Laboratorios Jaloma S.A. de C.V. 3/9/12
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Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
Silver Spring MD 20993
VIA UPS MAIL
March 9, 2012
Mr. Juan Federico Wong Rodríguez
Laboratorios Jaloma S.A. de C.V.
Aquiles Serdán No. 438 Zona Oblatos
Jalisco, Guadalajara, México 44380
Dear Mr. Juan Federico Wong Rodríguez:
During our September 26-29, 2011 inspection of your pharmaceutical manufacturing facility, Laboratorios Jaloma S.A. de C.V. located at Aquiles Serdán No. 438 Zona Oblatos, Jalisco, Guadalajara, México, investigator(s) from the U.S. Food and Drug Administration (FDA) identified significant violations of current good manufacturing practice (CGMP) regulations contained in Title 21, Code of Federal Regulations, Parts 210 and 211. These violations cause your drug product(s) 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 or controls used for, their manufacture, processing, packing, or holding do not conform to, or are not operated or administered in conformity with, CGMP.
Specific violations observed during the inspection include, but are not limited, to the following:
1. Your firm does not have, for each batch of drug product, appropriate laboratory determination of satisfactory conformance to final specifications for the drug product, including the identity and strength of each active ingredient, prior to release [21 C.F.R. § 211.165(a)].
You have not demonstrated that (b)(4)% (b)(4) solutions ((b)(4) and (b)(4)) meet release specifications. You failed to perform the following critical tests listed in the current NF:
- Assay by high pressure liquid chromatography (HPLC)
- (b)(4) content by gas chromatography (GC)
- Organic impurities by HPLC:
• Procedure 1 - Limit of (b)(4) and (b)(4)
• Procedure 2 - Limit of (b)(4), (b)(4) and (b)(4)
- Acidity or alkalinity
- Identification B ((b)(4) <191>)
- Identification D (HPLC retention times obtained in Ratio of (b)(4) Components)
- Test for the absence of Pseudomonas aeruginosa
Your firm does not have the equipment (HPLC or GC) or standards necessary to perform all required testing, nor have you utilized a contract laboratory to conduct the tests you are unable to complete on site.
In your response include your commitment to test your drug products and ensure that they comply with the requirements of the current official compendia. You should also include documentation of testing to determine if all drug products manufactured and shipped to the United States after May 1, 2011 meet required specifications. Also include detailed explanations of how your firm will ensure that your (b)(4) solutions will be tested adequately in the future, including how this will be accomplished without the proper equipment or standards to perform the tests.
2. Your firm does not have laboratory control records which include complete data derived from all tests conducted to ensure compliance with established specifications and standards [21 C.F.R. § 211.194(a)].
For example, your laboratory notebooks are incomplete. Missing data included, but was not limited to lot numbers of reagents used, documentation of weights and volumes, and dates and signatures of second–person review for accuracy, completeness, and compliance. In addition, you failed to conduct and document growth promotion for media used for microbial testing of finished OTC products.
Your firm should include in its response a list of the specific SOPs and laboratory records that you plan to revise to ensure all test data is complete. Also, include in your response a retrospective evaluation of all the raw data missing for each product and lot produced, and provide a determination of the impact of the lack of such data may have on the quality of each product and lot currently on the market. Include information regarding the implementation dates and training program you will develop as part of your corrective action plan.
3. Your firm does not have a written testing program designed to assess the stability characteristics of drug products in order to determine appropriate storage conditions and expiration dates [21 C.F.R. § 211.166(a)].
You lack data to support the (b)(4)-year expiration date established for (b)(4)(b)(4) solution, (b)(4) solution, and (b)(4). Your firm did not complete stability studies to support the (b)(4)-year expiration dates.
In your response, you should include a statement regarding what your firm intends to do with product currently on the market for which you have no supporting stability data. You should also include a commitment to ensure that all drugs are tested according to an approved stability program. For any stability studies that may be ongoing at your firm, you should provide details regarding the stability studies, including, but not limited to, which products are included, how the studies are conducted, what testing is performed, where testing is performed, and the analytical method validation.
4. Your firm has not established written production and control procedures to assure that the drug products produced have the identity, strength, quality and purity they purport or are represented to possess [21 C.F.R. § 211.101].
Your firm manufactured multiple (b)(4) batches of (b)(4) solution using different quantities of the active pharmaceutical ingredient ranging from (b)(4) to (b)(4). All of these batches were labeled as having a concentration of (b)(4)% (b)(4).
