structure or function of the body. Forexample, your company?s website at www.23andme.com/health (most recently viewed on November 6,2013) markets the PGS for providing ?health reports on 254 diseases and conditions,? includingcategories such as ?carrier status,? ?health risks,? and ?drug response,? and specifically as a ?firststep in prevention? that enables users to ?take steps toward mitigating serious diseases? such asdiabetes, coronary heart disease, and breast cancer. Most of the intended uses for PGS listed on yourwebsite, a list that has grown over time, are medical device uses under section 201(h) of the FD&C Act.Most of these uses have not been classified and thus require premarket approval or de novoclassification, as FDA has explained to you on numerous occasions. Some of the uses for which PGS is intended are particularly concerning, such as assessments forBRCA-related genetic risk and drug responses (e.g., warfarin sensitivity, clopidogrel response, and5-fluorouracil toxicity) because of the potential health consequences that could result from false positiveor false negative assessments for high-risk indications such as these. For instance, if the BRCA-relatedrisk assessment for breast or ovarian cancer reports a false positive, it could lead a patient to undergoprophylactic surgery, chemoprevention, intensive screening, or other morbidity-inducing actions, while afalse negative could result in a failure to recognize an actual risk that may exist. Assessments for drugresponses carry the risks that patients relying on such tests may begin to self-manage their treatmentsthrough dose changes or even abandon certain therapies depending on the outcome of theassessment. For example, false genotype results for your warfarin drug response test could havesignificant unreasonable risk of illness, injury, or death to the patient due to thrombosis or bleedingevents that occur from treatment with a drug at a dose that does not provide the appropriately calibrated


anticoagulant effect. These risks are typically mitigated by International Normalized Ratio (INR)management under a physician?s care. The risk of serious injury or death is known to be high whenpatients are either non-compliant or not properly dosed; combined with the risk that adirect-to-consumer test result may be used by a patient to self-manage, serious concerns are raised iftest results are not adequately understood by patients or if incorrect test results are reported. Your company submitted 510(k)s for PGS on July 2, 2012 and September 4, 2012, for several of theseindications for use. However, to date, your company has failed to address the issues described duringprevious interactions with the Agency or provide the additional information identified in our September13, 2012 letter for (b)(4) and in our November 20, 2012 letter for (b)(4), as required under 21 CFR807.87(1). Consequently, the 510(k)s are considered withdrawn, see 21 C.F.R. 807.87(1), as weexplained in our letters to you on March 12, 2013 and May 21, 2013. To date, 23andMe has failed toprovide adequate information to support a determination that the PGS is substantially equivalent to alegally marketed predicate for any of the uses for which you are marketing it; no other submission forthe PGS device that you are marketing has been provided under section 510(k) of the Act, 21 U.S.C. §360(k). The Office of In Vitro Diagnostics and Radiological Health (OIR) has a long history of working withcompanies to help them come into compliance with the FD&C Act. Since July of 2009, we have beendiligently working to help you comply with regulatory requirements regarding safety and effectivenessand obtain marketing authorization for your PGS device. FDA has spent significant time evaluating theintended uses of the PGS to determine whether certain uses might be appropriately classified into classII, thus requiring only 510(k) clearance or de novo classification and not PMA approval, and we haveproposed modifications to the device?s labeling that could mitigate risks and render certain intendeduses appropriate for de novo classification. Further, we provided ample detailed feedback to 23andMeregarding the types of data it needs to submit for the intended uses of the PGS. As part of ourinteractions with you, including more than 14 face-to-face and teleconference meetings, hundreds ofemail exchanges, and dozens of written communications, we provided you with specific feedback onstudy protocols and clinical and analytical validation requirements, discussed potential classificationsand regulatory pathways (including reasonable submission timelines), provided statistical advice, anddiscussed potential risk mitigation strategies. As discussed above, FDA is concerned about the publichealth consequences of inaccurate results from the PGS device; the main purpose of compliance withFDA?s regulatory requirements is to ensure that the tests work. However, even after these many interactions with 23andMe, we still do not have any assurance that thefirm has analytically or clinically validated the PGS for its intended uses, which have expanded from theuses that the firm identified in its submissions. In your letter dated January 9, 2013, you stated that thefirm is ?completing the additional analytical and clinical validations for the tests that have beensubmitted? and is ?planning extensive labeling studies that will take several months to complete.?Thus, months after you submitted your 510(k)s and more than 5 years after you began marketing, youstill had not completed some of the studies and had not even started other studies necessary to supporta marketing submission for the PGS. It is now eleven months later, and you have yet to provide FDAwith any new information about these tests. You have not worked with us toward de novo classification,did not provide the additional information we requested necessary to complete review of your 510(k)s,and FDA has not received any communication from 23andMe since May. Instead, we have becomeaware that you have initiated new marketing campaigns, including television commercials that, togetherwith an increasing list of indications, show that you plan to expand the PGS?s uses and consumer basewithout obtaining marketing authorization from FDA. Therefore, 23andMe must immediately discontinue marketing the PGS until such time as it receivesFDA marketing authorization for the device. The PGS is in class III under section 513(f) of the FD&CAct, 21 U.S.C. 360c(f). Because there is no approved application for premarket approval in effectpursuant to section 515(a) of the FD&C Act, 21 U.S.C. 360e(a), or an approved application for aninvestigational device exemption (IDE) under section 520(g) of the FD&C Act, 21 U.S.C. 360j(g), the


PGS is adulterated under section 501(f)(1)(B) of the FD&C Act, 21 U.S.C. 351(f)(1)(B). Additionally, thePGS is misbranded under section 502(o) of the Act, 21 U.S.C. § 352(o), because notice or otherinformation respecting the device was not provided to FDA as required by section 510(k) of the Act, 21U.S.C. § 360(k). .FDA District Office: CDRH

11/20/2013 Shoney Scientific IndiaShoney Scientific India Product: Disposable Biopsy Punches, Dermal Curettes, Liposuction Cannulas, Cervical Dilators, andTongue Cleaners Date:11/20/2013Devices classified under 21 CFR 872.4565 (Punch, Biopsy, Surgical) are exempt from premarketnotification unless they exceed the limitations on exemption at 21 CFR 872.9(a). There is evidence thatthe Disposable Biopsy Punch is intended for uses that are different from those of legally-marketeddevices classified under 21 CFR 872.4565. Generic devices of this type are ?hand-held devicesintended to perform various tasks in general dentistry and oral surgery procedures.? However,according to your firm?s website (www.shoneysi.com), the Disposable Biopsy Punch indications for useinclude, but are not limited to, ?correcting vitiligo. The smaller sizes of the biopsy punch are also usedfor hair transplant.? Since the Disposable Biopsy Punch has a different intended use, it exceeds thelimitations described in 21 C.F.R. 872.9(a) and is not exempt from premarket notification.Our officerequests that Shoney Scientific India immediately cease activities that result in the misbranding oradulteration of the Disposable Biopsy Punch, such as the commercial distribution of the device for theuses discussed above. Given the serious nature of the violations of the Act, the devicesmanufactured by your firm are subjectto refusal of admission under section 801(a) of the Act, 21 U.S.C. § 381(a), in that they appear to beadulterated. As a result, FDA is taking steps to refuse entry of these devices into the United States,known as ?detention without physical examination,? until these violations are corrected. In order toremove the devices from detention, your firm should provide a written response to this Warning Letteras described below and correct the violations described in this letter. We will notify you if your firm?sresponse appears to be adequate, and we may need to re-inspect your firm?s facility to verify that theappropriate corrections and/or corrective actions have been made.FDA District Office: CDRH

11/20/2013 Blueshine/Hyperion MedicalBlueshine/Hyperion Medical Product: surgical lasers Date:11/20/2013The FDA has reviewed your firm?s websites, www.hyperionmed.com/hyperblue.html andwww.blueshine.biz, and determined that the HyperBlue 1530 and Blueshine Gold Series devices areadulterated under section 501(f)(1)(B) of the Act, 21 U.S.C. § 351(f)(1)(B), because your firm does nothave an approved application for premarket approval (PMA) in effect pursuant to section 515(a) of theAct, 21 U.S.C. § 360e(a), or an approved application for an investigational device exemption (IDE)under section 520(g) of the Act, 21 U.S.C. § 360j(g). These devices are also misbranded under section502(o) of the Act, 21 U.S.C. § 352(o), because your firm did not notify the agency of its intent tointroduce the devices into commercial distribution in that a notice or other information respecting themodification to the devices was not provided to the FDA as required by section 510(k) of the Act, 21U.S.C. § 360(k), and 21 C.F.R. 807.81(a)(3)(i). Specifically, your firm modified the Blueshine GoldSeries for the 980 nm wavelength, cleared under section 510(k) as K110375, by claiming that thedevice can also use 940 nm, 808 nm, and 532 nm wavelengths as single wavelengths or in combinationwith otherwavelengths. Additionally, your firm has added a 15mm hand piece to the HyperBlue 1530device. These modifications require a new submission under section 510(k) of the Act because theaddition of new wavelengths and hand pieces, when used with the cleared device, introduces additionalsafety and effectiveness questions.


FDA District Office: CDRH

9/18/2013 General Hearing Instruments, Inc.General Hearing Instruments, Inc.. Product: ready-wear-air conduction hearing aids Date: 9/18/2013This inspection revealed these devices are adulterated within the meaning of Section 501(h) of the Act[21 USC Section 351(h)], because the methods used in, or the facilities or controls used for, theirmanufacture, packing, storage, or installation do not conform with the Current Good ManufacturingPractice (CGMP) requirements of the Quality System (QS) regulation found at Title 21, Code of FederalRegulations, Part 820 (21 CFR 820). We received your response letter, with enclosures, datedSeptember 5, 2013, concerning our investigator?s observations noted on the Form FDA 483, List ofInspectional Observations (FDA 483), issued to you on August 15, 2013. We received yoursupplemental response, dated September 6, 2013, which noted your consult with Master Controls toreview, counsel, and guide you in properly implementing the corrective actions. We address theresponses below, in relation to each of the noted violations. The violations include, but are not limitedto, the following:2. Failure to adequately establish and maintain procedures for receiving, reviewing, and evaluatingcomplaints by a formally designated unit, as required by 21 CFR 820.198(a). Specifically, yourcomplaint procedure does not designate a specific unit handling complaints. In addition, you documentcomplaints in an electronic database; however, this is not addressed in your complaint procedure. You explain the complaint procedure is integrated into the CAPA procedure. The CAPA proceduredoes not adequately explain the specific responsibilities and steps your firm will take to record, evaluate,and address the complaint.3. Failure to adequately maintain your device master file, as required by 21 CFR 820.181. Specifically,you failed to include software specifications, quality assurance specifications, and packaging/labelingspecifications for your hearing devices.We agree with your proposed corrective action noted in item number 3.FDA District Office: New Orleans District

9/16/2013 Suzhou Armocon Technology CoSuzhou Armocon Technology Co Product: Vaginal Pessary (Luna Beads) and Tor II (penile ring) devices Date:9/16/2013This inspection revealed that these devices are adulterated within the meaning of section 501(h) of theAct, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for, theirmanufacture, packing, storage, or installation are not in conformity with the current good manufacturingpractice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations(CFR), Part 820. We received a response from you dated May 7, 2013 concerning our investigator’s observations notedon the Form FDA 483 (FDA 483), List of Inspectional Observations, which was issued to your firm. Weaddress this response below, in relation to each of the noted violations. These violations include, butare not limited to, the following:Failure to validate computer software for its intended use according to an established protocol whencomputer or automated data processing systems are used as part of production or the quality system,as required by 21 CFR 820.70(i). For example, your firm has been using the (b)(4) software program togenerate a unique serial number for each product since 2011. The serial number is used on the innerand outer packing of the finished device for tracking purpose. However, during the inspection, your firmstated to the FDA investigator that it has not validated the (b)(4) software program and it has noestablished protocol for doing so.We reviewed your firm’s response and conclude that it is not adequate. The response includedSerialization Procedure PRO-SP-0804, revision A. This procedure describes how your firm generates aunique serial number and uses it to track products throughout its shipment process. However, theprocedure does not describe how your firm will validate the computer software for its intended use.


FDA District Office: CDRH

9/11/2013 Vision RT Ltd., Dove HouseVision RT Ltd., Dove House Product: AlignRT® and AlignRT® Plus light beam patient position indicators Date:9/11/2013This inspection revealed that these devices are adulterated within the meaning of section 501(h) of theAct, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for, theirmanufacture, packing, storage, or installation are not in conformity with the current good manufacturingpractice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations(CFR), Part 820. We received a response from you dated May 7, 2013 concerning our investigator’s observations notedon the Form FDA 483 (FDA 483), List of Inspectional Observations, which was issued to your firm. Weaddress this response below, in relation to each of the noted violations. These violations include, butare not limited to, the following:Failure to establish and maintain adequate procedures for the identification, documentation, validationor where appropriate verification, review, and approval of design changes before their implementation,as required by 21 CFR 820.30(i). For example: SOP 010 Issue No. 2.1 "Product Development Lifecycle" dated February 26, 2013 §6.9 "Control ofDesign and Development Changes", SOP 32 Issue No. 1.0 "Hardware Change Control Procedure"dated June 06, 2005, SOP 0 13 Issue No. 4.1 "Software Change Control" dated August 1, 2012, Form024 Issue No. 1.0 "Software Change Request & Control" dated 0 January 27, 2010, and SOP 043 IssueNo. 1. 1 "Software Maintenance" dated August01, 2012 do not contain instructions for the validation orwhere appropriate verification of design changes before their implementation.Design changes were not implemented in accordance with design change procedures. For example: i. The Align RT® software was changed from Build No. (b)(4) to Build No. (b)(4). However, Form 024"Software Change Request & Control" was not used to document this pre-production design change. ii. The pre-production design change to (b)(4) was not implemented in accordance with SOP 32Issue1.0. iii. Complaint #234 received on March 25, 2013 includes records of an investigation, which states"(b)(4). " This software change is not documented on Form 024 "Software Change Request Form" inaccordance with SOP 013 Issue No. 4.1 §6.1.4. The adequacy of your response dated May 7, 2013, cannot be determined at this time since thesupporting documentation was not provided for our review. The design control procedures SOPs 010,032, 013, 043 and the Software Change Request Form, form-024, are to be revised to ensure designchanges are validated or where appropriate verified. All the design control procedures will also bereviewed to ensure they contain all the design control requirements (21 CFR 820.30). Theseprocedures and form were not provided for review to determine their adequacy. Training on the revisedprocedures will also be provided to the appropriate personnel. Vision RT will also review all of thedesign changes for Align RT to make sure they have been validated or where appropriate verified. Theanticipated completion date is June 21, 2013.Failure to establish and maintain adequate procedures to ensure that all purchased or otherwisereceived product and services conform to specified requirements, as required by 21 CFR 820.50. For example: Supplier approval documentation was not available for software that goes into the device


and software that is used in the manufacturing of the device. The adequacy of your response dated May 7, 2013, cannot be determined at this time since thesupporting documentation was not provided for our review. Corrective actions have been opened toensure the Purchasing Control procedure, SOP-003 is compliant with the purchasing controlrequirements in 21 CFR 820.50, reevaluate supplier approvals to make sure the necessary documentsare present, and training will be conducted on the revised procedures. The revised procedures andreassessment of supplier approvals were not provided for review. The anticipated completion date isAugust 2, 2013.FDA District Office: CDRH

9/11/2013 Dako Denmark A/SDako Denmark A/S. Product:HER2 CISH pharmDx kit as well as other FDA cleared or approved products Date: 8/21/2013This inspection revealed that these devices are adulterated within the meaning of section 501(h) of theAct, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for, theirmanufacture, packing, storage, or installation are not in conformity with the current good manufacturingpractice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations(CFR), Part 820. We received a response from Annika Berg, Corporate Vice President dated April 02, 2013 concerningour investigator’s observations noted on the Form FDA 483 (FDA 483), List of InspectionalObservations, that was issued to your firm. We address this response below, in relation to each of thenoted violations. These violations include, but are not limited to, the following: Failure to establish and maintain adequate procedures for receiving, reviewing, and evaluatingcomplaints by a formally designated unit, as required by 21 CFR 820.198(a). For example: a. Your firm failed to follow your procedure (QMS17, Complaint Process) for documentingcomplaints with an associated data search of similar complaints, in that an (b)(4) software complaintwas not associated with a data search of similar complaints. Your firm’s hardware and softwarecomplaint customer interface department manager stated that for software and hardware complaints,the department does not typically search for related complaints as required by the firm’s complainthandling procedure. Your firm’s QMS17 procedure states that complaints should be investigated in auniform manner. We reviewed your firm’s response dated April 02, 2013 and conclude that it is not adequate. Your firmdid not provide a justification for why the initial retrospective review of hardware-related complaints waslimited to those after August 11, 2011.b. Your firm failed to document the following (b)(4) repairs as complaints when the repairs met yourfirm’s complaint definition: (b)(4). We reviewed your firm’s response dated April 02, 2013 and conclude that it is not adequate. Your firmhas not provided evidence of completion of all your firm’s corrections, and corrective actions that wereundertaken to address Observation 3d of the FDA 483. In addition, your firm did not provide adescription and evidence that a systemic corrective action was considered to address this deficiency toinclude a retrospective review of all oral, written, and electronic information received allegingdeficiencies related to a device to ensure that it was appropriately determined if it is a complaint treatedas such when applicable. c. Your firm failed to determine, for (b)(4) service call complaints, whether the complaint was amedical device reportable event. The adequacy of the response dated April 02, 2013 cannot be determined at this time because yourfirm has not provided evidence of completion of all of your firm’s corrections, corrective actions, and


systemic corrective actions that were undertaken to address Observation 4 of the FDA 483. FDA District Office: CDRH

9/11/2013 Bio Focus Co. LtdBio Focus Co. Ltd. Product: Sure-Aid brand pregnancy tests Date: 8/26/2013This inspection revealed that these devices are adulterated within the meaning of section 501(h) of theAct, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for, theirmanufacture, packing, storage, or installation are not in conformity with the current good manufacturingpractice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations(CFR), Part 820. We received a response dated May 3, 2013 concerning our investigator’s observations noted on theForm FDA 483 (FDA 483), List of Inspectional Observations, that was issued to your firm. We addressthis response below, in relation to each of the noted violations. These violations include, but are notlimited to, the following.Failure to establish and maintain adequate procedures for validating the device design that includesoftware validation and risk analysis where appropriate, as required by 21 CFR 820.30(g). For example,your firm’s Design and Development Process procedure, BFQP-7020 Rev. 4 indicates that riskmanagement is performed by the (b)(4). The (b)(4) for the Sure-Aid Pregnancy Test (hCG test), (b)(4)40A-R-01 dated 2006.06.12, has not been updated to include all possible (b)(4) that have beenidentified by your firm. Specifically, (b)(4) for the Sure-Aid Pregnancy Test, BFF-7021-02 (effective2006.07.31), lists the potential (b)(4). Your firm did not have any other risk analysis or (b)(4) related tothe hCG rapid test strips. Page 4 of 6, sections 6.5.6 and 6.5.7 of the Sure-Aid Pregnancy TestManufacturing Process Control/Standard of Test document, BFQI-7020-302 Rev. 1 (effective2012.03.15) state that personnel should (b)(4). The (b)(4) does not identify the risks associated withthese identified non-conformances/defects in the hCG test strip and possible mitigations for these risks. We reviewed your firm’s response and conclude that it is not adequate. Your firm stated that the Riskanalysis and (b)(4) has been updated however it is unclear if all identified non-conformances or defectshave been included in the updated risk analysis and (b)(4). Your firm has not identified the cause of thisdeficiency and did not provide a description of the correction or corrective action implemented to ensurethat risk analysis are conducted as required. Additionally, your firm has not provided evidence that asystemic corrective action was considered to include a retrospective review of risk analysis of allproducts to ensure they were performed as required.FDA District Office: CDRH

9/9/2013 Agila Specialties Private LimitedAgila Specialties Private Limited Product: pharmaceutical manufacturing facility Date: 9/9/2013During our June 17, 2013 through June 27, 2013 inspection of your pharmaceutical manufacturingfacility, Agila Specialties Private Limited, Specialty Formulation Facility (SFF), located at BommasandraJigani Link Rd, Bangalore, India, investigators from the U.S. Food and Drug Administration (FDA)identified significant violations of current good manufacturing practice (CGMP) regulations for finishedpharmaceuticals, Title 21, Code of Federal Regulations, Part 210 and 211. These violations cause yourdrug products 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), in that the methods used in, or the facilities orcontrols used for, their manufacture, processing, packing, or holding do not conform to, or are notoperated or administered in conformity with, CGMP. We have conducted a detailed review of your firm’s response dated July 18, 2013 and note that it lackssufficient corrective actions.


