Title: Pharmaceutical Regulations
1Pharmaceutical Regulations
- Dana Rees Folley
- DWQ Pretreatment, Emergency Response, and
Collection Systems Unit (PERCS) - NC Pretreatment Consortium Annual Pretreatment
Workshop - September 19, 2006
2Pharmaceuticals - 40 CFR 439
- second most common categorical IU in NC 29 in
17 cities - grouped togethertown with 3 SIUs all 439town
with 80 SIUs - 2 439s - 5 subcategories - 4 ways to make drugs, plus
research
3Pharmaceuticals - 40 CFR 439
- Federal Categorical Regulation
- 10/27/1983 - EPA published original Rule in
Federal Register - Only regulated cyanide
- IU could certify cyanide not used or generated
then not considered categorical
4Pharmaceuticals - 40 CFR 439
- 5/2/95 - EPA published Proposed New Rule
added ammonia and many organics parameters - 9/21/98 - EPA published Final Rule in Federal
Register - BUT
5Pharmaceuticals - 40 CFR 439
- Revised Six Times!
- Most typos and reorganization
- But
- 3/4/99 preamble wording changes limits
changes due to rounding errors and typos - 3/13/03 - delete methyl cellulose altogether
- 3/16/99, 9/2/99, 6/11/03, 5/6/04
6Pharmaceuticals - 40 CFR 439
- EPAs Pharmaceutical Web-sitehttp//www.epa.gov/w
aterscience/guide/pharm/ - All FR publications
- Analytical Guidance
- Permit Guidance
- Pharmaceutical Info on PERCS Web-sitehttp//h2o.e
nr.state.nc.us/percs/ - Pharmaceutical Sections on Pretreatment Permit
Writing and Headworks Analysis Pages 40 CFR 439
7/1/05 version lots more
740 CFR 439 Applies to -
- Research and manufacturing of pharmaceuticals,
which are generally, but not exclusively,
reported under SIC codes - 2833 medicinal chemicals and botanical products
- 2934 pharmaceutical preparations
- 2836 biological products, except diagnostic
substances.
840 CFR 439 Applies to (cont.) -
- Other products manufactured by 4 subcategory
methods - fermentation, extraction, chemical
synthesis, mixing, compounding and formulation -
And - considered pharmaceutical active ingredient by
FDA - Or
- Multiple end-use products intended for use
primarily in pharmaceutical application
940 CFR 439 Applies to (cont.) -
- pharm products intermediates not subject to
other categorical regs, provided manufacturing
generates process wastewaters similar to those
derived from manufacture of pharmaceuticals (ex.,
citric acid) - Cosmetic preparations SIC 2844 containing
pharmaceutical active ingredients, or active
ingredients intended for treatment of a skin
condition
1040 CFR 439 Does Not Apply to
- 439.0(b)(4) and 439.0(c)(1) (11) - various
products that are excluded - Medical/dental/lab instruments, equipment,
services - Food/Beverage/Animal feed with vitamins,
antibiotics, pharmaceu-tically active, if mostly
non-pharm and characteristics dif from 439 - OCPSF Pharm CIUs where pharm portion lt50
- 439.2(j) special definition of process
wastewater that excludes more flows
1140 CFR 439 Does Not Apply to
- EPAs January 2006 Pharmaceutical Permit
Guidance-More exclusions clarifications - Page 3-3, 8-1516 439 could be used as BPJ for
bioengineering operations if products and
wastewater characteristics are similar to 439 - 8-16 Incidental Passivating Electropolishing
during cleaning of Process Tanks - Not 433 - Guidance on developing permit limits, monitoring
requirements, case studies
1240 CFR 439 Applicability
1340 CFR 439 Applicability
- Ask lots of questions!
