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August 8, 2003

Dockets Management Branch (HFA 305)

Food and Drug Administration

5630 Fishers Lane, Room 1061

Rockville, MD 20852

> **RE: DOCKET NO. 96N-0417, CURRENT GOOD MANUFACTURING PRACTICE IN
> MANUFACTURING, PACKING OR HOLDING DIETARY INGREDIENTS AND DIETARY
> SUPPLEMENTS; PROPOSED RULE**

To Whom It May Concern:

NBTY, Inc. is hereby submitting our comments concerning the proposed
rule covering cGMP's for dietary supplements.

For clarification purposes, please be advised that when we referenced
quotes from the USP or other publications we have underlined the text
and when we quoted from the proposed rules and preamble itself, we
utilized italics.

We respectfully request the agency's review and consideration of these
comments.

Sincerely,

Hans Lindgren

Senior Vice President of Operations

## 

## 

## 

## COMMENTS ON THE PROPOSED

## CURRENT GOOD MANUFACTURING PRACTICE IN

##  MANUFACTURING, PACKING, OR HOLDING DIETARY

##  INGREDIENTS AND DIETARY SUPPLEMENTS

## 

## DOCKET NO. 96N-0417

## SUBMITTED BY

## NBTY

### I. OPENING REMARKS

NBTY is a major American producer of Nutritional Supplements with sales
over \$1 Billion and we agree that some degree of regulation and
oversight is good for our industry and for the consuming public. We do
feel however that the proposed regulations are in some areas cumbersome
and unnecessarily rigid as regards the manufacture of Dietary
Supplements.

In the Dietary Supplement Health and Education Act of 1994, Congress
gave to FDA the authority to prescribe good manufacturing practices for
dietary supplements. In doing so Congress decreed that such regulations
shall be modeled after current good manufacturing practices for food. In
many areas the current proposed regulations are not modeled after food
and contain regulations that are not covered at all in the food cGMP.
Some in fact are more stringent that drug cGMP.

Further, in FDA's effort to combine both dietary ingredients and dietary
supplements a situation is created whereby excessive regulation is
imposed on the supplement manufacturer in order to cover some aspect of
ingredient manufacturers' operation that FDA deems important. We address
this issue further in the comment section.

Since Dietary Supplements are similar to drug dosage forms, we are not
opposed to using some of the wording found in drug cGMP to clarify a
regulation for the supplement industry as is currently done by USP. The
USP cGMP guidelines for Dietary Supplements have become the model for
much of the Dietary Supplement industry. Many companies, ours included,
have fashioned their operations to be in compliance with these
guidelines and are independently audited against them. Some of our
comments will include suggestions for change that come from the USP
document.

Again, we believe that regulation is good for our industry and that with
good, concise regulations we would elevate or eliminate those
manufacturers that have substandard operations. We believe that this can
be done without what we feel are unnecessary burdens included in the
current proposal.

We have studied the proposal and have attended several industry and FDA
meetings. We offer the following comments on those points that we feel
are over-burdensome on the industry as well as several other points that
FDA asked the industry to comment on. Included in each comment is our
rationale for why the proposal should be changed as well as suggested
alternative wording where applicable.

### II. NBTY COMMENTS.

### Part 111 Title.

The proposed title of this regulation is *CURRENT GOOD MANUFACTURING
PRACTICE IN MANUFACTURING, PACKING, OR HOLDING DIETARY INGREDIENTS AND
DIETARY SUPPLEMENTS.* It is our opinion that this is contrary to the
intent of the DSHEA of 1994. Congress was specific in its intent by
including only the term dietary supplements in the law (USC 342 (g) (2))
and we believe that Congress worded this part to prevent FDA from
imposing regulations that were not modeled after food cGMP.

In the proposed regulation FDA has included dietary ingredients but this
classification does not fit into the definition of Dietary Supplements
in USC. Section 321 (ff) is clear in defining a Dietary Supplement as a
product that contains dietary ingredients and that is intended for
ingestion in accordance with section 350 (c) (1); that is in tablet,
capsule, powder, softgel, gelcap or liquid form and if not in such a
form is not represented as a conventional food and is not represented as
a sole item of a meal or of the diet.

We believe that it is clear that dietary ingredients do not belong in
the same cGMP regulations as Dietary Supplements as they cannot be
defined in such a way as to allow them to be considered in the same
regulation as is done in this proposal. In DSHEA Congress specifically
stated Dietary Supplements and adds 321 (ff) to define a Dietary
Supplement which refers to the definitions of 350 (c) (1).

As stated in our remarks, we also believe that many parts of the current
proposal are intended to deal directly with dietary ingredient
manufacturers and processes especially as regards botanical ingredients.
However, since the proposed regulations combine the two, both ingredient
and supplement manufacturers need to comply even though these are
distinctly different operations.

We strongly suggest that the proposal be rewritten to conform to the
authority given to FDA by Congress; that is to prescribe regulations for
Dietary Supplements.

