Inspections, Compliance, Enforcement, and Criminal Investigations

Bio Lab-St. Joseph Corp 3/18/15

  

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

Food and Drug Administration
 Compliance Branch
466 Fermindez Juncos Avenue
San Juan, Pueno Rico 00901-3223
Telephone: (787) 729-8500
Fax: (787) 729-8765 

 

March 18, 2015
 
WARNING LETTER
15-SJN-WL-03
 
CERTIFIED MAIL - RETURN RECEIPT REQUESTED
 
David Velazquez Camarena,
General Manager
BioLab-St. Joseph Corp.
Avenida Teniente Nelson Martinez
N-59 Alturas de Flamboyan
Bayamon, Puerto Rico 00959
 
Re: Refer to CMS No. 415993 when replying to this letter
 
Dear Mr. Velazquez Camarena:
 
During an inspection of your firm located in Bayamon, P.R. on August 06, 2014, through August 27, 2014, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures microbiology culture media for in vitro diagnostic testing.  Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. 321(h), these products are devices because they are intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or are intended to affect the structure or function of the body.
 
This inspection revealed that these devices are adulterated within the meaning of section 501(h) of the Act (21 U.S.C. § 351(h)), in that the methods used in, or the facilities or controls used for, their manufacture, packing, storage, or installation are not in conformity with the Current Good Manufacturing Practice (CGMP) requirements of the Quality System (QS) regulation found at Title 21, Code of Federal Regulations (CFR), Part 820. We received a response from Mr. David Velazquez Camarena, General Manager, dated September 16, 2014, concerning our investigator’s observations noted on the Form FDA 483, List of Inspectional Observations that was issued to you. We address this response below, in relation to each of the noted violations. These violations include, but are not limited to, the following:
 

A.    Failure to establish and maintain procedures for implementing corrective and preventive action, as required by 21 CFR 820.100(a). For example,"Numero de Documento: (b)(4), CAPA (Corrective Actions Preventive Actions)”, section (b)(4) lists complaints, nonconformance investigations, and audits as the only quality data sources to be considered for the generation of CAPAs. The document lacks requirements for the analysis of all applicable quality data sources such as returned products to identify causes of nonconformances and lacks requirements to present significant corrective/preventive action information for management review.

 
Your response dated September 16, 2014, is not adequate. Your firm proposed to revise procedure "Numero de Documento: (b)(4), CAPA (Corrective Actions Preventive Actions)” to require analysis of all quality data and to include requirements to present significant corrective/preventive action information for management review. However, your firm failed to provide a copy of the proposed revised procedure indicating the quality data it proposes to include and to address the lack of requirements to present significant corrective/preventive action information for management review. Your firm did not provide evidence that employees were trained on the revised procedures. Also, consideration of systemic corrective actions to include a retrospective review of all CAPAs to ensure that all applicable quality data sources were considered to detect recurring quality problems and to ensure all CAPAs were implemented and reviewed, as required, was not provided. 
 

B.    Failure to adequately ensure that when the results of a process cannot be fully verified by subsequent inspection and test that the process shall be validated with a high degree of assurance and approved according to established procedure, as required by 21 CFR 820.75(a). For example:

 
a)    The firm failed to demonstrate, with a high degree of assurance and documented evidence that (b)(4) is effective in consistently delivering sterile culture media within specifications. Ms. (b)(6), the firm’s Production Supervisor, and Mr. David Velazquez, Owner and General Manager, indicated that (b)(4) is the most critical step in the manufacture of the culture media. The (b)(4) conducted using the (b)(4), serial number (b)(4), lacked documented evidence supporting the adequacy of the process, as follows:
 
i.    The performance qualification protocol, “(b)(4), S/N (b)(4)”, indicated (b)(4). Instead, the firm performed and documented in this performance qualification protocol (b)(4). There is no documentation in Table (b)(4) of this performance qualification protocol showing (b)(4) Model (b)(4), S/N (b)(4) to achieve adequate and expected results.
 
