Inspections, Compliance, Enforcement, and Criminal Investigations

Anigan, Inc. 7/25/18

 

  

Black HHS-Blue FDA Logo

 

 

 
Office of Medical Device and Radiological Health Operations (Division 3W)
19701 Fairchild
Irvine, CA 92612 

 

WARNING LETTER
CMS # 557163
                                                                                                           
UNITED PARCEL SERVICE
OVERNIGHT DELIVERY
 
July 25, 2018
 
Anigan, Inc.
Ai Chen Teo, President and General Manager
6550 Bennington Way
San Ramon, CA 94582-3902
 
Dear Ms. Teo:
 
The United States Food and Drug Administration (FDA) conducted an inspection of your firm’s medical device operations at 6550 Bennington Way, San Ramon, CA from April 16 – 19, 2018. During the inspection, an FDA investigator determined that your firm is a manufacturer of the Class II Super Jennie and EvaCup reusable menstrual cups.  Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 321(h), these products are devices because they are intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body.
 
This inspection revealed that these devices are adulterated within the meaning of section 501(h) of the Act, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for, their manufacture, packing, storage, or installation are not in conformity with the current good manufacturing practice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations (CFR), Part 820.
 
We received responses dated May 4, 2018, and June 2, 2018, from you concerning our investigator’s observations noted on the Form FDA 483, List of Inspectional Observations (FDA 483) that was issued on April 19, 2018. We address your response below, in relation to each of the noted violations. For your reference, FDA defines “establish” under 21 CFR Part 820.3(k) as “define, document (in writing or electronically), and implement.” These violations include, but are not limited to, the following:
 
1.    Procedures for design control have not been established per the requirements of 21 CFR Part 820.30(a).
 
You provided a Design Controls procedure, QMP-001, revision: NEW, and a Design Plan Record,QMP-001-01, during our recent inspection. This procedure does not note any effective or implementation date, or any evidence it has been reviewed or approved yet.  You told our investigator it became effective on April 6, 2018, and that prior to that date your firm had not established design controls for your menstrual cups distributed since 2014. The one-page document you provided when our investigator asked for the Design Plan was a list of size and other specifications whereas your procedure requires the design plan to describe required activities and responsibilities for each activity, along with review and updates at each phase of the design process. The Design Controls procedure provided also requires established design inputs which are documented, reviewed and approved, as well as design outputs to include definition of acceptance criteria to ensure critical outputs can be met. In addition, it requires design verification to demonstrate design outputs meet design inputs, and that design verification provides objective evidence. It states design validation must be performed under operating conditions and demonstrate the device meets user needs. Sufficient evidence was not provided during the inspection to demonstrate your firm has met the regulation or your own procedural requirements for design controls for the initial design, design transfer, or any subsequent design changes of either the Super Jennie or EvaCup menstrual cups your firm has been distributing since 2014.  
 
Your May 4th response states you have hired a consultant and will have a plan in place by June 30, 2018 for retroactively completing design controls and then will implement that plan by September 30, 2018 for the Super Jennie and EvaCups. However, the adequacy of your firm’s response cannot be determined at this time as you have not provided any objective evidence of corrections to date. Your firm has been distributing these devices for approximately four years without design controls in place to include at least (b)(4) Super Jennie Cups and (b)(4) EvaCups in 2017 alone.  In addition, you have not addressed how you will ensure the products you distribute between now and September 30, 2018 will conform to user needs and intended uses since design controls have not been properly defined or documented.
 
We have included an FDA guidance document titled, “Design Controls for Medical Device Manufacturers” to assist in your corrections. We request that you review this document and 21 CFR Part 820.30 and provide a summary of your corrections related to the design controls of these products when you feel they are complete to meet the requirements of your procedure. These will be further reviewed as part of your next inspection. 
 
