- Natura Bisse International S.A.
- Issuing Office:
- Center for Drug Evaluation and Research
| || |
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
| ||10903 New Hampshire Ave.|
Silver Spring, MD 20993
Via UPS Warning Letter 320-17-11
Return Receipt Requested
December 15, 2016
Ms. Veronica Fisas Verges, CEO
Natura Bisse International S.A.
Parque Tecnologico del Valles
Cerdanyola del Valles
Dear Ms. Fisas Verges:
The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Natura Bisse International S.A. at Parque Tecnologico del Valles, C/Artesans 12, Cerdanyola del Valles, Barcelona, from January 25 to 29, 2016.
This warning letter summarizes significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals. See 21 CFR, parts 210 and 211.
Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your drug products are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(B).
We reviewed your February 19, 2016, response in detail and acknowledge your subsequent correspondence.
Our investigator observed specific violations including, but not limited to, the following.
1. Your firm failed to 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 CFR 211.165(a)).
Our investigator observed that you did not test your over-the-counter (OTC) (b)(4) drug products for identity and strength prior to release.
In a previous inspection conducted from February 11 to February 15, 2013, FDA identified a similar deficiency. You proposed specific remediation for the failure to conduct testing for identity and strength in your March 7, 2013, response. Nonetheless, during our January 2016 inspection, FDA observed that you still failed to conduct testing for identity and strength before releasing your drugs. These repeated failures demonstrate that your facility’s oversight and control over the manufacture of drugs is inadequate.
In response to this letter, provide your corrective actionsto ensure that you conduct testing for identity and strength of each active ingredient for all products intended for the U.S. market. Provide your:
- Release testing program, including a written standard operating procedure (SOP) detailing the test methods you will use to test each product and the acceptance criteria for each test.
- Retroactive assessment of batches produced for the U.S. market within expiry. Include a list of all batches, the date each was released, and the date on which you or your contract laboratory conducted retroactive analysis. Provide the type of testing conducted for each batch, and the results of the tests. Indicate the actions you will take if you find that any of the batches you released were out of specification (OOS) for strength, identity, or any other attribute.
- Copies of quality agreement(s) covering the release testing performed by your contract laboratory
2. Your firm failed to ensure that its drug product bore an expiration date that was supported by appropriate stability testing (21 CFR 211.137(a)).
Our investigator observed that you failed to implement a stability testing program for any of your products. You had no test data to support the expiration dates of your drugs. Your failure to implement a stability program and generate data in support of your expiration dates limited your ability to detect and react to quality problems with your products.
For example, our investigator documented that you conducted a recall of multiple lots of (b)(4) in 2015. You recalled lots (b)(4), (b)(4), and (b)(4) in response to consumer complaints about product separation. Separation of creams such as your (b)(4) products is an indicator that the products are not stable over their labeled shelf lives.Because you did not adequately study the drug as part of a stability program, you were not made aware of the product separation issue until the product was already in the hands of consumers.
In a previous inspection, conducted from February 11–15, 2013, FDA cited a similar deficiency. You proposed specific remediation for your lack of a stability program in your March 7, 2013, response. Nonetheless, you had not implemented this corrective action at the time of our most recent inspection. These repeated failures demonstrate that your facility’s oversight and control over the manufacture of drugs is inadequate.
According to your response dated February 19, 2016, you will have an outside laboratory perform “assay for (b)(4) and microbiological analysis” on your products. Your response is inadequate because you have not provided enough information regarding the tests you or the outside laboratory will perform to ensure that the stability program will demonstrate that your products conform to their quality attributes over their labeled shelf lives.
In response to this letter, provide:
- Your stability testing program, including stability-indicating methods and acceptance criteria for each test to support the labeled storage conditions and expiry dates for your products. Indicate which methods, if any, you will perform at your own facility, and which will be performed at your contract laboratory.
- Retroactive assessment of the stability of batches produced for the U.S. market within expiry. Include a list of all batches, the date each was released, and the date on which you or your contract laboratory conducted retroactive analysis. Provide the type of testing conducted for each batch, and the results of the tests. Indicate the actions you will take if you find that any of the batches you released were OOS for strength, identity, or any other attribute.
- Copies of quality agreement(s) covering the stability testing performed by your contract laboratory
3. Your firm failed to follow required laboratory control mechanisms, including any changes made to them, which were drafted by the appropriate organizational unit and reviewed and approved by the quality control unit (21 CFR 211.160(a)).
Your laboratory lacks appropriate controls over laboratory log sheets recording microbiology, physico-chemical and organoleptic test results.
In your February 19, 2016, response, you stated that you amended your SOP PR-33 Documentation Management to require that log sheets and logbooks are to be controlled, reviewed, and approved by appropriate quality unit personnel.
Your response is inadequate because it did not include a copy of the SOP or sufficient details regarding your proposed changes.
In response to this letter, include your revised SOP PR-33. Also provide your investigation into how the uncontrolled documents may have affected the quality of your products, and your proposed corrective actions.
Violations cited in this letter are not intended as an all-inclusive list. You are responsible for investigating these violations, for determining the causes, for preventing their recurrence, and for preventing other violations.
FDA placed your firm on Import Alert 66-40 on October 28, 2016.
Until you correct all violations completely and we confirm your compliance with CGMP, FDA may withhold approval of any new applications or supplements listing your firm as a drug manufacturer.
Failure to correct these violations may also result in FDA continuing to refuse admission of articles manufactured at Natura Bisse International S.A. at Parque Tecnologico del Valles, Artesans, 12 Cerdanyola, into the United States under section 801(a)(3) of the FD&C Act, 21 U.S.C. 381(a)(3). Under the same authority, articles may be subject to refusal of admission, in that the methods and controls used in their manufacture do not appear to conform to CGMP within the meaning of section 501(a)(2)(B) of the FD&C Act, 21 U.S.C. 351(a)(2)(B).
After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done since our inspection to correct your violations and to prevent their recurrence. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.
Carlos M. Gonzalez, PhD
Consumer Safety Officer
U.S. Food and Drug Administration
White Oak Building 51, Room 4359
10903 New Hampshire Avenue
Silver Spring, MD 20993
Please identify your response with FEI 3008301076.
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research