ii.    The performance qualification protocol for the (b)(4), serial number (b)(4) and the final summary report for the (b)(4), serial number (b)(4) failed to specify and document the type of (b)(4) and corresponding lot numbers for (b)(4). The performance qualification protocol does not indicate the number of sterilization cycles to run in order to demonstrate reproducibility of this sterilization process and Table (b)(4) of this protocol only documents the results (b)(4).
 
b)    The firm failed to provide documented evidence demonstrating that the (b)(4) that do not compromise product sterility upon request by the investigator, as follows:
 
i.    The firm’s performance qualification and installation protocol "Protocolo de Instalacion y Cualificacion de la (b)(4) en Biolab Inc. Bayamon, Puerto Rico” currently used to qualify (b)(4) of the plastic bags lacked the date and signature of the individuals approving the validation. Ms. (b)(6), the firm’s Production Supervisor, indicated that this draft document will be verified by the firm’s new consultant prior to implementation.
 
ii.    Ms. (b)(6), the firm’s Production Supervisor, and Mr. David Velazquez, Owner and General Manager, were unable to provide fully documented validation activities and results demonstrating that the culture medium bag (b)(4) had been fully validated per an approved procedure upon request by the investigator. Additionally, procedure “Numero de Documento: (b)(4)”, lacks specific instructions for the inspection and testing of the bag seals. Ms. (b)(6) indicated to the investigator that the sealing process validation had not been completed.
 
Your response dated September 16, 2014, is not adequate. Your firm acknowledged that the validation of (b)(4) has not been fully completed and expects to have this resolved by January 2015. Your firm also intends to revise procedure “Numero de Documento: (b)(4)” to add specific instructions for the inspection and testing of the bag seals.
 
However, your firm failed to provide evidence that it completed the validation of (b)(4) or to address how it plans to complete the validation of the (b)(4) per an approved protocol. Your firm also failed to provide evidence of the consideration of a systemic corrective action to include review and evaluation of all other manufacturing processes requiring validation that may have similar deficiencies to ensure processes are validated according to approved procedures, as required. Lastly, evidence that employees were trained on revised procedures or plans to conduct training sessions on the revised procedures at your firm were not provided.
 

C.    Failure to establish and maintain procedures to ensure that all purchased or otherwise received product and services conform to specified requirements, as required by 21 CFR 820.50. For example, the firm has not established procedures to ensure that products received from suppliers and services are acceptable for their intended use. The requirements that must be met by suppliers, contractors, and consultants have not been defined and documented. Upon request by the investigator for the firm’s written procedures defining the type and extent of control exercised over the firm’s suppliers, (purchasing controls) to assess the suppliers’ capability in providing acceptable products, it was disclosed that the firm continues to lack establishing such procedures. Mr. David Velazquez, the firm’s Owner and General Manager, confirmed that the firm has not implemented procedures (as previously promised) to ensure that products received from suppliers and services conform to specified requirements.

 
Your response dated September 16, 2014, is not adequate. Your firm acknowledged that it does not have established procedures for purchasing control and that it will be developed by February 2015. Your firm did not provide evidence of training of employees on this new procedure nor evidence that systemic corrective actions were considered to include a retrospective review of all documents to ensure quality system procedures were established as required and evidence that the firm’s suppliers met the specified requirements as defined in the firm’s purchasing controls procedure for products and services purchased by the firm.
 