Our investigators observed specific violations during the inspection, including, but not limited to, thefollowing:6. Your firm failed to exercise appropriate controls over computer or related systems to assure thatonly authorized personnel institute changes in master production and control records, or other records(21 CFR 211.68(b)). Your firm’s (b)(4) “Jasco LC-Net II” HPLC instruments do not have restrictions in place to prevent anychange or deletion of analytical raw data. Additionally, there is no audit trail in place to determine anyprevious deletion of raw data. We acknowledge that you have discontinued usage of all Jasco systems in SFF and other siteseffective June 26, 2013, and will assess previous use of the Jasco systems. In your response, pleasesubmit an assessment of the integrity of the data from the Jasco systems only for lots of finishedproduct still within expiry as of the date of this letter.FDA District Office: Public Health Service

9/4/2013 Jabones Pardo S.A.Jabones Pardo S.A.. Product: pharmaceutical manufacturing facility Date: 8/22/2013an investigator from the U.S. Food and Drug Administration (FDA) identified significant violations ofcurrent good manufacturing practice (CGMP) regulations for finished pharmaceuticals, Title 21, Code ofFederal Regulations, Parts 210 and 211. These violations cause your drug products to be adulteratedwithin the meaning of Section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (the Act), 21U.S.C. 351(a)(2)(B), in that the methods used in, or the facilities or controls used for, their manufacture,processing, packing, or holding do not conform to, or are not operated or administered in conformitywith, CGMP. Our inspection also revealed that your firm failed to fulfill its registration obligations under Section510(i)(1) of the Act and its listing obligations under Sections 510(i)(2) and 510(j), which is prohibitedunder Section 301(p). 21 U.S.C. 360(i)(1) and (2), 360(j), and 331(p). Our investigator(s) observed specific violations during the inspection, including, but not limited to, thefollowing: Your firm failed to routinely calibrate, inspect, or check according to a written program designed toassure proper performance and to maintain adequate written records of calibration checks andinspections of automatic, mechanical, electronic equipment, or other types of equipment, includingcomputers, used in the manufacture, processing, packing, and holding of a drug product (21 CFR211.68(a)). Specifically, your firm failed to establish a validation program for the computer software MicrosoftDynamics used for production, inventory, lot number generation, and laboratory test methods used forraw material, bulk, and finished product test release. Your firm also uses the Microsoft Dynamicsprogram to assist your quality unit for product, document and component control. In response to this letter, provide your validation plan/protocol for the Microsoft Dynamics system.Include timelines and a schedule of all corrections.FDA District Office: CDRH

8/12/2013 Social Media Issue - Herbal Papaya, LLCOasis Herbal Papaya, LLC Product: Papaya Seed Extract”, “100% Papaya Leaf (Paw Paw Twig)”, “and “Papaya Leaf with RooibosTea Date: 8/12/2013This is to advise you that the U.S. Food and Drug Administration (FDA) reviewed your website at the


Internet address www.herbalpapaya.com in July 2013 and has determined that you take orders there forthe products “Papaya Seed Extract”, “100% Papaya Leaf (Paw Paw Twig)”, “and “Papaya Leaf withRooibos Tea”, which the website promotes for conditions that cause the products to be drugs undersection 201(g)(1)(B) of the Federal Food, Drug and Cosmetic Act (the Act) [21 U.S.C. § 321(g)(1)]. Thetherapeutic claims on your website establish that these products are drugs because they are intendedfor use in the cure, mitigation, treatment, or prevention of disease. As explained further below,introducing or delivering these products for introduction into interstate commerce for such uses violatesthe Act.Your Facebook account accessible at: https://www.facebook.com/HerbalPapaya, which includes a linkto your website at www.herbalpapaya.com, also includes evidence that your products are intended foruse as drugs. FDA District Office: Dallas District 

8/7/2013 Social Media Issue - Vibrant LifeVibrant Life Life Glow Plus, Super Life Glow, Life Glow Basic, Taheebo Life Tea, Vibrant Life MSM, Herbal MSM,and Organic Germanium Date: 8/7/2013This is to advise you that the Food and Drug Administration (FDA) reviewed your websites at theInternet addresses www.oralchelation.com, www.ChelationTherapyOnline.com,www.arthritisinformation.net, www.vibrantlifemsm.com, www.vibrantlifenews.com, www.bulkmsm.com,and www.heart-disease-bypass-surgery.com in April 2013 and athttps://www.facebook.com/oralchelation in May 2013 and has determined that you take orders there orprovide links to websites that take orders for the products Life Glow Plus, Super Life Glow, Life GlowBasic, Taheebo Life Tea, Vibrant Life MSM, Herbal MSM, and Organic Germanium, which yourwebsites promote for conditions that cause the products to be drugs under section 201(g)(1)(B) of theFederal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. § 321(g)(1)(B)]. The therapeutic claims onyour websites establish that the products are drugs because they are intended for use in the cure,mitigation, treatment, or prevention of disease. As explained further below, introducing or deliveringthese products for introduction into interstate commerce for such uses violates the Act.We also noted claims made on your Facebook page, accessible athttps://www.facebook.com/oralchelation.The following is an example of these claims: “My right foot swelled and started to turn black. I went to my family Doctor … The Specialist said I hadGout …” “I was given a prescription to have filled when my friend called and advised me to try Life GlowPlus … “ “I took Life Glow Plus for two months, 20 capsules a day, and my foot started to get well andthe swelling went down.”“In 2004 I had bypass surgery, which in three weeks failed. “… [H]aving exhausting all conventionaltreatments for heart disease, we went searching on the internet and discovered Life Glow Plus. “Withinone month … [M]y agina was much improved.” “I have been taking life Glow Plus for the past sevenyears and continue to enjoy its benefits Your above-referenced products are not generally recognized as safe and effective for theabove-referenced uses and, therefore, are “new drugs” under section 201(p) of the Act [21 U.S.C. §321(p)]. New drugs may not be legally introduced or delivered for introduction into interstate commercewithout prior approval from FDA, as described in section 505(a) of the Act [21 U.S.C. § 355(a)]. FDAapproves a new drug on the basis of scientific data submitted by a drug sponsor to demonstrate that thedrug is safe and effective. Furthermore, each of your above-referenced products is offered for conditions that are not amenable toself-diagnosis and treatment by individuals who are not medical practitioners; therefore, adequatedirections for use cannot be written so that a layperson can use these drugs safely for their intendedpurposes. Thus, these drugs are misbranded within the meaning of section 502(f)(1) of the Act [21U.S.C. § 352(f)(1)], in that their labeling fails to bear adequate directions for use. The introduction of amisbranded drug into interstate commerce is a violation of section 301(a) of the Act [21 U.S.C. §331(a)].


FDA is aware that Internet distributors may not know that the products they offer are regulated as drugsor that these drugs are not in compliance with the law. Many of these products may be legally marketedas dietary supplements if claims about diagnosis, cure, mitigation, treatment, or prevention of diseaseare removed from the promotional materials and the products otherwise comply with all applicableprovisions of the Act and FDA regulations. Under the Act, as amended by the Dietary Supplement Health and Education Act, dietary supplementsmay be legally marketed with truthful and non-misleading claims to affect the structure or function of thebody (structure/function claims), if certain requirements are met. However, claims that dietarysupplements are intended to prevent, diagnose, mitigate, treat, or cure disease (disease claims),excepting health claims authorized for use by FDA, cause the products to be drugs. The intended useof a product may be established through product labels and labeling, catalogs, brochures, audio andvideotapes, Internet sites, or other circumstances surrounding the distribution of the product. FDA haspublished a final rule intended to clarify the distinction between structure/function claims and diseaseclaims. This document is available on the Internet athttp://www.gpo.gov/fdsys/pkg/FR-2000-01-06/html/00-53.htm2 (codified at 21 C.F.R. § 101.93(g)). In addition, only products that are intended for ingestion may be lawfully marketed as dietarysupplements. Topical products and products intended to enter the body directly through the skin ormucosal tissues, such as transdermal or sublingual products, are not dietary supplements. For theseproducts, both disease and structure/function claims may cause them to be new drugs. Certain over-the-counter drugs are not new drugs and may be legally marketed without prior approvalfrom FDA. Additional information is available in Title 21 of the Code of Federal Regulations (21 C.F.R.)Parts 310 and 330-358, which contain FDA's regulations on over-the-counter drugs. FDA District Office: Los Angeles District 

7/18/2013 Wockhardt LimitedWockhardt Limited. Product: pharmaceutical manufacturing facility Date: 7/18/2013investigators from the U.S. Food and Drug Administration (FDA) identified significant violations ofcurrent good manufacturing practice (CGMP) regulations for finished pharmaceuticals, Title 21, Code ofFederal Regulations, Parts 210 and 211, and documented that your firm withheld truthful information,and delayed and limited the inspection. These violations cause your drug products to be adulteratedwithin the meaning of Section 501(a)(2)(B) and 501(j) of the Federal Food, Drug, and Cosmetic Act (theAct), 21 U.S.C. 351(a)(2)(B) and 351(j), in that the methods used in, or the facilities or controls used for,their manufacture, processing, packing, or holding do not conform to, or are not operated oradministered in conformity with, CGMP, and in that your drug products have been manufactured,processed, packed, or held in an establishment and the owner or operator has delayed, denied, orlimited an inspection, or has refused to permit entry or inspection, respectively. We have conducted a detailed review of your firm’s response of April 9, 2013 and note that it lackssufficient corrective actions. 3. Your firm failed to ensure that laboratory records included complete data derived from all testsnecessary to assure compliance with established specifications and standards (21 CFR 211.194(a)). For example, your firm’s laboratory records failed to include complete records of all stability testingperformed. The FDA investigators identified the practice of performing "trial" sample analysis for HighPerformance Liquid Chromatography (HPLC) analyses prior to collecting the “official” analytical data forstability testing. These “trials” were performed on multiple products, including (b)(4) Tablets (b)(4)mg,(b)(4)mg/(b)(4)ml, and (b)(4) Tablets. These trial runs were not recorded in the equipment use log, andsample preparation data associated with these analyses was destroyed, preventing any calculation oranalysis of the resulting data. Your response states that trial runs were conducted using only one of the(b)(4) HPLC instruments located in the stability laboratory, which happened to be the one instrument


that the FDA investigators reviewed during the inspection. Your response indicates that you haverevised procedures and re-trained your staff. Additionally, your quality control HPLC raw data files can be deleted from the hard drive using thecommon PC login used by all (b)(4) analysts. This deletion eliminates all records of sample injectionsand analyses. Your response indicates that this deletion function is only available on the software usedfor one of (b)(4) sets of HPLC instruments. You also indicated that you have changed the accesscontrol privileges such that laboratory analysts in a “user” role cannot delete or rename files. We also note that on March 20, 2013, your Quality Control Analyst stated to the investigator that he hadused "other samples" to complete the test methods for (b)(4) Injection, USP ((b)(4)mg/ml). <.p>. Your firm failed to record and justify any deviations from required laboratory control mechanisms (21CFR 211.160(a)).The FDA investigators identified a memo dated March 12, 2013 (a week before the inspection),documenting a computer “crash” that occurred on the central back-up and controller PC for (b)(4) HPLCinstruments. The memo describes the loss of instrument activity logs (audit trails). Our investigatorsfound that several of the HPLCs had the audit trail functions disabled; therefore, there is no assurancethat the data generated using these HPLCs is accurate. Your response indicates that your firmperformed an assessment of the historical HPLC chromatograms (raw data) generated on eachindividual HPLC unit prior to March 12, 2013 and verified it against previously printed chromatograms.Based on this analysis, your firm claimed that you had confirmed that the backup data is available foreach of the analyses and no analytical data has been lost due to the computer crash. However, yourfirm failed to provide a risk assessment for the products tested using the HPLC instruments that had theaudit trail functions disabled. This is especially noteworthy given the fact that prior to the inspection, atleast one QC officer had the ability to delete data on the affected system. The lack of reliability and accuracy of data generated by your firm’s laboratory is a serious CGMPdeficiency that raises concerns with all data generated by your firm. While we acknowledge thecommitment in your response to improve quality assurance, we remain concerned that yourinvestigation was not comprehensive enough to determine the extent and impact of the problem. Weare particularly concerned about your inability to implement a robust and sustainable Quality System. These findings include repeat citations from the January 2012 inspection and indicate that your qualitycontrol unit is not exercising its responsibilities and may not have the appropriate authority or ability tocarry out its responsibilities. FDA District Office: CDRH

7/15/2013 Social Media Issue - Neuliven Health, Inc.Neuliven Health, Inc. Product:Glucocil Date: 7/15/2013This is to advise you that the U.S. Food and Drug Administration (FDA) reviewed your website,www.glucocil.com in April 2013 and has determined that you take orders there for the product, Glucocil,which the website promotes for conditions that cause this product to be a drug under section201(g)(1)(B) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. § 321(g)(1)]. The claimson your website establish that this product is a drug because it is intended for use in the cure,mitigation, treatment, or prevention of disease. As explained further below, introducing or delivering thisproduct for introduction into interstate commerce for such uses violates the Act..Moreover, we note the following claims on social media accounts. On your Facebook page, which isaccessible at http://www.facebook.com/Glucocil: Under the “About Us” link: • “Lower fasting blood sugar levels up to 29%” • “Lower A1c levels significantly”


In a post dated, October 13, 2012: • “Glucocil is made for type 2 and pre-diabetics, helps them to lower blood sugar levels by … improvinginsulin sensitivity and production. Try the natural Glucocil at www.Glucocil.com” In a post dated, October 17, 2012: • “Maria, whose fasting blood sugar dropped 47 points (from 150 to 103) after taking Glucocil, has thisto say: ‘When my doctor told me that my sugar was a little high, I was devastated…. Then he told me tostart taking metformin twice a day. I felt awful for about a week, and out of desperation, I decided tosearch for an alternative remedy. This is when I found Glucocil. What a difference! It …regulated mysugar … Give this wonderful alternative a try as you can still take it along with your prescription,because in just a few days, you will see a big difference …’Try Glucocil at www.Glucocil.com.” In a post dated, November 5, 2012: • “A1c Dropped 4 Points!” • “Angela has this to say about Glucocil: "Glucocil really does work. My A1c used to run 11 or higher.Since taking Glucocil, my A1c is under 7, and I'm taking less medication…Try Glucocil atwww.Glucocil.com” On your Twitter account which is accessible at https://twitter.com/glucocil: In a post dated, August 23, 2011 and titled, “GNC To Carry Glucocil™ Blood Sugar Stabilizer: A NaturalAlternative for 80 Million Americans,” which links to the following press release of the same date,accessible at http://prweb.com/releases/2011/8/prweb8714808.htm and titled, “GNC To CarryGlucocil™ Blood Sugar Stabilizer” with the following claims: • “Says Dr. Lee Zhong, M.D., Ph.D., of Neuliven Health, “…. People with blood sugar concerns—andhealthcare providers—are grateful that Glucocil delivers “peace of mind without a prescription.””” • “Since using Glucocil, my blood sugar level has been under control…” • “After trying many natural remedies to lower and stabilize blood sugar levels, I have found Glucocil tobe the only product that performs remarkable results.” These same claims can be found on your website, on the webpage, “In the News” under the link,“August 2011.” We also noted that internet advertisements with the following claim link back to your website,www.glucocil.com. • “Naturally Reduce Blood Sugar Elevations by up to 44%!” • “Reduce Blood Sugar 44% Safely & Naturally, www.glucocil.com” Finally, we note the following claims on the product label and in promotional material that accompaniedthe sale of Glucocil: On the product label: • “Lowers Fasting … Blood Sugar Levels*”


In a letter to the consumer: • “Glucocil will immediately begin helping manage your blood sugar levels…” • “Glucocil helps stabilize your blood sugar levels throughout the day…” • “By taking Glucocil, you can better maintain healthy fasting … blood sugar levels sunup to sundown,which also helps lower your A1c.” Your product is not generally recognized as safe and effective for the above referenced uses and,therefore, this product is a “new drug” under section 201(p) of the Act [21 U.S.C. § 321(p)]. New drugsmay not be legally introduced or delivered for introduction into interstate commerce without priorapproval from FDA, as described in section 505(a) of the Act [21 U.S.C. § 355(a)], see also section301(d) of the Act [21 U.S.C. § 331(d)]. FDA approves a new drug on the basis of scientific datasubmitted by a drug sponsor to demonstrate that the drug is safe and effective. Furthermore, your product, Glucocil, is offered for conditions that are not amenable to self-diagnosisand treatment by individuals who are not medical practitioners; therefore, adequate directions for usecannot be written so that a layperson can use this drug safely for its intended purposes. Thus, this drugis misbranded within the meaning of section 502(f)(1) of the Act [21 U.S.C. § 352(f)(1)], in that itslabeling fails to bear adequate directions for use. The introduction of a misbranded drug into interstatecommerce is a violation of section 301(a) of the Act [21 U.S.C. § 331(a)].FDA District Office: Los Angeles District 

7/5/2013 Enraf-Nonius B.V.Enraf-Nonius B.V. . Product:motorized tables, ultrasound therapy, and diathermy devices Date: 7/5/2013This inspection revealed that these devices are adulterated within the meaning of Section 501(h) of theAct, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for, theirmanufacture, packing, storage, or installation are not in conformity with the current good manufacturingpractice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations(CFR), Part 820. These violations include, but are not limited to, the following:Failure to ensure that all inspection, measuring, and test equipment, including mechanical, automated,or electronic inspection and test equipment, is suitable for its intended purposes and is capable ofproducing valid results, as required by 21 CFR 820.72(a). For example, your firm’s design verificationprocedure does not require that test equipment and software are fully validated, as needed, and prior touse in design verification activities.<.p>FDA District Office: CDRH

7/1/2013 Fresenius Kabi Oncology LtdFresenius Kabi Oncology Ltd . Product: pharmaceutical manufacturing facility Date: 7/1/2013During our January 14, 15, 16, 17 & 18, 2013 inspection of your pharmaceutical manufacturing facility,Fresenius Kabi Oncology Ltd located at D-35 Industrial Area, Kalyani, Nadia, 741 235 West Bengal,India, investigator(s) from the U.S. Food and Drug Administration (FDA) identified significant deviationsfrom current good manufacturing practice (CGMP) for the manufacture of active pharmaceuticalingredients (APIs). These deviations cause your APIs to be adulterated within the meaning of Section501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. 351(a)(2)(B), in that themethods used in, or the facilities or controls used for, their manufacture, processing, packing, or holdingdo not conform to, or are not operated or administered in conformity with, CGMP.


