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发帖数: 177 | 1 【 以下文字转载自 LosAngeles 讨论区 】
发信人: qdssl (honeydot), 信区: LosAngeles
标 题: FDA查处美国海尔斯制药有限公司在中国热卖的一氧化氮等保健产品
发信站: BBS 未名空间站 (Sat May 5 13:27:59 2012, 美东)
Health One Pharmaceuticals, Inc. of El Monte, CA was warned by the FDA that
a September/October inspection of the company's dietary supplement
manufacturing facility revealed serious violations of FDA's Current Good
Manufacturing Practice (CGMP) in Manufacturing, Packaging, Labeling, or
Holding Operations for Dietary Supplements regulation, including failure to
conduct at least one appropriate test or examination to verify the identity
of a component that is a dietary ingredient
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:
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.
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).
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).
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.
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).
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)].
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)].
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 |
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