While different bulk quantities of the active pharmaceutical ingredient (b)(4) were used to formulate these lots of the same batch size, (b)(4) solution lot #s (b)(4), and (b)(4), all were labeled as containing (b)(4)% (b)(4). Your firm should include in its response a description of your corrective actions to ensure batch-to-batch uniformity and a timeline for implementation of these corrective actions. Please also provide a list of all lots of this product, the calculated assay, and tests results that determine whether each lot is within specifications. If you find any lot to be out-of–specification (OOS), please provide an immediate action plan if the lot was released to the market.
Additionally, you did not perform a second person verification of the weighing/measuring and (b)(4) of ingredients used to produce over-the-counter (OTC) products (e.g., (b)(4)% (b)(4) solution). You should include in your response your corrective actions to ensure verification of the weighing/measuring and (b)(4) of ingredients by a second individual. Please provide a timeframe for completion of this corrective action and provide a copy of the revised batch records in your response.
5. Your firm has not established written procedures to monitor the output of and to validate the performance of those manufacturing processes that may be responsible for causing variability in the characteristics of in-process material and the drug product [21 C.F.R. § 211.110(a)].
You failed to validate the manufacturing processes for (b)(4), (b)(4) solution, (b)(4) solution, and (b)(4).
Your response should include documention demonstrating that (b)(4), (b)(4) solution, (b)(4) solution, and (b)(4) have been successfully validated.
In addition to the items listed above, the investigators uncovered other deficiencies that lead us to question the effectiveness of your current quality system to achieve overall compliance with CGMP at your facility. An example is the failure to have a procedure in place to investigate OOS results. We recommend that you seek the advice of a third-party consultant to assist your firm with a complete evaluation of your firm’s compliance with CGMP requirements.
We remind you that you are responsible for ensuring that you firm’s drug manufacturing operations comply with applicable requirements, including the CGMP regulations. FDA expects Laboratorios Jaloma S.A. de C.V. to undertake a comprehensive and global assessment of your manufacturing operations to ensure that your processes, and ultimately, the drug products you manufacture, conform to FDA requirements.
The violations cited in this letter are not intended to be an all-inclusive statement of violations that exist at your facility. You are responsible for investigating and determining the causes of the violations identified above and for preventing their recurrence and the occurrence of other violations. If you wish to continue to ship your products to the United States, it is the responsibility of your firm to ensure compliance with all U.S. standards for CGMP and all applicable U.S. laws and regulations.
Until all corrections have been completed and FDA has confirmed corrections of the violations and your firm’s compliance with CGMP, FDA may withhold approval of any new applications or supplements listing your firm as a drug product manufacturer. In addition, until such time as your manufacturing practices are verified to comply with CGMPs, your firm will remain under FDA Import Alert, and FDA will continue to refuse admission of all articles manufactured at Laboratorios Jaloma S.A. de C.V. located at Aquiles Serdán No. 438 Zona Oblatos, Jalisco, Guadalajara, México into the United States. Because your firm is currently under Import Alert, the articles are subject to refusal of admission pursuant to section 801(a)(3) of the Act [21 U.S.C. § 381(a)(3)], in that the methods and controls used in their manufacture do not appear to conform to Current Good Manufacturing Practice within the meaning of section 501(a)(2)(B) of the Act [21 U.S.C. § 351(a)(2)(B)].
If, as a result of receiving this Warning Letter or in general, you are considering making a decision that will result in a decreased number of finished drug products or active pharmaceutical ingredients produced by your manufacturing facility, FDA requests that you contact CDER’s Drug Shortages Program immediately, as you begin your internal discussions, at email@example.com in order to ensure that your action(s) does not adversely affect the public health.
Within fifteen working days of receipt of this letter, please notify this office in writing of the specific steps that you have taken to correct violations. Include an explanation of each step being taken to prevent the recurrence of violations and copies of supporting documentation. If you cannot complete corrective action within fifteen working days, state the reason for the delay and the date by which you will have completed the correction. Additionally, your response should state if you no longer manufacture or distribute the drug products manufactured at this facility, and provide the date(s) and reason(s) you ceased production. Please identify your response with FEI # 3002600322.
If you have questions or concerns regarding this letter, contact Maan Abduldayem, Compliance Officer, at the below address and telephone number.
U.S. Food and Drug Administration
Center for Drug Evaluation and Research
White Oak, Building 51
10903 New Hampshire Ave
Silver Spring, MD 20993
Tel: (301) 796-3916
Fax: (301) 847-8741
Office of Manufacturing and Product Quality
Office of Compliance
Center for Drug Evaluation and Research