**Subpart A; 111.3 Definitions**.

NBTY objects to the definition given for the term sanitize, especially
the criteria for reduction of microorganisms at a 5 log level. This
criterion goes far beyond the food cGMP regulations (110.3 (o) which say
that *sanitize means to adequately treat food-contact surfaces by a
process that is effective in destroying \...*

This definition is also more restrictive than the intent found in the
drug section (211.67) where equipment cleaning is referenced as
*equipment and utensils shall be cleaned, maintained and sanitized at
appropriate intervals ...* There is no separate definition of sanitize
in the drug section.

The FDA argument that the Food Code should be used because dietary
supplements are consumed without further processing by the consumer
seems without merit. Pharmaceutical dosage forms are the same as Dietary
Supplements and there is no 5 log reduction covering them. Also, FDA is
looking to apply code that is intended for *retail outlets such as
restaurants and grocery stores and institutions such as nursing homes*.
While this attitude may be right for the preparation of foods for the
consumer, it has no place in the manufacture of Dietary Supplements

Since Dietary Supplements are essentially the same dosage forms as
drugs, we believe that the drug point of view on sanitize could prevail
for Dietary Supplements. That is without definition and with a
regulation on equipment cleaning and maintenance.

Another option would be to adopt a strategy similar to that of USP
(revised in 2^nd^ supplement USP 26) which is very much the same as the
current food cGMP wording where sanitize is defined as [the adequate
treatment of equipment, containers or utensils by a process that is
effective in destroying vegetative cells of microorganisms of public
health significance and in substantially reducing other undesirable
microorganisms but without affecting the product or its safety for the
consumer.]{.underline}

**Subpart C; Physical Plant. 111.15 (d) (3)**

This proposed regulation states that we must have documentation or
otherwise be able to show that any water that contacts components,
dietary ingredients, dietary supplements or any contact surface meets
the requirements of (d) (2) (water must comply with the National Primary
Drinking Water regulations).

There is no such regulation in food cGMP or in drug cGMP. On the food
side 110.37 (a) simply states that the water supply must be sufficient
for the operation intended and shall be derived from an adequate source.
On the drug side 211.48 (a) covers water under the heading of plumbing
and states that the water used must be potable and conveyed in an intact
plumbing system. There is no documentation burden in neither food nor
drugs and therefore there should be none in dietary supplements either.

An alternative approach to this is found in USP (revised in 2^nd^
supplement USP 26) under the general heading of plumbing. [Potable water
at a suitable temperature and under pressure as needed should be
supplied in a plumbing system free of defects that could contribute
contamination to any dietary product. Potable water should meet the
standards prescribed in the Environmental Protection Agency's Primary
Drinking water Regulations (40 CFR Part 14). Water not meeting such
standards should not be permitted in the potable water system for
Purified Water. If potable water is used as a raw material, it should be
further purified to satisfy compendial requirements.]{.underline}

Our recommendation would be to delete the reference to purified water in
the above USP statement and use their criteria in place of the FDA
proposed rule. Again, since there is no documentation burden in either
food or drug regulations, there should not be one for supplements.

**Subpart C; Physical Plant. 111.20 (d) (5)**

This part of the proposed regulations requires that *any physical plant
that you use in the manufacture, packaging, or holding of dietary
ingredients must ...*

*(d) Be designed and constructed in a manner that prevents contamination
of components, dietary ingredients, dietary supplements or contact
surfaces. The design and construction must include, but not be limited
to: ...*

*(5) Equipment that controls temperature and humidity ...*

Again there is no precedent for this requirement in either food or drug
cGMP. From the Dietary Supplement side, there is adequate evidence that
temperature and humidity do not stimulate reproduction of microorganisms
and pests. This is well documented in stability studies where
supplements are purposely subjected to heat and humidity for extended
periods of time. It is also documented by retesting of older ingredients
that were stored in an uncontrolled environment and subjected to heat
and cold as well as ambient humidity. There is no evidence, based on
finished product testing, that uncontrolled space leads to the
reproduction of microorganisms.

While there may be issues with raw unprocessed botanical and/or animal
derived ingredients, there is no issue with the powdered botanical and
animal derived ingredients used by the Dietary Supplement industry.

Temperature and humidity concerns should be addressed as they are in the
food and drug sections. In the drug section FDA calls for equipment for
adequate control while in the food cGMP we are asked to operate under
conditions and controls as are necessary to minimize the potential for
the growth of microorganisms ... As an alternative the wording from USP
(revised in 2^nd^ supplement USP 26) under the general heading of
Ventilation, Air Filtration, Air Heating and Cooling could be used.

[Adequate ventilation shall be provided as well as equipment for
adequate control over microorganisms, dust, humidity and temperature
when used in the manufacture of a dietary product to minimize odors and
vapors (including steam and noxious fumes) in areas where they may
adulterate dietary products; and to locate and operate fans and other
air-blowing equipment in a manner that minimizes the potential for
adulterating raw materials, in-process or finished dietary products, or
contaminating processing equipment, utensils, or packaging
materials.]{.underline}

There is also a considerable cost for the installation, maintenance and
operation of temperature and humidity control equipment. FDA does not
address the costs of this requirement other than to say that it is
costly (pg 12239).

