Reformulating Drug 
Products That Contain 
Carbomers Manufactured 
With Benzene  
Guidance for Industry 
 
 
 
This guidance is for immediate implementation.
 
 
FDA is issuing this guidance for immediate implementation in accordance with 21 CFR 
10.115(g)(2). Submit one set of either electronic or written comments on this guidance at any 
time. Submit electronic comments to https://www.regulations.gov. Submit written comments to 
the Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852. You should identify all comments with the docket number 
listed in the notice of availability that publishes in the Federal Register. 
 
For questions regarding this document, contact Pallavi Nithyanandan at 301-796-7546.  
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
 
December 2023 
Pharmaceutical Quality/CMC 
   
Reformulating Drug 
Products That Contain 
Carbomers Manufactured 
With Benzene  
Guidance for Industry 
 
 
 
Additional copies are available from: 
 
Office of Communications, Division of Drug Information 
Center for Drug Evaluation and Research 
Food and Drug Administration 
10001 New Hampshire Ave., Hillandale Bldg., 4th Floor  
Silver Spring, MD  20993-0002  
Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353; Email: druginfo@fda.hhs.gov 
https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
 
December 2023 
Pharmaceutical Quality/CMC
   
TABLE OF CONTENTS 
 
I.  INTRODUCTION..................................................................................................1 
II.  BACKGROUND ....................................................................................................2 
III.  RECOMMENDATIONS AND REQUIREMENTS ...........................................3 
REFERENCES ...................................................................................................................9 
APPENDIX .......................................................................................................................10 
 
 
  Contains Nonbinding Recommendations 
Reformulating Drug Products That Contain  
Carbomers Manufactured With Benzene  
Guidance for Industry1 
 
 
 
 
This guidance represents the current thinking of the Food and Drug Administration (FDA or 
Agency) on this topic.  It does not establish any rights for any person and is not binding on FDA 
or the public.  You can use an alternative approach if it satisfies the requirements of the 
applicable statutes and regulations.  To discuss an alternative approach, contact the FDA staff 
responsible for this guidance as listed on the title page.   
 
 
 
 
I.  INTRODUCTION  
 
The purpose of this guidance is to provide recommendations for applicants and manufacturers2 
on what tests should be performed and what documentation should be submitted or available to 
FDA to support the reformulation of drug products that use carbomers manufactured with 
benzene. Certain United States Pharmacopeia (USP) carbomer monographs currently allow for 
unacceptable levels of benzene, which raises safety concerns. FDA has requested that the USP 
omit (or remove) these monographs,3 and applicants and manufacturers may need to reformulate 
their drug products to avoid using these carbomers. This guidance provides recommendations for 
testing and documentation related to reformulation, taking into consideration the various routes 
of administration and dosage forms of affected drug products. For application holders, this 
guidance also recommends appropriate submission types to notify the Agency of such changes. 
 
 
1 This guidance has been prepared by the Office of Pharmaceutical Quality in the Center for Drug Evaluation and 
Research at the Food and Drug Administration. 
 
2 For purposes of this guidance, the term applicants and manufacturers refers collectively to applicants and 
application holders, owners of marketed drug products that are not the subject of approved applications (such as 
OTC monograph drug products), and drug product manufacturers.   
 
3 See FDAs request to USP at https://www.fda.gov/media/174455/download?attachment. A link to this letter can 
also be found on the following FDA web page: FDA alerts drug manufacturers to the risk of benzene contamination 
in certain drugs (https://www.fda.gov/drugs/pharmaceutical-quality-resources/fda-alerts-drug-manufacturers-risk-
benzene-contamination-certain-drugs). On November 18, 2022, in response to FDAs request, the USP issued a 
Notice of Intent to Revise, stating that it intends to omit the Carbomer 934, Carbomer 934P, Carbomer 940, 
Carbomer 941, and Carbomer 1342 monographs, with a targeted official date of August 1, 2025. See 
https://www.uspnf.com/notices-carbomer-omissions-20221118. 
1  Contains Nonbinding Recommendations 
The recommendations in this guidance are consistent with the International Council for 
Harmonisation (ICH) guidance for industry Q3C Impurities: Residual Solvents (December 1997) 
and the companion ICH guidance for industry Q3C  Tables and List (August 2018) (2018 ICH 
Q3C guidance),4 as well as applicable scale-up and post-approval changes (SUPAC) guidances.5 
The recommendations in this guidance apply to drug products subject to both new drug 
applications (NDAs) and abbreviated new drug applications (ANDAs) (hereafter application 
products), as well as other marketed drugs, including nonprescription drugs without an approved 
application governed by the provisions of section 505G of the Federal Food, Drug, and Cosmetic 
Act (FD&C Act) (21 U.S.C. 355h) (i.e., OTC monograph drugs). This guidance applies to 
topically applied liquid and semisolid dosage forms (e.g., creams, gels, lotions, ointments), 
immediate-release solid oral dosage forms, modified-release solid oral dosage forms, and oral 
suspensions.   
 