2.    Procedures for design validation have not been established per the requirements of 21 CFR Part 820.30(g).
 
As mentioned above, your Design Controls procedure, QMP-001, revision: NEW, Section 4.5.2, states design validation must be performed under operating conditions and demonstrate the device meets user needs. This procedure does not address risk analysis in design. This procedure also does not note any effective or implementation date, or any evidence it has been reviewed or approved, yet you told our investigator it became effective on April 6, 2018. 
 
EvaCup
When asked about design validation, you provided one document related to the EvaCup regarding “Reasons behind EvaCup Design” which addresses factors such as (b)(4) characteristics. This document has some documented explanation but does not include any test results or other evidence of design validation. It also does not define terms used such as “(b)(4)” or how the chosen (b)(4) will be met for the cup.
 
You provided the instructions for use for your EvaCup device which state it can be used for up to 12 hours and should be cleaned in a pot of boiling water for 5-8 minutes. During our inspection, you also provided printouts from your website, www.anigan.com showing the EvaCup should also be initially sterilized in boiling water for 10-15 minutes.  Review of your website after the inspection found the EvaCup should be initially sterilized for 5-10 minutes. When asked by our investigator, no evidence could be provided to demonstrate that: design validation was performed to ensure the devices conform to user needs and intended uses; to show testing was done under actual simulated use conditions; or that risk analysis was performed. These activities are necessary to validate intended uses such as the use of the cup for up to 12 hours, the cleaning method or timeframe suggested in boiling water, and the capacity of the material to handle these conditions over the 10 year life of the menstrual cups (as listed on the EvaCup packaging). Your website, www.anigan.com also mentions the EvaCup can “even last for up to 12 years” but documented evidence was also not provided to support this claim.
 
Super Jennie cup
You provided the instructions for use for your Super Jennie cup which state it can be used for up to 12 consecutive hours and recommends soaking the cup in a mixture of peroxide and water under the “Extra Tips” section. During our inspection, you also provided the “How to Use” instructions printed from your website, www.superjennie.com, for your Super Jennie cup which state it should be cleaned in a pot of boiling water for 10-15 minutes before first use and at the end of each menstrual cycle. Review of your website after the inspection found currently the cleaning instructions say to boil for 5-10 minutes. When asked about design validation, no documents were provided for your Super Jennie cups and no evidence could be provided to demonstrate that: design validation was performed to ensure the devices conform to user needs and intended uses; to show testing was done under actual simulated use conditions; or that risk analysis was performed. These activities are necessary to validate intended uses such as the use of the cup for up to 12 hours, the cleaning method or timeframe suggested in boiling water or with a peroxide solution, and the capacity of the material to handle these conditions over the 10year life of the menstrual cups (as listed on your www.superjennie.com website).
 
Your May 4th response states you have removed the reference to soaking the cup in a peroxide solution, however no evidence was provided to demonstrate this correction and no discussion of the amount of labeling that may remain in stock for potential use was mentioned. This response also states you plan to initiate biological testing and sterilization validation with “an acceptable testing lab” by July 1, 2018, but no additional details or evidence were provided;, therefore the adequacy of that response cannot be evaluated.
 
Risk Analysis
In addition, you told our investigator that risk analysis has not been conducted for either model of the menstrual cups sold by your firm. These cups are labeled for use up to 12 hours and potential risks to the user for this time period have not been documented, or mitigated, if necessary. Other potential considerations for risk such as: the inability of the user to remove the device; placing the device incorrectly; use with an IUD; use after birth of a baby; use of colored silicone placed inside the vagina; material properties of the silicone for biocompatibility and necessary “(b)(4)” or flexibility; compatibility of the silicone with lubricant recommended for ease of insertion on your website (www.anigan.com); use of the appropriate size for the user; heat stability of the material in boiling water; stability of the material in a peroxide solution (per the Super Jennie IFU); or other potential risks that might affect a user have not been considered. We have included our guidance document titled “Applying Human Factors and Usability Engineering to Medical Devices” which provides additional guidance for risk analysis considerations in design phases in section 2. This may be useful when considering your corrections.
 
