VIII  SEQ CHAPTER \h \r 1 .  Comments on Physical Plant and Grounds 

(Final Subpart C)

	A.  Organization of Final Subpart C

     Proposed subpart C contained two provisions regarding physical
plants.  Table 4 lists the sections in final subpart C and identifies
the corresponding proposed sections that form the basis of the final
rule. 

Table 4. - Derivation of Sections in Final Subpart C

Final Rule	2003 CGMP Proposal

§ 111.15 What Sanitation Requirements Apply to Your Physical Plant?   
§ 111.15

§ 111.16 What Are the Requirements Under this Subpart for Written
Procedures?	N/A

§ 111.20 What Design and Construction Requirements Apply to Your
Physical Plant?	§ 111.20

§ 111.23 Under this Subpart, What Records Must You Make and Keep?	§
111.15(d)(3) and
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●	Reflects that the final rule applies to persons who manufacture,
package, label, or hold dietary supplements unless subject to an
exclusion in § 111.1.  

●	Requires you to have documentation or otherwise be able to show that
water that is used in a manner such that the water may become a
component of the dietary supplement, e.g., when such water contacts
components, dietary supplements, or any contact surface, meets
applicable Federal, State, and local requirements and does not
contaminate the dietary supplement.

2. Changes After Considering Comments

	The final rule:

●	Includes requirements similar to the food CGMP requirements in §
110.20(a) for keeping the grounds bordering your physical plant in a
condition that protects against contamination;  

●	Clarifies that sanitation supervisors can be qualified by education,
training, or experience;

●	Modifies the minimum requirements for water that is used in a manner
such that the water may become a component of the dietary supplement,
e.g., when such water contacts components, dietary supplements, or any
contact surface.  Such water must, at a minimum, comply with applicable
Federal, State, and local requirements and not contaminate the dietary
supplement. 

●	Simplifies the sanitation requirements for toxic materials, bathroom
facilities, and hand-washing facilities,

●	Simplifies and clarifies the design requirements for floors, walls,
and ceilings, fans and other air-blowing equipment, equipment that
controls temperature and humidity, and the use of safety-type glass or
glass-like materials,

●	Requires written procedures for cleaning the physical plant and for
pest control,

●	Requires that you make and keep records of the written procedures.

	C.  General Comments on Proposed Subpart C 

     (Comment 83)  Several comments say we should have different
sanitation requirements for dietary ingredient manufacturers than for
dietary supplement manufacturers.  These comments state that the
manufacture of synthetic or highly processed dietary ingredients
includes extensive purification steps, especially toward the end of the
manufacturing process, and that these steps remove contaminants that may
have been introduced at earlier stages in the manufacturing process. 
These comments consider some stages of the dietary ingredient
manufacturing process to not be subject to the same strict controls as
those used for manufacturing finished dietary supplements.

     (Response)  As discussed in subpart A, section VI, the final rule
applies to persons who manufacture, package, label, or hold dietary
supplements and who are not subject to an exclusion in § 111.1 and does
not apply to establishments that only manufacture dietary ingredients. 
This comment has been responded to in the response to comment 29. 

     (Comment 84)  Some comments assert that one or more proposed
requirements are unconstitutionally vague under the Fifth Amendment and
are arbitrary and capricious under section 706(2)(B) of the APA. The
comments would delete the following proposed requirements: 

●	§ 111.15(e) which would require plumbing to be “of an adequate
size and design and be adequately installed and maintained;” 

●	§ 111.15(g) which would require bathrooms to be “adequate” and
“readily accessible; ”

●	§ 111.15(h) which would require hand-washing facilities “to be
adequate, convenient, and furnish running water at a suitable
temperature; ” 

●	§ 111.15(h)(i) which would require hand-washing and, where
appropriate, hand-sanitizing facilities “at each location in your
physical plant” where good hygienic practices require employees to
wash or to sanitize or both wash and sanitize their hands;

●	§ 111.20(a) which would require your physical plant to “be
suitable in size, construction, and design to facilitate maintenance,
cleaning, and sanitizing operations;” and

●	§ 111.20(d)(6) which would require aisles or working spaces between
equipment and walls to be, adequately unobstructed and of adequate
width.

     In general, these comments assert the 2003 CGMP Proposal did not
define terms or phrases (such as “adequately” or “at each
location”) in a way that persons who are subject to the rule can
discern the meaning of the term or phrase.  These comments argue that
the proposed rule imposes no limitations on enforcement officers on the
exercise of their discretion and, thus, invites exercise of unbridled
discretion and disparate decision making.

      (Response)  As discussed in section V we disagree that the terms
that the comments objected to in the 2003 CGMP Proposal are
unconstitutionally vague, need to be defined, may result in
discriminatory enforcement, and we are retaining the terms in the final
rule.

D.  What Sanitation Requirements Apply to 

 Your Physical Plant and Grounds? 

(Final § 111.15)

1.  Final § 111.15(a) 

     The preamble to the 2003 CGMP Proposal (68 FR 12157 at 12184)
stated that we were not proposing requirements similar to the food CGMP
requirements found in § 110.20(a) for keeping the grounds bordering
your physical plant in a condition that protects against contamination
of components or dietary supplements in order to limit the burden to
manufacturers.  However, we invited comment on whether we should include
such requirements in a final rule.  After considering the comments, we
have drafted final § 111.15(a) to require you to keep the grounds of
your physical plant in a condition that protects against the
contamination of components, dietary supplements, or contact surfaces. 
The methods for adequate ground maintenance include:

(1)  Properly storing equipment, removing litter and waste, and cutting
weeds or grass within the immediate vicinity of the physical plant so
that it does not attract pests, harbor pests, or provide pests a place
for breeding;

(2) Maintaining roads, yards, and parking lots so that they do not
constitute a source of contamination in areas where components, dietary
supplements, or contact surfaces are exposed;

(3) Adequately draining areas that may contribute to the contamination
of components, dietary supplements, or contact surfaces by seepage,
filth or any other extraneous materials, or by providing a breeding
place for pests; 

(4) Adequately operating systems for waste treatment and disposal so
that they do not constitute a source of contamination in areas where
components, dietary supplements, or contact surfaces are exposed; and

(5) If your plant grounds are bordered by grounds not under your
control, and if those other grounds are not maintained in the manner
described in this section, you must exercise care in the plant by
inspection, extermination, or other means to exclude pests, dirt, and
filth or any other extraneous material that may be a source of
contamination.

     (Comment 85)  Several comments say the final rule should require
the maintenance of external areas similar to the food CGMP requirement
at § 110.20(a) for keeping the grounds outside the facility adequately
maintained.  These comments state that such a requirement is basic, is
equally important to facilities that manufacture conventional foods and
to facilities that manufacture dietary supplements, and that there is no
reason why this requirement should differ from food CGMPs.  One comment
asserts such a requirement is basic to the industry and it should not be
dismissed as a burden to the industry.  Some comments also assert that a
provision similar to § 110.20(a) would help train staff and would
explain to plant maintenance personnel what is required and why.

     One comment says there should be some minimum requirement for
sanitation and cleanliness in the area surrounding the plant and that
requirements for drainage and trash removal should be adequate. 