This guidance does not address toxicological considerations related to the unavoidable use of 
benzene in drug products, drug substances, or inactive ingredients.  
 
FDA is implementing this guidance without prior public comment because the Agency has 
determined that prior public participation is not feasible or appropriate (see 21 CFR 10.115(g)(2) 
and (g)(3)). FDA made this determination because benzene is a known human carcinogen. By 
providing recommendations on how applicants and manufacturers can reformulate certain drug 
products, the Agency seeks to facilitate the transition away from using carbomers manufactured 
with high levels of benzene. Publishing this guidance without prior public comment addresses 
the immediate public health need to expedite the discontinuation of the use of these carbomers 
and provides a less burdensome risk-based approach to applicant submissions, relative to 
existing guidances on SUPAC.   
 
In general, FDAs guidance documents do not establish legally enforceable responsibilities. 
Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
as recommendations, unless specific regulatory or statutory requirements are cited. The use of 
the word should in Agency guidances means that something is suggested or recommended, but 
not required. 
 
 
II.  BACKGROUND 
 
Carbomers are a group of polymers composed of acrylic acid. They are widely used as inactive 
ingredients in drug products as fillers, emulsifiers, gelling agents, and binding agents. There are 
carbomers currently used as inactive ingredients that are manufactured using benzene as a 
polymerization solvent. Benzene is a known human carcinogen. As such, both the 2018 ICH 
Q3C guidance and USP General Chapter <467> Residual Solvents designate benzene as a 
Class 1 solvent (i.e., Solvents That Should Be Avoided) and recommend that it not be employed 
in the manufacture of drug substances, excipients, and drug products. However, there are still 
 
4 We update guidances periodically. For the most recent version of a guidance, check the FDA guidance web page at 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents.  
 
5 See the SUPAC guidances listed in the References section of this guidance.   
2  Contains Nonbinding Recommendations 
several grades of carbomers manufactured using benzene as a solvent that are used in 
pharmaceutical products even though alternative grades of carbomers manufactured without the 
use of benzene are available.  
 
At the time of publication of this guidance, carbomers manufactured with benzene that are used 
in FDA-regulated drug products may fall under the United States Pharmacopeia-National 
Formulary (USP-NF) monographs Carbomer 934, Carbomer 934P, Carbomer 940, Carbomer 
941, or Carbomer 1342. These monographs permit benzene levels as high as 5,000 parts per 
million (ppm). In comparison, the USP-NF Carbomer Homopolymer, Carbomer Copolymer, and 
Carbomer Interpolymer monographs cover carbomers that are manufactured without benzene 
and limit benzene as an impurity to no more than 2 ppm. To avoid confusion, and because of the 
safety concerns associated with these unacceptable levels of benzene permitted by these 
monographs, FDA has asked the USP to remove (or omit) the Carbomer 934P, Carbomer 940, 
Carbomer 934, Carbomer 1342, and Carbomer 941 monographs from the USP-NF compendium. 
FDA is issuing this guidance to help facilitate and expedite the reformulation of drug products 
that use carbomers manufactured with benzene.  
 