We have conducted a detailed review of your firm’s response of February 11, 2013, and note that itlacks sufficient corrective actions. Our investigator(s) observed specific violations during the inspection, including, but not limited to, thefollowing: 1. We observed and documented practices during the inspection that kept some samples, data andresults outside of the local systems for assessing quality. This raises serious concerns regarding theintegrity and reliability of the data generated at your Kalyani plant. For example, a. Our review of the Chromeleon and Empower II software found that your firm was testing samplesunofficially, and not reporting all results obtained. Specifically, “test,” “trial” and “demo” injections ofintermediate and final API samples were performed, prior to performing the tests that would be reportedas the final QC results. b. Out-of-specification or undesirable results were ignored and not investigated. c. Samples were retested without a record of the reason for the retest or an investigation. Only passingresults were considered valid, and were used to release batches of APIs intended for US distribution. d. Unacceptable practices in the management of electronic data were also noted. The management ofelectronic data permitted unauthorized changes, as digital computer folders and files could be easilyaltered or deleted. Your inability to detect and prevent poor data integrity practices raises serious concerns about the lackof quality system effectiveness. It is imperative that the data generated and used to makemanufacturing and quality decisions at your firm is trustworthy and reliable. Senior management initiallyinformed FDA investigators that they were unaware of information generated at the Kalyani plant thatmay have an impact on the quality of API. Your senior management, at the local and corporate levels, isresponsible for assuring that strict corporate standards, procedures, resources, and communicationprocesses are in place to detect and prevent breaches in data integrity, and that such significant issuesare identified, escalated, and addressed in a timely manner. This responsibility starts with designingcomputerized systems with appropriate security features and data audit trails, as well as many otherelements that assure proper governance of your computerized systems. This indicates that yourcurrent quality risk management approach, for identifying and controlling any potential risks to thequality of the drugs you manufacture, was not properly functioning. <.p>Your laboratory control records do not include data derived from all of the tests necessary to establishcompliance with standards. For example, the inspection found multiple raw data chromatograms in digital files labeled “test” and“demo,” that were injected prior to the sample injections that were used to conclude that batches werein conformance with the specification. They were: a. A “demo” chromatogram injected 3/6/12 and the official organic impurities injection on 4/6/12 for(b)(4) batch (b)(4). b. A “demo” chromatogram injected 3/6/12 and the official organic impurities injection on 4/6/12 for(b)(4) batch (b)(4). c. A “test” chromatogram injected 12/9/08 and the official related substances injection on 12/10/08 for(b)(4) batch (b)(4). d. Two “test” chromatograms injected 12/4/08 and the official related substances injections on 12/5/08for (b)(4) batch (b)(4).


e. Five “trial” chromatograms injected 7/5/11 between the official related substances injections whichoccurred both before and after the “trial” injections for batch (b)(4) of (b)(4). The final injections weremade on 12/6/11 for this batch. Your response indicated that for the data identified above, the product impact assessment was unclear. Please provide your assessment of the electronic audit trail information that describes thecircumstances surrounding the collection of this data. Your response also indicates that you have an ongoing investigation with a goal to identify additionaldata, similar to that above, which is located in your electronic records. As stated in item 1 of this letter,we expect your firm to extend your data integrity investigation to all relevant lots and data. Theinvestigation should identify any data found in your electronic record repositories (or other locations)that is not also described in your product release files and/or batch records. Also, it should include areview of all chronological records that clarify which equipment was used for the testing of the APIbatches. Finally, it should include a review of the audit trail from the software that describes surroundingevents for each piece of extra data identified that represents a finished API batch. In your response tothis letter, provide a timeline for completion of this investigation, and a summary of your audit findings..Your laboratory’s written procedure failed to establish proper retesting practices for out-of-specificationresults. For example, (b)(4) USP (b)(4) batch (b)(4)-month stability interval assay test, was initially performed 03/10/12 and ahandwritten note on the system suitability chromatogram printout read, “not considered.” Justification forthe decision to retest was not available. Your firm invalidated (b)(4) batch #(b)(4) related substance test results of 02/02/12 that were performedin duplicate. On the same day a retest was run. The FDA investigator was informed that the analystappeared to have encountered an unknown peak at the (b)(4) minutes retention time. Justification forthe decision to retest was not available. Your response indicates that that a combination of your inadequate SOPs, ineffective training andcorporate audits failed to identify these deviations. Please provide your assessment of the adequacy of

6/19/2013 Transonic Systems, Inc.Transonic Systems, Inc. Product:COstatus system Date: 6/19/2013This inspection revealed that these devices are adulterated within the meaning of section 501(h) of theAct (21 U.S.C. § 351(h)), in that the methods used in, or the facilities or controls used for, itsmanufacture, packing, storage, or installation are not in conformity with the current good manufacturingpractice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations(CFR), Part 820. We received your firm’s response dated April 8, 2013, concerning our Investigator’sobservations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, which wasissued to you at the close of the inspection. We address this response below, in relation to each of theviolations. These violations include, but are not limited to, the following:Design validation did not ensure the device conforms to defined user needs and intended uses, asrequired by 21 CFR 820.30(g). Specifically, design verification and validation activities for the COstatussystem were executed under the VR COstatus Rev. 2 COstatus Acquisition Software VerificationReport, dated 1/29/10; VRHCM101-002 Rev. 1 Verification Report for the HCM101 Monitor, dated1/3/08; and the COstatus Beta-site Feedback Summary; COstatus Acquisition Software ValidationReport, dated 3/31/10. These activities have failed to demonstrate that the COstatus system conformsto defined user needs and intended uses. For example, intended use of providing clinically relevant datato healthcare providers treating critically ill patients; the platform must be able to be moved easily from


patient to patient. Your response to this violation is inadequate as there is no commitment to perform an appropriatedesign validation. Results of the validation of the device software were not adequately documented, as required by 21CFR 820.30(g). Specifically, the COstatus Acquisition Software Validation Report, Rev. 1, wasapproved on 3/31/10. This validation was executed using three HCM101 monitors (s/n: A81019,A81020& A81096). The validation results for the three monitors were not maintained. The reportdocuments results of one system without a documented conclusion. The adequacy of your response to this observation cannot be determined at this time. In your responseto this violation you state that a work instruction (ENG 11.0, Validation and Verification TemplateInstructions) and form (QAF523, Verification, Validation, and Baseline Test) were created in responseto this observation. However, you did not provide these documents in your response for review. Acceptance criteria were not established prior to the performance of validation activities, as required by21 CFR 820.30(g). Specifically, COstatus system verification and validation activities were executedunder the VR COstatus Rev. 2 COstatus Acquisition Software Verification Report, dated 1/29/10;VRHCM101-002 Rev. 1 Verification Report for the HCM101 Monitor, dated 1/3/08; COstatus Beta-siteFeedback Summary; and the COstatus Acquisition Software Validation Report, dated 3/31/10.Acceptance criteria were not established prior to executing these activities. Your response to this violation is inadequate because you fail to address why acceptance criteria wasnot established and documented prior to the execution of validation activities. Also, your response failsto demonstrate how you plan to correct this violation moving forward. Your validation reports shouldhave had a documented conclusion of whether or not established acceptance criteria wereachieved.<.p>FDA District Office: New York District

6/6/2013 Medinvents NVMedinvents NV Product: Spirotome (biopsy instruments). Date: 6/6/2013Our inspection revealed that your firm’s devices are misbranded under section 502(t)(2) of the Act, 21U.S.C. § 352(t)(2), in that your firm failed or refused to furnish material or information respecting thedevices that is required by or under section 519 of the Act, 21 U.S.C. 360i, and 21 CFR Part 803 -Medical Device Reporting. These violations include, but are not limited to, the following: Failure to establish and maintain adequate procedures for validating the device design, includingsoftware validation and risk analysis, where appropriate, as required by 21 CFR 820.30(g). Forexample, your firm did not include all medical devices manufactured and (b)(4) sterilized. Your firmestablished a procedure for (b)(4) load sizes for each device type, but no evidence to support the loadsizes was documented.FDA District Office: CDRH

6/4/2013 Techlem Medical CorporationTechlem Medical Corporation Product: hospital stretchers Date: 6/4/2013This inspection revealed that these devices are adulterated within the meaning of section 501(h) of theAct, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for, theirmanufacture, packing, storage, or installation are not in conformity with the current good manufacturingpractice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations


(CFR), Part 820. These violations include, but are not limited to, the following: Failure to validate computer software for its intended use according to an established protocol whencomputers or automated data processing systems are used as part of production or the quality system,as required by 21 CFR 820.70(i). Specifically, (b)(4), developed by (b)(4), is used to transfer and makechanges to drawings used to manufacture devices. There is no protocol or documentationdemonstrating that this software has been validated for its intended use.<.p>FDA District Office: CDRH

5/28/2013 RPG Life Sciences LimitedRPG Life Sciences Limited Product: pharmaceuticals. Date: 5/28/2013Our investigator observed specific violations during the inspection, including, but not limited to, thefollowing:Your firm failed to ensure that laboratory records included complete data derived from all testsnecessary to assure compliance with established specifications and standards (21 CFR 211.194(a)).Additionally, during an audit of the data submitted in support of the (b)(4) regarding (b)(4) tablets USP(b)(4) mg, our investigator requested to review the electronic analytical raw data to compare the valuesfor (b)(4) assay and degradation products. However, your firm provided only the printed copies of theraw data because your firm did not have the software program available to view the electronic raw data.Your firm failed to establish and exercise adequate controls over computers to prevent unauthorizedaccess or changes to electronic data.For example, the computers that control your analytical laboratory instruments, including an HPLC,(b)(4) GCs, and an FTIR, lacked control mechanisms to prevent unauthorized access to, changes to, oromission of data files. a. Your analysis of (b)(4) USP batch (b)(4) exceeded the (b)(4) residual solvent limit on February 29,2012. Your firm did not report or investigate this OOS result, and deleted the related electronic records.During our inspection, your analyst admitted that he also deleted other uninvestigated failing and/orOOS electronic data from the laboratory database in January 2013 prior to our inspection. Your QCSenior Manager also acknowledged this laboratory-wide electronic data deletion practice. b. During our inspection, your analysts demonstrated to our investigators that they could delete anyelectronic analytical data files from the laboratory computers and external backup hard drives. Adequate controls prevent improper deletion of essential data. You stated in your response that youare procuring a centralized server and software, which will prevent electronic data deletion. Eachanalyst will have an individual user ID and password. You also trained your analysts not to deleteelectronic analytical data and report all laboratory incidences to managers. We will verify theeffectiveness of these corrective actions during our next inspection. You are responsible for the accuracy and integrity of the data generated by your firm. A firm mustmaintain all raw data generated during each test, including graphs, charts, and spectra from laboratoryinstrumentation. These records should be properly identified to demonstrate that each released batchwas tested and met release specifications. FDA District Office: CDRH

5/21/2013 FDA Mobile App Compliance LetterPuget FDA Mobile App Compliance Letter Product:Letter to Biosense Technologies Private Limited concerning the uChek Urine Analyzer Date: 5/21/2013It has come to our attention that you are currently marketing the uChek Urine analyzer, which isintended for use with Siemens Multistix SG10, Siemens Multistix SG, Siemens Uristix, Bayer Diastix,


and Bayer Keto-Diastix reagent strips for the qualitative and semi-quantitative determination of urineanalytes including glucose, urobilinogen, pH, ketone, blood, protein, bilirubin, nitrite, leukocyte, andspecific gravity. The uChek Urine analyzer appears to meet the definition of a device as that term isdefined in section 201(h) of the Federal Food Drug and Cosmetic Act.Please note that though the types of urinalysis dipsticks you reference for use with your application arecleared, they are only cleared when interpreted by direct visual reading. Since your app allows a mobilephone to analyze the dipsticks, the phone and device as a whole functions as an automated stripreader. When these dipsticks are read by an automated strip reader, the dipsticks require newclearance as part of the test system. Therefore, any company intending to promote their device for usein analyzing, reading, and/or interpreting these dipsticks need to obtain clearance for the entireurinalysis test system (i.e., the strip reader and the test strips, as used together). For an example ofthis type of device system, and a summary of the type of data used to support clearance of the system,see the decision summary for k111221(http://www.accessdata.fda.gov/cdrh_docs/reviews/K111221.pdf1). We have conducted a review of our files, and have been unable to identify any Food and DrugAdministration (FDA) clearance number for the uChek Urine analyzer. We request that you provide uswith the FDA clearance number for the uChek Urine analyzer. If you do not believe that you arerequired to obtain FDA clearance for the uChek Urine analyzer, please provide us with the basis for thatdetermination. Please provide the requested information within thirty (30) business days.We have assigned a unique document number that is cited above. The requested information shouldreference this document number and should be submitted to:James L. Woods, WO66-5688Deputy DirectorPatient Safety and Product QualityOffice of In Vitro Diagnostics and Radiological Health10903 New Hampshire AvenueSilver Spring, MD 20993If you have questions relating to this matter, please feel free to call Amy Ghering at 301-796-1656 or [email protected], or log onto our web site at www.fda.gov2 for general information relating toFDA device requirements. Sincerely yours, James L. WoodsDeputy Director,Patient Safety And Product QualityOffice of In Vitro Diagnostics and Radiological HealthCenter for Devices and Radiological Health--

5/9/2013 Apnea Sciences IncApnea Sciences Inc Product: adjustable dental guards for snoring and sleep apnea Date: 5/9/2013This inspection revealed that your ApneaRx and SnoreRx devices are adulterated within the meaning ofSection 501(h) of the Act (21 U.S.C. § 351(h)), in that the methods used in, or the facilities or controlsused for, their manufacture, packing, storage, or installation are not in conformity with the current goodmanufacturing practice (cGMP) requirements of the Quality System regulation found at Title 21, Code ofFederal Regulations (CFR), Part 820. We received a response from Ruth A. Fallon, Esq, datedDecember 14, 2012, concerning our investigators’ observations noted on the Form FDA 483 (FDA 483),List of Inspectional Observations, which was issued to your firm. We address this response below, inrelation to each of the noted violations. These violations include, but are not limited to, the following:Procedures to ensure that all purchased or otherwise received product and services conform tospecified requirements have not been established, as required by 21 CFR 820.50. Specifically,


a) You have not established purchasing control procedures.b) You do not have procedures for the potential supplier evaluation, acceptance, and approval basedon their abilities to meet specified requirements.c) You do not have any documented evaluation and control of their suppliers, contractors of SnoreRxand ApneaRx devices and consultants of the products and services provided.d) You did not identify the list of their suppliers, contractors and consultants and the approval of thesupplier, consultants and contractors of their products and services.e) You do not have any agreement that the suppliers and consultants agree to notify your firm of thechanges in the product or services provided. You use a contract manufacturer for the finished devices,and a computer software company for the internet prescription device ordering and complaint process,and you do not have any such agreement in place. Your response to each subpart is listed below: a) “The ISO audit by (b)(4) the previous week verified that we do have a purchasing system.” Your response is not adequate. Your Quality System Manual (QSM), Rev A, dated 10/09/2012, Section7.4 - Purchasing, states “ASC has established documented procedures to ensure that purchasedproduct and/or services conform to purchase requirements.” However, during the inspection there wereno written procedures available for supplier evaluation; supplier selection; defining the extent of controlto be exercised over the products, services, suppliers, contractors and consultants; and supplierapprovals. b) “This finding is not supported by either the facts, or the evidence.” Your response is not adequate. During the inspection you did not have the subject written proceduresavailable and you have not provided any evidence that you have established them. c) “The policy and procedure protocol will be amended to have an onsite ASC manager present tovalidate that quality control procedures are followed and verified during the manufacturing process.” Your response is not adequate. You did not include any written procedures for evaluating your contractmanufacturer and you have not identified a timeframe for establishing and implementing the onsiteevaluation audits. In addition, you have not addressed the other suppliers of products such as thesoftware used for internet prescription device ordering and returns/complaints, or for consultants hiredfor regulatory assistance. d) “Apnea Sciences has one contract manufacturer who was thoroughly evaluated and qualified.” Your response is not adequate. You have not provided any evidence that you have established andmaintained records of acceptable suppliers, contractors and consultants. In addition, you have notprovided any evidence that you have evaluated and qualified the contract manufacturer mentioned inyour response. e) “The contract manufacturer cannot make changes, because we own the molds, to do so would bea material breach of the law.” Your response is inadequate. Your contract manufacturer receives raw materials and manufactures,labels and packages finished devices according to specifications you have provided. You do not haveany agreement requiring the manufacturer to notify you of the changes in the products or servicesprovided. In addition, you use a computer software company for the internet prescription deviceordering and complaint process and you do not have any such agreement in place.. FDA District Office: Los Angeles District Office