- Read regulation with SIU and have them explain
terms in regular words and words used in the
industry - and have them explain what they do and why they
think they are or are not covered by which parts - Confirm with PERCS
- Document in IUP Synopsis
- Including why not covered
14Each Subpart-5 Sets of Limits
- BPT, BCT, BAT, NSPS For direct dischargers,
i.e., pharmaceutical has their own NPDES permit - PSES - Pretreatment Standards for Existing
Sources - PSNS - Pretreatment Standards for New Sources
- Dont confuse with NSPS New Source Performance
Standards
15Each Subpart-5 Sets of Limits
- PSES PSNS 439 Limits Identical
- Only Issue When must comply
- New Source Date 5/2/95
- begin construction or significant change
after this date New Source. See 403.3(m) for
details. - Existing Sources must comply by 9/21/2001
- New Sources must comply immediately upon start-up
16439 Subpart A - Fermentation
- Process operations that utilize a chemical change
induced by a living organism or enzyme,
specifically bacteria, or the microorganisms
occurring in uni-cellular plants such as yeasts,
molds, or fungi to produce a specific product - PSES PSNS limit cyanide, ammonia, and 22
organic compounds - Same limits as Subpart C
17439 Subpart B - Extraction
- Process operations that derive pharmaceutically
active ingredients from natural sources such as
plant roots and leaves, animal glands, and
parasitic fungi by chemical and physical
extraction - PSES PSNS limit 5 organic compounds
- Same limits as Subpart D
18439 Subpart C - Chemical Synthesis
- Process operations that utilize a chemical
reaction or series of chemical reactions in the
manufacturing process of a specified product - PSES PSNS limit cyanide, ammonia, and 22
organic compounds - Same limits as Subpart A
19439 Subpart D Mixing, Compounding Formulation
- Mixing, compounding, and formulating operations
means processes that put (previously
manufactured) pharmaceutical products into dosage
forms - Includes ampules, tablets, capsules, vials,
ointments, medicinal powders, solutions, and
suspensions - both human and veterinary use
- PSES PSNS limit 5 organic compounds
- Same limits as Subpart B
2040 CFR 439 Subpart E - Research
- process wastewaters, products, or services
resulting from research and product development
activities - no PSES or PSNS yeah!!
21Categorical versus Local Limits
- Categorical-Technology Based
- 439 pollutants and untreated concentrations
- Pre-treatment technologies available, and
expected effluent - Cost of installing operating close down too
many CIUs? - If no, and CIU technology has higher removal rate
than typical POTW, assign expected effluent as
pretreatment categorical limit - Compare costs to environmental benefits, but not
deciding factor
22Categorical versus Local Limits
- Local Limits Technically Based
- How much and still protect stream, WWTP bugs,
sludge, people - Ammonia,Cyanide Regular HWA/AT
23Pharmaceutical Organics Headworks Analysis (POHWA)
- Spreadsheet and Directions on PERCS HWA web-page
- Download
- Fill in blue outlined fields (ask PERCS for
stream flows) - Complete Allocation Table, including other IUPS
with Organics limits (ex. OCPSF) - Reduce IUP limits below categorical to resolve
over allocation - Submit with IUP
24Proposed New NC Benzene Water Quality Standard
- NC Water Quality Standard for Class C Waters
proposed as part of Triennial Review - Reduce from 71.4 ug/l to 51 ug/l
- Benzene Class WS Waters - No change
- DWQ Planning Section, Classification Standards
Unit, Jeff Manning ext. 579 - http//www.ncwaterquality.org/csu/TriRCurrent.html
TRIENNIALReview - Triennial Review - changes for other
(non-pharmaceutical) parameters, too.
2540 CFR 439 Ammonia Limits
- Subpart A Fermentation 439.16, .17
- Subpart C Chemical Synthesis .36, .37
- PSES and PSNS Ammonia limits not applicable to
CIU if POTW nitrifies as defined in 439.1(I) - Discuss in IUP Synopsis
- Still may need IUP Ammonia Limit to protect WWTP
(CIU average discharge gt5 MAHL) - If have Limit, Composite POTW min. 1/6 months
SIU up to POTW
2640 CFR 439 Cyanide Limits
- Subpart A Fermentation .16, .17
- Subpart C Chemical Synthesis .36, .37
- PSES and PSNS Cyanide limits not applicable if
CIU certifies to POTW that manufacturing
processes neither use or generate cyanide - Discuss in IUP Synopsis
- If have Limit, Grab POTW min-1/6 months SIU
up to POTW - Can composite preserved grabs over 24 hours
- 1983 cyanide limits for Subpart B and D are
withdrawn
27439 Organic Pollutant Analysis
- 9/21/98 Federal Register also modified 40 CFR 136
- 40 CFR 136.3(a)Table IF Approved Methods for
each parameter - New EPA Methods 1666, 1667, 1671
- 40 CFR 141 Drinking Water Methods 502.2 and 524.2
- ASTM Methods D3371, D3695, D4763
- 40 CFR 136.3(b)(40) Lists Method Sources
28439 Organic Pollutant Analysis
- Subparts A and C 2 or 3 Approved Methods to
cover all POCs - Subparts B and D 524.2 for acetone and methylene
chloride, 1666 for three acetates - Only one lab does 1666 (main method)
- 1666 expensive, plus more to do multiple
methods - NC DWQ Lab Certification not available for most
Table IF Methods
29439 Organic Pollutant Analysis
30439 Organic Pollutant Analysis
- 136.3(d)(f) allows Alternative Methods
- EPA August 1999 Guidance allows transfer of
analytes to another method (Table IF or
Alternative) - Must show that will adapt Alternative Method
and/or Analyte Transfer to meet QA/QC of
applicable Table IF Method - POTWs choice to allow Alternative Method or
Analyte Transfer to be explored - Lab must submit documentation to NC DWQ Lab
Certification Unit for approval
31439 Organic Pollutant Analysis
- Example A few NC labs approved by NC DWQ Lab
Cert to use 6210D from Standard Methods for the
3 Subpart BD acetates, with conditions - One also approved to modify 6210D for acetone and
methylene chloride - 6210D is now 6200B in Standard Methods 20th
edition - Other Alternative Method Options
- 40 CFR 136 Methods 601, 602, 604, 612, 624, 625,
1624, and 1625 - Solid Waste Method 8260B
- Maybe others?