D.    Failure to establish and maintain procedures for acceptance of incoming product and to document acceptance or rejection, as required by 21 CFR 820.80(b). For example, according to Ms. (b)(6), the firm’s Production Supervisor, SOP "Numero de Documento: (b)(4), "Recibo de Mercancia" requires departmental technicians (b)(4) to ensure they meet the firm's quality standards. Section (b)(4) of this procedure requires that these inspections include: verifying quantity and type of product received against purchasing and shipping documents; temperature, lot numbers, expiration dates, outer and inner packaging conditions, and evaluating the product against established specifications including outer packaging must be closed and without any stains and inner packaging must be closed and without any puncture or tears. However, the firm failed to document the result of these incoming inspections to ensure that the raw materials used for manufacturing and packaging purposes, were adequate. Upon request to see the documentation of the results of the incoming visual inspections by the investigator, Ms. (b)(6), the firm’s Production Supervisor, stated that results of incoming inspections were not documented. Review by the investigator of the receiving logs, “Registro de Recibo de Medios de Cultivos Deshidratados y Suplementos” (Receiving log for Culture Media and Supplements) and “Registro de Recibo de Mercancia” (Merchandise Receiving Log) covering general merchandise, culture media, and supplements received at the firm from 4/18/2014 to 8/18/2014 disclosed to the investigator that Biolab continues to fail to document the results of incoming inspections as required by the firm’s procedure.

 
Your response dated September 16, 2014, is not adequate. Your firm stated that it will start documenting the results of the incoming visual inspections as required by the procedure, "Numero de Documento: (b)(4), "Recibo de Mercancia". However, your firm failed to provide a revised copy of this procedure to require specific documentation of the results of incoming activities. Your firm also failed to provide evidence that employees were trained on how to effectively perform visual inspections and to adequately document these activities per revised procedures and evidence that receiving acceptance activities were completed on the general merchandise, culture media, and supplements received at the firm from 04/18/2014 to 08/18/2014. In addition, evidence of consideration of a systemic corrective action to include a retrospective review of acceptance activities to ensure they were completed and documented as required was not provided.
 

E.    Failure to maintain a record of the investigation, when an investigation is made under this section, by the formally designated unit identified in paragraph (a) of this section, as required by 21 CFR 820.198(e). For example, the firm’s complaint handling procedure “Numero de Documento: (b)(4), Reclamacion o Quejas de Clientes”, states that any customer complaint will be investigated. The procedure also indicates that if the complaint is received more than ten days from the product manufacturing date, the contamination is attributed to incorrect handling of the product by the consumer. However, details about the handling and storage conditions employed by the customer are not considered as part of the investigation to challenge the ten days requirement established. Without this information, the firm is unable to adequately determine the possible cause and thus identify an effective corrective action. Ms. (b)(6), the firm’s Production Supervisor, indicated that the new version of procedure (b)(4) still needs to be revised to include requirements to document record of a complete investigation and the procedure has not been approved by the firm.

 
Your response dated September 16, 2014, is not adequate. Your firm stated that it will start conducting investigations of complaints involving the possible failure of a device to meet specification even if the complaint is received passed the ten days requirement established. Your firm also indicated that the complaints procedures will be revised by November 2014. However, your firm failed to indicate what revisions it plans to incorporate into the revised procedure and failed to provide evidence of consideration of a systemic corrective action to include a retrospective review of all complaints to ensure complaint investigations include details about the handling and storage conditions to ensure that corrective actions are adequate and records of the investigations were maintained. Lastly, your firm did not provide evidence of employee training on the revised procedures as a plan to remedy this deficiency.
 
F.    Failure to establish and maintain procedures to adequately control environmental conditions where these environmental conditions could reasonably be expected to have an adverse effect on product quality, as required by 21 CFR 827.70(c). For example, there is no assurance that the controls in place to prevent the presence of viable particles inside the firm's processing areas are adequate to prevent any potential contamination of the culture media. Specifically:
 
a)    (b)(4) are used to maintain constant disinfection of the areas and the airstream. The firm’s procedures “Numero de Documento: (b)(4), Procedimiento Operacional Para Probar La Efectividad (b)(4) and “Numero de Documento: (b)(4), Muestro De La Luz Ultravioletas” require (b)(4) E. coli or S. aureus before exposure to the (b)(4) Review of the (b)(4)  monitoring records disclosed inadequate documentation of inspection activities of the (b)(4), as the records failed to include details about the exposure time and (b)(4) used for testing purposes to ensure adequacy. Ms. (b)(6), the firm’s Production Supervisor, stated that the firm always uses (b)(4), but does not document this information.
 