	(Response)  We agree that a requirement to maintain grounds is equally
important for facilities that manufacture conventional foods and for
facilities that manufacture dietary supplements.  Although some
requirements in § 110.20(a) are not strictly limited to drainage and
trash disposal, the comment suggesting the requirements to maintain
grounds be limited to drainage and trash disposal did not explain why,
for example, it would not be as important for a facility that
manufactures dietary supplements to maintain roads, yards, and parking
lots so that they do not become a source of contamination as it already
is for facilities that manufacture conventional foods.  Therefore, the
final rule is adding § 111.15(a), which is similar to § 110.20(a) with
editorial revisions consistent with the rest of this final rule.   

2.  Final § 111.15(b)(1) 

     Final § 111.15(b)(1) (proposed § 111.15(a)) requires you to
maintain your physical plant in a clean and sanitary condition.  Final
§ 111.15(b)(2) requires you to maintain your physical plant in repair
sufficient to prevent components, dietary supplements, or contact
surfaces from becoming contaminated.    

     We did not receive comments specific to proposed § 111.15(a). 

3.  Final § 111.15(c) 

     Final § 111.15(c) (proposed § 111.15(b)) sets forth requirements
for cleaning compounds, sanitizing agents, pesticides, and other toxic
materials.  

Final § 111.15(c) includes changes that we are making for clarity and
consistency.  We added other “toxic” materials because some
paragraphs within final § 111.15(c) simply refer to the cleaning
compoundsagents, sanitizing agents, and pesticides as “toxic
materials,” and because proposed § 111.15(b)(2) addressed the use and
storage of toxic materials that are not within the general category of
cleaning compoundsagents, sanitizing agents, or pesticides.

     Final § 111.15(c)(1) requires you to use cleaning compounds and
sanitizing agents that are free from microorganisms of public health
significance and that are safe and adequate under the intended
conditions of use.  Final § 111.15(c)(1) is similar to proposed §
111.15(b)(1), except that we inserted “that are” before “safe and
adequate.”  We consider this to be a non-substantive, editorial
change.  Proposed § 111.15(b)(1) was, itself, patterned after §
110.35(b)(1), which: (1) requires cleaning compounds and sanitizing
agents used in cleaning and sanitizing procedures to be free from
undesirable microorganisms and safe and adequate under the conditions of
use, and (2) provides that compliance may be verified by any effective
means including purchase of these substances under a supplier’s
guarantee or certification or examination of these substances for
contamination.

(Comment 86)  Several comments ask us to clarify our expectations with
respect to substantiating that a cleaning compound or sanitizing agent
is free from microorganisms of public health significance and is safe
and adequate under conditions of use.  Some comments suggest proposed §
111.15(b)(1) provide for the use of certifications or guarantees from a
supplier because our investigators otherwise may not recognize such
documents as evidence of compliance.  Several comments say it is not
necessary for a manufacturer to test these types of products, and that a
continuing product guarantee, combined with a statement of intended use
from the manufacturer of the cleaning compound or sanitizing agent,
should satisfy the requirements. 

     (Response)  When assessing compliance with final § 111.15(c)(1),
we would not treat a firm that manufactures, packages, labels, or holds
a dietary supplement differently than we would treat a facility that
manufactures, packages, labels, or holds conventional foods.  Therefore,
we intend to accept, as the comments request, a supplier’s guarantee
or certification that a cleaning compound or sanitizing agent is free
from microorganisms of public health significance and is safe and
adequate under the conditions of use for the purpose of determining
compliance with final § 111.15(c)(1).  

	Final § 111.15(c)(2) requires you to not use or hold toxic materials
in a physical plant in which components, dietary supplements or contact
surfaces, are manufactured or exposed, unless those materials are
necessary: (1) To maintain clean and sanitary conditions; (2) for use in
laboratory testing procedures;(3) for maintaining or operating the
physical plant or equipment; or (4) for use in the plant’s operations.


     We did not receive comments specific to proposed § 111.15(b)(2). 
We have made a non-substantive edit to § 111.15(c)(2) by moving
“contact surfaces” to be the last item on the list.

	Final § 111.15(c)(3) requires you to identify and hold cleaning
compounds, sanitizing agents, pesticides, pesticide chemicals, and other
toxic materials in a manner that protects against contamination of
components, dietary supplements, or contact surfaces.  Final §
111.15(c)(3) is similar to proposed § 111.15(b)(3).  

     We did not receive comments specific to proposed § 111.15(b)(3),
but replaced “toxic cleaning compounds” with “cleaning
compounds,” and added “other toxic materials.”  

4.  Final § 111.15(d) 

     Final § 111.15(d) (proposed § 111.15(c)) sets forth requirements
for pest control.  Section § 111.15(d) is almost identical to proposed
§ 111.15(c).  

     Final § 111.15(d)(1) requires you to not allow animals or pests in
any area of your physical plant.  Final § 111.15(d)(1) allows guard or
guide dogs in some areas of your physical plant if the presence of the
dogs will not result in contamination of components, dietary
supplements, or contact surfaces.  Final § 111.15(d)(2) requires that
you take effective measures to exclude pests from your physical plant
and to protect against the contamination of components, dietary
supplements, and contact surfaces on the premises by pests.  Final §
111.15(d)(3) requires that you not use insecticides, fumigants,
fungicides, or rodenticides unless you take precautions to protect
against the contamination of your components, dietary supplements, or
contact surfaces.

	(Comment 87)  Several comments claim proposed § 111.15(c) would
require that sealed equipment outside of the plant (e.g. storage tanks,
vessels, piping) be enclosed to prevent pests from roaming around these
areas.  The comments say there is no need to shelter outdoor equipment
if it is properly sealed.  These comments state that dietary supplements
are sometimes manufactured in extensive, highly automated facilities in
which large tanks and vessels are interconnected via piping, and that in
these cases “the physical plant” and “the equipment in the
plant” converge so that some or much of the equipment is effectively
located outdoors.  Thus, the comments ask us to revise proposed §
111.15(c) to clarify that it applies only to interior areas of the
physical plant. 

     (Response)  Equipment such as that described by the comments, if
properly sealed, should protect components, dietary supplements, and
contact surfaces from contamination with pests.
FinalSection§ 111.15(d) does not require that sealed equipment outside
of the plant, such as storage tanks, vessels, or piping, be enclosed,
e.g., inside a building.  Final § 111.15(d)(2) requires that you take
effective measures to exclude pests from your physical plant and to
protect against the contamination of components, dietary supplements, or
contact surfaces on the premises by pests.  Moreover, final § 111.15(a)
includes several requirements designed to limit or exclude pests around
all parts of the exterior of your physical plant.  Therefore, although
you do not have to enclose your outside equipment, you must take
measures to exclude pests from areas outside of the plant. 

5.  Final § 111.15(e) 

     Final § 111.15(e)(proposed § 111.15(d)) sets forth requirements
for the water supply of your physical plant.  

     Final § 111.15(e)(1) requires that you must provide water that is
safe and sanitary at suitable temperatures and under pressure as needed
for all uses where water does not become a component of the dietary
supplement.  

