Inspections, Compliance, Enforcement, and Criminal Investigations
GM Manufacturing, Inc. 7/23/12
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
|Los Angeles District|
Irvine, CA 92612-2506
VIA UNITED PARCEL SERVICE
July 23, 2012
Mr. Mao L. Yang, CEO
GM Manufacturing, Inc.
1500 W 135th St.
Gardena, CA 90249-2230
Dear Mr. Yang:
On January 23 through February 13, 2012, the U.S. Food and Drug Administration (FDA) inspected your dietary supplement manufacturing facility located at 1500 W 135th St., Gardena, CA. Our investigation revealed significant violations of the Current Good Manufacturing Practice (CGMP) regulation for dietary supplements, Title 21, Code of Federal Regulations, Part 111 (21 CFR Part 111). These violations cause your dietary supplement products to be adulterated under Section 402(g)(1) of the Federal Food, Drug and Cosmetic Act (the Act), 21 U.S.C. § 343(g)(1), because they have been prepared, packed or held under conditions that do not meet the CGMP regulations for dietary supplements. These observations were presented to you in a FDA-483 at the conclusion of our inspection on February 13, 2012.
You may find the Act and the FDA's regulations through links in the FDA's home page at http:www.fda.gov.
The inspection revealed the following violations:
1. Your firm failed to verify, for the finished batches of your dietary supplements identified below, that either every finished dietary supplement batch or a subset of the finished dietary supplement batches that you identify through a sound statistical plan meet product specifications for identity, purity, strength, and composition, as required in 21 CFR 111.75(c). Specifically, you did not provide adequate documentation of your basis for determining that your finished (b)(4) (batch production record dated 12/14/11), (b)(4) (batch production record dated 12/13/11), (b)(4) (batch production record dated 11/30/11), and (b)(4) (batch production record dated 12/8/11) meet the specifications for identity, purity, strength and composition.
We received your response to the FDA-483 on March 1, 2012. Your response indicated that the firms that contract with you to manufacture these products perform the finished product testing and that you were willing to provide their lab reports. Your response is inadequate in that you did not provide documentation showing the verification of the finished product specifications.
2. Your firm failed to conduct at least one appropriate test or examination to verify the identity of a component that is a dietary ingredient, prior to its use, as required by 21 CFR 111.75(a)(1)(i).
Specifically, your firm receives dietary ingredient, bulk proprietary blends containing multiple dietary ingredients from the company that contacts with you to manufacture dietary supplements, but our investigator found you did not conduct at least one test or examination to verify the identity of the dietary ingredients for the following products:
• (b)(4) batch production record dated 1/6/12
• (b)(4) batch production record dated 1/27/12
• (b)(4) batch production record dated 11/30/11
• (b)(4) batch production record dated 1/27/12
• (b)(4) batch production record dated 12/13/11
• (b)(4) batch production record dated 12/14/11
We received your response to the FDA-483 on March 1, 2012. Your response indicates that the company for whom you manufacture products conducts tests on the finished products. However, this response does not address testing dietary ingredients prior to their use to manufacture dietary supplements.
3. Your firm failed to qualify the suppliers of components other than dietary ingredients by establishing the reliability of the suppliers' certificates of analysis through confirmation of the results of the suppliers' tests or examinations, before using those components, as required by 21 CFR 111.75(a)(2)(ii)(A), and failed to maintain documentation of how the supplier was qualified, as required by 21 CFR 111.75(a)(2)(ii)(C). Under 21 CFR 111.75(a)(2), a certificate of analysis may be relied upon to confirm the identity of a component that is not a dietary ingredient and to determine whether applicable component specifications established in accordance with 21 CFR 111.70(b) are met. In order to rely on a certificate of analysis from a supplier of the component, the following requirements of 21 CFR 111.75(a)(2)(ii) must be met: (A) qualify the supplier by establishing the reliability of the supplier's certificate of analysis through confirmation of the results of the supplier's tests or examinations; (B) the certificate of analysis must include a description of the test or examination method(s) used, limits of the test or examinations, and actual results of the tests or examinations; (C) maintain documentation of how the supplier was qualified; (D) periodically re-confirm the supplier's certificate of analysis; and (E) the documentation setting forth the basis for qualification (and re-qualification) of any supplier must be reviewed and approved by quality control personnel. For example, we reviewed the certificate of analysis for the component (b)(4) provided by your supplier and used in the manufacturing of the product (b)(4) our firm failed to qualify the supplier by establishing the reliability of the certificate of analysis through confirmation of the results of the supplier's tests or examinations.
We received your response to the FDA- 483 on March 1, 2012. You reference that you always collect certificates of analysis (COAs) from your material providers, and hold them accountable for the materials provided to you. Your response is inadequate in that you did not commit to the requirements of qualifying your supplier's COA before it use.
4. Your firm failed to prepare and follow a written master manufacturing record (MMR) for each unique formulation of dietary supplement that you manufacture, and for each batch size, to ensure uniformity in the finished batch from batch to batch, as required by 21 CFR 111.205(a). For example, our investigator found that you did not prepare an MMR for the (b)(4) Dietary Supplement, (b)(4) Dietary Supplement, and Dietary Supplement.
We received your response to the FDA-483 on March 1, 2012. You indicated you are working on updating your forms, but it is unclear to us if that includes preparing MMRs. Your response is inadequate in that you provided no MMR records for review and made no commitment on preparing them.
5. Your batch production records (BPRs) failed to include complete information relating to the production and control of each batch of dietary supplement product you manufacture, as required by 21 CFR 111.255(b) and 111.260.
