- Delivery Method:
- VIA UPS
Recipient NameMr. Mark Lowenstein
Recipient TitlePresident and Owner
- Ecometics, Inc.
19 Concord Street
Norwalk, CT 06854-3706
- Issuing Office:
- Division of Pharmaceutical Quality Operations I
10 Waterview Blvd, 3rd FL
Parsippany, NJ 07054
CMS # 569167
April 16, 2019
VIA UPS OVERNIGHT
Mr. Mark Lowenstein
President and Owner
19 Concord Street
Norwalk, CT 06854-3706
Dear Mr. Lowenstein:
The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Ecometics, Inc. (FEI: 1250013) at 19 Concord Street, Norwalk, Connecticut, from August 17 to September 7, 2018.
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).
Our inspection also revealed that your firm failed to fulfill its registration and listing obligations under section 510 of the FD&C Act, which is prohibited under section 301(p), 21 U.S.C. 360 and 331(p). As a result, your drugs are misbranded under section 502(o) of the FD&C Act, 21 U.S.C. 352(o). These drug products are also misbranded pursuant to section 502(a), 21 U.S.C. 352(a) and section 502(f)(2), 21 U.S.C. 352(f)(2) of the FD&C Act.
We reviewed your September 28, 2018, response in detail and acknowledge receipt of your subsequent correspondence.
During our inspection, our investigator observed specific violations including, but not limited to, the following.
Current Good Manufacturing Practice Violations
1. Your firm failed to establish and follow adequate written procedures for cleaning and maintenance of equipment (21 CFR 211.67(b)).
You have not demonstrated that your cleaning procedures are adequate to prevent cross-contamination between the over-the-counter (OTC) products and non-drug products manufactured at your facility. During our inspection, our investigators noted that you manufacture several drug products, including (b)(4), and (b)(4) (an oral antiseptic) on the same equipment you use to manufacture non-drug products such as insect repellent, hair removal creams, and dyes.
Inadequate removal of residues from manufacturing equipment during cleaning can lead to contamination of drug products subsequently manufactured on the non-dedicated equipment. It is unacceptable as a matter of CGMP to continue manufacturing drugs using the same equipment that you use to manufacture toxic products such as insect repellent.
In your response, you stated that a master validation cleaning plan covering equipment used to manufacture multiple products is under development. Your response was inadequate. You have not provided adequate information about or supporting documentation for your proposed corrective action to assure appropriate cleaning validation studies for the drugs manufactured by your firm.
In response to this letter, discontinue manufacturing drugs on shared equipment with non-pharmaceuticals in your facility. If you intend to continue to manufacture both pharmaceutical and non-pharmaceutical products at your facility, provide a plan to show how you will separate the areas in which you will maintain dedicated manufacturing equipment for your pharmaceutical manufacturing and industrial product manufacturing operations.
In addition, conduct a risk assessment for all drugs you have previously manufactured on equipment shared with non-pharmaceutical products. For each product, assess the risk of potential contamination due to shared equipment and provide your plans for addressing the product quality and patient safety risks for any product still in distribution, including potential recalls or market withdrawals.
2. Your firm failed to conduct, for each batch of drug product, appropriate laboratory testing, as necessary, required to be free of objectionable microorganisms (21 CFR 211.165(b)).
You released drug products to the U.S. market such as such as (b)(4), and (b)(4) without testing for total aerobic microbial count and objectionable microorganisms.
Testing is essential to ensure that the drug products you manufacture conform to all pre-determined quality attributes that are appropriate for their intended use, including microbiological specifications.
In your response, you stated that production specifications for all OTC products will be updated to include microbial testing. Your response was inadequate because you failed to provide details for establishing your finished product specifications for the (b)(4), and (b)(4) drug products. You also failed to provide evidence that you have performed microbial testing on each batch you manufactured before batch disposition and release decisions.