**Subpart E; Production and Process Controls 111.35 (g)**

Under this section the wording clearly requires that testing be done on
every finished batch. This includes testing of all ingredients so long
as there is a scientifically valid analytical method for testing. From
this section, the FDA commentary on the section and FDA's comments at
meetings, it is clear that the intent is that everything be tested;
either as a raw material or as an ingredient in a finished product or
both. FDA comments that reliance on a supplier certification or
guarantee (certificate of analysis) is not appropriate leading us to
believe that the intent is to test all incoming materials as well as all
finished batches. The use of scientifically valid skip lot or reduced
testing programs is not permitted in this proposed rule for either
components or finished batches. The proposal also states that if any of
a dietary supplements' ingredients cannot be tested in the finished
batch then each such component must be tested upon receipt. This has
been confirmed by FDA at meeting to include both active and inactive
ingredients.

The drug cGMP is much less restrictive calling for *appropriate
laboratory determination of satisfactory conformance to the final
specifications for the drug product, including the identity and strength
of each active ingredient prior to release* (211.165 (a))*.* There is no
reference to testing in food cGMP except as regards microorganism
contamination.

On the component side of this issue, the drug cGMP allows that a
suppliers certificate of analysis can be accepted in lieu of testing
with certain provisions including at least one identification test and
the establishment of a suppliers reliability (211.84 (d) (2)).

Here again the proposed regulations are much more restrictive than food
cGMP and drug cGMP. While we believe that testing is a key issue in
Dietary Supplement manufacturing, we see the proposed regulation as
going too far by calling for the testing of every component of every
finished batch and,

because of the use of common ingredients across many products where one
would not know in which products a component could not be tested, the
testing of every component received.

As an alternative we again cite USP (revised in 2^nd^ supplement USP 26)
for both finished product and component testing. This guideline allows
for reliance on a suppliers certificate of analysis under certain
conditions, allows for skip-lot sampling plans in lieu of testing every
batch based on statistical confidence and process verification and it
also allows for skip-lot testing of finished Dietary Supplements.

The text as it relates to this regulation follows in 2 sections:

**[Testing and Release for Distribution]{.underline}**

[There should be appropriate laboratory determination of satisfactory
conformance to specifications for the finished product, including the
identity and strength prior to release. Based upon adequate process
verification, in-process controls, or statistical confidence, a skip lot
or composite sampling plan is an alternative to testing every
batch.]{.underline}

**[Testing and Approval or Rejection]{.underline}**

[Each lot of raw materials, product containers and closures should be
sampled, tested, or examined, as appropriate and released for use by the
quality control unit. Based on adequate process verification, in-process
controls and statistical confidence, a skip lot sampling plan is an
alternative to testing every batch.]{.underline}

**After guidelines for how to sample the testing text continues:**

[Use the following procedure to examine and test the
samples:]{.underline}

[At least one test should be conducted to verify the identity of each
raw material of a product if skip-lot testing is used. Such tests may
include any appropriate test with sufficient specificity to determine
identity including chemical and laboratory tests, gross organoleptic
analysis, microscopic identification, or analysis of constituent
markers.]{.underline}

[Each raw material should be tested fro conformity with all appropriate
written specifications for purity, strength and quality. However, a
report of analysis may be accepted from the supplier of a raw material,
provided that the manufacturer establishes the reliability of the
supplier's analyses and provided that at least one identity test is
conducted on such raw material by the manufacturer.]{.underline}

We believe that this wording is much more in line with the currently
accepted methods of testing raw materials and release of finished
product and components. This wording is also similar to that in drug
cGMP while recognizing that Dietary Supplements are foods and require
less scrutiny than drugs.

**Subpart E; Production and Process Controls 111.35 (k)**

Additional testing requirements are proposed in this section. *The types
of contamination include, but are not limited to:*

*Filth, insects, or other extraneous material*

*Microorganisms; and*

*Toxic substances.*

In this section is another instance where the potential dietary
ingredient problems reach into the Dietary Supplement area. While filth,
insects or other extraneous matter may be detectable in unprocessed
botanicals, there is little possibility that they can be detected in
botanical powders. Additionally, if the supplier of a dietary ingredient
performs the arduous process of screening for toxic substances, why is
the Dietary Supplement manufacturer required to repeat this process.

The issue of toxic substances is not covered at all in drug cGMP and in
food cGMP there is a statement that considers whether a material is
susceptible to contamination and the food cGMP allows for purchasing
materials under a supplier's guarantee (110.80 (a) (3)).

As most Dietary Supplement manufacturers already do test incoming
botanical ingredients, and any other ingredients that may be prone to
microorganism growth, compliance with that part of this section would
not be problematic. However this section also covers toxic substances
and while FDA comments on this matter consider only aflatoxin, they also
state that *if a toxic substance is a type of contamination that may
adulterate or lead to adulteration of the dietary ingredient or dietary
supplement, you must perform an appropriate test to detect the toxic
substance,* this leaves this as a very changeable issue.

Toxic substance is not defined and through industry and FDA meetings on
these regulations we now believe that they would include heavy metals
and pesticides. NBTY has already decided on a program of pesticide
screening and heavy metal testing on all botanical ingredients. We have
been working with our suppliers and have agreed upon cost increases to
cover the additional costs for this testing. However the wording of this
proposed regulation will lead to redundant testing, as we would still
need to test the same dietary ingredients again when we receive them as
reliance on the suppliers guarantee is not considered appropriate by
FDA.