5/6/2013 Invatec S.p.A.Invatec S.p.A. , subsidiary of Medtronic, Inc. Product: Amphirion Plus Percutaneous Translumenal Angioplasty (PTA) Catheter and the Driver CECatheter. Date: 5/6/2013This inspection revealed that these devices are adulterated within the meaning of section 501(h) of theAct, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for, theirmanufacture, packing, storage, or installation are not in conformity with the current good manufacturingpractice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations(CFR), Part 820. Failure to validate computer software for its intended use according to an established protocol, asrequired by 21 CFR 820.70(i). For example, Section 7.3.5 of Invatec’s Process Validation Procedure(#PRC/04/07/.00.10), dated October 16, 2012, states, “When the manufacturing or test equipment contains software or firmware that is used to operate theequipment, the software will be validated for its intended use per PRC/03A/06.00.01.”The adequacy of your firm’s response dated February 23, 2013, cannot be determined at this time. Yourfirm states that, after the close of the inspection, Invatec performed a review of all Amphirion Plussoftware validation requirements and confirmed that these activities were conducted in accordance withthe General Principles of Software Validation; Final Guidance for Industry and FDA Staff, January 11,2002, and that your firm conducted (b)(4), and other tests. Neither the results of the software validationrequirements, nor the results of the (b)(4), were submitted to FDA for review. Invatec also: 1. Promised to revise its Process Validation Procedure (PRC/04/07.00.10, revision 2, 16 Oct. 2012) toinclude reference to Convalida dei Process Control System Procedure (PRC/o3A/06.00.02, rev 6, 16Apr. 2012);2. Promised to train personnel involved in Process Validation;3. Promised to conduct a retrospective assessment of all activities used for the risk assessment ofAmphirion Plus in relation to compliance with Convalida dei Process Control System Procedure;4. Promised to revise the conclusions associated with the Amphirion Plus Convalida dei ProcessControl System risk assessment documentation, where required, as output of Action #1.3. Your firm’s response dated April 3, 2013, states that your firm has completed revision of its ProcessValidation Procedure, completed training of personnel in the revised validation procedure, completed aretrospective assessment of all activities used for risk assessment of the Amphirion Plus PTA Catheter,and revised the conclusions associated with the Amphirion Plus PTA Catheter Convalida dei ProcessControl System Procedure. However, documentation or evidence of the corrections, corrective actions,revised procedures, retrospective assessment of risk, and revisions of your firm’s conclusions has notbeen provided to FDA for review.FDA District Office: CDRH

3/16/2013 Puget Sound Blood Center and ProgramPuget Sound Blood Center and Program Product: blood and blood products Date: 3/16/2013During the inspection, FDA investigators documented significant deviations from applicable currentGood Manufacturing Practice (cGMP) regulations for blood and blood products, Title 21, Code ofFederal Regulations (21 CFR), Parts 606, 610 and 640 and the cGMP regulations for finishedpharmaceuticals, 21 CFR Part 211. These deviations cause your blood products to be adulteratedwithin the meaning of Section 501(a)(2)(B) of the Food, Drug and Cosmetic Act (the Act). [21 U.S.C.351(a)(2)(B)]. These deviations include but are not limited to the following:


Failure to check input to and output from the computer or related system of formulas or other records ordata for accuracy [21 CFR 211.68(b)]. For example, (a) On June 3, 2012, you identified that donor and patient identification numbers are carried forwardfrom previous override functions when an override is performed by the same user. This causes thepatient and donor numbers to be replaced with incorrect identification numbers on laboratory overridereports. On June 8, 2012, this issue was reported to the computer software manufacturer, however,you failed to implement the computer system workaround identified by them. For example, on January6, 8, and 10, 2013, at least three units were missing the Patient number and Order number from thePSBC Transfusion Service Laboratory Override Report. (b) ORF-000055354 documents a problem where demographic changes, including blood type, CMVstatus and name changes can be lost if a different user is updating the record in another session. OnSeptember 4, 2012, this issue was reported to the computer software manufacturer, however, you failedto implement the computer system workaround that the manufacturer identified. During the inspection,your software was tested by BCS staff who confirmed that this event continues to occur whendemographic changes are made by different users<.p>FDA District Office: Seattle District

3/5/2013 Fresenius Medical Care, North AmericaFresenius Medical Care, North America Product:Optiflux Polysulfone Dialyzers Date: 3/5/2013This inspection revealed that these devices are adulterated within the meaning of section 501(h) of theAct, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for, theirmanufacture, packing, storage, or installation are not in conformity with the current good manufacturingpractice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations(CFR), Part 820. We received responses dated December 28, 2012, January 2, 2013 and February 7, 2013, concerningour investigator’s observations noted on the Form FDA 483 (FDA 483), List of InspectionalObservations, which was issued to your firm. We address this response below, in relation to each of thenoted violations. These violations include, but are not limited to, the followingtion to the noted violation.This violation includes, but is not limited to, the following:2) Failure to establish and maintain adequate procedures for validating the device design. Designvalidation shall be performed under defined operating conditions on initial production units, lots, orbatches, or their equivalents. Design validation shall ensure that devices conform to defined user needsand intended uses and shall include testing of production units under actual or simulated useconditions. Design validation shall include software validation and risk analysis, where appropriate, asrequired by 21 CFR 820.30(g). For example: a. The design validation for the (b)(4) of Optiflux Polysulfone (PS) dialyzers (b)(4) is incomplete. Aclinical study, (b)(4), was conducted (b)(4). The study indicated that (b)(4). The study was conductedapproximately (b)(4) the dialyzers were released for distribution in 2001. Furthermore, you were notable to provide documentation demonstrating that the study was conducted using (b)(4). We have reviewed your responses dated 12/28/2012, 1/2/12013 and 2/7/2013, and do not considerthem to be adequate. The responses indicated that the clinical trial results (b)(4). However, the clinicaltrial was conducted under (b)(4). Therefore, this clinical trial constituted design validation activities forthe (b)(4) dialyzers. See also the comments regarding design validation/verification and evaluation ofplatelet adhesion under #1 above.FDA District Office: Denver District


3/1/2013 VE Valley Electronics GmbHVE Valley Electronics GmbH Product:fertility devices Date: 3/1/2013Our inspection revealed that the Lady Comp, Baby Comp, and Pearly fertility devices are misbrandedunder section 502(t)(2) of the Act, 21 U.S.C. § 352(t)(2), in that your firm failed or refused to furnishmaterial or information respecting the devices that is required by or under section 519 of the Act, 21U.S.C. § 360i, and 21 CFR Part 803 - Medical Device Reporting. We received a response from yourfirm dated October 26, 2012, concerning our investigator’s observations noted on the Form FDA 483(FDA 483), List of Inspectional Observations, that was issued to your firm. We address this responsebelow, in relation to the noted violation. This violation includes, but is not limited to, the following:Failure to establish and maintain procedures for defining and documenting design output in terms thatallow an adequate evaluation of conformance to design input requirements. Design output proceduresshall contain or make reference to acceptance criteria and shall ensure that those design outputs thatare essential for the proper functioning of the device are identified. Design output shall be documented,reviewed, and approved before release, as required by 21 CFR 820.30(d). For example, the SoftwareQualification for the Lady Comp, Baby Comp, and Pearly Comp does not define acceptance criteria forthe (b)(4) test. Your firm’s response dated October 26, 2012, appears to be adequate in that your firm revised thedesign validation plan to include the (b)(4) tests. Your firm also revised the test plan for the fertilitydevices to define the (b)(4) tests that included the pass/fail acceptance criteria. Your firm implementedthe validation and test plans through the completion of the (b)(4) tests for the fertility devices on October26, 2012. Your firm provided a copy of the validation and test plans and completed test report for ourreview. . Failure to establish and maintain adequate procedures to ensure that formal documented reviews ofthe design results are planned and conducted at appropriate stages of the device's designdevelopment, as required by 21 CFR 820.30(e). For example, the design control procedure (P03 02)requires that design reviews be completed at the end of the completion of all technical documentation. The design review for the Lady Comp device was completed June 16, 2008, prior to the completion ofthe software qualification for the Lady Comp device, which was completed October 17, 2008. Nodesign review was conducted after the software qualification. The adequacy of your firm’s response, dated October 26, 2012, cannot be determined at this time. Your firm completed a new design review for the Lady Comp device that included software validation.Additionally, your firm stated that training would be conducted on the current design review procedure. However, the evidence of implementation to include the training documentation was not provided in theresponse.FDA District Office: Public Health Service

2/11/2013 Social Media Issue - Oasis ConsumerHealthcareOasis Consumer Healthcare Product:Halo Date: 2/11/2013This letter is to advise you that the United States Food and Drug Administration (FDA) has reviewedyour firm's marketing of your product, Halo claims on your Twitter page (available at https://mobile.twitter.com/halogermdefense) include thefollowing:• "Get your #flu vaccine & keep Halo handy to help prevent the flu this season ....."• ''Getting on a plane, train or bus to get to your Thanksgiving destination? Bring along@HaloGermDefense! Protection from the #airyoushare."Furthermore, the "about" section of your Facebook account (athttps://www.facebook.com/HaloGermDefense/info) provides:


• "Just in time for back to school and the cough and cold season, Oasis Consumer Healthcare ismaking it safer to breathe the air you share for up to six hours with just three sprays with their new,unique Halo™ Oral Antiseptic. Halo is the first-ever, patent-pending, oral antiseptic spray that has beenscientifically proven to kill 99.9% of infectious germs, including a broad spectrum of bacteria andviruses, such as rhinovirus (the virus that causes the common cold), influenza, strep, whooping cough(Bordetella pertussis), and H1N1."Accordingly, Halo is a drug, as defined by section 201(g)(1) of the Federal Food, Drug, and CosmeticAct (the Act), 21 U.S.C. § 321(g)(1), because it is intended for use in the diagnosis, cure, mitigation,treatment, or prevention of disease, or to affect the structure or function of the body of man or otheranimals.We note, although your product includes a Drug Facts panel with information that corresponds toconditions proposed under the Over-the-Counter (OTC) Human Use Tentative Final Monograph (TFM)for Oral Antiseptic Drug Products (59 FR 6084, Feb. 9, 1994), your product is marketed for intendeduses that are not addressed under this rulemaking or any other rulemaking under the OTC DrugReview. Oral antiseptics are applied topically to the oral cavity to help prevent infection in woundscaused by cuts, scrapes, or injury following minor dental procedures. Your product's intended use underthe Drug Facts Panel is as a "[f[irst aid to help prevent infection in minor oral irritations." However, asindicated by the intended uses cited above, your product labeling includes claims that are well beyondthe uses covered under the TFM for Oral Antiseptic Drug Products.Based on its labeled uses, Halo is a new drug, as defined by section 201(p) of the Act, 21 U.S.C. §321(p), because it is not generally recognized as safe and effective for its labeled uses. Under sections301(d) and 505(a) of the Act, 21 U.S.C. §§ 331(d) and 355(a), a new drug may not be introduced ordelivered for introduction into interstate commerce unless an FDA-approved application is in effect for it.Your sale of Halo without an approved application violates these provisions of the Act.Furthermore, because this product is offered for conditions that are not amenable to self-diagnosis andtreatment by individuals who are not medical practitioners, adequate directions cannot be written so thata layman can use it safely for its intended uses. Thus, Halo labeling fails to bear adequate directions forits intended uses, causing it to be misbranded under section 502(f)(1) of the Act, 21 U.S.C. §352(f)(1).FDA District Office: Public Health Service 

1/29/2013 FSSB Chirurgische Nadeln GMBHFSSB Chirurgische Nadeln GMBH Product:sterile and non-sterile needles and sutures Date: 1/29/2013This inspection revealed that these devices are adulterated within the meaning of section 501(h) of theAct, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for, theirmanufacture, packing, storage, or installation are not in conformity with the current good manufacturingpractice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations(CFR), Part 820.These violations include, but are not limited to, the following:Failure to validate computer software for its intended use according to an established protocol whencomputers or automated data processing systems are used as part of production or the quality system,as required by 21 CFR 820.70(i). For example, your firm uses custom automatic machines in theneedle production process. Your firm stated that it performed software validation for the automaticmachines and that the software protocol was tested, but these validation activities were notdocumented. . FDA District Office: CDRH

1/29/2013 AAMI Wireless WorkshopA workshop with approximately 80 invited medical wireless experts was held in October 2012. Thisreport, at the link provided, documents the discussion and outcomes of this workshop. A follow-upmeeting is planned for March 2013.


1/29/2013 2012 FDA Software Warning Letter CountThe total number of FDA software, computer system, and electronic records warning letters in 2012 isapproximately 30 which is up from 18 in 2011 and fewer in 2009 and 2010. This is based on thekeyword searches we perform on a regular basis but is not guaranteed to be comprehensive.

12/17/2012 LifeWatch Services, Inc.LifeWatch Services, Inc. Product:cardiac event monitors Date: 12/17/2012This inspection revealed that these devices are adulterated within the meaning of section 501(h) of theAct, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for, theirmanufacture, packing, storage, or installation are not in conformity with the current good manufacturingpractice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations(CFR), Part 820.These violations include, but are not limited to, the following:Failure to adequately establish procedures for corrective and preventive actions, as required by 21 CFR820.100(a). Specifically,Information regarding failed software verification testing, including investigation and final acceptancedetermination, was not included in the CAPA process;Failure to adequately establish procedures for design verification, as required by 21 CFR 820.30(f). Forexample, your firm’s procedures, SOP-18-007, Limited Market Release Process, and SOP-05-001,Design Control Process, have failed to ensure that acceptance criteria for the Limited Market Releaseof either new devices or changes to existing devices are adequate and unambiguous for the verificationof design. We have reviewed your firm’s responses and have determined that they are inadequate in that they donot provide assurance that verification activities are being performed and documented for newlyimplemented software changes and/or upgrades. Additionall, your firm cannot ensure through objectiveevidence that design verification results meet required criteria. FDA District Office: Chicago District

12/4/2012 Energist Limited.Recipient: Energist Limited Product:Ultra Plus Variable Pulsed Light (VPL), iPulse i150, i200, and i300 Pulsed Light Systems, and anozzle for the Portrait Plasma System Date: 12/4/2012Our inspection revealed that your firm’s devices are misbranded under section 502(t)(2) of the Act 21U.S.C. § 352(t)(2), in that your firm failed or refused to furnish material or information respecting thedevice that is required by or under section 519 of the Act, 21 U.S.C. § 360i, and 21 CFR Part 803 -Medical Device Reporting. We received responses from Rob Davies, Regulatory Affairs Officer, datedMay 29, 2012, and June 27, 2012, concerning our investigator’s observations noted on the Form FDA483 (FDA 483), List of Inspectional Observations that was issued to your firm. We address thisresponse below, in relation to each of the noted violations. In addition, FDA has noted nonconformances with regards to section 501(h) of the Act (21 U.S.C. §351(h)), which are deficiencies within your firm’s quality system pertaining to current goodmanufacturing practice requirements specified in the Quality System regulation found at 21 CFR Part820. These nonconformities include, but are not limited to, the following:1. Failure to validate computer software for its intended use according to an established protocol, asrequired by 21 CFR 820.70(i).For example, the process validation report for the software used in the (b)(4), including the Ultraplusdevices, does not show the software version or the equipment used for the validation.Your firm’s responses to this observation appear to be adequate. Your firm performed a correctiveaction by revalidating the (b)(4) software version 1.07, by validating the software met user needs andintended uses and documenting the equipment used during the revalidation. 


FDA District Office: CDRH

12/3/2012 Alcon LenSx, Inc.Alcon LenSx, Inc. Product:LenSx Laser System Date: 12/3/12Our inspection also revealed that these devices are adulterated under section 501(f)(1)(B) of the FDCA,21 U.S.C. § 351(f)(1)(B), because your firm does not have an approved application for premarketapproval (PMA) in effect pursuant to section 515(a) of the FDCA, 21 U.S.C. § 360e(a), or an approvedapplication for an investigational device exemption under section 520(g) of the FDCA, 21 U.S.C. §360j(g). These devices are also misbranded under section 502(o) the FDCA, 21 U.S.C. § 352(o),because your firm did not notify the agency of its intent to introduce the device into commercialdistribution in that a notice or other information respecting the modification to the device was notprovided to FDA, as required by section 510(k) of the FDCA, 21 U.S.C. § 360(k), and 21 CFR807.81(a)(3)(i). For a device requiring premarket approval, the notification required by section 510(k) isdeemed satisfied when a PMA is pending before the agency. [21 CFR 807.81(b)]. The kind ofinformation that your firm needs to submit in order to obtain approval or clearance for the device isdescribed on the Internet athttp://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/default.htm1 . The FDA will evaluate the information that your firm submits and decide whether the product maybe legally marketed. Specifically, the Alcon LenSx Laser System was cleared via K101626, with operating software version2.02. Your firm has since made multiple revisions to the software, and the LenSx Laser System wasrunning software version 2.13 at the time of the inspection. FDA reviewed your software changes fromversion 2.02 to version 2.13 and determined that some changes are significant with respect to youroriginal premarket clearance submission and may affect the safety and efficacy of the device. A new510(k) is required for these changes. Examples include but are not limited to: Software Release Notes Version 2.12, #15: (b)(4)– This change allows for the user to make (b)(4)corneal surface. Software Release Notes Version 2.12, #19: (b)(4)– Pre-op Biometrics Lens Thickness max range waschanged from (b)(4). Software Release Notes Version 2.13, #10: (b)(4)– Minimum allowed distance between cornea incisionswas changed from (b)(4). It is your responsibility to report to FDA all significant modifications, including software changes thatmay change the design or performance and/or affect the safety and efficacy of your devices . FDA District Office: Los Angeles District

11/29/2012 Mindray DS USA, Inc.Recipient: Mindray DS USA, Inc. Product:Class II medical devices such as patient monitors, chemistry analyzers and ultrasound systems Date: 11/29/2012The inspection revealed these devices are adulterated under Section 501(h) of the Act [21 USC 351(h)],because the methods used in, or the facilities or controls used for, its manufacture, packing, storage, orinstallation are not in conformity with the current good manufacturing practice requirements of theQuality System regulation found at Title 21, Code of Federal Regulations (CFR), Part 820. We received a response...dated August 23, 2012, concerning our investigator's observations noted onthe Form FDA 483 (FDA 483) that was issued to your firm. We address this response below, in relationto each of the noted violations.