Your May 4th response states you plan to develop a risk analysis procedure by June 30, 2018, have a risk analysis plan in place by July 15, 2018, and complete risk analysis reports for both cup models by July 30, 2018. However, the adequacy of your firm’s response cannot be determined at this time since you have not provided any objective evidence of corrections to date. In addition, you have not addressed how you will ensure the products you distribute between now and July 30, 2018 will conform to user needs and intended uses since design validation has not been performed.
 
Your firm has not met the regulation or your own procedural requirements for design validation of the initial design or any potential subsequent design changes of either the Super Jennie or EvaCup menstrual cups your firm has been distributing since 2014. Design validation is discussed in section G of our “Design Controls for Medical Device Manufacturers” guidance document, which we have attached in addition to the Human Factors guidance for your reference while making corrections. We request that you review these documents and 21 CFR Part 820.30 and when you provide the summary of design controls documentation requested under item 1 of this letter, that should also help us understand your corrections to this item. Design controls and design validation will be reviewed as part of your next inspection.
 
3.    Procedures for receiving, reviewing, and evaluating complaints by a formally designated unit have not been established per the requirements of 21 CFR Part 820.198.
 
During our recent inspection, you provided a Complaints and Medical Device Reporting and Removal procedure, QMP-015, revision: NEW. This procedure does not note any effective or implementation date, or any evidence it has been reviewed or approved yet you told our investigator it became effective on April 6, 2018, and that prior to that date your firm had not established complaint handling procedures for your menstrual cups distributed since 2014 despite having received approximately 60 complaints per your President since that time. The procedure requires documentation of the complaint, reportability assessment, evaluation for investigation and documenting details as necessary, and recording of any corresponding CAPA record identification numbers.
 
No complaint records could be provided to our investigator aside from a single example during our recent inspection. The example provided did not include required information per 820.198 and the complaint itself was not documented in the complaint record. Instead, template language remained where the complaint issue should have been recorded and the complaint issue was only noted in the complaint log. We noted your May 4, 2018 response included an updated record for this complaint.
 
Your May 4th response also states you plan to re-review your complaint handling procedure by May 7, 2018 and that you plan to prepare summary documents and evaluate all complaints received prior to April 6, 2018 by August 15, 2018. Your June 2nd response mentions that you have hired a quality systems consultant, but no other updates related to this observation were included in that response. The adequacy of your firm’s response cannot be determined at this time since you have not provided any objective evidence of corrections to date. 
 
Your firm should review the requirements of 21 CFR Part 820.198 and ensure your procedure meets these regulatory requirements for implementation. We request that you notify our office when your planned corrections as delineated in your first response are complete. Complaint handling will be reviewed as part of your next inspection.
 
4.    Procedures for finished device acceptance have not been adequately established per the requirements of 21 CFR Part 820.80(d). 
 
Your firm’s “Acceptance Activities” procedure, QMP-006, revision: NEW, section 4.3.3.1, requires your firm to ensure “packaging is prepared in accordance with packaging specifications within the DMR.” However, per the Device Master Record (DMR) and Master Document List (MDL) you provided to our investigator, you have not established specifications for all of your packaging and labeling, such as the Super Jennie Size 1 and Super Jennie Size 2 Retail box specifications, and therefore cannot ensure your finished devices meet specified requirements. Furthermore, you stated to our investigator that you have no finished device acceptance records for any of your menstrual cups, which you began distributing in 2014, to include at least (b)(4) Super Jennie Cups and (b)(4) EvaCups in 2017 alone.
 
Your May 4th response states you are revising your procedures to reduce the potential for label mix-ups, and will clarify the processes and requirements of acceptance activities and release of product by July 30, 2018. Your June 2nd response did not provide any specific updates on this item. Therefore, we cannot evaluate the adequacy of your firm’s response and proposed corrective actions at this time as you have not provided objective evidence of corrections to date, such as a revised procedure or records associated with acceptance activities. 
 