We feel strongly that this section be reworked to include reliance on a
suppliers certification as regards toxic substances. For the purposes of
uniformity, testing for microorganisms could also be waived based on a
supplier's certification. Since finished product testing for
microorganisms is also covered in this same section of this proposal,
this should suffice to cover any microorganism concerns and would be
able to determine if there is any contamination from an ingredient or
from a process.

This could be accomplished by using the USP again (revised in 2^nd^
supplement USP 26). This would read:

[There should be appropriate laboratory determination of satisfactory
conformance to specifications for the finished product, including the
identity and strength prior to release. Based upon adequate process
verification, in-process controls, or statistical confidence, a skip lot
or composite sampling plan is an alternative to testing every
batch.]{.underline}

[There should be appropriate laboratory testing, as necessary of each
batch or dietary supplements required to be free of objectionable
microorganisms....]{.underline} This section goes on with procedures for
testing and requirements for written procedures.

Testing for other toxic substances should be left on the dietary
ingredient level as a raw material and provisions should be made to
allow acceptance of certification from suppliers that the material has
been tested and found acceptable.

**Subpart E; Production and Process Controls 111.35 (h) (4) (iii)**

This section states that *you must not reprocess any component, dietary
ingredient or dietary supplement if it is rejected because of
contamination with microorganisms or other contaminants, such as heavy
metals.*

While we agree on the heavy metals issue, we disagree as regards
microorganism contamination. Such contamination may be that a product is
over the specification for TPC or yeast and mold; a situation that can
be corrected by additional treatment. This should be left to the
disgression of the quality control unit and could be included in (ii) of
the same section.

**Subpart E; Production and Process Controls 111.45 (b) (7)**

This section requires that a copy of the label used be made part of the
master manufacturing record. We object to this part of the proposed
rule. As a manufacturer of many brands including several private labels
for every bulk product, we feel that it would be a daunting task to keep
a master batch record up to date. This is so because of the constant
updating of labels and the inclusion of new labels for new customers.

Also, this seems to be modeled after drug cGMP and there is no reference
to master production records in food cGMP. As an alternative, we suggest
wording similar to USP (revised in 2^nd^ supplement USP 26) where a
positive identification of all labeling used is permitted. Their wording
is:

[A description of the product containers, closures, and packaging
materials, including a specimen or copy of each label and all other
labeling signed and dated by the person or persons responsible for
approval of such labeling or, in lieu of specimens or copies of each
label or other labeling, a positive identification of all labeling
used.]{.underline}

**Subpart E; Production and Process Controls 111.45 (b) (8)**

This section requires that a corrective action plan for use when a
specification is not met be included as part of the written instructions
incorporated in a master batch record.

FDA has no comments on this subject in the preamble and there is no such
requirement in drug cGMP and, as previously mentioned, there is no
reference to master production record in food cGMP.

This part should be deleted from the proposal as there is no viable way
to assemble this information on complex multiple vitamin and mineral
formulas where there could be innumerable combinations of possible
specification deviations.

Additionally, this should be covered by written procedures in such a way
that it should be the responsibility of the quality control unit to
review out of specification problems on a batch level and to approve any
corrective actions to be taken.

**Subpart E; Production and Process Controls 111.50 (c) (4)**

This part asks for the date and time of maintenance, cleaning and
sanitizing of equipment to be part of each batch production record.

FDA has no comments on this part of the proposed rule and there is no
reference to this level of detail for batch records in drug cGMP nor is
there a reference in food regulation.

As discussed earlier, many Dietary Supplement manufacturers currently
operate under USP cGMP guidelines. For those who do, there is a
comprehensive equipment log procedure for each piece of equipment or
equipment room. This part should be rewritten to allow continued
compliance using equipment use and cleaning logs and this part should be
added under Subpart D; 111.25. The wording from USP (revised in 2^nd^
supplement USP 26) would suffice for this:

[A written record of major equipment cleaning and use shall be
maintained in individual equipment logs that show the day, product and
lot number of each batch processed. The persons performing the cleaning
shall record in the log that the work was performed. Entries in the log
should be in chronological order.]{.underline}

**Subpart E; Production and Process Controls 111.60 (b) (1) (iii) (D)**

This part requires that there be laboratory control processes that cover
*Packaging and labels received to determine that the materials meet
specifications;*

This should not be a laboratory issue and this subject is already
covered in111.37 (b) (11) (i) which, in our opinion, is where it
belongs. This is also covered in 111.40 (b).

In both the drug cGMP and USP cGMP this is covered under a packaging and
labeling section and FDA should consider placing it there.

**Subpart E; Production and Process Controls 111.60 (b) (1) (iii) (E)**

This part requires that there be laboratory control processes that cover
*each batch of packaged and labeled dietary ... to ensure that the label
specified in the master manufacturing record has been applied.*

This has already been expressed in 111.37 (b) (12) (iv) and in our
opinion does not belong in the laboratory section but in 111.37 as a
quality control unit function. This is also covered under 111.70 (b) (7)
as a general responsibility under label operations.