 
III.  RECOMMENDATIONS AND REQUIREMENTS 
 
Under section 501(a)(2)(b) of the FD&C Act (21 U.S.C. 351(a)(2)(B)), a drug that is not 
manufactured, processed, packed, or held in conformity with current good manufacturing 
practice to assure that the drug meets requirements for safety, and quality and purity 
characteristics, which it purports or is represented to possess, is considered adulterated.6 
Manufacturers should not use benzene in the manufacture of drugs. The 2018 ICH Q3C guidance 
states that Class 1 solvents, such as benzene, generally should not be employed in the 
manufacture of drug substances, excipients, or drug products because of their unacceptable 
toxicity.7  
 
The 2018 ICH Q3C guidance and USP General Chapter <467> provide guidance on limited 
cases where the presence of benzene may be tolerated. Specifically, both sources note that if 
benzene use is unavoidable to produce a drug product with a significant therapeutic advance, 
then its level should be restricted to the level recommended in the 2018 ICH Q3C guidance and 
USP General Chapter <467>, unless otherwise justified.  
 
 
6 Entities that manufacture drug products that may be at risk for benzene contamination should test their drugs 
accordingly and should not release any drug product batch that contains benzene at levels above 2 ppm, consistent 
with the recommendations described in the 2018 ICH Q3C guidance. If any drug product batches with benzene 
levels above 2 ppm are already in distribution, the manufacturer should contact FDA to discuss the voluntary 
initiation of a recall. See https://www.fda.gov/drugs/pharmaceutical-quality-resources/fda-alerts-drug-
manufacturers-risk-benzene-contamination-certain-drugs. 
 
7 See the 2018 ICH Q3C guidance at p. 5. 
3  Contains Nonbinding Recommendations 
For drugs that are recognized in an official compendium, manufacturers that use Carbomer 934P, 
Carbomer 940, Carbomer 934, Carbomer 1342, and Carbomer 941 as solvents will be required to 
reformulate to avoid use of these carbomers in their drug products once the USP monographs 
have been removed.8 However, pending the USPs removal of the monographs for these 
carbomers that contain unacceptable levels of benzene, FDA recommends that manufacturers 
select an alternative grade of carbomer that is manufactured without the use of benzene and has 
similar chemical composition (e.g., carbomer homopolymer) and physical properties (e.g., 
viscosity, rheology).  
 
When switching to non-benzene-containing grades of carbomers, applicants and manufacturers 
should consider the following information regarding chemistry, manufacturing, and controls; in 
vitro release or dissolution testing; and in vivo bioequivalence documentation.   
 
  Applicants are responsible for evaluating the effects of any postapproval compositional 
change on the identity, strength, quality, purity, and potency of the drug product as these 
factors may relate to the safety or effectiveness of the drug product before distribution of 
the drug product made with the change.9 Applicants must submit proposed formulation 
changes through supplements to their applications.10  
 
  For applicants and manufacturers (including manufacturers of OTC monograph drugs) 
making such a formulation change, information to support compliance with current good 
manufacturing practice requirements11 must be documented and made available for FDA 
to review during an inspection under section 704(a)(1) of the FD&C Act (21 U.S.C. 
374(a)(1)) or when requested by FDA in advance or in lieu of an inspection as described 
in section 704(a)(4) of the FD&C Act (21 U.S.C. 374(a)(4)). 
 
  The studies that should be conducted following reformulation of drug products with 
alternative carbomers include tests for critical quality attributes for drug products (e.g., 
applicable comparative physicochemical and structural characterizations), and in some 
cases, additional bioequivalence studies depending on the dosage form, route of 
administration, intended use, and the scope/level of the proposed change as determined 
by the principles described in the applicable SUPAC guidances. Below is an outline of 
 
8 Although section 501(b) of the FD&C Act (21 U.S.C. 351(b)) provides in part that a drug, including an inactive 
ingredient, is adulterated if it is a drug the name of which is recognized in an official compendium and its quality 
falls below the standard set forth in the compendium, unless that difference in quality is plainly stated on its label, 
the drug must also meet the safety standard as stated in section 501(a)(2)(B) of the FD&C Act.  
 
9 See section 506A of the FD&C Act (21 U.S.C. 356a), 21 CFR 314.70, and 21 CFR 314.97. A holder of an 
approved application under section 505 of the FD&C Act (21 U.S.C. 355) must assess the effects of the change 
before distributing a drug product made with a manufacturing change (see 21 CFR 314.70(a)(2) and 21 CFR 
314.97(a)). In addition, information to support compliance with current good manufacturing practice requirements 
must be documented (see, for example, 21 CFR 211.100(a), 21 CFR 211.160(b), 21 CFR 211.180(e), and 21 CFR 
211.194(a)). 
 