We request that you review 21 CFR Part 820.80 and notify our office once the corresponding procedures and specifications have been fully established, including implementation of those procedures. We also ask that you include in your correspondence a description of the difference between your Super Jennie and EvaCup Retail Box Specifications and your Super Jennie and EvaCup Online Box Specifications, both of which are listed as packaging and labeling specifications in your DMR.
 
5.    Procedures for quality audits have not been established per the requirements of 21 CFR Part 820.22.
 
You provided a Quality System Audits procedure, QMP-013, revision: NEW, which states you will establish an audit schedule to ensure the quality system is examined with sufficient frequency (Section 4.1.1), and keep records of the audits upon completion (Section 4.3.1 and Section 5.0). Your firm’s Audit Log is blank and no records of audits were provided to show a single internal audit had been performed since you began manufacturing and distributing menstrual cups in 2014. This procedure also does not require a re-audit when the results of an audit required corrective action. Additionally, this procedure does not note any effective or implementation date, or other evidence it has been reviewed or approved, even though you stated to our investigator it became effective April 6, 2018.
 
Your May 4th response committed you to having an external auditor selected by May 15, 2018, and that you will ensure all quality systems are audited no later than May 22, 2018; however, your June 2nd response did not provide any specific updates on this item. Therefore, we cannot evaluate the adequacy of your firm’s response and proposed actions at this time as you have not provided objective evidence of corrections to date. 
 
We request that you review 21 CFR Part 820.22 to ensure your procedure meets all regulatory requirements. Please provide us a date when your first audit has been completed and be prepared to show evidence of the audit (but not the results) during your next inspection.
 
6.    Management with executive responsibility has not reviewed the suitability and effectiveness of the quality system per the requirements of 21 CFR Part 820.20(c).
 
You provided a Management Review procedure, QMP-012, revision: NEW, Section 4.1, which states your firm will conduct management reviews (b)(4). This procedure does not note any effective or implementation date, or any evidence it has been reviewed or approved, yet you told our investigator it became effective April 6, 2018. No related procedure preceding that date was provided during our inspection. Your firm was distributing medical devices but did not conduct management reviews to meet the requirements of 21 CFR 820.20 from 2014 – 2017.
  
Your May 4th response states your firm will revise your “Quality Plan” by June 15, 2018, to require management reviews be conducted (b)(4) for at least (b)(4) to ensure the adequacy and suitability of the quality system. Your June 2nd response did not provide any specific updates on this item. Therefore, we cannot evaluate the adequacy of your firm’s response and proposed actions at this time as you have not provided objective evidence of corrections to date. 
 
We request that you review 21 CFR Part 820.20 and provide a summary of your corrections, including the (b)(4) review schedule (once established), and evidence of the completion of your first review. 
 
7.    Document control procedures have not been adequately established and maintained per the requirements of 21 CFR Part 820.40. 
 
You provided a Document Control procedure, QMP-002, revision: NEW, which was not implemented; none of the procedures provided during the recent inspection included documented effective dates or evidence that the procedures were reviewed and approved. For example:
 
a.    Your Document Control procedure, QMP-002 with no effective date, requires a Document Change Order (DCO) be initiated when a new document is required, or for revision of existing documents. Per this procedure, DCOs are required to be reviewed and approved prior to implementation. One of the two DCOs provided during the inspection, document number “QMS doc,” which you explained was the initial approval for the implementation of all documents, was reviewed and approved on April 11, 2018. However, you stated to our investigator throughout the inspection that procedures, such as QMP-002, became effective April 6, 2018. 
b.    Procedure QMP-002, Section 4.2.1.1, also requires DCOs to identify the affected documents within the DCO and include descriptions of the changes being made. DCO “QMS doc” does not identify the affected documents. 
c.    Procedure QMP-002, Section 4.1.2 and 4.1.3, also requires a Master Document List (MDL), used for documenting your controlled documents, to include the document number, document title, current revision, and effective date. The MDL provided during the inspection does not list any effective dates.
d.    Procedure QMP-002, Section 4.1.1.1, requires controlled documents be revision controlled to ensure utilization of only the current revision. However, the labeling for your menstrual cups, including the instructions for use (IFU), did not have document control numbers. All other documents on the MDL only have the notation of “NEW” as the revision number.
 