32439 Organic Pollutant Analysis
- Analytical Methods for Determination of
Pollutants in Pharmaceutical Manufacturing
Industry, EPA July 1998 - Methods 1666, 1667, and 1671
- Analytical Method Guidance for the Pharmaceutical
Manufacturing Point Source Category, EPA August
1999 - Alterative methods and analyte transfer
procedures - Solutions to matrix problems
- Choosing the best method
- Questions and answers
33439 Organic Pollutant Analysis
- NC DWQ Lab Certification not available for most
Table IF Methods - Available for some but not all Alterative Methods
- Pretreatment Permits typically require Certified
Lab (Part II, 4) - POTWs must include special test method language
in IUP - Updated Example IUP Language on Permit Writing
Page
34439 Organic Pollutant Analysis
- David Livingston
- NC DWQ Laboratory Certification Unit
- 919-733-3908, ext. 272
- david.livingston_at_ncmail.net
- http//h2o.enr.state.nc.us/lab/index.htm
35Surrogate Organic Pollutants 40 CFR 439.1(o)
- Allows monitoring for one pollutant to serve as
surrogate for a group of other specific
pollutants - Must receive same level of pretreatment as
surrogate and be in same treatability class as
surrogate See Table 2 of Appendix A - Violation of limit for surrogate means are
considered to violate limits for all pollutants
represented by that surrogate
36Surrogate Organic Pollutants 40 CFR 439.1(o)
- Where more than one surrogate is available in
treatability class, must use surrogate with
highest concentration at that CIU - Optional but must be approved by POTW
- Example Subpart B D Method 1666 for three
acetates plus Method 524.2 for acetone and
methylene chloride - Acetone can be Surrogate for all three acetates,
so dont need Method 1666
37Organic Pollutants Not Usedor Generated 40 CFR
439.4
- Determination based on
- Review of all raw materials in use
- Assessment of process chemistry, products and
by-products resulting from each manufacturing
process - Submit to POTW for approval
- Annual reconfirmation sample still required -
by POTW or SIU - Updated Example IUP Language on Permit Writing
Page
38Organics Sampling
- Limit in IUP Min once per year by POTW SIU
sampling-up to POTW - Pollutant neither used or generatedAnnual
re-confirmation sample by POTW or SIU (POTWs
choice) - Grab or Composite - POTWs choice, must be
representative of CIUs discharge without
jeopardizing the integrity of the volatile
organic compounds found in the sample - Can collect series of grabs in 24 hour period and
composite them in lab if Method allows
39Costs of Organics Sampling
- Organic sampling may cost 1,000 or more
- POTW Cost Recovery
- Permitting Fees
- Sample Collection Fees
- Sample Analysis Fees
- Administration Fees
40Organics Sampling in LTMP/STMP
- May be required if SIU discharges a significant
amount - Case by Case Basis
41439 IUP Limits
- Concentration based 439 limits apply directly if
sample location contains NO dilution wastestreams
see 403.6(e) - Otherwise, Combined Wastestream Formula (CWF)
uses process to total flow ratio to adjust 439
limit down - if CWF limit below detection, cannot apply CWF.
Instead, SIU must provide process only sample
location - Can convert to Equivalent Mass Limits per 40 CFR
403.6(c)(5)
42Potential Impact to Other Industrial Users
- Directly-None
- Indirectly-YES!
- New HWA and New MAHLs may bring new things to
light - Identify New Pollutants of Concern (POCs)
- May need data from other industrial users
- Collection system data
43Overwhelmed?
44Thank You!
- Dana Folley
- NC DWQ PERCS
- (919) 733-5083 ext. 523
- dana.folley_at_ncmail.net
- http//h2o.enr.state.nc.us/percs/
- http//www.epa.gov/ost/guide/
- http//www.epa.gov/waterscience/guide/pharm/
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