10 Applicants must notify FDA of a change to the conditions established in an approved application. See 21 CFR 
314.70 and 21 CFR 314.97. 
 
11 See, for example, 21 CFR 211.100(a), 21 CFR 211.160(b), 211.180(e), and 211.194(a). 
4  Contains Nonbinding Recommendations 
the relevant dosage forms and the respective SUPAC guidances, if one is available for 
that dosage form. The recommended test documentation and submission type12 for 
different dosage forms are summarized in the Appendix. Release testing (based on 
approved specifications for application products), batch records, stability data, and 
dissolution/in vitro release testing (IVRT) data (as applicable) should be documented for 
all dosage forms.  
 
  Semisolid dosage forms. Applicants and manufacturers should follow the 

recommendations in the guidance for industry Nonsterile Semisolid Dosage Forms: 
Scale-Up and Postapproval Changes: Chemistry, Manufacturing, and Controls; In 
Vitro Release Testing and In Vivo Bioequivalence Documentation (May 1997) 
(SUPAC-SS guidance) for the appropriate tests and studies to be conducted and 
documented, as well as for the recommended submission type, if applicable.  
 
  When substituting a carbomer manufactured with benzene with an alternative 
carbomer that has similar chemical composition and physical properties and in a 
similar quantity,13 applicants and manufacturers should follow the 
recommendations for level 2 changes (see the SUPAC-SS guidance, section 
III.B.). Additional chemistry documentation can include physicochemical and 
structural characterization data (e.g., evaluation of pH and rheology for one batch 
of the pre- and post-change products). An IVRT study to compare the pre- and 
post-change batches should be generated, and applicants should include this 
information in their submission. For application products, a changes being 
effected in 30 days (CBE-30) supplement should be submitted. 
 
  When substituting with ingredient(s) that do not meet the above parameters 
(including non-carbomer ingredients), recommendations for level 3 changes 
should be followed (see the SUPAC-SS guidance, section III.C.). For application 
products, a prior approval supplement (PAS) should be submitted. 
 
  Immediate-release solid oral dosage forms. Applicants and manufacturers should 

follow the recommendations in the guidance for industry Immediate Release Solid 
Oral Dosage Forms: Scale-Up and Postapproval Changes: Chemistry, 
Manufacturing, and Controls, In Vitro Dissolution Testing, and In Vivo 
Bioequivalence Documentation (November 1995) (SUPAC-IR guidance) for the 
appropriate tests and studies to be conducted and documented, as well as for the 
recommended submission type, if applicable, except as otherwise noted in this 
guidance. 
 
  When substituting a carbomer manufactured with benzene with an alternative 
carbomer that has similar chemical composition and physical properties and in a 
 
12 SUPAC guidances use the term filing documentation to describe recommended application submission types and 
filing categories associated with a change in the chemistry, manufacturing, and controls of a drug. 
 
13 Not exceeding the range noted in the SUPAC-SS guidance, section III.B.1. 
5  Contains Nonbinding Recommendations 
similar quantity,14 applicants and manufacturers should follow the 
recommendations for level 2 changes (see the SUPAC-IR guidance, section 
III.B.). However, for application products, a CBE-30 supplement should be 
submitted rather than a PAS.15 Applicants and manufacturers should use risk 
assessment approaches to assess the potential effect of the change on drug quality 
and manage the risk appropriately.16 The change from a carbomer manufactured 
with benzene to one manufactured without benzene is not expected to 
significantly alter quality or performance for an immediate-release dosage form 
because the new carbomer should provide similar structural characteristics and 
performance for the drug, presuming the applicant or manufacturer is using 
carbomers that meet established quality requirements.  
 
  When substituting with ingredient(s) that do not meet the above parameters, 
recommendations for level 3 changes should be followed (see the SUPAC-IR 
guidance, section III.C.). For application products, a PAS should be submitted.  
 