In both the drug cGMP and USP cGMP this is covered under a packaging and
labeling section and FDA should consider placing it there.

**Subpart E; Production and Process Controls 111.65 (c) (4)**

This part concerns testing and we believe that it does not belong in a
manufacturing section but should fall under the quality control section
if it is to be a part of these regulations. In reading FDA comments in
the preamble it appears that the requirement is for testing of equipment
and utensils, both chemical and microbiological, between jobs. If this
reading is true, then this part is much more cumbersome than that found
in the drug cGMP where they rely on procedures. This is also much
simpler in food regulations. The wording here is confusing when read
with the FDA comments in the preamble.

This proposed part should be deleted and the subject covered as part of
111.25 if it refers to equipment.

This is already covered in relation to components, dietary ingredients
and dietary supplements.

**Subpart F; Holding and Distribution 111.80**

This part seems straightforward in the proposed regulations but becomes
very cumbersome when read with FDA's comments in the preamble. FDA's
comments state that *this proposed provision includes the holding of
components, dietary ingredients, dietary supplements in your physical
plant and in any point in the distribution process ...*

The addition of the distribution process in this section has no
precedence in either drug cGMP or food regulations. Drug cGMP relies on
written procedures for both holding and distribution and the food cGMP
takes a similar simple approach to this issue by saying that storage and
transportation shall be under conditions that will protect the food.

Again we point to USP (revised in 2^nd^ supplement USP 26) for
alternative wording on the matter of distribution:

[Written procedures describing the distribution of dietary supplements
shall be established and followed and should include the
following"]{.underline}

> [A procedure whereby the oldest approved stock of a product is
> distributed first (Deviation from this requirement is permitted if
> such deviation is temporary and adequate).]{.underline}
>
> [A system by which the distribution of each lot of product can be
> readily determined to facilitate its recall if necessary.]{.underline}

This approach serves to clarify the distribution regulations without the
undue burden of having to control "any point in the distribution
process".

**Subpart F; Holding and Distribution 111.85 --What requirements apply
to returned dietary supplements or dietary ingredients?**

This section is much more restrictive than the drug cGMP regulation and
there is no reference to this subject in the food regulations. We know
of no precedence that would cause FDA to be so restrictive as regards
this subject especially in view of the fact that the drug cGMP is not as
harsh.

As a manufacturer and distributor dealing in distribution to our own
stores, wholesale distribution and mail order distribution, we find that
this part of the proposed cGMP so restrictive that it would result in
costs in the millions of dollars annually. The types of returns that we
deal with range from individual bottles from mail order consumers to
small shipments of many products in our wholesale division. Neither of
these types of returns would lend themselves to the restrictions in
111.85 (b) which requires both examination and testing.

A realistic approach may be found in USP (revised in 2^nd^ supplement
USP 26):

**[Returned Dietary Supplements]{.underline}**

[Returned products should be identified as such and held. If the
conditions under which returned dietary products have been held, stored,
or shipped before or during their return, or if the condition of the
product, its container, carton or labeling, as a result of storage or
shipping, casts doubt on the safety, identity, strength, quality, or
purity of the product, the returned product should be destroyed unless
examination, testing or other investigations prove the product meets
appropriate standards of safety, identity, strength, quality or
purity]{.underline}*.*

This section of USP goes on to cover reprocessing and salvage.

We believe that the USP wording allows for the inspection of returned
materials and that our inspection of the condition of the returned
product can be used to determine that a product can be returned to
inventory. This can be covered by internal procedure and can be based on
experience in testing random lots of product stored under conditions
that include extremes in heat and humidity and which do not affect the
container or closure system.

**III INVITED COMMENTS (1):**

**From 12209 regarding written procedures for laboratory operations:**
*We invite comment on whether we should require, in a final rule,
written procedures for your laboratory operations and should require
that the person who performs the laboratory processes document, at the
time of performance, that the laboratory processes were performed. If
comments assert that written procedures are necessary, comments should
include an explanation of why the requirement is necessary to prevent
adulteration including how such a requirement would ensure the identity,
purity, quality, strength, and composition of the dietary ingredient or
dietary supplement. Conversely, if comments assert that written
procedures are not necessary, comments should include an explanation of
why the requirement is not necessary including how, in the absence of
the requirement, one can prevent adulteration and ensure the identity,
purity, quality, strength, and composition of the dietary ingredient or
dietary supplement. Further, we seek comment on whether any of the
proposed requirements in this section are not necessary to prevent
adulteration and to ensure the identity, purity, quality, strength, and
composition of the dietary ingredient or dietary supplement. If comments
assert that certain provisions are not necessary, comments should
include an explanation of why the requirement is not necessary including
how, in the absence of the requirement, one can prevent adulteration and
ensure the identity, purity, quality, strength, and composition of the
dietary ingredient or dietary supplement. If comments agree that the
proposed requirements are necessary for reasons other than those we have
provided, the comments should so state and provide an explanation*.

