PDA Biotechnology Survey of Bioburden Monitoring Practices During Manufacture of the Active Pharmaceutical Ingredient

The purpose for this survey is to better understand the amount and type of bioburden testing that is performed during the manufacture of biopharmaceuticals. The results of this survey will be published by PDA for review and discussion. Please select one person from your company to respond by August 1, 2006 so that the results can be summarized at the PDA/FDA Annual Conference in September.

Please list your company affiliation (this will only be used to ensure that each company is counted only once in the survey):

_______________________________________________________________

Please indicate your company type:

 Biotech company, with its own manufacturing/testing facility

 Contract manufacturer, with its own testing facility

 Contract testing lab

Process/Product Background

(Select only 1 box under each category; if you want to select multiple categories, please submit a separate survey response for each)

Which conditions best describe the API process that will be discussed by you:

Your cell culture manufacturing process to be described :

Mammalian cell culture Microbial cell culture

Your product development stage:

 Early clinical trial material manufacture (Phase 1 and 2)

Later clinical trial material manufacturer (Phase 3) Commercial product manufacture

Your biotech product type:

Therapeutic recombinant protein or monoclonal antibody Vaccine Gene or cellular therapy Other ______________________________

Raw Materials

Which of the following raw materials are tested for bioburden:

 WFI

Biologically-based materials Fetal calf serum Prepared vendor media Media additives (hormones, lipids, etc.) Other __________________________ None of these
Which test method do you use for determining bioburden counts of raw materials:

 Pour plate method

 Spread plate method

 Membrane filtration

Most probable number (MPN) method in broth tubes Compendial sterility test

 Other: ___________________

Which of the following types of media are used in bioburden determination:

 Aerobic Trypticase Soy Agar (SCDM)

Aerobic fungal Agar, such as SABA (Sab Dex or similar) Aerobic TSA (SCDM) with lecithin and Tween Anaerobic TSA (SCDM) or TSA with blood R2A agar plate medium Other: ________________________
How long are the bioburden plates incubated for raw materials:

 TSA (SCDM) incubated at _____ degrees C for ____ days

 SABA (SAB Dex) incubated at ____ degrees C for ____ days

 ____________(enter media type) incubated at ____ degrees C for ____ days

 Other: __________________________________________________

How many replicates are tested for each raw material bioburden sample:
Single plate, single dilution Single plate at each dilution, multiple dilutions Duplicate plates, single dilution Duplicate plates at each dilution, multiple dilutions Triplicate plates, single dilution Triplicate plates at each dilution, multiple dilutions

 Other: __________________________________________________

Is inhibition neutralization required for raw material bioburden testing:

 Yes (please explain how)

 Dilution(s) in saline without neutralizers

 Dilution(s) in neutralizers such as lecithin and tween

 Membrane filtration with neutralizing rinses

 Other: ______________________________

 No

What is the acceptance criterion/action limit for the bioburden testing:

 Report result only

 0 CFU/unit

 <1 CFU/unit

 <10 CFU/unit

 <100 CFU/unit

 Other: __________________

Are your units:  CFU/mL,  CFU/100mL,  CFU/gm,  CFU/10gms

How is the bioburden result reported with confluent or spreading growth:

 TNTC

 Above acceptance criteria/action level