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Pharmaceutical Regulations

Pharmaceutical Regulations. Dana Rees Folley DWQ Pretreatment, Emergency Response, and Collection Systems Unit (PERCS) NC Pretreatment Consortium Annual Pretreatment Workshop September 19, 2006. Pharmaceuticals - 40 CFR 439. second most common categorical IU in NC – 29 in 17 cities

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Pharmaceutical Regulations

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  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 • EPA’s Pharmaceutical Web-sitehttp://www.epa.gov/waterscience/guide/pharm/ • All FR publications • Analytical Guidance • Permit Guidance • Pharmaceutical Info on PERCS Web-sitehttp://h2o.enr.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 <50% • 439.2(j) – special definition of process wastewater that excludes more flows

  11. 40 CFR 439 Does Not Apply to • EPA’s January 2006 Pharmaceutical Permit Guidance-More exclusions + clarifications • Page 3-3, 8-15+16: 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 • Don’t 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 >5% 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 • POTW’s 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 B+D 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@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 don’t 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 generated:Annual “re-confirmation” sample by POTW or SIU (POTW’s choice) • Grab or Composite - POTW’s choice, must be representative of CIU’s 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 MAHL’s 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 (919) 733-5083 ext. 523 dana.folley@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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