For example, the BPRs for your dietary supplements, for (b)(4) (batch production record dated 1/6/12) and for (b)(4) (batch production record dated 1/27/12) did not include the following required information:
• The batch, lot or control number for the finished batch of the dietary supplement [21 CFR 111.260(a)(1)].
• The identity of the equipment used in producing the batch [21 CFR 111.260(b)].
• The date and time of the maintenance, cleaning, and sanitizing of the equipment and processing lines used in producing the batch, or a cross reference to records [21 CFR 111.260(c)].
• A unique identifier assigned to each component, packaging and label used [21 CFR 111.260(d)].
• The identity and weight of each component used [21 CFR 111.260(e)].
• A statement of the actual yield [21 CFR 111.260(f)].
• Documentation that the finished dietary supplement meets specification established in accordance with 21 CFR 111.70 (e) and (g) [21 CFR 111.260(i)].
• Documentation of the date of each step of the master manufacturing record was performed [21 CFR 111.260G)(1)] and the initials of person performing each step and the initials of person verifying each step [21 CFR 111.260G)(2)].
• An actual or representative label, or a cross-reference to the physical location of the actual or representative label specified in the master manufacturing record [21 CFR 111.260(k)(2)].
• Documentation at the time of performance that quality control personnel approved and released, or rejected, the batch for distribution [21 CFR 111.260(1)(3)].
• Documentation at the time of performance of any required material review and disposition decision [21 CFR 111.260(m)].
We received your response to the FDA-483 on March 1, 2012. Your response indicates that you have some of the required information, but that is not included your batch production record. Further, you have not provided documentation, or the updated production worksheets referenced in your response that demonstrates your batch production records will include complete information relating to the production and control of each batch.
6. Your firm failed to have separate or defined areas of adequate size or other control systems to prevent mixups or contamination of components, dietary supplements, or contact surfaces, with microorganisms, chemicals, filth, or other extraneous material, as required by 21 CFR 111.20(c). Specifically, you failed to separate the manufacturing of different types of dietary supplements, as required by 21 CFR 111.20(c)(3). Our investigator observed that your employees were encapsulating (b)(4) and (b)(4) in the same room at the same time in close proximity to each other. Employees were observed sweeping powder around the machine with a brush, further contributing to the aerosolizing of powder particulates into the manufacturing area.
We received your response to the FDA-483 on March 1, 2012. You state that there is adequate space between the manufacturing equipment, and that the products made on them would not get on one another. You claim that the ventilation system pulls all the particles in the air toward the vents and filters. Your response is inadequate because you provided no assurance that you are addressing the conditions observed during the inspection.
7. Your firm failed to maintain your physical plant in a clean and sanitary condition [21 CFR 111.15(b)(1)] and failed to maintain, clean, and sanitize, as necessary, all equipment, utensils, and any other contact surfaces used to manufacture, package, label, or hold components or dietary supplements [21 CFR 111.27(d)]
For example, our investigator observed powder residue throughout the facility covering manufacturing equipment, boxes of components, ceiling vents, floors, and walls. Specifically:
• The large (b)(4) mixer was covered in powder residue. Inside the blender was an unidentified mixed powder from a previous run that was produced at least one month previously. The exterior parts and surrounding area of the blending machine were covered with a layer of powder.
• Your two tableting machines were covered in reused metallic bags that were also covered in powder residue. When the bags were lifted, powder was observed all on the tableting machines.
• Boxes of bulk capsules kept in the manufacturing room were observed to be covered in powder residue.
• The floors and walls in the manufacturing room were also covered in powder residue.
Your response is inadequate. You state that you perform a "big cleaning" of your manufacturing room once a month, but you have not provided a cleaning log or documentation that this cleaning has been performed. You state that you hose everything with a high pressure hose. We are concerned that this practice could produce back splash and contribute to the contamination of equipment in your manufacturing area. The conditions observed during the inspection indicate that your current methods of cleaning the facility are inadequate. You have not demonstrated that you have implemented practices to eliminate these conditions.
8. Your firm failed to establish and follow written procedures for the responsibilities of the quality control operations, including written procedures for conducting a material review and making a disposition decision, and for approving or rejecting any reprocessing, as required by 21 CFR 111.103. Our investigator found that you had no written procedures for your firm's quality control operations.
This letter is not an all-inclusive list of violations at your facility. It is your responsibility to ensure that your establishment and the products you market comply with the Act and all applicable FDA regulations, including the CGMP regulations for dietary supplements. Failure to promptly correct the violations specified above may result in enforcement action without further notice. Enforcement action may include seizure of violative products and/or injunction against the manufacturers and distributors of violative products.
Please advise this office in writing within 15 days from your receipt of this letter of the specific steps you have taken to correct the violations noted above and to ensure that similar violations do not occur. Your response should include any documentation necessary to show that correction has been achieved. If you cannot complete all corrections before you respond, state the reason for the delay and the date by which you will complete the corrections.
Your response should be sent to:
Mr. Blake Bevill
Director, Compliance Branch
Food and Drug Administration
Los Angeles District Office
Irvine, CA 92612
If you have any questions about the content of this letter, please contact Dr. William Vitale, Compliance Officer, at 949-608-2919.
Alonza E. Cruse, Director
Los Angeles District
cc: Ms. lngeborg Small, Chief
California Department of Public Health
Food and Drug Branch
1500 Capitol Avenue, MS 7602
P.O. Box 997435
Sacramento, CA 95899-7435