We believe that written procedures should govern laboratory operations
thus creating a standard for testing of products or groups of products
and establishing parameters for passing or failing product. Such
procedures could also outline the parameters for skip lot testing or
reduced testing plans which we believe are necessary to the efficient
running of the laboratory operation.

Many in our industry follow USP cGMP which requires written procedures
and specifications be in place to cover production and process controls.
These are intended to prevent adulteration and to ensure the identity,
purity, quality, strength and composition of the dietary ingredient or
dietary supplement.

**III INVITED COMMENTS (2):**

**From 12211 regarding written procedures for manufacturing:** *We
invite comment on whether we should require, in a final rule, that you
establish and follow written procedures to implement the manufacturing
operations required in proposed § 111.65. If comments assert that
written procedures are necessary, comments should include an explanation
of why the requirement is necessary to prevent adulteration including
how such a requirement would ensure the identity, purity, quality,
strength, and composition of the dietary ingredient or dietary
supplement. Conversely, if comments assert that written procedures are
not necessary, comments should include an explanation of why the
requirement is not necessary including how, in the absence of the
requirement, one can prevent adulteration and ensure the identity,
purity, quality, strength, and composition of the dietary ingredient or
dietary supplement. Further, we seek comment on whether any of the
proposed requirements in this section are not necessary to prevent
adulteration and to ensure the identity, purity, quality, strength, and
composition of the dietary ingredient or dietary supplement. If comments
assert that certain provisions are not necessary, comments should
include an explanation of why the requirement is not necessary including
how, in the absence of the requirement, one can prevent adulteration and
ensure the identity, purity, quality, strength, and composition of the
dietary ingredient or dietary supplement. If comments agree that the
proposed requirements are necessary for reasons other than those we have
provided, the comments should so state and provide an explanation.*

We believe that written procedures should govern all manufacturing
operations thus creating a standard for cleaning and operating equipment
and establishing parameters for meeting product specifications. Such
procedures should be designed to ensure that the dietary supplements
have the identity, strength, quality, and purity they are intended to
have.

Many in our industry follow USP cGMP which requires written procedures
and specifications be in place to cover production and process controls.
These are intended to prevent adulteration and to ensure the identity,
purity, quality, strength and composition of the dietary ingredient or
dietary supplement.

**III INVITED COMMENTS (3):**

**From 12213 regarding written procedures for packaging:** *We invite
comment on whether we should require, in a final rule, that you
establish and follow written procedures for packaging and label
operations that implement the requirements of this section. If comments
assert that written procedures are necessary, comments should include an
explanation of why the requirement is necessary to prevent adulteration
including how such a requirement would ensure the identity, purity,
quality, strength, and composition of the dietary ingredient or dietary
supplement. Conversely, if comments assert that written procedures are
not necessary, comments should include an explanation of why the
requirement is not necessary including how, in the absence of the
requirement, one can prevent adulteration and ensure the identity,
purity, quality, strength and composition of the dietary ingredient or
dietary supplement. Further, we seek comment on whether any of the
proposed requirements in this section are not necessary to prevent
adulteration and to ensure the identity, purity, quality, strength, and
composition of the dietary ingredient or dietary supplement. If comments
assert that certain provisions are not necessary, comments should
include an explanation of why the requirement is not necessary including
how, in the absence of the requirement, one can prevent adulteration and
ensure the identity, purity, quality, strength, and composition of the
dietary ingredient or dietary supplement. If comments agree that the
proposed requirements are necessary for reasons other than those we have
provided, the comments should so state and provide an explanation.*

We believe that written procedures should govern all packaging and
labeling operations thus creating a standard for cleaning and operating
equipment and establishing parameters for labeling specifications. Such
procedures should be designed to ensure that the dietary supplements
have the identity, strength, quality, and purity they are intended to
have.

Many in our industry follow USP cGMP which requires written procedures
and specifications be in place to cover production and process controls.
These are intended to prevent adulteration and to ensure the identity,
purity, quality, strength and composition of the dietary ingredient or
dietary supplement.

**III INVITED COMMENTS (4):**

**From 12214 regarding holding components:** *We invite comment on
whether we should require, in a final rule, that you establish and
follow written procedures for holding components, dietary ingredients,
dietary supplements, packaging, and labels. If comments assert that
written procedures are necessary, comments should include an explanation
of why the requirement is necessary to prevent adulteration including
how such a requirement would ensure the identity, purity, quality,
strength, and composition of the dietary ingredient or dietary
supplement. Conversely, if comments assert that written procedures are
not necessary, comments should include an explanation of why the
requirement is not necessary including how, in the absence of the
requirement, one can prevent adulteration and ensure the identity,
purity, quality, strength, and composition of the dietary ingredient or
dietary supplement.*

We believe that written procedures should govern all holding operations
thus creating a standard for quarantine and storage and establishing
parameters for storage conditions. Such procedures should be designed to
ensure that the dietary supplements have the identity, strength,
quality, and purity they are intended to have.

Many in our industry follow USP cGMPs that require written procedures
and specifications be in place to cover production and process controls.
These are intended to prevent adulteration and to ensure the identity,
purity, quality, strength and composition of the dietary ingredient or
dietary supplement.