     We did not receive comments specific to proposed § 111.15(d)(1). 
We have modified the phrase “safe and of adequate sanitary quality”
to read “safe and sanitary.”  To avoid confusion with the definition
of “quality” we have adopted solely for purposes of this final rule,
we deleted the references to “quality” as it applies to water
standards.  We consider this change to be non-substantive and still
require water that is not a component of a dietary supplement to meet a
safe and sanitary standard.

     Final § 111.15(e)(2) requires that water used in a manner such
that the water may become a component of the dietary supplement, e.g.,
when such water contacts components, dietary supplements, or any contact
surface, must, at a minimum, comply with applicable Federal, State, and
local requirements and not contaminate the dietary supplement.  Final
§ 111.15(e)(2) derives from proposed § 111.15(d)(2) which would
require that water that contacts components, dietary supplements, or any
contact surfaces must, at a minimum, comply with the applicable National
Primary Drinking Water (NPDW) regulations and any State and local
government requirements.  Final § 111.15(e)(2) includes changes we are
making after considering comments discussed immediately below.

 	(Comment 88)  Several comments state the water quality that is
required for conventional foods is sufficient for dietary supplements. 
The comments argue that no additional water standards are listed in the
CGMPs for low-acid canned foods in part 113 or in the CGMPs for
acidified foods in part 114.  These comments argue that, if “safe and
of adequate sanitary quality” is sufficient to ensure the quality of
the water used in most food products, then it is also adequate to ensure
the quality of the water used in dietary supplements.  

     Other comments would revise the final rule to allow different
standards and requirements for water that contacts or is used in dietary
supplements compared to water that contacts components, including
dietary ingredients.  These comments state current food CGMP regulations
require only that water supplies that contact food (defined to include
ingredients and raw materials) be “safe and of adequate sanitary
quality.”  These comments say that this would be consistent with the
act’s basis for CGMP requirements for foods, i.e., that food is not
prepared “under unsanitary conditions whereby it may have become
contaminated with filth, or whereby it may have been rendered injurious
to health” (see 21 U.S.C. 342(a)(4)).  Several comments state the
final rule should adopt a similar rationale for components, including
dietary ingredients.  These comments explain that components, including
dietary ingredients, are not in a form in which they will be consumed
and are subject to further processing prior to consumption. 

     Several comments say that requiring water used for cleaning contact
surfaces to meet EPA regulations is an unnecessary burden for companies
that do not have access to municipal water.  According to these
comments, potable water should be sufficient.

	(Response)  In the preamble to the 2003 CGMP Proposal (68 FR 12157 at
12185), we stated that water should, at a minimum, be potable and that
water that is “safe and of adequate sanitary quality” should be
potable.  We also said water that contacts components, dietary
supplements, or contact surfaces should, at a minimum, meet EPA’s NPDW
regulations and State, and local requirements.  We proposed to require
that water used in operations where water contacts components, dietary
supplements, or any contact surfaces meet the NPDW regulations because
of the potential for contamination if water were used that did not
adhere to the microbial standards, for example, in the NPDW regulations.
 Finally, we stated these requirements were minimum requirements and
that water that is more pure than that required under the NPDW
regulations may be desired.  

	The comments stated some manufacturers may not have access to municipal
water, and therefore, that meeting the NPDW regulations for cleaning
contact surfaces would be too burdensome.  These comments asserted that
potable water would be sufficient.  The comments do not provide a
definition of “potable water.”  We have defined “potable water,”
in the regulations on interstate conveyance sanitation in part 1250 to
be, in part, water that meets the standards prescribed in the EPA’s
National Primary Drinking Water Standards (NPDWS) Regulations in 40 CFR
part 141.  

We would consider it to be a rare situation where a dietary supplement
manufacturer uses well water and has no access to municipal water. 
Nonetheless, to the extent that a manufacturer uses water that is not
subject to Federal oversight, the manufacturer would have to comply with
any State or local regulations that apply to food manufacturing
facilities using such water in food processing.  

Manufacturers that use water from a municipal source, which is subject
to the EPA NPDW regulations, should not be subject to a lesser standard
in this final rule than what is already required of them by EPA.  Thus,
to accommodate manufacturers  subject to EPA’s NPDW regulations for
the water that they use in the manufacture of dietary supplements, as
well as those dietary supplement manufacturers who are not subject to
EPA’s NPDW regulations, we are modifying the rule to state water that
is used in a manner such that the water may become a component of the
dietary supplement, e.g., when such water contacts components, dietary
supplements, or any contact surface, must, at a minimum, comply with
applicable Federal, State, and local requirements and not contaminate
the dietary supplement.  We decline to use “safe and of adequate
safety” that some comments state is sufficient because it is for
conventional foods.  We believe that requiring that water comply with
Federal, State and local requirements and not contaminate dietary
supplements provides a clear standard as to what is required. 

	(Comment 89)  Some comments assert that water that is used to
manufacture components or dietary ingredients where such components or
dietary ingredients are subject to further processing prior to
consumption, should be subject to the “safe and of adequate sanitary
quality” standard in § 110.37.

(Response)  We acknowledge that such components and dietary ingredients
are subject to the requirement in § 110.37.  If the manufacturers do
not fall within the scope of final § 111.1, such manufacturers would be
subject to the CGMP requirements in part 110.  

	To the extent that such comments request the “safe and of adequate
sanitary quality” language apply to water used in the manufacture of a
dietary supplement, we decline to make that change.  Water that is safe
and sanitary would not necessarily comply with, for example, the NPDW
regulations.  A requirement stating “safe and of adequate sanitary
quality” or, as stated in the final rule, the requirement of “safe
and sanitary” could be seen as a lesser standard than water that
complies with “applicable Federal, State, and local requirements.” 
We want to make clear that you must comply with applicable Federal,
State, and local requirements related to the water that you use for food
processing that would otherwise be required of you, and not to some
lesser standard that you may consider is “safe and sanitary” when
water is used in a manner such that the water may become a component of
the dietary supplement, e.g., when such water contacts a component,
dietary supplement, or any contact surface.  Foreign manufacturers would
need to comply with the water standard required in this final rule and
achieve the same level of performance as is required of domestic
manufacturers.  The water used in domestic or foreign manufacturing must
not contaminate the dietary supplement.  To clarify that the water used,
whether by a domestic or foreign manufacturer, must not be a source of
contamination, we are adding the words “and not contaminate the
dietary supplement” in final § 111.15(e)(2).  We also want to make
it clear that water includes what is in the water, e.g. any of its
contaminants in addition to H2O.  For example, when we speak of drinking
water, we do not just mean the H2O, we mean the iron, lead, sulfur, and
any other contaminants contained in the water.  

     (Comment 90)  Several comments suggest water should meet some or
all standards of the USP monograph for sterile, purified water and say
that the standard in the USP monograph is a higher, and presumably
safer, standard than the NPDW standard.  The comments state the USP’s
water deionization and purification systems requirements are already
common in the industry.

 	(Response)  We do not discourage firms from using water in dietary
supplement manufacturing that meets USP standards, including deionized
or purified water, but we do not require, as a CGMP, the use of USP
standards.  This final rule sets forth minimum requirements for persons
who manufacture, package, label, or hold a dietary supplement.  Thus,
firms may use water that exceeds our minimum requirements.