b)    The cleaning and sanitizing operations of the production and packaging areas established under "Numero de Documento: (b)(4), Limpieza Areas de Produccion" are inadequate as follows:
 
Review of the cleaning and sanitization procedure (b)(4) disclosed that the firm failed to follow this procedure as it has started using additional detergents and sanitizing agents (such as (b)(4) that were not approved for use as indicated in procedure (b)(4).
 
Your response dated September 16, 2014, is not adequate. Your firm proposed to reevaluate the process of the ultraviolet lamps and detergents used. However, your firm did not indicate how it plans to address the issue of inadequate documentation of inspection activities of (b)(4). Your firm also failed to provide evidence that employees have been retrained in proper documentation procedures and to provide (b)(4) monitoring records to show that proper documentation is being performed. Your firm failed to provide a copy of the newly established SOP for cleaning and sanitation of the gowning area and evidence that employees have been trained on these established procedures. Your firm also failed to provide evidence of consideration of a systemic corrective action to include a retrospective review of other environmental controls to ensure they are implemented as required by regulation and the firm’s procedures.
 

G.    Failure to establish procedures for quality audits and conduct such audits to assure that the quality system is in compliance with the established quality system requirements and to determine the effectiveness of the quality system, as required by 21 CFR 820.22. For example:

 
The procedure to conduct internal audits "Numero de Documento: (b)(4), Auditorias Internas", lacks instructions for reaudits of deficient matters, if necessary as required by regulation.
 
Your response dated September 16, 2014, is not adequate. Your firm proposed to revise "Numero de Documento: (b)(4), Auditorias Internas (b)(4) and to include requirements for reaudits. Your firm plans to complete this revision by January 2015; therefore, the firm could not provide a copy of the revised procedure as evidence of implementation. Also, evidence that training of employees on the revised procedures will be completed was not provided. Your firm did not provide evidence that a systemc corrective action was considered to include a retrospective review of the firm’s quality system to ensure reaudits were conducted when required.
 

H.    Failure to establish procedures for identifying training needs and ensure that all personnel are trained to adequately perform their assigned responsibilities, as required by 21 CFR 820.25(b). For example:

 
a)    The firm lacked documented evidence showing that the firm's employees, including the General Manager and Production Supervisor, have received formal training in Good Manufacturing Practices (GMP) as they apply to their specific tasks and the medical devices manufactured at the firm as required by the firm’s procedure, “Numero de Documento”: (b)(4), “Procedimiento Para Adiestramiento y Manejo de Documentacion del Personal”. The firm’s procedure requires the employees to receive (b)(4) of GMP training (b)(4). Upon request by the investigator, the firm was unable to provide documentation showing that the firm’s production personnel had been trained in the Quality System regulation. Ms. (b)(6), the firm’s Production Supervisor, and Mr. David Velazquez, Owner and General Manager, indicated that the GMP trainings had not been completed.
 
b)    Upon request by the investigator, the firm was unable to provide documentation showing that personnel conducting the inspection of the sealed bags, containing the sterile culture media plates, have been trained to detect all possible defects that may be encountered affecting the packaging seal integrity.
 
Your response dated September 16, 2014, is not adequate. Your firm stated that the supervisor, general manager and general employees have completed training on the Quality System regulation and ANSI. Your firm also plans to provide specific instructions and re-train employees on effective packaging seal evaluation process. However, your firm failed to provide evidence of the training completed on the Quality System regulation and ANSI and to provide information on how and when it plans to develop and implement a procedure to include information of possible defects that may affect the packaging seal integrity. Lastly, evidence that consideration of a systemic corrective action was completed to include a retrospective review of all training records to ensure that employees were trained as required was not provided.
 
