DESIGNING YOUR ENVIRONMENTAL MONITORING PROGRAM FOR MOLD. Presented by Aaron Bisceglia

Transcription

1 DESIGNING YOUR ENVIRONMENTAL MONITORING PROGRAM FOR MOLD Presented by Aaron Bisceglia

2 AGENDA Introduction What is an EM Program and why is it important to ensure product quality? What is Mold and why is it so critical to gear a portion of your EM program specifically for mold? Regulatory observations related to Mold and why the heightened focus on mold Setting acceptance criteria Setting appropriate controls to mitigate against mold Investigating Mold Excursions and Adverse trends Trending and data compilation Questions? References

3 INTRODUCTION 14 years experience in QC Microbiology Managed EM programs for past 9 years of career Have developed and revised EM programs at multiple companies Have been a front room presenter to FDA for EM programs at multiple companies Why I chose this topic

4 WHAT IS AN EM PROGRAM AND WHY IS IT CRITICAL FOR PRODUCT QUALITY? An EM program allows for detection of contamination and measures the effectiveness of your controls An effective EM program will often help detect contamination and allow for proactive contamination mitigation before contamination reaches product Regulatory agencies require environmental monitoring of the areas where product is manufactured

5 WHAT IS MOLD? Mold are multicellular filamentous fungi Mold develop hyphae which are tubular structures mold used to find and distribute food Hyphae grow and intertwine until they form a network of threads called a mycelium Morphology consists of powdery fluffy aerial growths above media Ubiquitous to all environments, however grow best in warm, damp, humid conditions. There are over 100,00 species with small percentage as known human pathogens Examples of common cleanroom Mold genuses are Aspergillus Cladisporium, Alternaria, and Penicillium

6 WHAT ARE MOLD SPORES? Mold produce spores small 1-50 µm ( could fit on a pin head), which are released into the air during reproduction Mold spores can survive harsh environmental conditions and are resistant to most disinfectants spores are numerous and spread easily through HEPA-filtered airflow patterns Mold colony can produce and release billions of spores daily.

7 WHAT ARE MYCOTOXINS? Some mold species can produce mycotoxins Mycotoxins are secondary metabolites produced by molds and other fungi Mycotoxins are present throughout mold colony, including the spores Mold produce mycotoxins as an evolutionary advantage to kill of other competing organisms or to weaken host defenses Three genera are responsible for the majority of the mycotoxins with which FDA is concerned: the Aspergillus Penicillium and Fusarium

8 WHAT ARE MYCOTOXINS Some mycotoxins such as aflatoxin b most potent natural carcinogen known Satratoxin from Stachybotrys chartarum black mold was thought to have been the active component in biological weapon Yellow Rain Most mycotoxins are stable compounds that are not destroyed during product processing or home cooking FDA recommends mycotoxin analysis methodology involving quantitative and qualitative analysis through HPLC or thin layer chromatography

9 WHAT ARE MYCOTOXINS? Mycotoxin Associated Mold Genera Effect on Human Body Aflatoxin Aspergillus carcinogen, immune suppression, primary target Liver Citrinin Penicillim Aspergillus nephrotoxin Fumonisin Fusarium carcinogen Ochratoxin Aspergillus, Penicillium nephrotoxin Patulin Penecillium immunological, neurological and gastrointestinal Trichothecenes Fusarium, Stachybotrys, Trichoderma, Trichothecium immunological, neurological and gastrointestinal

10 REGULATORY OBSERVATIONS RELATED TO MOLD AND CLEAN ROOMS Abundance of mold related excursions within aseptic processing areas without identifying appropriate corrective action. No data to support the appropriateness of the disinfectants used, inadequate or absence of disinfectant efficacy studies your firm s microbiology laboratory does not perform species identification on a routine basis of the yeast and molds detected in your production area Mold observed in cleanrooms Stains discoloration and appearance of clean rooms, Persistent mold problem not resolved There was no assurance that yeast and mold will grow at the Incubation temperature used to detect bacteria growth

11 RECALLS RELATED TO MOLD As per FDA data analysis , approximately one quarter of all product contaminations were related to fungi. Many Food related recalls In 1996, the FDA recalled an opthalmic solution because it was contaminated with Fusarium. New England Compounding contaminated steroid injections More than 60 people died, and 700 were infected contaminated with a fungus Exserohilum rostratum, Aspergillus fumigatus,and the common cleanroom mold Cladosporium rostratum, Aspergillus fumigatus (one patient).

12 GENERATE YEAST/MOLD SPECIFIC DATA Selective media: Rose Bengal w/ Chloramphenicol and Sabouraud Dextrose Agar Tryptic Soy Agar broad spectrum media will also recover mold, but must validate Mold prefer temperatures 20-25ºC Build SOPs to count specifically for yeast and mold Separation of mold data will allow for generation specific mold trends.

13 HOW TO SET MOLD SPECIFIC ACCEPTANCE CRITERIA? Perform statistical analysis using historical data, to set mold specific acceptance criteria Aseptic Facilities, ISO 7 areas really should not have any mold, so action level should be set low 1-2 CFUs. Utilize risk assessment to justify levels Don t set mold levels arbitrarily

14 SETTING APPROPRIATE CONTROLS Cleaning and disinfection program with risk assessment. Frequency, cleaning agent, cleaning sites (drains etc ) Proper traffic and material flow Cleaning of materials / Disinfectant efficacy study including sporicidal Gowning and Vendor qualification

15 SETTING APPROPRIATE CONTROLS Aseptic technique and behavior training Hygiene controls such as handwashing HVAC HEPA Filtration and facility design Contamination response plans Quality oversight!

16 INVESTIGATING MOLD EXCURSIONS Trending is key Personnel interviews Cross-functional walk-throughs of the affected area Look for water source damp areas drywall, refrigerators, condensation, recent leaks, areas of discoloration food source such as corrugated cardboard bags boxes paper markers Analyst / operator technique and training

17 INVESTIGATING MOLD EXCURSIONS HVAC returns and Dampers installed HEPA filters Were materials properly cleaned, was cleaning agent affective against mold spores Develop an overview map of the excursions Seasonal variation and year to year comparison

18 INVESTIGATING MOLD EXCURSIONS Map area activities with mold recovery Regulatory agencies expect facilities to make every effort to get to a root cause. If you cannot find a root cause the investigations should document review of above areas.

19 TRENDING AND DATA COMPILATION Build trending systems with specific components for mold to allow for mold specific trending Separate charts for yeast and mold Define Adverse Trend!

20 QUESTIONS?

21 REFERENCES Russell, A.D. (2003) Similarities and differences in the responses of microorganisms to biocides. J An-timicrob Chemother 52: Microbial diversity in pharmaceutical product recalls and environments.jimenez L 1. FDA.gov: Bacteriological Analytical Manual Chapter 18 Yeasts, Molds and Mycotoxins Authors: Valerie Tournas, Michael E. Stack, Philip B. Mislivec, Herbert A. Koch and Ruth Bandler PDA tech report 13 USP <1116> FDA field manual DOCUMENT NO.: IV-07 VERSION NO.: 1.6 FINAL EFFECTIVE DATE: REVISED: Orientation and training Oxford Journals Volume 104, Issue 1Pp Stachybotrys chartarum, Trichothecene Mycotoxins, and Damp Building Related Illness: New Insights into a Public Health Enigma MycotoxinsJ. W. Bennett1,* and M. Klich2 Clin. Microbiol. Rev. July 2003 vol. 16 no July