     (Comment 91)  The preamble to the 2003 CGMP Proposal recognized
that foreign firms might not be subject to EPA water requirements or
adhere to such requirements, but also stated that water quality is an
important part of CGMP (68 FR 12157 at 12185).  Thus, in the preamble to
the 2003 CGMP Proposal, we invited comment on how we might ensure that
foreign firms meet the same water quality requirements as domestic
firms.  Several comments respond to our request for comments specific to
the applicability of the water standards to foreign firms.  Several
comments recommend we not distinguish between domestic and foreign firms
with regard to water quality.  The comments claim all firms must compete
on a “level playing field.”  These comments state water quality
standards vary from country to country, and many countries do not have
requirements that are comparable to those in the United States.  The
comments say foreign manufacturers should not be permitted to import
products into the United States that do not meet the same safety
standards as domestic goods.

     Other comments ask us to consider the water quality requirement to
be met if the water complies with the NPDW standard or any equivalent
water quality standard that is ensured by a foreign public agency.

	(Response)  We agree that foreign firms should be required to meet the
water safety and sanitary requirements required of domestic firms and
achieve the same level of performance of domestic firms.  As discussed
in this section, foreign firms are required to meet all requirements and
would need to comply with their own national or local water safety
requirements and not contaminate the dietary supplement.

     (Comment 92)  One comment would combine proposed § 111.15(d)(1)
and (2) into a single paragraph.  The comment says the two proposed
paragraphs are redundant.  Proposed § 111.15(d)(1) would require that
you provide water that is safe and of adequate sanitary quality, at
suitable temperatures, and under pressure as needed, in all areas where
water is necessary for: (1) Manufacturing dietary ingredients or dietary
supplements; (2) making ice that comes in contact with components,
dietary ingredients, dietary supplements, or contact surfaces; (3)
cleaning any surface; and (4) employee bathrooms and hand-washing
facilities.  Proposed § 111.15(d)(2) would require that water that
contacts components, dietary ingredients, dietary supplements, or any
contact surface must at a minimum comply with the NPDW regulations
prescribed by the EPA under 40 CFR part 141 and any state and local
government requirements.

     (Response)  We disagree that proposed § 111.15(d)(1) and (d)(2)
were redundant.  For example, as described in the proposed sections,
nonpotable water that would have been “safe and of adequate sanitary
quality” for use in flushing toilets may not have been “safe and of
adequate sanitary quality” for use in the manufacture of a liquid
dietary supplement.  

     Final § 111.15(e)(1) requires that you provide water that is safe
and sanitary, at suitable temperatures, and under pressure as needed,
for all uses where water does not become a component of the dietary
supplement.  Final § 111.15(e)(2) requires that water that is used in a
manner such that the water may become a component of the dietary
supplement, e.g., when such water contacts components, dietary
supplements, or any contact surface, must, at a minimum, comply with
applicable Federal, State, and local requirements and not contaminate
the dietary supplement.  As an example of how the requirements would
apply, water that contains lead at a level that is 20 times higher than
the maximum accepted level in EPA’s NPDW standards for lead may not be
safe for use in the manufacture of dietary supplement that is consumed
in four two-ounce portions per day, but may be safe for use in cleaning
the floors of the physical plant.  Therefore, to emphasize that water
that is “safe and sanitary” may be different depending on its use,
the final rule continues to separate § 111.15(e)(1) and (e)(2)
(formerly proposed § 111.15(d)(1) and (d)(2)).  

	Additionally, to emphasize the importance of the water that is used in
the manufacture of a dietary supplement, where the water is used in a
manner such that the water may become a component of the dietary
supplement, final § 111.23(c) (proposed § 111.15(d)(3)) requires you
to have documentation and keep records that such water meets the
requirements of final § 111.15(e)(2).  In contrast, there is no
corresponding requirement for documentation in final § 111.23 that
other water, such as water that is used to clean floors or used in
employee bathrooms, meets requirements of final § 111.15(e)(1).

     (Comment 93)  Several comments state, if we retain a water standard
requirement based on the EPA NPDW standard, then it is important to
include provisions recognizing the acceptability of municipal water
sources and the frequency of testing required for other water sources. 
Some comments recommend water should meet the USP standard for purified
water and point out that the USP standard provides an assurance of the
water’s consistency and provides a system that can be monitored. 

     Several comments suggest we include timetables for water testing or
describe water testing frequency requirements.  These comments state we
should apply something analogous to the 2003 CGMP Proposal requirements
for infant formula which would require manufacturers to conduct the
tests with sufficient frequency to ensure that the water meets the
EPA’s NPDW standard, but not less frequently than annually for
chemical contaminants, every four years for radiological contaminants,
and weekly for bacteriological contaminants.  Other comments refer to
the amendments to the bottled water regulations at § 165.110 which
require a minimum yearly monitoring of source water and finished bottled
water products for chemical contaminants for which allowable levels have
been established in the bottled water quality standard.

	(Response)  Final § 111.23(c) requires you to have documentation that
water, when used in a manner such that the water may become a component
of the dietary supplement, e.g., when such water contacts a component,
dietary supplement, or contact surface, meets the requirements of final
§ 111.15(e)(2).  You must meet the requirement for final
§ 111.15(e)(2) at the point of use, rather than at the point of
delivery i.e., at the point the water may become a component of the
dietary supplement, such as when the water contacts components, dietary
supplements, or any contact surface (such as when the water comes out of
the faucet or comes out of a spigot from a holding tank where you store
water).  Thus, you must ensure that the water used in a manner such that
the water may become a component of the dietary supplement, not the
water source before it enters your facility, meets the NPDW regulations,
or if not subject to the NPDW regulations, that it meets any other
applicable Federal, State, and local requirements and does not
contaminate the dietary supplement.  

	For example, if the water that enters your facility is subject to the
EPA NPDW regulations, then the water must comply with such requirements
at the point of use, i.e., when it contacts the components, dietary
supplement, or any contact surface (such as when the water comes out of
the faucet or out of a spigot from a holding tank where you store
water). You could rely on a certificate of analysis under
§ 111.75(a)(2)(ii) from the supplier of the water (e.g., the
municipality) to ensure that the water entering your facility complies
the applicable Federal, State and local requirements. However, you must
ensure that nothing happens to the water that may contaminate the water
once it enters your facility and before the water may become a component
of the dietary supplement at the point of use. Certain contaminants or
microorganisms may be introduced into the water from the facility. 
Thus, you may need to establish specifications and procedures to prevent
contamination from pipes through which the water travels in the facility
or from vessels in which the water is held in the facility prior to use.
You may need to test for certain contaminants, e.g., lead or
microorganisms, at point of use to ensure there is no contamination of
the water within your facility.  Such tests may not need to include all
of the chemical, microbiological, or contaminant testing already
certified by the supplier to determine whether the water entering your
facility complies with Federal, State and local requirements.  Rather,
you would need to evaluate what, if any, introductions of contaminants
are likely to occur within your facility and determine whether
additional tests are needed to verify that the water, at point of use,
will comply with Federal, State, and local requirements and not
contaminate the dietary supplement.  Alternatively, you may decide not
to rely on a certificate of analysis and instead conduct your own
testing at point of use to determine if the water complies with
applicable Federal, State, and local requirements.  We decline to set
out testing requirements or frequency of testing in this final rule in
lieu of giving manufacturers the flexibility to decide on the
appropriate testing and frequency of such testing to ensure that the
water meets the requirements in final § 111.15(e)(2).  We may consider
issuing guidance, as needed, on our recommendation for testing based on
water sources and the purposes for which the water is used.  If you rely
on a certificate of analysis from the supplier of the water, we
recommend that you qualify your facility by conducting appropriate tests
at the point of use to verify that no other tests are necessary or that
any additional tests you have chosen are sufficient to establish that
the water that is used in a manner such that the water may become a
component of the dietary supplement, e.g., when such water contacts
components, dietary supplements or any contact surface, meets the
requirements of final § 111.15(e)(2).  We also recommend that you
requalify your facility at the point of use at appropriate intervals.  

