Pharmaceutical Regulations

1
Pharmaceutical Regulations

• Dana Rees Folley
• DWQ Pretreatment, Emergency Response, and
  Collection Systems Unit (PERCS)
• NC Pretreatment Consortium Annual Pretreatment
  Workshop
• September 19, 2006

2
Pharmaceuticals - 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

3
Pharmaceuticals - 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

4
Pharmaceuticals - 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

5
Pharmaceuticals - 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

6
Pharmaceuticals - 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

7
40 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.

8
40 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

9
40 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

10
40 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

11
40 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

12
40 CFR 439 Applicability
13
40 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

14
Each 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

15
Each 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

16
439 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

17
439 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

18
439 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

19
439 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

20
40 CFR 439 Subpart E - Research

• process wastewaters, products, or services
  resulting from research and product development
  activities
• no PSES or PSNS yeah!!

21
Categorical 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

22
Categorical versus Local Limits

• Local Limits Technically Based
• How much and still protect stream, WWTP bugs,
  sludge, people
• Ammonia,Cyanide Regular HWA/AT

23
Pharmaceutical 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

24
Proposed 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.

25
40 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

26
40 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

27
439 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

28
439 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

29
439 Organic Pollutant Analysis
30
439 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

31
439 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?

32
439 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

33
439 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

34
439 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

35
Surrogate 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

36
Surrogate 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

37
Organic 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

38
Organics 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

39
Costs of Organics Sampling

• Organic sampling may cost 1,000 or more
• POTW Cost Recovery
• Permitting Fees
• Sample Collection Fees
• Sample Analysis Fees
• Administration Fees

40
Organics Sampling in LTMP/STMP

• May be required if SIU discharges a significant
  amount
• Case by Case Basis

41
439 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)

42
Potential 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

43
Overwhelmed?
44
Thank You!

• Dana Folley
• NC DWQ PERCS
• [phone] 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/

45
(No Transcript)