Your May 4th response states your firm will correct the MDL, as well as begin issuing control numbers for your labeling, and correcting the documentation of your implementation of the quality management documents using the DCO form. In your response, you committed to making these corrections by June 30, 2018. Your June 2nd response did not provide any specific updates on this item. We cannot evaluate the adequacy of your firm’s response and proposed actions at this time as you have not provided objective evidence of corrections to date. 
 
We request that you review 21 CFR Part 820.40 to ensure your procedure meets all regulatory requirements, and provide evidence your MDL is corrected, as well as evidence you have effectively implemented your document control procedures.
 
Your firm should take prompt action to correct the violations addressed in this letter.  Failure to promptly correct these violations may result in regulatory action being initiated by the FDA without further notice.  These actions include, but are not limited to, seizure, injunction, and civil money penalties.  Also, federal agencies may be advised of the issuance of Warning Letters about devices so that they may take this information into account when considering the award of contracts. Additionally, premarket approval applications for Class III devices to which the Quality System regulation violations are reasonably related will not be approved until the violations have been corrected.  Requests for Certificates to Foreign Governments will not be granted until the violations related to the subject devices have been corrected.
 
In addition, your May 4, 2018, response included supporting documentation of your corrective actions in response to deficiencies found in your evaluation of suppliers and auditors, as noted in observation 7 on the FDA 483, Inspectional Observations. We have reviewed your response and the supporting documentation, in addition to your Purchasing Controls procedure, QMP-003, revision: NEW, with no effective date. Per this procedure, “critical” suppliers should have an executed Supplier Quality Agreement, or, in place of an agreement, your procedure indicates regular supplier audits may be warranted. Based on the current procedure, it is not clear if your firm is requiring any of your critical suppliers to have a quality agreement, or whether you are requiring your firm to conduct regular audits of the critical suppliers. Please clarify your intent in your response.
 
Please notify this office in writing within fifteen business days from the date you receive this letter of the specific steps your firm has taken to correct the noted violations, as well as an explanation of how your firm plans to prevent these violations, or similar violations, from occurring again.  Include documentation of the corrections and/or corrective actions (which must address systemic problems) that your firm has taken.  If your firm’s planned corrections and/or corrective actions will occur over time, please include a timetable for implementation of those activities.  If corrections and/or corrective actions cannot be completed within fifteen business days, state the reason for the delay and the time within which these activities will be completed. Your firm’s response should be comprehensive and address all violations included in this Warning Letter.
 
If you have questions regarding any issues in this letter, please contact Compliance Officer Lauren Priest at 303-236-9663 or at Lauren.Priest@fda.hhs.gov. Please send your reply electronically to Shari Shambaugh, Program Division Director, at oradevices3firmresponse@fda.hhs.gov.
 
Finally, you should know that this letter is not intended to be an all-inclusive list of the violations at your firm’s facility.  It is your firm’s responsibility to ensure compliance with applicable laws and regulations administered by FDA.  The specific violations noted in this letter and in the Inspectional Observations, FDA 483, issued at the close of the inspection may be symptomatic of serious problems in your firm’s manufacturing and quality management systems.  Your firm should investigate and determine the causes of the violations, and take prompt actions to correct the violations and bring the products into compliance. 
 
 
Sincerely,
/S/ 
Shari J. Shambaugh
Program Division Director
Office of Medical Device & Radiological Health Operations
Division 3/West

Page Last Updated: 07/30/2018
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