     If you use water from a private source, you must use water that
complies with any State and local requirement and does not contaminate
the dietary supplement.  You may need to perform appropriate water
treatment procedures, including filtration, sedimentation, and
chlorination to satisfy final § 111.15(e)(2).

     (Comment 94)  Several comments would delete proposed §
111.15(d)(2), arguing that it is unnecessary to state a requirement that
water meet EPA’s NPDW standards.  These comments state that if water
is used in processing or at critical points in the cleaning process,
then a manufacturer will already have established specifications for its
appropriate use. 

	(Response)  We agree that a manufacturer will need to establish
specifications, under final § 111.70(a), for any point, step, or stage
in the manufacturing process where control is necessary to ensure the
quality of the dietary supplement, and for water that is used in a
manner such that the water may become a component of the dietary
supplement.  For reasons set forth in response to comment 88, final
§ 111.15(e)(2) establishes the minimum standards for water that will
be used in a manner such that the water may become a component the
dietary supplement, e.g., when such water contacts components, dietary
supplements, or any contact surface.  Thus, we disagree that proposed
§ 111.15(e)(2) be eliminated. 

6.  Final § 111.15(f) 

     Final § 111.15(f)(proposed §111.15(e)) sets forth requirements
for the plumbing of your physical plant.  

     Final § 111.15(f) requires your plumbing to be of an adequate size
and design and be adequately installed and maintained to: (1) Carry
sufficient amounts of water to required locations throughout the
physical plant; (2) properly convey sewage and liquid disposable waste
from your physical plant; (3) avoid being a source of contamination to
components, dietary supplements, water supplies, or any contact surface,
or creating an unsanitary condition; (4) provide adequate floor drainage
in all areas where floors are subject to flooding-type cleaning or where
normal operations release or discharge water or other liquid waste on
the floor; and (5) not allow backflow from, or cross-connection between,
piping systems that discharge waste water or sewage and piping systems
that carry water used for manufacturing dietary supplements, for
cleaning contact surfaces, or for use in bathrooms and hand-washing
facilities. 

     We did not receive comments specific to proposed § 111.15(e),
other than comments arguing that certain text was unconstitutionally
vague and arbitrary and capricious.  We address those comments in
section V. 

7.  Final § 111.15(g) 

     Final § 111.15(g)(proposed § 111.15(f)) sets forth requirements
for sewage disposal and requires you to dispose of sewage into an
adequate sewage system or through other adequate means.  

     We did not receive comments specific to proposed § 111.15(f).

8.  Final § 111.15(h) 

	Final § 111.15(h)(proposed § 111.15(g)(1)) sets forth requirements
for the bathrooms of your physical plant. Final § 111.15(h) requires
you to provide your employees with adequate, readily accessible
bathrooms, and that the bathrooms be kept clean and not be a potential
source of contamination to your components, dietary supplements, or
contact surfaces.  

(Comment 95)  Several comments state companies should be given
flexibility in designing their bathrooms.  These comments assert the
food CGMP requirements allow flexibility in bathroom design, so the
dietary supplement CGMP rule should do the same.  The comments would
delete proposed § 111.15(g)(1) through (g)(3), which pertained to: (1)
Keeping the bathrooms in good repair at all times; (2) providing
self-closing doors; and (3) providing doors that do not open into areas
where components, dietary ingredients, dietary supplements, or contact
surfaces are exposed to airborne contamination, except where alternate
means have been taken to protect against contamination.  

     (Response)  We agree that it is unnecessary to require specific
bathroom features such as those in proposed § 111.15(g)(1) through
(g)(3) because you may be able to achieve compliance through other means
better suited to your operations.  Accordingly, we are revising the rule
by deleting proposed paragraphs (g)(1) through (g)(3) as requested by
the comments.  However, we continue to believe that mechanisms such as
self-closing doors and doors that do not open onto areas where
components, dietary supplements, or contact surfaces are exposed to
contamination will help protect against contamination.

9.  Final § 111.15(i) 

     Final § 111.15(i)(proposed § 111.5(h)) sets forth requirements
for the hand-washing facilities of your physical plant.  Final §
111.15(i) requires you to provide hand-washing facilities that are
designed to ensure that an employee’s hands are not a source of
contamination of components, dietary supplements, or any contact
surface, by providing facilities that are adequate, convenient, and
furnish running water at a suitable temperature.  

	Final Section § 111.15(i) differs from the proposal in that the
proposal would list six specific features of a hand washing facility,
such as effective hand-cleaning and sanitizing preparations (proposed §
111.15(h)(2)), air driers, sanitary towel service, or other suitable
drying devices (proposed S 111.15(h)(3)), and trash bins that are
constructed to protect against recontamination (proposed §
111.15(h)(4)).

     (Comment 96)  Several comments state we should give firms the
flexibility to design their hand washing facilities.  According to these
comments, substituting the word “may” for the word “must” would
accomplish this.  The comments argue that, as with bathrooms, an overall
sanitation requirement should be sufficient, and that, as long as there
is a strong and enforceable standard, firms should have the flexibility
to adopt only those measures that are needed to meet the underlying
requirement.  

	(Response)  We agree that it is unnecessary to require specific
hand-washing mechanisms because you may be able to achieve compliance
through other means better suited to your operations.  However, we
disagree that an overall sanitation requirement would be sufficient,
because such a requirement would not clearly state the purpose of the
requirement, which is to ensure that an employee’s hands are not a
source of contamination of components, dietary supplements, or any
contact surface.  

     We are revising proposed § 111.15(h) (now renumbered as final §
111.15(i)) in the final rule in two respects.  First, the final rule
states that the hand-washing facilities are to be designed to ensure
that an employee’s hands are not a source of contamination.  Second,
final § 111.15(i) states that the hand-washing facilities are to be
adequate, convenient, and furnish running water at suitable temperatures
but does not provide the specific hand-washing mechanisms detailed in
the 2003 CGMP Proposal.  

10.  Final § 111.15(j) 

     Final § 111.15(j) (proposed § 111.15(i)) sets forth requirements
for trash disposal at your physical plant.  Final § 111.15(j) requires
that you convey, store, and dispose of trash to: (1) minimize the
development of odors; (2) minimize the potential for trash to attract,
harbor, or become a breeding place for pests; (3) protect against
contamination of components, dietary supplements, any contact surface,
water supplies, and grounds surrounding your physical plant; and (4)
control hazardous waste to prevent contamination of components, dietary
supplements, and contact surfaces.