**III INVITED COMMENTS (5):**

**From page 12214 regarding written procedures for holding in process
materials:** *We invite comment on whether we should require, in a final
rule, that you establish and follow written procedures for holding in
process material. If comments assert that written procedures are
necessary, comments should include an explanation of why the requirement
necessary to prevent adulteration including how such a requirement would
ensure the identity, purity, quality, strength, and composition of the
dietary ingredient or dietary supplement. Conversely, if comments assert
that written procedures are not necessary, comments should include an
explanation of why the requirement is not necessary including how, in
the absence of the requirement, one can prevent adulteration and ensure
the identity, purity, quality, strength, and composition of the dietary
ingredient or dietary supplement.*

We believe that written procedures should govern all holding operations
thus creating a standard for quarantine and storage and establishing
parameters for storage conditions. Such procedures should be designed to
ensure that the dietary supplements have the identity, strength,
quality, and purity they are intended to have.

Many in our industry follow USP cGMPs that require written procedures
and specifications be in place to cover production and process controls.
These are intended to prevent adulteration and to ensure the identity,
purity, quality, strength and composition of the dietary ingredient or
dietary supplement.

**III INVITED COMMENTS (6):**

**From 12215 -- 16 regarding procedures for returned dietary
supplements:** *We invite comment on whether we should require, in a
final rule, that you establish and follow written procedures for
identifying, quarantining, and salvaging returned dietary ingredients
and dietary supplements. If comments assert that written procedures are
necessary, comments should include an explanation of why the requirement
is necessary to prevent adulteration including how such a requirement
would ensure the identity, purity, quality, strength, and composition of
the dietary ingredient or dietary supplement. Conversely, if comments
assert that written procedures are not necessary, comments should
include an explanation of why the requirement is not necessary including
how, in the absence of the requirement, one can prevent adulteration and
ensure the identity, purity, quality, strength, and composition of the
dietary ingredient or dietary supplement.*

We believe that written procedures should govern all return and salvage
operations thus creating a standard for quarantine and salvage and
establishing parameters for proper salvage conditions. Such procedures
should be designed to ensure that the dietary supplements have the
identity, strength, quality, and purity they are intended to have.

Many in our industry follow USP cGMPs that require written procedures
and specifications be in place to cover production and process controls.
These are intended to prevent adulteration and to ensure the identity,
purity, quality, strength and composition of the dietary ingredient or
dietary supplement.

**III INVITED COMMENTS (7):**

**From 12216 regarding recordkeeping:** *We invite comment on whether we
should require, in a final rule, that you make and keep records on the
distribution of dietary ingredients and dietary supplements that you
manufacture, package, or hold.*

We believe that procedures should be required that are sufficient to
give the ability to find dietary supplements that were manufactured,
packaged or held.

**III INVITED COMMENTS (8):**

**From page 12217 regarding written procedures:** *We invite comment on
whether we should require, in a final rule, that you establish and
follow a written procedure for receiving, reviewing, and investigating
consumer complaints. If comments assert that written procedures are
necessary, comments should include an explanation of why the requirement
necessary to prevent adulteration including how such a requirement would
ensure the identity, purity, quality, strength, and composition of the
dietary ingredient or dietary supplement. Conversely, if comments assert
that written procedures are not necessary, comments should include an
explanation of why the requirement is not necessary including how, in
the absence of the requirement, one can prevent adulteration and ensure
the identity, purity, quality, strength, and composition of the dietary
ingredient or dietary supplement.*

We believe that written procedures should govern all consumer complaints
investigations and reviews thus creating a standard for response to each
complaint. Such procedures would have no effect on the efficacy of the
product but would set a process for receipt, review and investigation.

Many in our industry follow USP cGMP which requires written procedures
and specifications be in place to cover production and process controls.

**III INVITED COMMENTS (9):**

**From page 12218 regarding the plain language technique:** *We invite
the public to comment on the plain language techniques used in this
proposed rule. In developing your comments, please consider addressing
the following points:*

*Do you like the proposed rule's appearance?*

*Do plain language techniques make the document easier to read and
understand? and*

*Do you have other suggestions to improve the format?*

We believe that the traditional approach found in existing food and drug
regulations creates a clearer picture of the requirements of each
section.

**III INVITED COMMENTS (10):**

**From page 12232 regarding health benefits from preventing a rare
catastrophic event:** We would like comments regarding our estimate of
such an event.

We do not believe that the existence of these type of cGMP regulations
would have prevented or minimized the events from 1989. This event was
singular and unique and would not have been detected under the
provisions of this proposal.

**III INVITED COMMENTS (11):**

**From page 12239 regarding testing costs:** *We ask for comments on the
costs to develop tests, for the number of tests and the costs for
performing each test to comply with this requirement.*

The FDA assumptions for large establishments (309 batches per year) are
significantly removed from our reality. NBTY produces more than the FDA
annual average each month. Based on June 2003 production NBTY produced
560 batches of product equivalent to \~6700 batches per year. Using the
FDA cost assumption of \$650 / batch the NBTY testing investment would
be \$4,355,000 / year.

We believe that this part of the FDA cost analysis needs to be redone
using a better model.

