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U.S. Department of Health and Human Services

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Enforcement Actions

Health One Pharmaceuticals Inc. 3/28/12

  

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

Public Health Service
Food and Drug Administration
 
Los Angeles District
Pacific Region
19701 Fairchild
Irvine, CA 92612-2506
Telephone:    949-608-2900
FAX:    949-608-4415 

 

WARNING LETTER
 
 
 
VIA UNITED PARCEL SERVICE
SIGNATURE REQUIRED
 
 
March 28, 2012   
W/L 22 -12                                                                                                                                                                                                                                                                                                                                      
 
Richard S. Yeh   
President/Owner
Health One Pharmaceuticals, Inc.
9480 Telstar Ave. Ste 5
El Monte, CA 91731
 
Dear Mr. Yeh:
 
The United States Food and Drug Administration (FDA) conducted an inspection of your dietary supplement manufacturing facility, Health One Pharmaceuticals, Inc., located at 9480 Telstar Ave. El Monte, California from September 14, 2011 to October 5, 2011. The inspection revealed serious violations of FDA’s Current Good Manufacturing Practice (CGMP) in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements regulation, under Title 21, Code of Federal Regulations (CFR), Part 111 (21 CFR Part 111).  At the conclusion of the inspection, you were issued a Form FDA 483, List of Inspectional observations, which listed a number of the violations that cause the dietary supplement products you manufacture, (b)(4), (b)(4), (b)(4), and (b)(4), to be adulterated within the meaning of section 402(g)(1) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. § 342(g)(1)] in that these products have been prepared, packed, or held under conditions that do not meet CGMP requirements for dietary supplements. 
 
We have received your written response on October 26, 2011, concerning our investigator’s observations noted on the Form FDA 483, List of Observations that was issued to you on October 5, 2011. Our comments regarding the adequacy of the actions you took to correct the objectionable conditions and practices observed during the inspection are detailed after the applicable violation, noted below.
 
The significant violations documented during the inspection include, but are not limited to, the following:
 
1.      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 manufactures the product (b)(4) Dietary Supplement which contains dietary ingredients, (b)(4). However, our investigator found that you did not conduct at least one test or examination to verify the identity of any of these dietary ingredients for lot # (b)(4), as required by 21 CFR 111.75(a)(1)(i). 
 
2.      Instead, your firm relied on certificates of analysis (COAs) from your suppliers for individual dietary ingredients. Further, your firm also indicated that you conduct visual inspection of the dietary ingredients based on the description listed on the COAs. A COA from a supplier may not be used to verify the identity of any component that is a dietary ingredient (see 21 CFR 111.75(a)(2) for requirements for components that are not dietary ingredients).
 
In your response, received by our district office on October 26, 2011, you indicated a proposed correction of conducting validity testing on every material received based on the appearance, odor, color, texture, and particle size. You indicated that you will also invest in a Near-Infrared Spectroscopy (NIR) equipment. We find this response inadequate because these types of tests, referred to as organoleptic testing, are inadequate in distinguishing between similar powders, such as white willow bark botanical and vitamin-C, which are both white powders. Further, particle size, if caused by milling, would be an insufficient marker because the manipulation of the size of the particle can vary from batch to batch of the dietary ingredient. You did not provide proof that you purchased the NIR equipment, and you did not provide detailed information on how you intend to prepare for and use the NIR equipment. 
 
3.      Your firm failed to verify, for the finished batches of dietary supplement products, that either every finished dietary supplement batch or subset of the finished dietary supplement batches that you identify through a sound statistical sampling plan meet the finished product specifications for identity, purity, strength, and composition, as required by 21 CFR 111.75(c).   Specifically, our inspection disclosed that batch records, including your “Product Release Notice” for the released finished dietary supplement products, listed below, lacked documentation to verify that such products meet the product specifications for the identity, purity, strength and composition.
 
a.    (b)(4), lot #s (b)(4)
b.    (b)(4), lot # (b)(4)
c.    (b)(4), lot# (b)(4)
 
4.      Your firm failed to establish in-process specifications for any point, step, or stage in the Master Manufacturing Record (MMR) where control is necessary to help ensure that specifications are met for the strength and composition of the dietary supplements, as required by 21 CFR 111.70(c)(1). Specifically, your firm performs in-process quality control checks every (b)(4) minutes for the weight of capsules; however, you did not establish an in-process specification on your “Capsule Formulation” sheet. Thus, there is no established specification for this examination to be compared with in order to determine if the specification is met. For example, your firm recorded the weight of (b)(4) capsules (lot # (b)(4)) on the Encapsulation Sheet; however, there is no established in-process specification for the weight of these capsules.. A specification for capsule weight can affect both the strength and composition of the finished product. 
 