     (Comment 97)  One comment suggests deleting proposed § 111.15
(i)(1) concerning minimizing the development of odors, because, the
comment claimed, minimizing odors is not a “true” CGMP requirement.

     (Response)  We disagree that minimizing the development of odors is
not part of CGMP.  Odor from trash is often an indication of problems
with microbial contamination, such as decomposition, decay, and the
growth of harmful bacteria.  In addition, odor from trash can attract
pests.  By conveying, storing, and disposing of trash to minimize the
development of odors, you will help reduce the potential for problems
with microbial contamination and pests.  

11.  Final § 111.15(k) 

     Final § 111.15(k) (proposed § 111.15(j)) sets forth requirements
for sanitation supervisors at your physical plant.  Final § 111.15(k)
requires that you assign one or more employees to supervise overall
sanitation.  Each supervisor must be qualified by education, training,
or experience to develop and supervise sanitation procedures.  Final §
111.15(k) differs from proposed § 111.15(j) in that the proposal would
require that each supervisor be qualified by training and experience.  

     (Comment 98)  Several comments suggest revising proposed §
111.15(j) to state that sanitation supervisors may be qualified by
education, training, or experience (or any combination thereof) to
develop and supervise sanitation procedures.  In contrast, several
comments say that sanitation supervisors should be qualified by both
training and experience.

     (Response)  Consistent with our response to comment 76 in section
VII, final § 111.15(k) provides that sanitation supervisors, like other
supervisors, must be qualified by education, training, or experience to
develop and supervise sanitation procedures.  As we also stated in
response to comment 76, we acknowledge that some supervisory personnel
may need a different range of education, training or experience than
others.  However, we have decided to give firms the flexibility to
decide the appropriate amount of education, training, or experience for
a given job function.  If that includes a combination of attributes, the
firm should select and train employees accordingly.   

E._ What Are the Requirements Under This Subpart 

for Written Procedures?

(Final § 111.16)

	We received many comments that recommend written procedures for various
provisions.  We address the need for written procedures generally in
section IV.  We also respond to  comments on specific provisions in the
same section.

	We are adding a new final § 111.16, titled, “What Are the
Requirements Under This Subpart for Written Procedures?,” to require
you to establish and follow written procedures for fulfilling certain
requirements of subpart C.  You must establish and follow written
procedures for cleaning the physical plant and for pest control.

F.  What Design and Construction Requirements Apply to Your  Physical
Plant?

(Final § 111.20)

     Final § 111.20 addresses physical plant design and construction
requirements.  

1.  Final § 111.20(a) and (b) 

     Final § 111.20(a) and (b) require that any physical plant that you
use in the manufacturing, packaging, labeling, or holding of dietary
supplements: (1) Be suitable in size, construction, and design to
facilitate maintenance, cleaning, and sanitizing operations; and (2)
have adequate space for the orderly placement of equipment and holding
of materials as is necessary for maintenance, cleaning, and sanitizing
operations and to prevent contamination and mix-ups of components and
dietary supplements during manufacturing, packaging, labeling, or
holding.  

     We did not receive comments specific to proposed § 111.20(a) or
(b), other than comments arguing that certain text in proposed §
111.20(b) was unconstitutionally vague and arbitrary and capricious.  We
address those comments in this section and section V.  

2.  Final § 111.20(c) 

     Final § 111.20(c) requires that any physical plant you use in the
manufacturing, packaging, labeling, or holding of dietary supplements
provide for the use of proper precautions to reduce the potential for
mix-ups or contamination of components, dietary supplements, or contact
surfaces, with microorganisms, chemicals, filth, or other extraneous
material. 

	Under final § 111.20(c) your physical plant must have, and you must
use, separate or defined areas of adequate size or other control
systems, such as computerized inventory controls or automated systems of
separation, to prevent contamination and mix-ups of components and
dietary supplements during the following operations: (1) Receiving,
identifying, holding, and withholding from use, components, dietary
supplements, packaging, and labels that will be used in or during the
manufacturing, packaging, labeling, or holding of dietary supplements;
(2) separating, as necessary, components, dietary supplements,
packaging, and labels that are to be used in manufacturing from
components, dietary supplements, packaging, or labels that are awaiting
material review and disposition decision, reprocessing, or are awaiting
disposal after rejection; (3) separating the manufacturing, packaging,
labeling, and holding of different product types including different
types of dietary supplements and other foods, cosmetics, and
pharmaceutical products; (4) performing laboratory analyses and holding
laboratory supplies and samples; (5) cleaning and sanitizing contact
surfaces; (6) packaging and label operations; and (7) holding components
or dietary supplements.

     (Comment 99)  Several comments would change “computerized
inventory controls” to “adequate inventory controls” in proposed
§ 111.20(c).  The comments say that a requirement to use a computerized
system is too prescriptive and that inventory controls that are not
computerized may be equally effective in achieving compliance with
proposed § 111.20(c).  

     (Response)  These comments may have misinterpreted proposed §
111.20(c).  Computerized inventory controls are an example of the type
of system that may be appropriate; § 111.20(c) does not require you to
have a computerized system in the first instance.  Thus, final §
111.20(c) continues to use computerized inventory controls as an example
of a central system.  

     (Comment 100)  Several comments ask us to clarify the degree of
separation that is intended under proposed § 111.20(c) when it referred
to “separate or defined areas” of a physical plant.  These comments
state that it is unclear if we expect a firm not to manufacture multiple
products in a single room or area.  The comments state that, if this is
the case, this would be equivalent to the drug CGMP requirements and
would be excessive.  The comments argue that, if the proper controls are
in place, manufacturing and packaging of multiple products is possible
in a single room or area without compromising product identity, quality,
strength, purity, and composition.

     (Response)  Final § 111.20(c) states that you must have and use
separate or defined areas of adequate size or other control systems,
such as computerized inventory controls or automated systems of
separation.  The preamble of the 2003 CGMP Proposal explained that if
your physical plant does not allow for physically separate areas, you
could develop an alternative approach for segregating components and
dietary supplements at points when they are received, stored, and
rejected (68 FR 12157 at 12188).  We interpret the comments as asking
whether alternative approaches for segregating products could be used,
even if physically separate areas were available in a facility, so that
different materials could be processed in the same area.  Final
§ 111.20(c) allows you to use “separate or defined areas of adequate
size or other control systems;” thus, you can comply with this
requirement by manufacturing multiple products in the same room or area
instead of using a physically separate location, as long as you have
systems in place to prevent contamination and mix-ups of components and
dietary supplements.  

3.  Final § 111.20(d)

	Final § 111.20(d) requires that any physical plant you use in the
manufacturing, packaging, labeling, or holding of dietary supplements be
designed and constructed in a manner that prevents contamination of
components, dietary supplements, or contact surfaces.  