  Modified-release solid oral dosage forms. Applicants and manufacturers should 

follow the recommendations in the guidance for industry SUPAC-MR: Modified 
Release Solid Oral Dosage Forms: Scale-Up and Postapproval Changes: Chemistry, 
Manufacturing, and Controls; In Vitro Dissolution Testing and In Vivo 
Bioequivalence Documentation (September 1997) (SUPAC-MR guidance) for the 
appropriate tests and studies to be conducted and documented, as well as for the 
recommended submission type, if applicable, except as otherwise noted in this 
guidance.   
 
  When substituting a carbomer manufactured with benzene with an alternative 
carbomer that has similar chemical composition and physical properties and in a 
similar quantity,17 applicants and manufacturers should follow the 
recommendations for level 2 changes (see the SUPAC-MR guidance, sections 
III.B. and IV.B.). For application products, when the carbomer is a release-
controlling excipient, a PAS should be submitted. However, when the carbomer is 
a non-release-controlling excipient, a CBE-30 supplement should be submitted 
rather than a PAS.18 Applicants and manufacturers should use risk assessment 
 
14 Not exceeding the range noted in the SUPAC-IR guidance, section III.B.1.b. 
 
15 Section 506A of the FD&C Act addresses manufacturing changes made postapproval and defines some types of 
changes as major changes. Generally, major manufacturing changes require applicants to file a PAS. However, FDA 
may change the reporting category for changes to specifications and reformulation. See section 506A(c)(2)(A) of the 
FD&C Act. 
 
16 See the ICH guidance for industry Q9(R1) Quality Risk Management (May 2023). 
 
17 Not exceeding the range noted in the SUPAC-MR guidance, section III.B.1.b. 
 
18 Section 506A of the FD&C Act addresses manufacturing changes made postapproval and defines some types of 
changes as major changes. Generally, major manufacturing changes require applicants to file a PAS. However, FDA 
may change the reporting category for changes to specifications and reformulation. See section 506A(c)(2)(A) of the 
FD&C Act. 
6  Contains Nonbinding Recommendations 
approaches to assess the potential effect of the change on drug quality and 
manage the risk appropriately.19 Provided the carbomer is a non-release-
controlling excipient, the change from a carbomer manufactured with benzene to 
one manufactured without benzene is not expected to significantly alter quality or 
performance for a modified-release dosage form, because the new carbomer 
should provide similar structural characteristics and performance for the drug, 
presuming the applicant or manufacturer is using carbomers that meet established 
quality requirements.  
 
  When substituting with ingredient(s) that do not meet the above parameters 
(including non-carbomer ingredients), recommendations for level 3 changes 
should be followed (see the SUPAC-MR guidance, sections III.C. and IV.C.). For 
application products, a PAS should be submitted. 
  
  Oral suspensions.  

 
  Oral suspensions are not addressed in current SUPAC guidances. 
 
  Testing to demonstrate that the reformulated product meets specifications and 
executed batch records should be documented and, for application products, 
provided. Applicants and manufacturers should perform stability testing 
according to an established stability protocol. For application products, the 
supplement supporting reformulation should include 3 months of accelerated 
stability data for 1 batch, and 1 batch should be placed on long-term stability 
studies. Before marketing, manufacturers of marketed drug products without an 
application should also compile 3 months of accelerated stability data for 1 batch 
and place 1 batch on long-term stability studies.  
 
  When substituting a carbomer manufactured with benzene with the same 
quantity20 of an alternative carbomer that has similar chemical composition and 
physical properties, a CBE-30 supplement should be submitted rather than a PAS 
for application products.  
 
  When substituting with ingredient(s) that do not meet the above parameters 
(including non-carbomer ingredients or a change in quantity), a PAS should be 
submitted for application products. 
 
  Applicants and manufacturers should use risk assessment approaches to assess the 
potential effect of the change on drug quality and manage the risk appropriately.21 
 
 
19 See ICH Q9(R1). 
 
20 Applicants should provide a rationale to justify any potential changes in quantity. 
 
21 See ICH Q9(R1). 
7  Contains Nonbinding Recommendations 
  For dosage forms and/or routes of administration (e.g., ophthalmic, buccal) that are not 
covered in this guidance, applicants should contact FDA for recommendations. For NDA 
products, the applicant should contact the specific products review division. For ANDA 
products, the applicant should contact FDA through a controlled correspondence for 
recommendations.  
 