These violations include, but are not limited to, the following:Failure to adequately establish procedures for corrective and preventive action, pursuant to 21 CFR820.100(a). For example:E. Failure Investigation and Corrective/Preventive Action Form No. 497, dated 08/02/2011, stated thatDPM Central Station had a software anomaly which caused the trend data for a patient to be replacedby another patient. On 05/12/2011, your firm released a product correction letter to the field to correctthe issue via a software upgrade. The CAPA effectiveness verification method was identified asverifying that all documents in the corrective action have been modified. However, your firm was notable to provide any documentation to demonstrate that the CAPA has been verified for effectivenessand that it does not adversely affect the finished device.F. Failure Investigation and Corrective/Preventive Action Form No. 476, dated 09/03/2010, stated thatDPM 6/7 Monitor failed to contain the disclosure and calculator functions following a software upgrade,and your firm attributed the failures to an inaccurate software upgrading procedure. On 08/11/2010,your firm released a product correction letter to the field to correct the issue via a software upgrade.However, your CAPA effectiveness verification method was indicated as "not applicable" and there waslack of documentation to indicate that the CAPA has been verified for effectiveness and that it does notadversely affect the finished device.We reviewed your firm's response and conclude that it is not adequate. Your response states that youwill implement appropriate corrective actions based on root causes and conduct risk analysis, whereappropriate. You have not provided this data for our review.2. Failure to review, evaluate, and investigated complaints involving the possible failure of a device,labeling, and packaging to meet any of its specifications, pursuant to 21 CFR 820.198(c).For example:A written complaint investigation had not been conducted for 15 units of the O2, Auto ID, Multi-GasModule, Part No. 6800-30-50502, which is part of the DPM 6/Beneview T5 Monitor, in which thesoftware could not be upgraded.4. Failure to validate device software, pursuant to 21 CFR 820.30(g). For example:A. Your firm conducted a field correction after discovering software anomalies of the V Series Monitor,including software versions below 2.2.0.41 that caused the V Patient Server synchronization failures.Your firm released software version 2.0.0.29, which included the synchronization capabilities, however,the partial and full verification studies that were completed did not test the VPS synchronizationcapability for the following: NIBP, arrhythmia, and heart rate algorithms; departmental default settingsfor different patient sizes. Further, your firm failed to conduct a full integration performance verificationstudy as required by Protocol 0088-00-0334-0833.B. Your firm conducted a field correction after discovering software anomalies in the released softwareversions below 2.2.0.19 that caused the system to reset and reboot resulting in incorrect or no alarmsettings if a patient discharge is followed by a patient admission within a 4 second time period andincorrect alarm and patient settings and no display of patient data if a dialog is opened within a 10second time period after VPS is selected in the patient ID mismatch dialog for attaching the VPSmodule. Your firm released Software Version 2.2.0.1.9 to include a fix for the timing issue, in whichCAPA Report, No. 500, dated 01/10/12, attributed the timing issue to the software discharge function.Your firm failed to conduct a full integration performance verification study as required by Protocol0088-00-0334-0833. The adequacy of your firm's response cannot be determined at this time. As part of your correction youhave committed to the following: enhancing the Software Development Process EOP 2001 to require adefinition of a minimum set of testing to be performed on every final software version prior to release toproduction and to add detail to the software design sections; changing the SRB process SOP0002-06-6819 to require justification of testing chosen for each software change; enhancing the Testand Validation Protocol SOP 0002-09-0004 to detail how to handle test amendme.nts, ChangeVerification Forms, and reviewer responsibilities; conduct training for generating verification protocol;and creating a System Level Regression Test to verify the essential performance of the V SeriesMonitor, which will be executed prior to each release of software to the field. Please provide thisinformation as it is completed so" that it can be reviewed.5. Failure to correctly translate the device design into production specifications, pursuant to 21 CFR


820.30(h). Specifically, your firm lacks a written procedure to ensure that device designs are correctlytranslated into production specifications. For example:A. The DPM 6/7 Monitor failed to contain the disclosure and calculator functions following a softwareupgrade which was completed to update the firm's logo for released units, as well as finished units,pending distribution. Your firm attributed these failures to an inaccurate software upgrading procedure.There is no assurance that a design transfer procedure has been adequately established for DPM 6/7Monitor to allow a verification of the proper functioning of the software following each softwareupgrading or device reconfiguration process to ensure an accurate translation of the device design andconformance to predefined user needs and intended uses.We reviewed your firm's response and conclude that it is not adequate. Your response states that youhave created calibration procedures for the (b)(4) analyzer and the (b)(4) Simulator, however, you didnot provide any calibration testing results for these pieces of equipment to demonstrate how theseprocedures are effective and have been implemented.Our inspection also revealed that your firm's DPM 6/7 Monitor and the DPM Central Station devices aremisbranded under Section 502(t)(2) of the Act, 21 U.S.C. § 352(t)(2), in that your firm failed or refusedto furnish material or information. respecting the device that is required by or under Section 519 of theAct, 21 U.S.C. § 360i, and 21 CFR Part 806 - Medical Devices; Reports of Corrections and Removals.Significant violations include, but are not limited to, the following:7. Failure to submit a written report to FDA of any correction or removal of a device to remedy aviolation of the act caused by the device, which may present a risk to health, unless the information hadalready been provided as set forth in 21 CFR 806.10(f) or the correction or removal action is exemptfrom the reporting requirements under 806.1(b), as required by 21 CFR 806.10(a)(2). For example:A. The DPM 6/7 Monitor failed to contain disclosure and calculator functions following a softwareupgrade for updating the firm's logo. The failures were attributed to an inaccurate software upgradingprocedure. On 08/11/2010, your firm issued a correction letter to hospital administrators and informedthe users of the software anomalies, and requested that the users contact your firm for a softwareupgrade to restore the missing functions, including full disclosure and drug, hemodynamic, renal,oxygenation, and ventilation calculations.B. The DPM Central Station had a software anomaly which caused the trend data for a patient to bereplaced by another patient's data, causing possible documentation errors in diagnosis and treatmentplan development. On May 12, 2011, your firm issued a correction letter to hospital administrators andinformed the users of the software anomaly and the field correction to the issue which was a softwareupgrade.Your firm's response to this observation appears to be adequate. Your firm submitted field Correctionand Removal Reports for each event, dated August 23, 2012, for the DPM 6/7 Monitor and the DPM

11/20/2012 Leisure Products, Inc.Recipient: Leisure Products, Inc. Product:sunlamp products Date: 11/20/2012The inspection revealed these devices are adulterated under Section 501(h) of the Act [21 USC 351(h)],because the methods used in, or the facilities or controls used for, its manufacture, packing, storage, orinstallation are not in conformity with the current good manufacturing practice requirements of theQuality System regulation found at Title 21, Code of Federal Regulations (CFR), Part 820. Failure to establish and maintain procedures for receiving, reviewing, and evaluating complaints by aformally designated unit, as required by 21 CFR 820.198(a). For example, there are no writtencomplaint procedures.We reviewed your firm’s response and concluded it was not adequate. Although the response statescomplaint procedures are being established, there is no indication the software to be installed on theservice technicians computers has been validated. In addition, a systemic corrective action is notaddressed in your response.FDA District Office: New Orleans District


11/19/2012 MedArt A/SRecipient: MedArt A/S Product: Imedical laser devices Date: 11/9/2012Our inspection revealed that your firm’s devices are misbranded under section 502(t)(2) of the Act, 21U.S.C. § 352(t)(2), in that your firm failed or refused to furnish material or information respecting thedevice that is required by or under section 519 of the Act, 21 U.S.C. § 360i, and 21 CFR Part 803 -Medical Device Reporting. Failure to establish and maintain adequate procedures to control the design of the device in order toensure that specified design requirements are met, as required by 21 CFR 820.30(a).Section 4.2-7, titled, Development of Key Functionality, requires the firm to assess risk and re-assessrisk as needed. Although Model 720 was released on November 25, 2010, Software Risk ManagementSummary Doc. No.: 105927 was assessed in Version 7 on July 14, 2011. The Design History File didnot include clinical risk analysis specific to the intended use of Model 720 design. We reviewed your firm’s responses dated July 14, 2012, and August 12, 2012, and conclude that theyare not adequate. Your firm provided copies of new and revised documents regarding some Model 720design deficiencies. Specifically, (i) To address design plan deficiencies, your firm discusses performance of a software risk assessmenton July 14, 2012, but there is no reference to software design, verification, or validation in the abovedocument. Although the revised document was written, approved, and signed by Mr. __ as theproject engineer, the Development Manager, and the Quality Manager, there is no other signature toindicate that this plan was reviewed by someone other than Mr.__, and approved. FDA District Office: CDRH 

11/9/2012 InControl Medical, LLCRecipient: InControl Medical, LLC Product: InTone™ non-implanted electrical stimulator Date: 11/9/2012This inspection revealed that these devices are adulterated within the meaning of section 501(h) of theAct, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for, theirmanufacture, packing, storage, or installation are not in conformity with the Current Good ManufacturingPractice (CGMP) requirements of the Quality System (QS) regulation found at Title 21, Code of FederalRegulations (21 CFR), Part 820. Failure to establish adequate procedures for design validation, which is required by 21 CFR 820.30(g). Specifically, documented evidence of design validation for the InTone™ medical device does not exist. Documentation and/or approvals are lacking for:A. Validation being performed under defined operating conditions on initial production units, lots, orbatches or their equivalents;B. Evidence to support that the InTone™ medical device conforms to defined user needs and intendeduses, and for evidence of testing of production units under actual or simulated use conditions; C. Software validation for the control unit used with the stimulation unit;D. Risk analysis; andE. Results of the validation, including identification of the design, method(s), the date, and theindividual(s) performing the validation.FDA District Office: Minneapolis District 

11/5/2012 Social Media Issue - The Avalon EffectThe Avalon Effect Product: Quantum Series Personal Wellness Pack Date: 11/5/2012The Food and Drug Administration (FDA) has learned that your firm is marketing the Quantum SeriesPersonal Wellness Pack in the United States without marketing clearance or approval, in violation of theFederal Food, Drug, and Cosmetic Act (the Act). The product is a device within the meaning of section


201(h) of the Act, 21 U.S.C. § 321(h), because it is intended for use in the diagnosis of disease or otherconditions or in the cure, mitigation, treatment, or prevention of disease, or to affect the structure orfunction of the body. The Act requires that manufacturers of devices that are not exempt obtainmarketing approval or clearance for their products from the FDA before they may offer them for sale. This helps protect the public health by ensuring that new devices are shown to be both safe andeffective or substantially equivalent to other devices already legally marketed in this country for whichapproval is not required. The Office of Compliance, in FDA's Center for Devices and Radiological Health, recently reviewed yourfirm’s website, www.theavaloneffect.com, and various linked websites. This review identified a numberof claims for the Quantum Series Personal Wellness Pack that cause this product to meet the Act’sdefinition of a device. For example, your firm’s web page at www.theavaloneffect.com/benefits.aspincludes the following statements: "I hurt my hip and in 15 minutes that pain was gone with no bruising after having used the Avalon Effect.Love this machine!""I have been using the Avalon light therapy on my clients and have had nothing but positive feedbackfrom everyone. They experience everything from a more relaxed state of mind, to migraine headachesgoing away, to muscle relaxation, to more joint flexibility.""For more than a decade I'd been waking up with chronic muscular tension and pain in my jaw, neck,shoulder, and hip. Freed from chronic pain, I have copious energy, a sense of joy and I no longer feelprematurely old at 51." In addition, FDA’s review of your firm’s Tumblr site at www.theavaloneffect.tumblr.com (last visited onOctober 30, 2012) and your firm's Facebook site at www.facebook.com/theavaloneffect, which arelinked directly from your website’s main page at www.theavaloneffect.com, found the following “device”claims for the Quantum Series Personal Wellness Pack: "Fungal meningitis""MRSA""Concussions""Lupus""Lyme disease""Aneurysms""Skin cancer""Atherosclerosis""Allergies""Alzheimer’s disease""Leg ulcers" The above-listed disease claims that appear on your firm's Tumblr site include a hyperlink to an audiorecording of a call hosted by Tinka Smith, Avalon Founder, in which she discusses the use of theQuantum Series Personal Wellness Pack for the symptoms of the listed diseases. FDA also found “device” claims on your firm’s other websites and on the Avalon Effect’s web pages onthird party websites, all of which are linked directly from your website at www.theavaloneffect.com: www.theavalonsummit.com (for example, at www.theavalonsummit.com/?page_id=9, last visited onOctober 30, 2012)www.quantumlighteffect.com (for example, atwww.quantumlighteffect.com/explanation-of-light-system-with-wes-burwell, last visited on October 30,2012mobile.twitter.com/TheAvalonEffect (last visited on October 30, 2012)www.facebook.com/theavaloneffect (last visited on October 30, 2012)


www.youtube.com/user/TheAvalonEffect (for example, atwww.youtube.com/watch?v=mAAJPedf1Ww&list=UUUDV-RshWoAD62pbU-Ir8bg&index=22&feature=plcp, http://www.youtube.com/watch?v=Rh8FTHSnncE&feature=plcp, last visited October 30, 2012). Furthermore, FDA notes that the Quantum Series Personal Wellness Pack is marketed with claims forthe product to affect the structure or function of the body; these claims likewise cause the product tomeet the Act’s definition of a device. Examples of these claims are found on the following websites, allof which are linked from your website at www.theavaloneffect.com: “Explanation of Light System with Wes Burwell”(www.youtube.com/watch?v=t5cxkctlano&list=UUUDV-RshWoAD62pbU-lr8bg&index=1&feature=plcp,last visited on October 31, 2012)“Understanding the frequencies of Avalon”(https://www.fuzemeeting.com/replay_meeting/99d6ea4d/2297913, last visited on October 31, 2012) A review of our records reveals that your firm has not obtained marketing approval or clearance beforeyour firm began offering your product for sale, which is a violation of the law. Specifically, the QuantumSeries Personal Wellness Pack is adulterated under section 501(f)(1)(B) of the Act, 21 U.S.C. §351(f)(1)(B), because your firm does not have an approved application for premarket approval (PMA) ineffect pursuant to section 515(a) of the Act, 21 U.S.C. § 360e(a), or an approved application for aninvestigational device exemption (IDE) under section 520(g) of the Act, 21 U.S.C. § 360j(g). The deviceis also misbranded under section 502(o) of the Act, 21 U.S.C. § 352(o), because your firm did not notifythe agency of its intent to introduce the device into commercial distribution, as required by section510(k) of the Act, 21 U.S.C. § 360(k). FDA District Office: CDRHn 

10/31/2012 Alere San Diego, IncRecipient: Alere San Diego, Inc Product: Triage brand cardiac marker devices Date: 10/31/2012This inspection revealed that these devices are adulterated within the meaning of section 501(h) of theAct, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for, theirmanufacture, packing, storage, or installation are not in conformity with the current good manufacturingpractice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations(CFR), Part 820. We received a response dated July 17, 2012, concerning our investigator’sobservations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, that was issuedto your firm. We address this response below, in relation to each of the noted violations. Theseviolations include, but are not limited to, the following:Failure to establish and maintain adequate procedures for defining and documenting design output interms that allow an adequate evaluation of conformance to design input requirements, as required by21 CFR 820.30(a). For example: a. Your current procedure QTP-1694-14 – Triage Family Final Release Specifications, Revision E,which is utilized by your firm for the final release specifications associated with your cardiac markerproduct lines, is not in alignment with the package inserts with respect to %CV. We reviewed your firm’s response and conclude that it is not adequate. On October 1, 2012, FDA andyour firm reached an agreement on the final release specifications. However, the response is notadequate because: 1) your firm has not provided documentation or evidence to demonstrate that finalrelease specifications have been implemented; and 2) product development and change controlprocedures that require release test specifications to be reviewed against the applicable package inserthave not been written and implemented and training has not been completed. b. Procedure QTP-1694-14 – Triage Family Final Release Specifications, Revision E, provides productto product variation (P2P) ranging up to (b)(4) difference for the Triage cardiac markers between the


mean of two lots when tested with the same sample. We reviewed your firm’s response and conclude that it is not adequate. Your firm has revised the P2Pspecification to reduce the amount of variation that is allowed. The response is not adequate becauseyour firm has not yet completed a program meant to reduce analytical variation for the Triage productline. In addition, your firm is still working on further tightening of the P2P specifications for the TriageCardiac products. c. Your current Procedure QTP-1827-5 – TOX +MTD – Final Release Specifications, Revision F, whichis utilized for the final release specifications associated with your drugs of abuse/TOX + MTD productline, is not in alignment with the product insert with respect to the number of false positive and falsenegative (b)(4) calibrator recovery test results allowed for the lot release acceptance criteria versus theclaimed number of false positive and negative results, as depicted within the product insert. We have reviewed your firm’s response and conclude that it is not adequate. Your firm has changed theTriage TOX Final Release Specifications to reject any lot with one or more failures at (b)(4). Your firmhas also validated that the software (b)(4) used for data analysis has correctly implemented thespecification changes. Your firm has provided training records for the QC analysts who use thesespecifications. The response is not adequate because your firm has not completed the revision of theproduct development and change control procedures to require that release test specifications arereviewed against the applicable package insert..Failure to establish and maintain adequate procedures for identifying valid statistical techniquesrequired for establishing, controlling, and verifying the acceptability of process capability and productcharacteristics as required by 21 CFR 820.250(a). For example: a. On 4/15/2009 thru 5/20/2009, via Triage Final Release Procedure QTP-1694-Revision I, andindividual Triage Cardiac Family Release Procedures - to include BNP/QTP-1694-5, Revision D,Cardiac panel/QTP-1694-6, Revision F, Profiler SOB/QTP-1694-8, Revision F, CardioProfiler/QTP-1694-7, Revision F, and D-Dimer/QTP-1694-9, Revision E - your firm implemented a“trimmed mean” methodology for the final release criteria, which was applied to all manufactured lots.The trimmed mean technique allowed the removal of the (b)(4) and (b)(4) of n sample measurementsprior to calculating the arithmetic mean. For example, if (b)(4). If (b)(4). As such, the data used for finalrelease/determination of within run precision, which is expressed as % CV, did not include the removedtrimmed mean data. This may allow lots, which were originally out-of-specification, to be released. Anexample of a lot that was acceptable after applying the trimmed mean methodology is (b)(4), whereinitially the % CV for TnI was calculated as (b)(4). After (b)(4) test results were removed/trimmed, thenew % CV was calculated as (b)(4). We reviewed your response and conclude that it is not adequate. Your firm has removed the trimmedmean method from the analysis of product release test data for the Triage cardiac family of products.The documents that govern the release test process and specifications for these products have beenrevised and your firm has provided documentation of training on these procedures. All lots releasedafter these documents were instituted use data analysis that does not use the trimmed mean method.Your firm has also revised the software (b)(4) that is used to analyze production release data to ensurethat the trimmed mean methodology is not used in analyzing release data. Your firm has provided acopy of the validation procedure used to validate the software to confirm that the software used thecorrect analysis to release product. The response is not adequate because your firm has not completeda review of your procedures and revised procedures to ensure that changes to the release testprocesses, including statistical methods, be approved by certain designated individuals. Your firm hasalso not completed the review of release test processes at the site to ensure that the appropriateanalytical methods are used.FDA District Office: Los Angeles District 