     Final § 111.20(d)(1) requires the design and construction to
include: (1) Floors, walls, and ceilings that can be adequately cleaned
and kept clean and in good repair; (2) fixtures, ducts, and pipes that
do not contaminate components, dietary supplements, or contact surfaces
by dripping or other leakage or condensate; (3) adequate ventilation or
environmental control equipment, such as air flow systems, including
filters, fans, and other air-blowing equipment, that minimize odors and
vapors (including steam and noxious fumes) in areas where they may
contaminate components, dietary supplements, or contact surfaces; (4)
equipment that controls temperature and humidity, when such equipment is
necessary to ensure the quality of the dietary supplement; and (5)
aisles or working spaces between equipment and walls that are adequately
unobstructed and of adequate width to permit all persons to perform
their duties and to protect against contamination of components, dietary
supplements, or contact surfaces with clothing or personal contact.   

	Final § 111.20(d)(1)(i) through (v) is similar to proposed §
111.20(d)(1), (2), (3), (5), and (6) respectively.  Additionally, as
explained immediately below, we have made other changes to proposed §
111.20(d)(1) (final § 111.20(d)(1)(i)) and proposed § 111.20(d)(5)
(final § 111.20(d)(1)(iv)).  

	(Comment 101)  Several comments argue that the requirement of proposed
§ 111.20(d)(1) that floors, walls, and ceilings be made of “smooth
and hard surfaces,” if read literally, could be interpreted to
prohibit the use of ceilings with drop-in tiles.  These comments assert
that, while there may be areas in a manufacturing plant where drop-in
ceilings are inappropriate given the height of the ceiling, the nature
of the product, or the type of operation conducted in that area, such
ceilings are adequate in many areas of a manufacturing facility, and
certainly are appropriate in places where product is labeled or stored. 
The comments argue that replacing such ceilings with surfaces that are
“smooth and hard” is unnecessary.  Several other comments argue that
they could find no precedent in any food CGMP regulations for a
provision specifying “smooth and hard surfaces” for ceilings, but
did identify a precedent in the section of drug CGMP requirements
relating to “aseptic processing.”  The comments state that adopting
such a drug CGMP requirement is inappropriate for dietary supplements.  

     The comments say the overall purpose of proposed § 111.20(d)(1)
should be to ensure that facilities can be kept in a clean and sanitary
condition.  The comments would revise proposed § 111.20(d)(1) to
require physical plants to have surfaces that can be adequately cleaned,
but would give manufacturers the flexibility to use appropriate surfaces
in different parts of a plant.

     The comments also argue that the rule’s specificity establishes a
conundrum for certain manufacturers to conform to other Federal
regulations, i.e., OSHA noise levels.  The comments argue that firms
should be allowed to simultaneously conform to both OSHA and FDA
requirements.

     (Response)  We agree that a smooth and hard surface may not be
necessary in every case to prevent contamination  of the dietary
supplement.  However, you may need floors, walls, and ceilings that are
constructed of smooth and hard surfaces to prevent contamination of the
dietary supplement when, for example, physical attributes of components
(e.g., particle size or electrostatic charge) would make it difficult to
keep floors, walls and ceilings clean.  Consequently, we conclude that a
requirement that the physical plant have floors, walls and ceilings that
can be adequately cleaned and kept clean and in good repair to prevent
contamination of the dietary supplement is sufficient.  We are revising
final § 111.20(d)(1) to remove the language concerning smooth and hard
surfaces.  The final rule gives you the flexibility to determine how
best to construct your facility in order to prevent contamination and to
ensure the quality of the dietary supplements you manufacture, package,
label, or hold.  

	Section 111.20(d)(1)(ii) of the final rule (proposed § 111.20(d)(2))
requires your physical plant design and construction to have fixtures,
ducts, and pipes that do not contaminate components, dietary
supplements, or contact surfaces by dripping or other leakage, or
condensate.  Final § 111.20(d)(1)(iii) (proposed § 111.20(d)(3))
pertains to adequate ventilation or environmental control equipment.  We
added “or other leakage” to clarify that the requirement relates to
“leakage” regardless of whether the leakage is in the form of
“dripping.”

	(Comment 102)  Proposed § 111.20(d)(5) would require your physical
plant design and construction to include equipment that controls
temperature and humidity.  Several comments suggest adding a qualifier
to the temperature and humidity control requirements so that controls
are only required as necessary to prevent adulteration.  The comments
state there is adequate evidence that temperature and humidity do not
stimulate reproduction of microorganisms and pests in dietary
supplements.  The comments also argue that retesting older ingredients
stored in an uncontrolled environment and subjected to heat, cold, and
ambient humidity produced no evidence of reproduction of microorganisms.
 According to the comments, temperature and humidity may present issues
with raw, unprocessed botanical ingredients or animal-derived
ingredients, but there is no proven issue with the powdered botanical
and animal derived ingredients used by the dietary supplement industry.

     Several comments argue against requiring temperature and heat
controls, asserting that most equipment used to manufacture dietary
supplements is often cleaned with large amounts of hot water, and
therefore temperature and humidity controls are not practical.

	(Response)  We agree that controls for temperature and humidity should
only be required when necessary to ensure the quality of the dietary
supplement, and we are revising final § 111.20(d) accordingly. 
However, we disagree that there is adequate evidence that temperature
and humidity do not stimulate reproduction of microorganisms in dietary
supplements.  It is well-recognized that microorganisms such as bacteria
will grow in a warm environment and that microorganisms, such as molds,
will grow in a moist environment.  In addition, if the comments are
suggesting that this final rule should only include requirements that
derive from specific, already known examples that the absence of a
requirement directly led to a problem with a dietary supplement, we
disagree.  CGMP requirements can help prevent products from becoming
adulterated during the manufacturing process, and, in certain cases,
controlling temperature and humidity may be necessary to ensure the
quality of the dietary supplement. 

     With respect to the comments stating that using hot water to clean
equipment makes control of temperature and humidity impractical, we
advise that a firm unable to control temperature and humidity in those
parts of its facility where control is necessary to ensure the quality
of the dietary supplement because it uses hot water to clean equipment
would not be in compliance with final § 111.20(c).  The provision
requires that your physical plant have, and that you use, separate and
defined areas of adequate size, or other control systems, to prevent
contamination during operations such as cleaning contact surfaces (final
§ 111.20(c)(5)).

     Final § 111.20(d)(2) (proposed § 111.20(d)(4)) requires that,
when fans and other air-blowing equipment are used, such fans and
equipment be located and operated in a manner that minimizes the
potential for microorganisms and particulate matter to contaminate
components, dietary supplements, or contact surfaces.

   	(Comment 103)  Several comments interpret proposed § 111.20(d)(4)
as requiring fans and air-blowing equipment.  These comments state this
type of equipment is not always needed and may, in some instances, be
more likely to cause adulteration than prevent it.  The comments ask us
to clarify that fans and other air-blowing equipment are only required
when they are necessary to prevent adulteration.  

     (Response)  Proposed § 111.20(d)(4) was intended to require that
any fans and other air-blowing equipment you use be located and operated
in a manner that minimizes the potential for microorganisms and
particulate matter to contaminate components, dietary supplements, or
contact surfaces.  