  The above recommendations generally apply to premarketing changes as well as 
postmarketing changes. However, in the event of premarketing changes, applicants 
should contact FDA for recommendations. For pending NDAs, the applicant should 
contact the specific products review division. For pending ANDAs, the applicant should 
contact the project manager specified for the ANDA. For communications before 
submitting an ANDA, applicants should refer to the guidance for industry Controlled 
Correspondence Related to Generic Drug Development (December 2020) and the 
guidance for industry Formal Meetings Between FDA and ANDA Applicants of Complex 
Products Under GDUFA (October 2022) for additional information describing the 
procedures on how to clarify regulatory expectations regarding individual drug 
development programs. 
 
8  Contains Nonbinding Recommendations 
REFERENCES22 
 
Abbreviated New Drug Application-Related Guidances 
 
Guidance for industry Controlled Correspondence Related to Generic Drug Development 
(December 2020) 
 
Guidance for industry Formal Meetings Between FDA and ANDA Applicants of Complex 
Products Under GDUFA (October 2022) 
 
ICH Guidances 
 
ICH guidance for industry Q3C  Tables and List (August 2018) 
 
ICH guidance for industry Q3C Impurities: Residual Solvents (December 1997) 
 
ICH guidance for industry Q9(R1) Quality Risk Management (May 2023) 
 
ICH guidance for industry Q10 Pharmaceutical Quality System (April 2009) 
 
Pharmaceutical Quality System/Quality System Guidances 
 
Guidance for industry Quality Systems Approach to Pharmaceutical CGMP Regulations 
(September 2006) 
 
Scale-Up and Post-Approval Changes Guidances 
 
Guidance for industry Immediate Release Solid Oral Dosage Forms: Scale-Up and Postapproval 
Changes: Chemistry, Manufacturing, and Controls, In Vitro Dissolution Testing, and In Vivo 
Bioequivalence Documentation (November 1995)  
 
Guidance for industry Nonsterile Semisolid Dosage Forms: Scale-Up and Postapproval 
Changes: Chemistry, Manufacturing, and Controls; In Vitro Release Testing and In Vivo 
Bioequivalence Documentation (May 1997) 
 
Guidance for industry SUPAC-MR: Modified Release Solid Oral Dosage Forms: Scale-Up and 
Postapproval Changes: Chemistry, Manufacturing, and Controls; In Vitro Dissolution Testing 
and In Vivo Bioequivalence Documentation (September 1997)  
 
 
 
22 We update guidances periodically.  For the most recent version of a guidance, check the FDA guidance web page 
at https://www.fda.gov/regulatory-information/search-fda-guidance-documents. 
9  Contains Nonbinding Recommendations 
APPENDIX 
 
This table summarizes the recommended test documentation and filing documentation (for 
application products) for different dosage forms.  
 
Dosage Form   Test Documentation  Filing Documentation 
Semisolid Dosage Forms    Chemistry    CBE-30* supplement 
documentation    PAS* (level 3 change 
  In vitro release  only) 
documentation  
  Physicochemical and 
structural 
characterization data 
  In vivo 
bioequivalence 
documentation as 
appropriate  
Immediate-Release Solid    Chemistry    CBE-30 supplement 
Oral Dosage Forms  documentation    PAS (level 3 change 
  Dissolution  only) 
documentation  
  In vivo 
bioequivalence 
documentation as 
appropriate  
Modified-Release Solid Oral    Chemistry    CBE-30 supplement 
Dosage Forms  documentation    PAS (when level 3 
  Dissolution  change and/or when 
documentation   carbomer is release-
  In vivo  controlling excipient) 
bioequivalence 
documentation as 
appropriate 
Oral Suspensions    Chemistry    CBE-30 supplement 
documentation    PAS (when 
  Dissolution  substituting with 
documentation   alternative excipients 
  In vivo  that do not have 
bioequivalence  similar chemical 
documentation as  composition and 
appropriate   physical properties) 
* CBE-30 = changes being effected in 30 days; PAS = prior approval supplement 
10