10/16/2012 Social Media Issue - Quincy BioscienceManufacturiQuincy Bioscience Manufacturing Inc. Product: Prevagen Date: 10/16/2012This letter concerns your products Prevagen, which is labeled to contain 10 mg apoaequorin, PrevagenExtra Strength, labeled to contain 20 mg apoaequorin, and Prevagen Professional, labeled to contain40 mg apoaequorin. These products are labeled as dietary supplements. FDA reviewed your websites at www.prevagen.com, www.prevagenES.com, www.prevagenpro.com,www.hopetrials.com, www.prevagenreviews.com, www.quincybioscience.com,www.facebook.com/prevagen and www.youtube.com/user/prevagen in August 2012. Based on thisreview, the agency has determined that your products Prevagen, Prevagen Extra Strength, andPrevagen Professional are being promoted for conditions that cause these products to be drugs undersection 201(g)(1)(B) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 321(g)(1)(B).The therapeutic claims on your websites (see “Unapproved New Drugs” section below) establish thatthese products are drugs because they are intended for use in the cure, mitigation, treatment, orprevention of disease. In addition, statements on your www.hopetrials.com website establish thatQuincy Bioscience has been sponsoring clinical trials to investigate the use of apoaequorin to treat orprevent disease for which there is no investigational new drug application (IND) in effect. Theinvestigation and marketing of your products for these uses violates the Act. Your Prevagen, Prevagen Extra Strength, and Prevagen Professional products are not generallyrecognized as safe and effective for the above referenced uses and, therefore, these products are “newdrugs” under section 201(p) of the Act, 21 U.S.C. § 321(p). New drugs may not be legally marketed inthe United States without prior approval from FDA as described in section 505(a) of the Act, 21 U.S.C.§ 355(a). FDA approves a new drug on the basis of scientific data submitted by a drug sponsor todemonstrate that the drug is safe and effective. Your Prevagen products are offered for conditions that are not amenable to self-diagnosis andtreatment by individuals who are not medical practitioners; therefore, adequate directions for use cannotbe written so that a layperson can use these drugs safely for their intended purposes. Therefore, yourproducts are also misbranded within the meaning of section 502(f)(1) of the Act, 21 U.S.C. § 352(f)(1),in that the labeling fails to bear adequate directions for use. The introduction of a misbranded drug intointerstate commerce is a violation of section 301(a) of the Act, 21 U.S.C. § 331(a).FDA District Office: Minneapolis District 

10/9/2012 SMT-Schilling Metalltechnik GmbHRecipientSMT-Schilling Metalltechnik GmbH Product:Class II K/Guide Wires Date: 10/9/2012This inspection revealed that these devices are adulterated within the meaning of section 501(h) of theAct, 21 U.S.C. 351(h), in that the methods used in, or the facilities or controls used for, theirmanufacture, packing, storage, or installation are not in conformity with the Current Good ManufacturingPractice (CGMP) requirements of the Quality System (QS) regulation found at Title 21, Code of FederalRegulations (C.F.R.), Part 820. These violations include, but are not limited to, the following:Failure to adequately ensure that all equipment used in the manufacturing process meets specifiedrequirements and is appropriately designed, constructed, placed, and installed to facilitate maintenance,adjustment, cleaning, and use, as required by 21 CFR 820.70(g). For example, your firm has notvalidated the equipment and tools used in the manufacturing of its K-Wires/Guide Wires. Your firm’s response dated August 3, 2012, is not adequate. The response included a MasterValidation Plan for the SMT K/Guide Wire (F.B.06.1.1), an “Equipment Qualification (EQ) Checklist”(CEQ-00041), a completed EQ for identified equipment (EQ-P00040 & EQ-P00041), and a CAPA(#0073) associated with this observation. Your firm provided evidence of process control procedures


for equipment identified in its CAPA. However, your firm did not address process controls for thesoftware identified during the inspection. Your firm also did not provide evidence of a correction orcorrective action for establishing and maintaining adequate process control procedures for the entireprocess. Additionally, your firm did not provide evidence of a systemic corrective action for ensuringadequate process control procedures for all processes.Failure to validate, for its intended use, computer software used as part of production or the qualitysystem according to an established protocol, as required by 21 CFR 820.70(i). For example, your firmuses an (b)(4) software system to (b)(4). This software system has not been validated by the firm.Your firm’s response dated August 3, 2012, is not adequate. The response included a MasterValidation Plan for the SMT K/Guide Wire (F.B.06.1.1), an “Equipment Qualification (EQ) Checklist”(CEQ-00041), a completed EQ for identified equipment (EQ-P00040 & EQ-P00041), and a CAPA(#0073) associated with this observation. Your firm provided evidence of process control proceduresfor equipment identified in its CAPA. However, your firm did not address process controls for thesoftware identified during the inspection. Your firm also did not provide evidence of a correction orcorrective action for establishing and maintaining adequate process control procedures for the entireprocess. Additionally, your firm did not provide evidence of a systemic corrective action for ensuringadequate process control procedures for all processes.FDA District Office: CDRH 

10/9/2012 Alere, IncRecipient:Alere, Inc. Product:Triage brand cardiac marker devices Date: 10/9/2012This inspection revealed that these devices are adulterated within the meaning of section 501(h) of theAct, 21 U.S.C. 351(h), in that the methods used in, or the facilities or controls used for, theirmanufacture, packing, storage, or installation are not in conformity with the Current Good ManufacturingPractice (CGMP) requirements of the Quality System (QS) regulation found at Title 21, Code of FederalRegulations (C.F.R.), Part 820. We received a response from Mark Gladwell, President and GeneralManager, dated July 17, 2012, concerning our investigator’s observations noted on the Form FDA 483(FDA 483), List of Inspectional Observations, that was issued to your firm. We address this responsebelow, in relation to each of the noted violations. These violations include, but are not limited to, thefollowing:Failure to establish and maintain adequate procedures for defining and documenting design output interms that allow an adequate evaluation of conformance to design input requirements, as required by21 CFR 820.30(a). For example:a. Your current procedure QTP-1694-14 – Triage Family Final Release Specifications, Revision E,which is utilized by your firm for the final release specifications associated with your cardiac markerproduct lines, is not in alignment with the package inserts with respect to %CV. We reviewed your firm’s response and conclude that it is not adequate. (b)(4). The final releasespecifications have not been decided on yet. The response is not adequate because: 1) final releasespecifications have not yet been implemented; and 2) product development and change controlprocedures that require release test specifications to be reviewed against the applicable package inserthave not been written and implemented and training has not been completed. b. Procedure QTP-1694-14 – Triage Family Final Release Specifications, Revision E, provides productto product variation (P2P) ranging up to (b)(4) difference for the Triage cardiac markers between themean of two lots when tested with the same sample. We reviewed your firm’s response and conclude that it is not adequate. Your firm has revised the P2Pspecification to reduce the amount of variation that is allowed. The response is not adequate becauseyour firm has not yet completed a program meant to reduce analytical variation for the Triage productline. In addition, your firm is still working on further tightening of the P2P specifications for the TriageCardiac products.


c. Your current Procedure QTP-1827-5 – TOX +MTD – Final Release Specifications, Revision F, whichis utilized for the final release specifications associated with your drugs of abuse/TOX + MTD productline, is not in alignment with the product insert with respect to the number of false positive and falsenegative (b)(4) calibrator recovery test results allowed for the lot release acceptance criteria versus theclaimed number of false positive and negative results, as depicted within the product insert. We have reviewed your firm’s response and conclude that it is not adequate. Your firm has changed theTriage TOX Final Release Specifications to reject any lot with one or more failures at (b)(4). Your firmhas also validated that the software (b)(4) used for data analysis has correctly implemented thespecification changes. Your firm has provided training records for the QC analysts who use thesespecifications. The response is not adequate because your firm has not completed the revision of theproduct development and change control procedures to require that release test specifications arereviewed against the applicable package insert.Failure to establish and maintain adequate procedures for identifying valid statistical techniquesrequired for establishing, controlling, and verifying the acceptability of process capability and productcharacteristics as required by 21 CFR 820.250(a). For example: a. On 4/15/2009 thru 5/20/2009, via Triage Final Release Procedure QTP-1694-Revision I, andindividual Triage Cardiac Family Release Procedures - to include BNP/QTP-1694-5, Revision D,Cardiac panel/QTP-1694-6, Revision F, Profiler SOB/QTP-1694-8, Revision F, CardioProfiler/QTP-1694-7, Revision F, and D-Dimer/QTP-1694-9, Revision E - your firm implemented a“trimmed mean” methodology for the final release criteria, which was applied to all manufactured lots.The trimmed mean technique allowed the removal of the (b)(4) and (b)(4) of n sample measurementsprior to calculating the arithmetic mean. For example, if (b)(4). If (b)(4). As such, the data used for finalrelease/determination of within run precision, which is expressed as % CV, did not include the removedtrimmed mean data. This may allow lots, which were originally out-of-specification, to be released. Anexample of a lot that was acceptable after applying the trimmed mean methodology is (b)(4), whereinitially the % CV for TnI was calculated as (b)(4). After (b)(4) test results were removed/trimmed, thenew % CV was calculated as (b)(4). We reviewed your response and conclude that it is not adequate. Your firm has removed the trimmedmean method from the analysis of product release test data for the Triage cardiac family of products.The documents that govern the release test process and specifications for these products have beenrevised and your firm has provided documentation of training on these procedures. All lots releasedafter these documents were instituted use data analysis that does not use the trimmed mean method.Your firm has also revised the software (b)(4) that is used to analyze production release data to ensurethat the trimmed mean methodology is not used in analyzing release data. Your firm has provided acopy of the validation procedure used to validate the software to confirm that the software used thecorrect analysis to release product. The response is not adequate because your firm has not completeda review of your procedures and revised procedures to ensure that changes to the release testprocesses, including statistical methods, be approved by certain designated individuals. Your firm hasalso not completed the review of release test processes at the site to ensure that the appropriateanalytical methods are used.FDA District Office:Los Angeles District 

8/28/2012 Social Media Issue - Trinity Sports Group,Inc.Trinity Sports Group, Inc. Product:Neuro Impact Concussion Response Formula Date: 8/28/2012This is to advise you that the U.S. Food and Drug Administration (FDA) reviewed your websites,www.neuroimpact.net and www.trinitysportsgroupinc.com, in June 2012 and has determined that your"Neuro Impact Concussion Response Formula" product is promoted for conditions that cause theproduct to be a drug under section 201(g)(1)(B) of the Federal Food, Drug, and Cosmetic Act (the Act)[21 U.S.C. § 321(g)(1)(B)]. The claims on your websites and the name of your product, "Neuro Impact


Concussion Response Formula," establish that your product is a drug because it is intended for use inthe cure, mitigation, treatment, or prevention of disease. The marketing of your product with theseclaims violates the Act. In the "About" section:• "Neuro-Impact is the world[']s first supplement formulated specifically to assist concussion recovery.Developed to help those who suffer a concussion recover more rapidly ... Neuro-Impact has thedynamic ability to minimize long-term effects and decrease recovery time ... "From your April 8, 2012 response to a comment on your Timeline post dated April 7, 2012:• "[T]his product is formulated to work for those suffering from a concussion."From your Timeline post dated April 3, 2012:• "[I]n the first two days of [Neuro Impact's] availability, we have treated 3 soccer concussions, 3gymnastic concussions, and 1 hockey concussion."We also observed the following therapeutic claims on your Twitter account (@Neuroimpact), accessedat https://twitter.\com/neuroimpact:In your post dated March 8, 2012:• "Something more than the "wait and see" treatment needs to be done. []NeuroImpact is thatsomething. #concussion"In your post dated March 1, 2012:• "[W]e can help with Kobe's concussion and every other concussion. Would love to show you how.@NeuroImpact":FDA District Office: Dallas District 

8/16/2012 IsoAid, LLCRecipient:IsoAid, LLC Product:Advantage Iodine-125™ and Advantage PD-103™ Brachytherapy Seeds, and theAdvantage-Strand™/Advantage-Load™ Brachytherapy Kit Date: 8/16/2012This inspection revealed that these devices are adulterated within the meaning of section 501(h) of theAct, 21 U.S.C. 351(h), in that the methods used in, or the facilities or controls used for, theirmanufacture, packing, storage, or installation are not in conformity with the Current Good ManufacturingPractice (CGMP) requirements of the Quality System (QS) regulation found at Title 21, Code of FederalRegulations (C.F.R.), Part 820. We received responses from you dated May 10, 2012 and June 25,2012, concerning our investigator’s observations noted on the Form FDA 483, InspectionalObservations, which was issued to you. We address these responses below, in relation to the notedviolations. These violations include, but are not limited to, the following:Failure to validate computer software for its intended use according to an established protocol, whencomputers or automated data processing systems are used as part of production or a quality system,according to established procedure, as required by 21 C.F.R. 820.70(i). For example, there are noprocedures that describe the qualification and maintenance of the Sorting software for decaycalculations on brachytherapy seeds sorted into inventory. There are no software verification andvalidation requirements defined in your firm's procedures, and there are no records documenting thatthe Sorting software is fully validated for its intended uses. Your firm updated the Sorting software inMay 2009, to address a “glitch” when sorting brachytherapy seeds and their respective activity intoproperly labeled containers; however, your firm failed to validate the updated software prior toimplementation for use. There are no procedures or documents that describe changes and versionupdates to the Sorting software. There are no documents that define the software’s features andfunctions, operating environment, or hardware requirements. The adequacy of your responses dated May 10, 2012 and June 25, 2012, cannot be determined at thistime because they lack details regarding your corrective actions and their implementation. Weacknowledge your June 25, 2012 response includes the procedure, Software Validation, SOP 09-27,Rev. 0. However, this procedure does not appear to be signed and dated as issued and effective foruse. Further, you have not demonstrated your firm has conducted any software verification andvalidation activities in accordance with the procedure. Failure to establish and maintain procedures for investigating the cause of nonconformities relating to


product, processes, and the quality system, as required by 21 C.F.R. 820.100(a)(2), and to adequatelydocument all activities required under Corrective and Preventive Action, and their results, as required by21 C.F.R. 820.100(b). For example: a. Your firm initiated three Corrective and Preventive Action (CPA) (#CP021 on July 22, 2008, #CP022on February 12, 2009, and #CP023 on May 14, 2009) in response to multiple complaints, to include butnot limited to: complaints (#C022, #C026, #C027, and #C031) involving out-of-specification radioactivityof Brachytherapy seeds. Review of CPA Forms #CP021, #CP022, and #CP023, disclosed that thedocumentation of correction and preventative actions was incomplete and not conducted in accordancewith Sections 6.3 - 6.5 of CPA procedure SOP 14-01, Rev. 5, dated May 29, 2007. Further, these threeCPA Forms do not include the details of any stated investigation conducted, their results, or that thesoftware updates do not have an adverse effect on the finished device.FDA District Office:Florida District 

8/7/2012 Asept Pak IncRecipient:Asept Pak Inc Product:Sterile Sodium Chloride Date: 8/7/2012This inspection revealed that these devices are adulterated within the meaning of section 501(h) of theAct (21 U.S.C. § 351(h)), in that the methods used in, or the facilities or controls used for, theirmanufacture, packing, storage, or installation are not in conformity with the current good manufacturingpractice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations(CFR), Part 820. These violations include, but are not limited to, the following:Failure to document process validation activities, as required by 21 CFR 820.75(a). For example: a) Your procedure for validation/qualification of processes, software, and equipment indicated theminimum requirements for equipment and utilities are installation qualification (IQ), operationalqualification (OQ), and performance qualification (PQ). You failed to document appropriate equipmentqualifications (i.e. IQ and OQ) on compounding tanks prior to executing process and product specificperformance qualifications. During processing devices such as Sterile Sodium Chloride 0.9%, USP andSterile Water, USP both for wound irrigation various compounding tanks can be used. For example,your validation for Sterile Sodium Chloride 0.9%, USP (b)(4) used only the (b)(4)L compounding tank,and lot/batch number ANR/F11110 used the (b)(4)L compounding tank. We note that two of your compounding tanks use air sparging and one compounding tank uses an agitator for compounding theSodium Chloride 0.9% USP. Additionally, each of the three compounding tanks holds a differentvolume; and b) Your procedure for validation/qualification of processes, software, and equipment requires thatprocesses are controlled and monitored to ensure that the specified conditions continue to be met. Youfailed to define and document the monitoring and control method for your in-process controlsassociated with the BFS manufacturing process to ensure the specified requirements continue to bemet. These include, but not limited to, the BFS major system components (resin hopper, molds,vacuum system, hydraulic system, filling system, parison air support, fill nozzles system environment,parison knife, and programmable logic controller), and fill volume accuracy control.FDA District Office: New York District 

8/6/2012 Sure On Industries Ltd.Recipient:Sure On Industries Ltd. Product: non-sterile surgical pleated masks, respirators and examination gowns Date: 8/6/2012This inspection revealed that these devices are adulterated within the meaning of section 501(h) of theAct, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for, theirmanufacture, packing, storage, or installation are not in conformity with the current good manufacturingpractice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations(CFR), Part 820. We received a response from Michael Huang on June 15, 2012, concerning our


investigator’s observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations,that was issued to your firm. This response is not adequate because it states that your firm’s “CARreports” for the 6 observations will be submitted before the end of July 2012. No additional informationregarding systemic corrective actions has been provided. The violations identified during the inspectioninclude, but are not limited to, the following:Failure to establish and maintain procedures for validating the device design, including softwarevalidation and risk analysis, where appropriate, as required by 21 CFR 820.30(g). For example, yourfirm has a written procedure for design controls, SQ2-04200; however, it does not describe therequirement for risk analysis.FDA District Office: CDRH 

7/25/2012 Horiba Instruments, Inc dba Horiba MedicalRecipient:Horiba Instruments, Inc Product:ABX Micros 60 Hematology Analyze, ABX Micros 60 IM2 Date: 7/25/2012This inspection also revealed that the devices noted above are adulterated within the meaning ofsection 501(h) of the Act, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controlsused for, their manufacture, packing, storage, or installation are not in conformity with the current goodmanufacturing practice requirements of the Quality System regulation found at Title 21, Code of FederalRegulations (CFR), Part 820. We received a response from Carl Levine, Director of Service andCompliance, dated March 22, 2012, concerning our investigator’s observations noted on the Form FDA483 (FDA 483), List of Inspectional Observations that was issued to your firm. We address thisresponse below, in relation to each of the noted violations. These violations include, but are not limitedto, the following:Failure to validate computer software adequately for its intended use according to an establishedprotocol, as required by 21 CFR 820.70(i). For example, there is no protocol and documentation to demonstrate that the software used to produce(b)(4) for the ABX Micros 60 IM2 has been validated. We reviewed your firm’s response and concluded that it is not adequate. Your firm’s response does notinclude any information including a systemic corrective action. In addition a copy of the validationprotocol and results of the outcome of the retrospective review of software used to produce (b)(4) forthe ABX Micros 60 IM2 was not provided.Failure to establish and maintain device master records as required by 21 CFR 820.181. For example, there is no device master record for the ABX Micros 60 IM2, including labelingspecifications, component specifications, and software specifications. We reviewed your firm’s response and conclude that it is not adequate. Your firm did not provide a copyof SOP-0074, the device master record, documentation of training on the procedure, and the outcomeof the retrospective review of products applicable to Device Master Regulations and shipped sinceJanuary 2010.FDA District Office: Los Angeles District 