     Nevertheless, given the comments’ misinterpretation, we are
revising proposed § 111.20(d)(4) (now renumbered as final §
111.20(d)(2)) to state that, “When fans and other air-blowing
equipment are used,” those fans and equipment must be located and
operated in a manner that minimizes the potential for contamination by
microorganisms and particulate matter.  This should clarify that the
rule does not mandate the use of fans and air-blowing equipment.

	(Comment 104)  Some comments state that exhaust and venting equipment
can, under certain circumstances, be a source of microbial
contamination.  The comments would revise proposed § 111.20(d)(4) to
read:  “Fans and other air-blowing or exhaust and venting equipment
located and operated in a manner that minimizes the potential for
microorganisms and particulate matter to contaminate components, dietary
ingredients, dietary supplements, or contact surfaces.”

     (Response)  We decline to revise the rule as suggested by these
comments as there is no need to do so.  We consider exhaust equipment
and venting equipment to be types of fans or air-blowing equipment and
therefore covered by the term  “fans and other air-blowing
equipment.”

4.  Final § 111.20(e) 

     Final § 111.20(e) (proposed § 111.20(e)) requires that any
physical plant that you use in the manufacturing, packaging, labeling,
or holding of dietary supplements provide adequate light in: (1) All
areas where components or dietary supplements are examined, processed,
or held; (2) all areas where contact surfaces are cleaned; and (3)
hand-washing areas, dressing and locker rooms, and bathrooms.  

     We did not receive any comments specific to proposed § 111.20(e). 

5.  Final § 111.20(f) 

	Final § 111.20(f) (proposed § 111.20(f)) requires that any physical
plant you use in the manufacturing, packaging, labeling, or holding of
dietary supplements use safety-type light bulbs, fixtures, skylights, or
other glass or glass-like materials when the light bulbs, fixtures,
skylights, or other glass or glass-like materials are suspended over
exposed components or dietary supplements in any step of preparation,
unless your physical plant is otherwise constructed in a manner that
will protect against contamination of components or dietary supplements
in case of breakage of glass or glass-like materials.  

	We did not receive any comments specific to proposed § 111.20(f).  On
our own initiative, we are making clarifying changes to final §
111.20(f) by:

Adding “or glass-like materials” after the word, “glass.” 
Although proposed § 111.20(f) only specified glass, its intent was to
cover any material that could shatter and contaminate components,
dietary supplements or contact surfaces.  Therefore, we are adding
glass-like material to final § 111.20(f) to cover fixtures and
skylights that use non-glass materials (such as acrylic and
polycarbonate materials) but could still contaminate components, dietary
supplements, or contact surfaces if shattered or broken.

Further, we are stating that the requirement applies when the light
bulbs, fixtures, skylights, or other glass or glass-like materials are
suspended over exposed components or dietary supplements in any step of
preparation.  We made this change to prevent the rule from being
misinterpreted as requiring firms to suspend light bulbs, fixtures,
skylights, or other glass over components or dietary supplements in
every step of preparation.

6.  Final § 111.20(g)  	

Final § 111.20(g) (proposed § 111.20(g)) requires that any physical
plant you use in the manufacturing, packaging, labeling, or holding of
dietary supplements provide effective protection against contamination
of components and dietary supplements in bulk fermentation vessels. 
Such protection includes: (1) Use of protective coverings; (2) placement
in areas where you can eliminate harborages for pests over and around
the vessels; (3) placement in areas where you can check regularly for
pests, pest infestation, filth or any other extraneous materials; and
(4) use of skimming equipment.  

     We did not receive comments specific to proposed § 111.20(g).  We
have made non-substantive, grammatical changes to the provision by
replacing “by any effective means” with “effective” before the
word protection and “including consideration of” with “by, for
example:”. 

7.  Final § 111.20(h) 

	Final § 111.20(h) (proposed § 111.20(h)) requires that any physical
plant you use in the manufacturing, packaging, labeling or holding of
dietary supplements use adequate screening or other protection against
pests, where necessary.  

     (Comment 105)  One comment argues that proposed § 111.20(h) should
be deleted because it is redundant when compared to proposed §
111.15(c) which would require you to not allow animals or pests in any
area of your physical plant, except for guard or guide dogs in certain
circumstances.

     (Response)  We disagree that final § 111.20(h) is redundant to
proposed § 111.15(c)(now renumbered as final § 111.15(d)).  Although
both paragraphs deal with pests, final § 111.20(h) establishes a design
requirement (i.e., a specific requirement to use adequate screening or
other protection), while final § 111.15(d) sets forth a sanitation
requirement (i.e., to not allow animals or pests in your physical
plant).  Therefore, we are retaining § 111.20(h) in the final rule.

G.  Under This Subpart, What Records MustDo You Make and Keep? 

(Final § 111.23)

     Final § 111.23(a) requires you to make and keep records required
under this subpart in accordance with subpart P.

	Final § 111.23(b) requires that you make and keep records of the
written procedures for cleaning the physical plant and for pest control.
 This provision was added to ensure that the written procedures now
required under final § 111.16 are maintained as required under subpart
P.

 	Final § 111.23(c)(1) (proposed § 111.15(d)(3)) requires that you
make and keep records that water, when used in a manner such that the
water may become a component of the dietary supplement, meets the
requirements of final § 111.15(e)(2).  

	

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part 110, we have responded to this issue in section V.  The absence of
a provision in drug CGMP requirements does not preclude us from
requiring it in this final rule establishing CGMP requirements for
dietary supplements for which we have no pre-approval scheme for
ingredients used in such a product.

	(Comment 107)  Several comments ask us to clarify that, if a municipal
water supply is used in a facility, the municipal water report is
acceptable documentation of water quality.  These comments say that a
city’s yearly report of its municipal water quality should be
sufficient documentation, and that independent testing should not be
required.  Several comments claim that our officials made statements to
this effect during a public meeting held on May 6, 2003.

     The comments also assert that water quality in a community is
typically well known due to public notification that is required by EPA
or due to other resources.  These comments say that municipal water
supplies are also well controlled as a result of EPA regulations, and
that, if water quality in a community or country is suspect, we can move
aggressively to enforce the standards.  The comments argue that,
overall, our enforcement burden would be less than requiring every
company in the industry to maintain and produce documentation related to
water quality.

     (Response)  A yearly municipal report is a good starting point for
documenting water meets the requirements of final § 111.15(e), however,
such a report cannot stand on its own as the only assurance that the
water of the regulated body (such as persons subject to this final rule)
complies with these regulations.  A municipal water report offers
reasonable assurance that the water entering your plant satisfies the
requirements of EPA’s NPDW regulations.  However, as discussed above,
the requirement to show that the water that is used in a manner such
that the water may become a component of the dietary supplement, e.g.,
when such water contacts components, dietary supplements, or any contact
surface, meets the requirements of § 111.15(e)(2), applies to water at
the point of use - i.e., after it has passed through your plumbing
system.  

     If you use a municipal water supply, you should take steps to
ensure that you are at all times aware of problems, such as an acute
problem with microbial contamination or a long-term problem associated
with lead pipes that are present in some parts of the city water supply,
that may not be reflected in the municipal water report. 

FDA-Internal-Deliberative-Confidential

Final Subpart C 9-28-05, 6-26-06, 3-30-07, 5-04-07

page   PAGE  340 

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