5.      Your firm’s quality control operations for the master manufacturing record and the batch production records failed to include reviewing and approving all master manufacturing records and all modifications to the master manufacturing records as well as reviewing and approving all batch production-related records, as required by 21 CFR 111.123(a)(1) and (2). Specifically, your examination of weighting capsules every (b)(4) to check capsule weight on the (b)(4) (lot # (b)(4)) encapsulation sheet was not reviewed and approved by quality control operations. Further, your firm failed to make and keep written documentation, at the time of performance, that quality control personnel performed the review, approval, or rejection requirements by recording the following: (i) date that the review, approval, or rejection was performed; and (ii) signature of the person performing the review, approval, or rejection, as required by 21 CFR 111.140(b)(2).
 
In your response, received by our district office on October 26, 2011, you indicated that you will set up guidelines for quality control operations, including written procedures dealing with batch records and specifications, among other things. However, your response is inadequate in that we did not receive any written procedures by the dates you indicated in your response. Further, your response does not address quality control’s responsibilities for master manufacturing records.
 
6.      Your firm’s master manufacturing records (MMR) for the dietary supplement products (b)(4), (b)(4), and (b)(4) failed to identify specifications for the points, steps, or stages in the manufacturing process where control is necessary to ensure the quality of the dietary supplements and that the dietary supplements are packaged and labeled as specified in your MMR, as required by 21 CFR 111.205(b)(1). Your firm’s MMRs for these products failed to establish controls and procedures to ensure that each batch of dietary supplements that you manufacture meets the specifications identified, as required by 21 CFR 111.205(b)(2). Your firm’s MMRs for these dietary supplement products, failed to include the following information required by 21 CFR 111.210:
  • A complete list of components to be used, as required by 21 CFR 111.210(b). For example, the capsule ingredients for these products were not listed;
  • An accurate statement of the weight or measure of each component to be used, as required by 21 CFR 111.210(c);
  • The identity and weight or measure of each dietary ingredient that will be declared on the Supplement Facts label, as required by 21 CFR 111.210(d). For example, the identity and weight of each dietary ingredient was not listed for “(b)(4),” and “Customer powder;”
  • A statement of theoretical yield of a manufactured dietary supplement expected at each point, step, or stage of the manufacturing process where control is needed to ensure the quality of the dietary supplement, and the expected yield when you finished manufacturing the dietary supplement, including the maximum and minimum percentages of theoretical yield beyond which a deviation investigation of a batch is necessary and material review is conducted and disposition decision is made, as required by 21 CFR 111.210(f);
  • Written instructions, including specifications for each point, step, or stage in the manufacturing process where control is necessary to ensure the quality of the dietary supplement and that the dietary supplement is packaged and labeled as specified in the master manufacturing record, as required by 21 CFR 111.210(h)(1);
  • Procedures for sampling in the MMRs, as required by 21 CFR 111.210(h)(2);
  • Written instructions for your manual operations, as follows:
o    one person to add and another person to verify the addition of the components, as required by 21 CFR 111.210(h)(3)(ii)(A);
o    one person adding the component and another person verifying the addition, as required by 21 CFR 111.210(h)(3)(ii)(B);
  • The written instructions in your master manufacturing records did not include corrective action plans to use when a specification is not met, as required by 21 CFR 111.210(h)(5). 
In your response, received by our district office on October 26, 2011, you indicated that you will create master manufacturing records to include each ingredient, each manufacturing steps, specifications and its ranges, theoretical yields. However, your response did not address, among other things, procedures for sampling and corrective action plans. You indicated you will send a reference MMR for our evaluation by November 28, 2011. This response is inadequate in that it does not fully address the deviations in your MMRs. Further, we have not received any MMRs to date. 
 
7.      Your firm’s batch production records (BPR) did not include complete information relating to the production and control of each batch and the requirements to be included in a batch record, as required by 21 CFR 111.255(b) and 111.260. Specifically, your firm’s BPR for the (b)(4) dietary supplement did not include the following required information:
    1. The identity of the equipment and processing lines used in producing the batch, as required by 21 CFR 111.260(b). Specifically, the identity of the blender was not listed on the batch record.
    2. The date and time of the maintenance, cleaning, and sanitizing of equipment and processing lines used in producing the batch or a cross reference to records, such as individual equipment logs, where this information is retained, as required by 21 CFR 111.260(c).  
    3. The unique identifier that you assigned to each component, as required by 21 CFR 111.260(d). For example, your batch record lacks unique identifiers for the following components: (b)(4)
    4. A statement of the actual yield and percentage of theoretical yield at appropriate   phases of processing, as required by 21 CFR 111.260(f). Specifically, the actual and theoretical yields after the blending and encapsulation operations were not listed on the batch records. 
    5. Documentation that the finished dietary supplement meets specifications established in accordance with § 111.70(e) and (g), as required by 21 CFR 111.260(i).
    6. Documentation of the manufacture of the batch at the time of performance, as required by 21 CFR 111.260(j).  Specifically, the following information was not documented in your BPR at the time of performance:
i.    The date on which each step of the master manufacturing record was performed [21 CFR 111.260(j)(1)];
ii.    The initials of the person responsible for weighing or measuring of each component used in a batch [21 CFR 111.260(j)(2)(i)];
iii.    The initials of the person responsible for verifying the weight or measure of each component used in the batch [21 CFR 111.260(j)(2)(ii)];
iv.    The initials of the person responsible for adding the component to the batch [21 CFR 111.260(j)(2)(iii)]; and
v.    The initials of the person responsible for verifying the addition of components into a batch [21 CFR 111.260(j)(2)(iv)].
    1. Documentation at the time of performance of packaging and labeling operations, as required by 21 CFR 111.260(k).
i.  The unique identifier that you assigned to packaging and labels used, the quantity of the packaging and labels used, and reconciliation of any discrepancies between issuance and use of labels [21 CFR 111.260(k)(1)].
    1. Documentation at the time of performance that quality control personnel review of any monitoring operations, as required by 21 CFR 111.260(l)(1)(i).
In your response, received by our district office on October 26, 2011, you indicated that you will create batch records. Your response appears to address some of the deficiencies. However, you did not address the specific items above. You indicated you will send a reference batch record for our evaluation by November 28, 2011. To date, we have not received any batch record to review.
 