6/26/2012 Social Media Issue - Alistrol Health, Inc.Alistrol Health, Inc. Product: “Alistrol,” “Naavudi,” “CLE Vitamin D3,” and “Depression Fighters” product websites Date: 6/26/2012This is to advise you that the Food and Drug Administration (FDA) reviewed your websites at theInternet addresses: www.alistrol.com, www.alistrol.net, www.drophighbloodpressure.com,www.highbloodpressure-treatment.net, www.naavudi.com, and www.depressionfighters.com in June2012, and the promotional materials distributed with your products, and has determined that your“Alistrol,” “Naavudi,” “CLE Vitamin D3,” and “Depression Fighters” products are promoted for conditions


that cause these products to be drugs under section 201(g)(1)(B) of the Federal Food, Drug, andCosmetic Act (the Act) [21 U.S.C. § 321(g)(1)(B)]. The therapeutic claims on your websites and in thepromotional materials establish that these products are drugs because they are intended for use in thecure, mitigation, treatment, or prevention of disease. The marketing of your products with these claimsviolates the Act.We also note claims found on your Facebook page accessed athttp://www.facebook.com/pages/Alistrol/171767636213230?sk=wall. Several examples of these includethe following:In a post dated March 15, 2012, titled, “Reduce your blood pressure even faster with this powerful duoof natural remedies” which includes a link to an article titled, “Why Vitamin D and Alistrol Make a GreatTeam” that is posted on the blog on your website, www.alistrol.com.In a post dated March 14, 2012, titled, “We’ve got proof that our products work. Hear it straight fromour customers!” which includes a link to the webpage titled, “Success Stories” on your website,www.alistrol.com. The post summarizes the link as follows: “Find a solution to high blood pressure,natural treatment to cure blood pressure using herbs. Natural supplements for lowering high bloodpressure. Get Alistrol today.”In a post dated February 23, 2012 titled, “Two natural remedies, when combined, will reduce bloodpressure even faster. Read all about it in today's blog post” which includes a link to an article titled,“Vitamin D and Alistrol Together Reduce High Blood Pressure More Quickly” that is posted on the blogon your website, www.alistrol.com. In addition, these claims are supplemented by the metatags you use to bring consumers to yourwebsite. These metatags include: For your website, www.alistrol.com:“[H]igh blood pressure medication, High blood pressure remedies, Lower blood pressure, How to lowerblood pressure, High blood pressure treatment, Natural treatment for high blood pressure, Naturalremedies for high blood pressure, Natural blood pressure remedies, Natural remedy for high bloodpressure, Controlling high blood pressure, Blood pressure remedies, Blood pressure treatment” For your website, www.depressionfighters.com:“AntiDepressants, best depression remedy, Anti Depression, depression natural treatment, anxietydepression treatment, treat depression naturally, depression management and treatment” For your website, www.naavudi.com:“Diabetes, Diabetes Supplement, Diabetes Medicine, Alternative Diabetes Medicine, DiabetesTreatment, Diabetes Management, Treatment diabetes, Diabetes symptoms, Diabetes diet…Bloodsugar control, Diabetic Remedies, Natural Blood Sugar Control” Claims on your websites, promotional materials, and product labels establish that your products aredrugs because they are intended for use in the cure, mitigation, treatment, or prevention of disease. Your products are not generally recognized as safe and effective for the above referenced conditionsand therefore, these products are “new drugs” under section 201(p) of the Act [21 U.S.C. § 321(p)]. New drugs may not be legally marketed in the U.S. without prior approval from FDA as described insection 505(a) of the Act [21 U.S.C. § 355(a)]. FDA approves a new drug on the basis of scientific datasubmitted by a drug sponsor to demonstrate that the drug is safe and effective. Furthermore, your products are offered for conditions that are not amenable to self-diagnosis andtreatment by individuals who are not medical practitioners; therefore, adequate directions for use cannotbe written so that a layperson can use these drugs safely for their intended uses. Thus, your productsare misbranded within the meaning of section 502(f)(1) of the Act [21 U.S.C. § 352(f)(1)], in that theirlabeling fails to bear adequate directions for use. The introduction of a misbranded drug into interstatecommerce is a violation of section 301(a) of the Act [21 U.S.C. § 331(a)]. FDA District Office: Pacific Region 


6/15/2012 Shamrock Medical Solutions Group LLCRecipient:Shamrock Medical Solutions Group LLC . Product:Pharmeceuticals Date: 6/15/2012investigators from the Food and Drug Administration (FDA) identified significant violations of CurrentGood Manufacturing Practice (CGMP) regulations for Finished Pharmaceuticals, Title 21, Code ofFederal Regulations, Parts 210 and 211. These violations cause your drug products to be adulteratedwithin the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (the Act) [21U.S.C. § 351(a)(2)(B)] in that the methods used in, or the facilities or controls used for, theirmanufacture, processing, packing, or holding do not conform to, or are not operated or administered inconformity with, CGMP. In addition, your firm mislabeled drug products causing them to be misbrandedunder section 502(b)(2) of the Act [21 U.S.C. § 352(b)(2)]. By introducing adulterated and misbrandeddrugs into interstate commerce you are in violation of section 301(a) of the Act [21 U.S.C. § 331(a)]. Specific violations observed during the inspection include, but are not limited to, the following: 1. Your firm has failed to exercise appropriate controls over computer or related systems to assure thatchanges in master production and control records, or other records, are instituted only by authorizedpersonnel [21 C.F.R § 211.68(b)]. For example, repackaging technicians changed master labels of repackaged products, which resultedin product packages labeled with incorrect strength or incorrect spelling of the drug name. You thenreleased these mislabeled drug products for distribution. Examples of incorrect labeling that resultedfrom technicians changing the master label include: Levothyroxine Sodium 150 mcg Tablet labeled asLevothyroxine Sodium 150 mg Tablet, and Metoclopramide 10 mg/10 ml labeled as Metroclopramide 10mg/10 ml. Your firm included a proposal to revise the labeling system computer software to restricttechnicians’ access to the master labeling program in the Corrective and Preventative Actions (CAPA)sections of four separate Incident Reports concerning mislabeled products. These proposals weresigned and submitted for approval to your Quality Assurance Unit (QAU) on March 31, 2011. However,to date, your firm has not reported any corrective or preventive actions taken to address theseviolations. We also note that you did not follow your SOP S-0002.00-PROD “Master Production andControl Record,” which requires your Quality Assurance Unit (QAU) or designee to review each masterproduction and control record before beginning repackaging and/or relabeling operations. Theserecords include the drug product name, strength, and dosage form, as well as copies of each label.However, your QAU review was inadequate in that the error was not noted. FDA District: Cincinnati District 

6/14/2012 American Optisurgical Inc.Recipient:American Optisurgical Inc. Product:TX1 Tissue Removal System Date: 6/14/2012This inspection revealed that these devices are adulterated within the meaning of section 501(h) of theAct [21 U.S.C. § 351(h)], in that the methods used in, or the facilities or controls used for, theirmanufacture, packing, storage, or installation are not in conformity with the Current Good ManufacturingPractice (CGMP) requirements of the Quality System (QS) regulation found at Title 21, Code of FederalRegulations (C.F.R.), Part 820.We received your responses dated March 7, 2012 and May 29, 2012, concerning our investigators’observations noted on the Form FDA 483, List of Inspectional Observations that was issued to you atthe conclusion of the inspection. We address these responses below, in relation to each of the notedviolations. These violations include, but are not limited to, the following:1) Failure to validate the design under actual or simulated use conditions, as required by 21 CFR820.30(g). For example, the Process Validation Report for the TX1 Tissue Removal Console, dated August 11,2011 did not reference that testing was conducted in actual or simulated conditions for which the


devices will used. Additionally, there was no documentation that the devices used for design validationwere subjected to your required 24 hour burn in process prior to installation of the production software.Your responses, dated March 7, 2012 and May 29, 2012 are inadequate. You have not demonstratedthat process validation for the TX1 Tissue Removal System has been performed under actual orsimulated use condition.Failure to validate software used as part of production for its intended use according to an establishedprotocol, as required by 21 CFR 820.70(i). For example, your firm has not validated:• The software that operates the (b)(4) used to fabricate and manufacture (b)(4) for the TX1 TissueRemoval System. • The burn in software used to test the TX1 Tissue Removal Console referenced in your ProcessValidation Report, dated August 11, 2011.Your responses, dated March 7, 2012 and May 29, 2012 were inadequate. You have not demonstratedthat the above referenced software has been validated for its intended use.Failure to adequately establish document control procedures, as required by 21 CFR 820.40. Forexample, your firm's document control procedures, QOP-42-01) Control of Documents, Rev. D do notaddress how to control or identify (b)(4) used to download the software in finished devices. These.procedures do not have signature requirements that demonstrate documents, such as device historyrecord documents· and design drawings have been approved. The documents are dated, and includethe name of the individual approving the documents, but lack a signature. The software used to storethe procedures, records and drawings do not have an electronic signature capability. Your firm'scontrolled documents do not reference historical changes made to them. As an example, "Red Line"changes to drawings referencing component assemblies and designs used for the Tenex TX1 Tissueremoval System did ·not have the date and initials or signature of the individuals conducting the "RedLine" changes to these documents. Your responses, dated March 7, 2012 and May 29, 2012 wereinadequate. Your promised corrective actions have not yet been implemented.FDA District: Los Angeles District 

6/11/2012 Oertel Medical GmbHRecipient:Oertel Medical GmbH Product:non-powered endoscopic grasping/cutting instruments Date: 6/11/2012Failure to validate computer software for its intended use according to an established protocol, whencomputers or automated data processing systems are used as part of production or a quality system,according to established procedure, as required by 21 CFR 820.70(i). For example, there are noprocedures that describe the qualification and maintenance of the Majesty Enterprise ResourcePlanning (ERP) software for production planning and maintenance of quality records. There are nosoftware verification and validation requirements defined in your firm's procedures, and there are norecords documenting that the Majesty system is validated or meets user needs and intended uses. TheMajesty ERP software was updated to version 28.6 on approximately December 21, 2011, by thevendor; however, the review and approval of the software verification report was not approved untilJanuary 26, 2012. There are no procedures or documents that describe changes and version updatesto the Majesty ERP system. There are no records that document the installation and first use date ofversion 28.2 in May 2011. There are no documents that define the system’s features and functions,operating environment, or hardware requirements. Your firm’s responses dated February 07, 2012, and February 24, 2012, are not adequate. Your firmdoes not state if there are other software programs in use or if your firm plans to verify and validateother software programs. Your firm has promised to develop a new software verification and validationprocedure and validate Majesty ERP software for its intended uses by April 13, 2012.Failure to establish and maintain adequate procedures to ensure that all purchased or otherwisereceived product and services conform to specified requirements, as required by 21 CFR 820.50. Forexample: a) The procedure, “(b)(4)(rev 1;20.01.12),” which addresses vendor selection qualification and


requalification of suppliers, has not been not implemented. There is no documentation that (b)(4), thesupplier of Majesty software, was qualified or re-qualified as a supplier. Your firm has been purchasingsoftware from this vendor since 1996. b) The requirements to requalify vendors in the purchasing procedure, “(b)(4)(rev 1;20.01.12),” arebased on the percentage of products received by your firm from the vendor. The (b)(4) thresholdrequired by your firm to re-qualify vendors is not based on the vendor’s ability to meet specifiedrequirements, including quality requirements. In addition, the criticality of the purchased product orservice is not evaluated for determining the needs to requalify suppliers. Your firm’s responses dated February 07, 2012, and February 24, 2012, are not adequate. Your firm’sresponses do not specifically address the deficiency cited and do not provide copies of revisedprocedures. Your firm has promised to revise its procedure and to develop a new procedure for supplierre-validation by April 13, 2012. Your firm also plans to re-evaluate suppliers upon completion of its newprocedure. In the interim, your firm plans to review records to ensure that all suppliers of products andservices have been captured in the system.CDRH 

6/5/2012 Michigan Medical InnovationsRecipient:Michigan Medical Innovations Product: DVT Care CA5 Compression Limb Sleeve Date: 6/5/2012This inspection revealed that this device is 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, its manufacture,packing, storage, or installation are not in conformity with the current good manufacturing practicerequirements of the Quality System regulation found at Title 21 , Code of Federal Regulations (CFR),Part 820. We received a response, dated April 27, 2012, concerning our Investigator's observationsnoted on the Form FDA 483, List of Inspectional Observations that was issued to you. We address thisresponse below, in relation to each of the noted violations. The violations found during the inspectionand subsequent review include, but are not limited to, the following:1. Failure to establish and maintain procedures for the identification, documentation, validation or,where appropriate, verification, review, and approval of design changes before their implementation, asrequired by 21 CFR 820.30(i). For example, your firm 's procedures QSM 1113 "DESIGN CONTROL"(Rev. A, Date: Jan. 2012) and QOP-7301 "DESIGN CONTROLS" (Rev. A, Date: 04/01/05) describe thecontrolled process for "device modifications and all updates and require all design changes to beinitiated (b)(4). However, thirty-six of forty nine design, software and device were initiated (b)(4) andfollowing your procedures, to include:a. Revision 41: initiated due to (b)(4)b. Revision 45: initiated due to (b)(4)c. Revision 62: initiated due to (b)(4).Failure to adequately ensure that, where the results of a process cannot be fully verified by subsequentinspection and test, the process is validated with a high degree of assurance and approved according toestablished procedures, as required by 21 CFR 820.75(a). For example, your procedure QSM 1113"DESIGN CONTROL" (Rev. A, Date: Jan 2012) states (b)(4). QOP-75-03 "VALIDATION OFPROCESSES & SOFTWARE" (Rev. A, no effective date) and QSM 1132 "VALIDATION OFPROCESSES & SOFTWARE" (Rev. A, Date: Jan 2012) state (b)(4). However, your firm has notvalidated in-process and finish device testing apparati and processes that ensure the device is beingmanufactured according to your specifications to include:a. Valve Assembly Test Kitb. Battery Testerc. Final functionality Testingd. Proper Valve Installation FDA office: Detroit District Office


5/23/2012 Tango3 LLCRecipient: BTS S.p.A. Product: water storage tank with ozone disinfection system Date: 5/23/2012This inspection revealed that this device is 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, theirmanufacture, packing, storage, or installation are not in conformity with the current good manufacturingpractice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations(CFR), Part 820. We received responses from your firm dated February 23, 2012, February 27, 2012, March 1, 2012 andApril 2, 2012, concerning our investigator’s observations noted on the Form FDA 483 (FDA 483), List ofInspectional Observations, that was issued to your firm. We address these responses below, in relationto each of the noted violations. These violations include, but are not limited to, the following:Failure to adequately perform design validation to ensure that devices conform to defined user needsand intended uses and include testing of production units under actual or simulated use conditions andto ensure that software validation and risk analysis are completed, as required by 21 CFR 820.30(g).For example, A. The disinfection validation (b)(4), and software validation for version 1.4 (b)(4), did not documentwhich system was used for validation and whether the critical parameters (i.e., (b)(4) were met. Inaddition, your firm did not adequately perform validation on the Tango3 system to determine if thepredetermined user needs and intended uses were met. For example, the initial validation was done ona Tango3 serial #1031. However, your firm has no information on the components and the softwareused to run the Tango3 serial #1031. B. Your firm’s risk analysis for the Tango3 was not completed. The Tango3 Hazard Analysisdocument identified (b)(4) as an issue. However, this analysis failed to assess critical aspects of the(b)(4). For example, the software allowed the system to (b)(4). However, your firm did not conduct anyhazard analysis to identify the risk associated with this malfunction. We reviewed your firm’s responses and conclude that they are not adequate. To mitigate the aboveissues, your firm performed several validations/tests including software validation per Tango3 SoftwareValidation Plan (software version 2.0) Revision B, system reliability tests (b)(4) of the components, and(b)(4) reliability), (b)(4) validation. Your firm updated the hazard analysis to include malfunctions relatedto patient injury. However, the responses did not (1) provide the (b)(4), (2) did not explain how the (b)(4)and (3) why the (b)(4) differOur inspection also revealed that the Tango3 water storage tank with ozone disinfection system isadulterated under section 501(f)(1)(B) of the Act, 21 U.S.C. § 351(f)(1)(B), because you firm does nothave an approved application for premarket approval (PMA) in effect pursuant to section 515(a) of theAct, 21 U.S.C. § 360e(a), or an approved application for an investigational device exemption (IDE)under section 520(g) of the Act, 21 U.S.C. § 360j(g). The water storage tank with ozone disinfectionsystem is also misbranded under section 502(o) of the Act, 21 U.S.C. § 352(o), because your firm didnot notify the agency of your firm’s intent to introduce the device into commercial distribution in that anotice or other information respecting the modification to the device was not provided to the FDA asrequired by section 510(k), 21 U.S.C. § 360(k), and 21 CFR 807.81(a)(3)(i). Specifically, your firmmodified the water storage tank with ozone disinfection system, cleared under K093641, by includingnew and modified components, labeling and software. Specifically, the following modifications weremade: (b)(4). These modifications may affect the safety of your device both to the user and thesubsequent dialysis patient. For a device requiring premarket approval, the notification required bysection 510(k) of the Act, 21 U.S.C. § 360(k), is deemed satisfied when a PMA is pending before theagency. 21 C.F.R. 807.81(b). The kind of information your firm needs to submit in order to obtainapproval or clearance for your device is described on the Internet athttp://www.fda.gov/cdrh/devadvice/3122.html. 1 The FDA will evaluate the information your firm submits


and decide whether your firm’s product may be legally marketed.FDA office: Cincinnati District Office