**III INVITED COMMENTS (12):**

**From page 12165 regarding recordkeeping:** *We seek comment on whether
the proposed recordkeeping requirements are not necessary to prevent
adulteration; to ensure the identity, purity, quality, strength, and
composition of the dietary ingredient or dietary supplement; to an
enforceable regulation; and for the other reasons cited. If comments
assert that recordkeeping provisions are not necessary, comments should
include an explanation of why recordkeeping requirements are not
necessary including how, in the absence of the requirements, one can
prevent adulteration, ensure the identity, purity, quality, strength,
and composition of the dietary ingredient or dietary supplement, ensure
an enforceable regulation, and the other reasons cited. If comments
agree that the recordkeeping requirements are necessary for reasons
other than those we have provided, the comments should so state and
provide an explanation.*

We believe that recordkeeping requirements as presented by industry,
NNFA and USP are necessary as evidence that products are manufactured
according to regulation. The presentations by industry, NNFA and USP
required recordkeeping as part of the procedures set forth.
Recordkeeping requirements as part of written procedures would be the
best way to ensure the identity, purity, quality, strength and
composition of dietary supplements.

**III INVITED COMMENTS (13):**

**From page 12187 regarding written procedures for maintenance, cleaning
and sanitation:** *We invite comment on whether written procedures for
maintenance, cleaning, and sanitation should be required in a final
rule. If comments assert that written procedures are necessary, comments
should include an explanation of why the requirement is necessary to
prevent adulteration including how such a requirement would ensure the
identity, purity, quality, strength, and composition of the dietary
ingredient or dietary supplement. Conversely, if comments assert that
written procedures are not necessary, comments should include an
explanation of why the requirement is not necessary including how, in
the absence of the requirement, one can prevent adulteration and ensure
the identity, purity, quality, strength, and composition of the dietary
ingredient or dietary supplement.*

We believe that written procedures should govern maintenance, cleaning
and sanitation thus creating a standard for properly doing this function
and establishing parameters for doing it right. Such procedures could
also outline the parameters for major and minor cleaning conventions in
the manufacture of dietary supplements.

Many in our industry follow USP cGMP which requires written procedures
and specifications to be in place to cover production and process
controls. These are intended to prevent adulteration and to ensure the
identity, purity, quality, strength and composition of the dietary
ingredient or dietary supplement

**III INVITED COMMENTS (14):**

**From page 12203 regarding expiration dating and stability testing:**
*We invite comment on whether any final dietary ingredient and dietary
supplement CGMP rule should contain provisions regarding expiration
dating and the feasibility of conducting tests needed to support such
dates. We also invite comments on whether to require expiration dating
on certain dietary ingredients and not others, for example, require
expiration dating of vitamin, mineral, and amino acid, but not of
botanical dietary ingredients.*

We strongly believe that expiration dating should be a requirement for
dietary supplements. This is currently true for most all dietary
supplements available through conventional methods of distribution.
Additionally, most all companies that offer expiration dating do back it
up with stability testing.

FDA's argument regarding testing (*We are not proposing expiration
dating at this time because we have insufficient scientific information
to determine the biological activity of certain dietary ingredients used
in dietary supplements, and such information would be necessary to
determine an expiration date. Further, because official validated
testing methods (i.e., AOAC or FDA) for dietary supplements are
evolving, especially for botanical dietary ingredients, few official
methods are available to assess the strength of a dietary ingredient in
a dietary supplement.*) does not consider that many supplement companies
have worked diligently to develop stability plans for their products.
Such plans are based on the same testing used to release product onto
the market in the first place.

In our stability protocol testing of the FDA example of Vitamin C
testing would include assay, dissolution assay, physical appearance
checks and microbiological testing at the end of the cycle.

Testing for a botanical would include assay of marker compounds, if
there is a valid method, disintegration, physical appearance checks and
microbiological testing at the end of the cycle. In both cases the
stability testing criteria is essentially the same as the testing that
was used to release the product into the market place at time of
manufacture.

We believe that without requiring expiration dating and the accompanying
stability testing FDA may be encouraging less emphasis on quality by
those manufacturers that already take shortcuts. We also believe that
traditional expiration dating and stability testing may not work for
dietary ingredients; especially raw botanicals and again urge FDA to
create a specific set of rules for the ingredient industry.

**III INVITED COMMENTS (15):**

**From page 12181 regarding animal derived dietary ingredients:** *We,
therefore, invite comment on whether there should be specific CGMP
requirements for the use of animal-derived materials, substances, or
tissues in dietary ingredients and dietary supplements. We invite
comment on these issues and specifically on whether there is a
scientific basis for FDA to treat animal derived dietary ingredients in
a manner that is different from, or that would offer less protection
than, what is recommended for animal-derived biologics when the same
public health and safety risks may be present. We also invite comment on
our legal authority with respect to these issues.*

We believe that there should be specific cGMP requirements for the use
of animal-derived materials, substances or tissues in dietary
supplements so long as such requirements reflect the thinking currently
existing in food regulation and guidance from FDA. We believe that the
any procedures from CBER guidance should not be extended to dietary
supplements as supplements are essentially foods and not
pharmaceuticals.