Our inspection also revealed that the Muller Hinton Agar, Mueller Hinton Blood, and Thayer-Martin Agar are adulterated under section 501(f)(1)(B) of the Act, 21 U.S.C. 351(f)(1)(B), because you do not have an approved application 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 (IDE) under section 520(g) of the Act, 21 U.S.C. 360j(g). The device is also misbranded under section 502(o) the Act, 21 U.S.C. 352(o), because you did not notify the agency of your intent to introduce the device into commercial distribution, as required by section 510(k) of the Act, 21 U.S.C. 360(k) and was not included in a list required by section 510(j), 21 U.S.C. 360(j). For a device requiring premarket approval, the notification required by section 510(k) of the Act, 21 U.S.C. 360(k), is deemed satisfied when a PMA is pending before the agency. 21 CFR 807.81(b). The kind of information you need to submit in order to obtain approval or clearance for your device is described on the Internet at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/default.htm. The FDA will evaluate the information you submit and decide whether your product may be legally marketed.
 
You should take prompt action to correct the violations addressed in this letter. Failure to promptly correct these violations may result in regulatory action being initiated by the Food and Drug Administration without further notice. These actions include, but are not limited to, seizure, injunction, and/or civil money penalties. Also, federal agencies are advised of the issuance of all Warning Letters about devices so that they may take this information into account when considering the award of contracts. Additionally, premarket approval applications for Class III devices to which the Quality System regulation deviations are reasonably related will not be approved until the violations have been corrected. Requests for Certificates to Foreign Governments will not be granted until the violations related to the subject devices have been corrected.
 
We are requesting that you promptly schedule a face-to-face meeting with the San Juan District Office to discuss the ongoing and continuing deviations noted in this letter. Additionally, we request that you submit to this office on the schedule below, certification by an outside expert consultant that he/she has conducted an audit of your establishment's manufacturing and quality assurance systems relative to the requirements of the device QS regulation (21 CFR, Part 820). You should also submit a copy of the consultant's report, and certification by your establishment's Chief Executive Officer (if other than yourself) that he or she has reviewed the consultant's report and that your establishment has initiated or completed all corrections called for in the report. The initial certifications of audit and corrections and subsequent certifications of updated audits and corrections (if required) should be submitted to this office by the following dates:
  • Initial certifications by consultant and establishment – June 30, 2015.
  • Subsequent certifications – December 31, 2015. After the report on December 31, 2015, submit annual reports by the end of the year for two consecutive years. 
Please notify this office in writing within fifteen (15) working days from the date you receive this letter of the specific steps you have taken to correct the noted violations, including an explanation of how you plan to prevent these violations, or similar violations, from occurring again. Include documentation of the corrective action (which must address systemic problems) you have taken. If your planned corrections will occur over time, please include a timetable for implementation of those corrections. If corrective action cannot be completed within 15 working days, state the reason for the delay and the time within which the corrections will be completed.
 
Your response should be sent to: Maridalia Torres, District Director, Food and Drug Administration, 466 Fernandez Juncos Avenue, San Juan, P.R. 00901–3223.  To schedule a meeting or ifyou have any questions about the content of this letter please contact: Margarita Santiago, Compliance Officer, at (787) 729-8702.
 
Finally, you should know that this letter is not intended to be an all-inclusive list of the violation(s) at your facility. It is your responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violation(s) noted in this letter and in the Inspectional Observations, Form FDA 483 (FDA 483), issued at the closeout of the inspection may be symptomatic of serious problems in your firm’s manufacturing and quality assurance systems. You should investigate and determine the causes of the violation(s), and take prompt actions to correct the violation(s) and to bring your products into compliance. 
 
Sincerely yours,
/S/                                                           
Maridalia Torres
District Director
San Juan District

Page Last Updated: 06/15/2015
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