5/10/2012 BTS S.p.A. FreeEMG and PocketEMGRecipient: BTS S.p.A. Product: FreeEMG and PocketEMG Date: 5/10/2012This inspection revealed that these devices are adulterated within the meaning of section 501(h) of theAct, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for, theirmanufacture, packing, storage, or installation are not in conformity with the current good manufacturingpractice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations(CFR), Part 820.Failure to establish and maintain adequate procedures to control all documents that are required by 21CFR 820. All obsolete documents shall be promptly removed from all points of use or otherwiseprevented from unintended use, as required by 21 CFR 820.40(a).For example: (b)(4) is the software version currently used for the FreeEMG and it is maintained within afolder on your firm's computer system. However, it was observed that the previous versions of thissoftware were not removed from the same electronic folder, were still marked as released, were stillavailable for use, and were not marked as obsolete.We reviewed your firm's response and conclude that it is not adequate. In the response to theobservation. your firm provided a print screen showing the change so that previous software revisionsare marked as obsolete and are made inaccessible. However, evidence that your firm reviewed otherfiles to ensure that obsolete procedures were removed was not provided. Evidence that your firmupdated procedures to ensure that obsolete documents were not made available was not provided.Also, your firm did not provide evidence to indicate that a systemic corrective action was considered(e.g., implementing a correction to prevent future occurrences and/or the use of obsolete documents forother products manufactured).FDA office: CDRH

5/8/2012 Mediagnost GmbHRecipient: Mediagnost GmbH. Product: Human Growth Hormone diagnostic kits Date: 5/8/12Failure to establish and maintain adequate procedures to control all documents, as required by 21 CFR820.40. For example:a. There are no procedures that address the control of electronic records.b. Access to two computer workstations that include in-process test data, finished device testing results,and access to the firm's network were not adequately controlled. The workstations have no accesslimitation controls or locks, all employees share the same user name and password, and the computersall access the firm's overall network and records.We reviewed your firm's responses and conclude that they are not adequate.Your firm did not provide a plan or documentation for correction of this observation. Your firm statedthat it will evaluate the current electronic data record system and will consider switching to apaper-based system. However, your firm has not supplied any information on its proposed correctiveactions.Issuer: Center for Devices and Radiological Health (CDRH)

5/7/2012 Social Media Issue - ThermaSolutionsIncorporatedQuincy ThermaSolutions Incorporated . Product: ThermoChem-HT 1000 System Date: 5/7/2012The Food and Drug Administration (FDA) has learned that your firm is marketing the ThermoChem-HT1000 System (ThermoChem-HT) in the United States. The product is a device within the meaning ofsection 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 321(h), because it isintended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or


prevention of disease, or to affect the structure or function of the body. As explained below, this deviceis being marketed without required clearance or approval in violation of the Act. .We are also aware that on your firm’s Twitter page, accessible at twitter.com/thermasolutions, your firmstates that “TSI has the first FDA approved medical device for creating hyperthermia in the abdominalcavity - heating and pumping a chemotherapy solution into the region.”The ThermoChem-HT 1000 device, with the intended uses described above, is adulterated undersection 501(f)(1)(B) of the Act, 21 U.S.C. § 351(f)(1)(B), because your firm does not have an approvedapplication for premarket approval (PMA) in effect pursuant to section 515(a) of the Act, 21 U.S.C. §360e(a), or an approved application for an investigational device exemption under section 520(g) of theAct, 21 U.S.C. § 360j(g). The device is also misbranded under section 502(o) of the Act, 21 U.S.C. §352(o), because your firm did not notify the agency of its intent to introduce the device into commercialdistribution, as required by section 510(k) of the Act, 21 U.S.C. § 360(k). For a device requiringpremarket approval, the notification required by section 510(k) of the Act is deemed satisfied when aPMA is pending before the agency, 21 CFR § 807.81(b). The kind of information that your firm needs tosubmit in order to obtain approval or clearance for the device is described on the Internet athttp://www.fda.gov/cdrh/devadvice/3122.html. The FDA will evaluate the information that your firmsubmits and decide whether the product may be legally marketed.The Office of Compliance requests that ThermaSolutions, Inc., immediately cease marketing theThermoChem-HT for unapproved uses such as those described above. Your firm should take promptaction to correct the violations addressed in this letter. Failure to promptly correct these violations mayresult in regulatory action being initiated by the FDA without further notice. These actions include, butare not limited to, seizure, injunction, and civil money penalties. Also, federal agencies may be advisedof the issuance of Warning Letters about devices so that they may take this information into accountwhen considering the award of contracts.FDA District Office: Public Health Service 

5/2/2012 Amplivox LimitedRecipient:Amplivox Limited Product: tympanometers and audiometers Date: 5/2/2012This inspection revealed that these devices are adulterated within the meaning of section 501(h) of theAct, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for, theirmanufacture, packing, storage, or installation are not in conformity with the current good manufacturingpractice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations(CFR), Part 820.We received a response from (b)(6), Quality Manager, Amplivox Limited, dated December 21, 2012,concerning our investigator’s observations noted on the Form FDA 483 (FDA 483), List of InspectionalObservations, that was issued to your firm. We address this response below, in relation to each of thenoted violations. These violations include, but are not limited to, the following:7. Failure to adequately validate computer software for its intended use according to an establishedprotocol, as required by 21 CFR 820.70(i). For example, upon request for the protocol used during the validation of your firm’s software-controlledaudiometer device calibration system, your firm stated that it did not have a pre-established protocol forconducting the validation. We reviewed your firm’s response and conclude that it is not adequate. Your firm did not submitsupporting documentation indicating that it will create a requirement that protocols be used during futuresoftware validations. Your firm’s response did not address why no protocol was used during thevalidation of the audiometer testing equipment software. Your firm’s response also did not includeevidence to indicate that a corrective action was implemented or that a systemic corrective action wasconsidered (including reviewing all software validations to ensure that the validations were conducted asrequired).FDA office: CDRH


4/24/2012 Social Media Issue - Vitality Distributing, IncVitality Distributing, Inc Product: avitae caffeinated water Date: 4/24/2012This is to advise you that the U.S. Food and Drug Administration (FDA) reviewed your website atwww.myavitae.com in March 2012 and has determined that your “avitae caffeinated water” product is promoted for conditions that cause the product to be a drug under section 201(g)(1)(B) of the FederalFood, Drug, and Cosmetic Act (the Act) [21 U.S.C. § 321(g)(1)]. The claims on your website establishthat this product is a drug because it is intended for use in the cure, mitigation, treatment, or prevention of disease. The marketing of your products with these claims violates the Act. . In addition to the above violations, we have the following comment regarding claims made on yourFacebook account (accessible at: https://www.facebook.com/avitae) and your Twitter (@avitaeusa)account (accessible at http://twitter.com/#!/avitaeusa). Posts made by the page administrator onNovember 9, 2011 on both your Facebook Timeline and your Twitter page include a link to an articleentitled, “A Coffee A Day May Keep The Doctor Away.” That article makes the following claims:•"[W]omen who regularly drink caffeinated coffee have a 20 percent lower risk of depression ... "•"It lowers the risk of cancer and diseases"•"Scares off Alzheimer's disease"FDA District Office: Cincinnati District 

4/7/2012 Community Blood Centers of Florida, Inc.Recipient:Community Blood Centers of Florida, Inc. . Product:blood and blood components Date: 4/7/2012The Food and Drug Administration (FDA) conducted an inspection of your firm, Community BloodCenters of Florida, Inc., from September 1, 2011 - December 19, 2011. During the inspection, FDAinvestigators documented deviations from applicable current Good Manufacturing Practice for FinishedPharmaceuticals (21 CFR Part 211) and current Good Manufacturing Practice (cGMP) regulations forblood and blood components, Title 21 Code of Federal Regulations (21 CFR) Parts 600, 610 and 640.These deviations cause your blood products 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)]. Thesedeviations include but are not limited to the following:1) Failure to maintain records that include, but are not limited to, records to relate the donor with the unitnumber of each previous donation from that donor [21 CFR 606.160(b)(1)(vii)]. At least thirteen ABOdiscrepancies were noted during the previous inspection in July, 2007 and the discrepant units were stillfound to be associated with the wrong donor records during the current inspection.a) Registration information for a donor was entered over the existing record of another donor. Thediscrepant record was registered under "John Doe" and your firm failed to update the donor records torelate the unit number to the actual donor.b) Registration information for a donor was entered over the existing record of another donor. Your firmfailed to identify the donor of the unit and it was discovered during the inspection that the discrepant unitwas still associated with the wrong donor record. Failure to use supplies and reagents in a manner consistent with the instruction provided by themanufacturer [21 CFR 606.65 (e)].c) Your firm's quality control unit failed to conduct a complete investigation of issues related to theinterface between your Regulated Software Collections Application (RSA) and BioMerieux ClinicalDiagnostics BAC-T Alert computer systems. You therefore failed to ensure the satisfactory transfer ofbacterial testing results of platelet products.6) Failure to maintain records concurrently with the performance of each significant step in thecollection, processing, compatibility testing, storage and distribution of each unit of blood and bloodcomponents so that all steps can be clearly traced [21 CFR 606.160 (a)(1)]. Failure of your distributionrecords to contain information to readily facilitate the identification of the name and address of theconsignee, the date and quantity delivered, the lot number of the unit(s) the date of expiration or thedate of collection, whichever is applicable, or for crossmatched blood and blood components, the nameof the recipient [21 CFR 606.165(b)].


FDA District: Florida District 

3/28/2012 SystemsOne, LLCRecipient: Prosec Protection Systems, Inc. Product: Electrophysiology Systems Integrator (EPSI) Date: 3/6/2012This inspection revealed that these devices are adulterated within the meaning of section 501(h) of theAct (21 U.S.C. § 351(h)), in that the methods used in, or the facilities or controls used for, theirmanufacture, packing, storage, or installation are not in conformity with the current good manufacturingpractice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations(CFR), Part 820. Your firm’s response to the Form FDA 483 (FDA 483), dated December 30, 2011, wasnot reviewed because it was not received within fifteen business days of issuance of the FDA 483. Theresponse may be evaluated along with any other written material provided in response to the violationscited in this Warning Letter. These violations include, but are not limited to, the following:1. Failure to establish and maintain adequate procedures for validating the device design, as requiredby 21 CFR 820.30(g). For example, your firm’s Chief Operating Officer stated that your firm does nothave a software validation procedure and has no documentation of software testing.FDA office: Florida District 

3/28/2012 Osypka Medical GmbHRecipient: Prosec Protection Systems, Inc. Product: manufactures external pacemakers and cardiac monitoring devices Date: 3/7/20124. Failure to promptly remove all obsolete documents from all points of use or otherwise prevent fromunintended use, as required by 21 CFR 820.40(a). For example: the 2011 calibration of stopwatch number 0611 used calibration work instruction version1.0 to perform the calibration. The latest calibration work instruction version for that instrument isversion 1.1, which had been used in 2010 to calibrate the same stopwatch. Your firm stated that thework instructions for calibration (b)(4) Your firm states that its software does not have the capability ofmoving the obsolete work instructions to a separate folder so that they can not be accessed and usedfor calibration activities. The adequacy of your firm’s response cannot be determined at this time. Your firm confirms that thesoftware which is used for the calibration of measuring equipment contains both the old and newversion of the calibration plan for (b)(4). Your firm states that the tester chose the wrong calibration planby mistake, leading to more testing than needed according to the new plan. Your firm states that it willdelete all obsolete calibration plans from the calibration software so that, in the future, the tester canonly chose the current test plan for each piece of equipment needing calibration. Additionally, your firmwill re-train the tester of the measurement equipment. Your firm has not provided documentation tosupport the implementation of these actions.FDA office: CDRH 

3/7/2012 Prosec Protection Systems, Inc.Recipient: Prosec Protection Systems, Inc. Product: My Child Identification Kit Date: 2/28/2012The inspection revealed that this device is 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, its manufacture,packing, storage, or installation is not in conformity with the current Good Manufacturing Practicerequirements of the Quality System regulation found at Title 21, Code of Federal Regulations (CFR),Part 820.These violations include, but are not limited to, the following:4. Failure to establish procedures for corrective and preventive action, as required by 820.100(a). Forexample:A) There is no written standard operating procedure for documenting corrective and preventive actions(CAPA) in the (b)(4) system, which is the software system used for documenting CAPA reports.


7. Failure to validate software which is used as part of the quality system for its intended use accordingto an established protocol, as required by 21 CFR 820.70(i).For example, the (b)(4) System, which is the system in place for documenting non-conformances, andcorrective and preventive actions since 2008, has not been validated according to an establishedprotocol. Further, there is no assurance that the system has the capability of storing or saving criticaldata, such as complaints, CAPA reports, and nonconformances.9. Failure to establish procedures for receiving, reviewing, and evaluating complaints by a formallydesignated unit, as required by 820.198(a).For example, your firm does not have a written standard operating procedure in place for thedocumentation of complaints in the (b)(4) System, which is the software system used for complainthandling.FDA office: New Jersey District Office 

2/29/2012 Omron (Dalian) Co., Ltd. blood pressuremonitorsRecipient: Omron (Dalian) Co., Ltd. Product: non-sterile blood pressure monitors Date: 2/14/2012This inspection revealed that these devices are adulterated within the meaning of section 501(h) of theAct (21 U.S.C. § 351(h)), in that the methods used in, or the facilities or controls used for, theirmanufacture, packing, storage, or installation are not in conformity with the current good manufacturingpractice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations(CFR), Part 820. We received a response dated November 7, 2011, concerning our investigator’sobservations noted on the Form FDA 483 (FDA 483), Inspectional Observations, that was issued toyour firm. We address this response below, in relation to each of the noted violations. These violationsinclude, but are not limited to, the following:2. Failure to validate computer software used as a part of production or the quality system for itsintended use according to an established protocol, as required by 21 CFR 820.70(i). For example, yourfirm could not provide any documentation to demonstrate that the software used for the 6111 PCB(Printed Circuit Board) check machine (b)(4) was validated for its intended use. Your firm’s DepartmentManager of Regulatory Affairs stated that the software used for the PCB check machine has not beenvalidated. The adequacy of your firm’s response cannot be determined at this time. Evidence of implementation ofyour firm’s corrections and corrective actions referenced in your response were not provided. FDA office: CDRH 

2/29/2012 Scottcare CorporationRecipient: Scottcare Corp. Product: telemetry devices Date: 2/21/2012This inspection revealed that the medical 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 formanufacturing, packing, storage, or installation are not in conformity with the Current GoodManufacturing Practice (CGMP) requirements of the Quality System (QS) regulation found at Title 21,Code of Federal Regulations (CFR), Part 820. We received your response dated January 26, 2012 toour investigator’s observations noted on the Form FDA 483, List of Inspectional Observations that wasissued to you. We address your response below, as it relates to each of the noted violations. Theseviolations include, but are not limited to, the following:7. Failure to establish and maintain adequate procedures for the identification, documentation,validation or where appropriate verification, review and approval of design changes before theirimplementation, as required by 21 CFR § 820.30(i). Specifically, your firm received a complaint from a customer on 8/24/11 reporting a potential seriousbug with the TeleSentry software, version 1.1.0 that they were beta testing at their site. This software


version has not been approved; and your “QSP03-008 DESIGN CHANGE CONTROL” procedure, RevC, dated 02/27/08 does not address and/or allow beta testing of software at customer locations prior torelease of the engineering change order. Your response to this observation can not be assessed at this time. Your response states you arecurrently evaluating the processes, controls and documentation to better define the release of softwareto Beta test sites. You further state you will provide the FDA with an update within 30 days regardingthis issue, and you will not provide software to customers without an approved ECO.FDA office: Cincinnati District Office 

2/23/2012 Medical Services International (MSI)Recipient:Innovatech Medical Resources L.P. Product:SterileOPUS Magnum 2 Knotless Fixation devices, OPUS SpeedScrew Knotless Fixationdevices, OPUS SmartStitch Perfectpasser Suture Cartridges, as well as other devices Date: 2/23/2012This inspection revealed that these devices are adulterated within the meaning of Section 501(h) of theAct, [21 U.S.C. § 351(h)], in that the methods used in, or the facilities or controls used for, theirmanufacture, packing, storage, or installation are not in conformity with the current good manufacturingpractice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations(CFR), Part 820. These violations include, but are not limited to, the following:Failure to establish and maintain procedures for validating the device design to ensure that devicesconform to defined user needs and intended use, to include software validation and risk analysis, asrequired by 21 CFR 820.30(g).Your firm failed to perform design validation to ensure that re-sterilization of bone fixation devices andtheir accessories conform to user needs and intended use. Additionally, your firm relabeled thesedevices with extended expiration dates for up to (b)(4) years without conducting or documenting riskanalysis to determine the risks to the device materials or package integrity. Your firm's Co-President,Mr. Fuller, stated that prior to re-sterilization, no risk analysis or product testing was done to determineeffect on product, packaging, or sterility.FDA District Office: Dallas District 

2/17/2012 Biochem Laboratories IncRecipient:Biochem Laboratories Inc. Product:TX1 Tissue Removal System Date: 2/17/2012Your firm has failed to exercise appropriate controls over computer or related systems to assure thatchanges in master production and control records, or other records, are instituted only by authorizedpersonnel [21 CFR 211.68(b)].For example:a. Your firm did not put in place requirements for appropriate usemames and passwords to allowappropriate control over data collected by your firm's computerized systems including UV, IR, HPLC,and GC instruments. All employees in your firm used the same usemame and password. In addition,you did not document the changes made to the software or data stored by the instrument systems.Without proper documentation, you have no assurance of the integrity of the data or the functionality ofthe software used to determine test results.b. Your firm had no system in place to ensure appropriate backup of electronic raw data and nostandard procedure for naming and saving data for retrieval at a later date.In your response, you state that you will maintain backup of electronic raw data and all technicians willhave their own user identification (ID) and password. Your response, however, is inadequate becauseyou do not describe how your firm intends to save and back-up the electronic raw data, nor whetheryour firm will implement audit trails on your computerized systems. Further, you do not provide atimeframe for accomplishing the intended corrective actions or describe the changes you have made torelevant SOP(s)..Issuing Office: New Jersey District 


1/25/2012 CuraeLase, Inc.Recipient: CuraeLase, Inc Product:CL 1000 IR Laser System Date: 12/9/2011Quality System Regulation ConcernsWe also note the following concerns regarding Quality System (QS) regulation requirements (21 CFRPart 820):6. Failure of the DMR for each device type to include or refer to the location of the device specifications,including software specifications, as required by 21 CFR 820.181 (a). For example, there was nodocumentation of the software specifications and testing of the software user interface and controlprogram. The device has an embedded software program that controls the time elements of the laserand treatments. When the protocol and time treatment duration is selected, the software controls howlong the laser is on and the total time, which varies from 5 to 20 minutes.The embedded software program was developed by the laser (resonator) manufacturer, (b)(4) Althoughthe overall requirements for the software program were communicated between (b)(4), theserequirements were not formalized FDA office: CDRH