In response to this letter, provide microbiological batch release specifications (i.e., total counts, identification of bioburden to detect objectionable microorganisms) for each of your drug products. In addition, provide microbiological analysis for retain samples of drugs distributed to the U.S. market within expiry. Specify actions you will take in response to any adverse test results including customer notifications and product recalls.
3. Your firm failed to use equipment in the manufacture, processing, packing, or holding of drug products that is of appropriate design, adequate size, and suitably located to facilitate operations for its intended use and for its cleaning and maintenance (21 CFR 211.63).
You have not established that your (b)(4) water system is adequately designed, controlled, maintained, and monitored to ensure it consistently produces water that meets the USP monograph for (b)(4) Water and appropriate microbial limits. Water from this unvalidated system is used as a component in your OTC drug products and for cleaning your manufacturing equipment.
Pharmaceutical water must be suitable for its intended use, and routinely tested to ensure ongoing conformance with appropriate chemical and microbial attributes.
In your response, you updated the procedure governing the maintenance of the (b)(4) water system. Your response was inadequate because it failed to address the potential risk of using an unvalidated water system in the manufacture of drug products at your facility.
In response to this letter, provide a comprehensive, independent assessment of your water system design and maintenance. In addition, provide a summary of the validation protocol(s) for your water system. Also include a summary of the improvements made to your system design and program for routine control and maintenance.
4. Your firm failed to follow an adequate written testing program designed to assess the stability characteristics of drug products (21 CFR 211.166(a)).
Your stability program is not adequate to demonstrate the quality of your drug product through expiry. For example, your stability test method validation for (b)(4) and (b)(4) drug products are not stability-indicating for active ingredients: dextromethorphan HBr, phenylephrine HCl, and chlorpheniramine maleate. Specifically, your method validation does not demonstrate that your stability test methods are reliable, meaningful, and specific for the content of degradation products and other components of interest in a drug product. Your management acknowledged that this is a repeat and still uncorrected observation from the September 2016 FDA inspection.
In addition, your firm failed to conduct ongoing stability testing for your topical analgesic, (b)(4), at various time intervals, as specified in your stability program. For example, you failed to perform testing at the (b)(4) interval for lots (b)(4) and (b)(4) and at the (b)(4) interval for lot (b)(4)
In your response, you indicated that a proposal to test your (b)(4) drug products for “peak purity” has been approved by your customer. However, your response was inadequate because you failed to provide details of the proposed corrective action. You indicated that the missed time interval samples were submitted for testing. However, your response did not include an investigation explaining how the time intervals were missed, or a summary of test results.
In response to this letter, provide a comprehensive, independent assessment and corrective action preventive action (CAPA) plan to ensure the adequacy of your stability program. Your CAPA plan should include, but not be limited to:
A remediated SOP describing your stability program.
Stability-indicating methods for each of your drug products.
An ongoing program in which representative batches of each product are added each year to the program to determine if shelf-life claims remain valid.
Specific attributes to be tested at each time interval.
Your firm acts as a contract manufacturer for OTC and prescription drug products.
Drugs must be manufactured in conformance with CGMP. FDA is aware that many drug manufacturers use independent contractors such as production facilities, testing laboratories, packagers, and labelers. FDA regards contractors as extensions of the manufacturer.
You have a quality agreement regarding the manufacture of drug products. You are responsible for the quality of drugs you produce as a contract facility, regardless of agreements in place with product owners. You are required to ensure that drugs are made in accordance with section 501(a)(2)(B) of the FD&C Act for safety, identity, strength, quality, and purity. See FDA’s guidance document Contract Manufacturing Arrangements for Drugs: Quality Agreements at https://www.fda.gov/downloads/drugs/guidances/ucm353925.pdf.
Repeat Observations at Facility
In a September 2016 inspection, FDA cited similar CGMP violations. You proposed specific remediation for these violations in your response.
Repeated failures demonstrate that executive management oversight and control over the manufacture of drugs is inadequate.
CGMP Consultant Recommended
Based upon the nature of the violations, we strongly recommend engaging a consultant qualified as set forth in 21 CFR 211.34 to assist your firm in meeting CGMP requirements.
Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance.
Drug Registration Violation
It was observed during the FDA’s inspection of your facility located in Norwalk, Connecticut (August 17–September 7, 2018) that Ecometics, Inc. manufactures a number of OTC and prescription drugs. Section 510(j) of the FD&C Act and 21 Code of Federal Regulations (CFR) Part 207 outlines the requirements for registration and listing of drug products. Your firm has failed to submit drug listing information to the FDA for many of the drugs manufactured at the above facility including (b)(4), (b)(4) and (b)(4).
Please note that even if you are the contract manufacturer organization for any of these drugs, you are required to register your facility and list all drugs manufactured at the facility. In addition, if the private label distributor (PLD) does not elect to list its own drug, the contract manufacturer is also responsible for listing the drug and must use a Labeler Code that uniquely identifies the PLD for which it manufactures or processes the drug under 21 CFR 207.33(c). If a PLD elects to list its drug product—identified by the PLD’s own NDC and label—FDA would not expect the contract manufacturer to list that NDC a second time but would nonetheless require the contract manufacturer to list the product it manufactures for the PLD, identified with the manufacturer’s own NDC. This is regardless of whether the drug is also marketed under the contract manufacturer’s name or solely under the PLD’s name.
Your firm failed to fulfill its listing obligations under section 510(j) of the FD&C Act, which is a prohibited act under section 301(p), [21 U.S.C. 360(j) and 331(p)]. In addition, your firm’s failure to fulfill its drug listing obligations misbrands the product under section 502(o) of the FD&C Act. Introduction or delivery for introduction into interstate commerce of a misbranded product is a prohibited act under section 301(a) [21 U.S.C. 352(o) and 331(a)].
Misbranding and Unapproved Drugs
Based on the information your firm submitted to FDA's Drug Registration and Listing System and the information collected during the August 17, 2018 through September 7, 2018 inspection, FDA found that your firm is distributing the following unapproved prescription drugs:
FDA's guidance Marketed Unapproved Drugs—Compliance Policy Guide (CPG) explains FDA's policies aimed at ensuring that all drugs marketed in the U.S. have been shown to be safe and effective. The CPG outlines FDA's enforcement policies to efficiently and rationally bring all drugs requiring approved applications into the approval process without adversely affecting public health, imposing undue burdens on consumers, or unnecessarily disrupting the market. Please see Marketed Unapproved Drugs—Compliance Policy Guide, at: https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070290.pdf.
We encourage you to contact FDA's unapproved drugs coordinator, Dr. Sally Loewke, at 301-796- 0710, for assistance in communicating with the FDA on the application process for your unapproved drugs.
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.
If you are considering an action that is likely to lead to a disruption in the supply of drugs produced at your facility, FDA requests that you contact CDER’s Drug Shortages Staff immediately, at email@example.com, so that FDA can work with you on the most effective way to bring your operations into compliance with the law. Contacting the Drug Shortages Staff also allows you to meet any obligations you may have to report discontinuances or interruptions in your drug manufacture under 21 U.S.C. 356C(b) and, allows FDA to consider, as soon as possible, what actions, if any, may be needed to avoid shortages and protect the health of patients who depend on your products.
Please correct the violations cited in this letter promptly. Failure to promptly correct these violations may result in legal action without further notice including, without limitation, seizure and injunction. Unresolved violations in this warning letter may also prevent other Federal agencies from awarding contracts.
Until these violations are corrected, we may withhold approval of pending drug applications listing your facility. We may re-inspect to verify that you have completed your corrective actions. We may also refuse your requests for export certificates.
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.
Please send your electronic response to orapharm1 firstname.lastname@example.org. Identify your response with FEI #1250013 and refer to Warning Letter CMS#569167.
If you have any questions, please contact Compliance Officer Juan Jimenez at email@example.com or 518-453-2314 X-1014.
Program Division Director/District Director
U.S. Food and Drug Administration
OPQO Division I/New Jersey District