8.    Your firm failed to maintain, clean, and sanitize, as necessary, all equipment, utensils, and any contact surfaces used to manufacture, package, label, or hold components or dietary supplements, as required by 21 CFR 111.27(d). Specifically, our investigator observed a powder reside on the product contact surfaces of your polisher machine, sifter, and a tableting machine in room (b)(4), all of these instruments are used to manufacture dietary supplements at your facility.
 
Further, your firm failed to make and keep documentation of the date of use, maintenance, cleaning and sanitizing of each individual equipment, unless such documentation is kept with the batch record, as required by 21 CFR 111.35 (b)(2). Specifically, your firm’s cleaning logs do not identify the individual equipment maintained, cleaned, and sanitized. For example, the log lists “machine cleaned with 70% IPA.”
 
In your response, received by our district office on October 26, 2011, you indicated that you will retrain employees on cleaning equipment and that a new sifter was ordered. Your response appears to address some of these deficiencies. However, you did not specifically address the tableting machine. We will evaluate your proposed corrections during our next inspection. 
 
9.    Your firm failed to have separate or defined areas of adequate size or other control systems to prevent contamination and mixups of components or dietary supplements while holding components or dietary supplements, as required by 21 CFR 111.20(c)(7). Specifically, our investigator observed components, including dietary ingredients, piled up and scattered all over your weighting and blending rooms. Some containers of products were observed without identifications and stored directly on the floors.
 
In your response, received by our district office on October 26, 2011, you indicated that you installed racks in the blending room and weighing areas. Your response is inadequate in that it does not address the unidentified containers and how you will correct this practice to prevent mixups.
 
10.    Your firm failed to collect representative samples of each unique lot of packaging and labels that you use to determine whether the packaging and labels meet established specifications in accordance with 21 CFR 111.70(d), as required by 21 CFR 111.80(a). 
 
Your firm failed to collect representative samples of each unique shipment, and of each unique lot within each unique shipment, of the product you receive for packaging or labeling as a dietary supplement to determine whether the received product meets established specification in accordance with 21 CFR 111.70(f), as required by 21 CFR 111.80(d). Specifically, your firm received the product (b)(4), but you did not collect a representative sample to determine if the product meets specifications under 21 CFR 111.70(f).
 
In your response, received by our district office on October 26, 2011, you indicated that you will begin to collect representative samples. However, your response is inadequate in that you did not address whether you will collect proprietary blends as representative samples for testing. 
 
This letter is not an all-inclusive list of violations at your facility. It is your responsibility to ensure that your establishment and your products comply with the Act and its implementing regulations. 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.
 
In addition, we have the following comments:
 
Your firm did not establish component specifications, for each component that you use in the manufacture of a dietary supplement, that are necessary to ensure that specifications of the purity, strength and composition of dietary supplements manufactured using the components are met, under 21 CFR 111.70(b)(2). Further, your firm did not establish limits on those types of contamination which may adulterate, or may lead to adulteration of the finished batch of the dietary supplements to ensure quality of the dietary supplements, under 21 CFR 111.70(b)(3).
 
Your firm also did not make and keep records of the specifications your firm established, under 21 CFR 111.95(b)(1).
 
Please respond in writing within fifteen (15) working days from your receipt of this letter. Your response should outline the specific actions you are taking to correct these violations and to prevent similar violations from occurring in the future.   If you cannot complete all corrections before you respond, you should explain the reason for your delay and state when you will correct any remaining violations.
 
Your response should be sent to:
 
Blake Bevill
Director, Compliance Branch
Food and Drug Administration
Los Angeles District Office
19701 Fairchild
Irvine, CA   92612
 
If you have any questions about the content of this letter, please contact Mei-Chen (Jessica) Mu, Compliance Officer, at 949-608-4477.
 
 
Sincerely,
/S/
Alonza E. Cruse, Director
Los Angeles District
 
 
Cc:       Ingeborg Small
            Branch Chief
            Food and Drug Branch
            California Department of Public Health
            1500 Capitol Avenue - MS 7602
            P.O. Box 997413
            Sacramento, California 95899-7435