ABCs of Validation. Ruth L. Petran. Corporate Scientist, Food Safety 03 April 2012

Transcription

1 1 ABCs of Validation Ruth L. Petran Corporate Scientist, Food Safety 03 April 2012

2 2 Topics Validation starts with product and process design Traditional validation Important to focus on in-plant situations Need science basis for these too Consider what might be out of your control

3 Validation is Fundamental to Assuring Food Safety 3 Process Identify all relevant hazards Focus on prevention to address all identified hazards - May be via HACCP or Pre-requisite programs Key is that preventive controls must be effective, addressing the hazards of concern Do they work? Do they achieve the intended control? Need to follow basic principles to do it right

4 4 Assessment of design relies on science Predictive modeling Literature references Use of safe harbors Microbiological challenge studies Or a combination of the above

5 5 Food Safety Starts with Design Kill organisms Keep organisms out Keep organisms from growing Challenge studies often used to confirm that the design is adequate to control hazard

6 Challenge Study considerations Conduct multiple trials Recovery method specificity and sensitivity Use multiple strains that are relevant Will a surrogate work? Vary critical factors to determine the margin of safety Confirm that the least lethal treatment is measured Consider all the potential variability (abuse) that might occur Source:

7 Choose Optimal Location to Run Study Laboratory Pathogens inoculated into media or product Pilot plant Dedicated pilot plants may use pathogens GMP pilot plants use surrogates Commercial facility Surrogates when pathogen presence is a rare event Occasionally can use pathogens when naturally present

8 8 In-plant Validation is also Crucial and Must be Scientifically Based as Well

9 In-plant Validation 9 We rely on processes/programs for control of hazards Need to ensure that these are effective Testing has a role here too Useful testing must be tailored to the application Testing is recommended to generate meaningful data - Impact quality or safety Choice of target organisms is product & process specific Method of choice must be based on science and resources available in an industrial setting.

10 Considerations for testing For what agent do you test? What is the limit of concern? How is the agent distributed? How long does it take to get results? What will you do with the data?

11 Which agent? Utility tests Spoilage, reduced shelf life, no health concern Total counts, yeast, mold, etc. ATP Indicator tests Measure of GLP Coliform, Enterobacteriaceae, etc. ATP Hazards Pathogens Allergens

12 12 What about sampling for a hazard? Recognize risks of attribute-based acceptance testing To consumers risk of accepting defective food To manufacturers risk of rejecting good food Use the right sample collection technique and maintain its integrity Chain of custody Pick the right sampling plan

13 13 Using data to develop sampling plan Hypothetical examples only Pathogens in raw poultry Consider 10% positive Pathogens in produce Consider 0.1% positive Allergen residue in finished product Consider % positive

14 Probability of Detection Number of samples analyzed Percent contaminated >

15 Proactive Process Control is Better Approach Represents application of data to provide more information Can help to assess many things Safety of food Adherence to GMP When processes need to be adjusted or changed

16 16 Cooking Process Design, example Goal = properly designed thermal process, pathogen free cooked chicken Consider what factors may affect reaching the goal Initial pathogen load in meat Plant environment equipment design, sanitation, temperature of processing area Chicken piece dimensions Belt speed Equipment capabilities steam availability, e.g. Consider expected variability End result = defined critical factors needed to achieve goal

17 17 Validating run time, example How long can plant run before sanitation? What type of sanitation processes need to be followed?

18 Microbial Sampling Testing safety into products does not work due to sampling probability Test to generate meaningful data Impact quality or safety Results may not be available before the product is shipped. Focus on process control supplemented with indicator organism testing to verify effective controls & trends.

19 CFU / ml Example: Aerobic Colony Count on blanched vegetable flume water Impact of sanitation versus water rinse Time (hrs) Bacterial count Rinse Only Clean & Sanitize Limit

20 Process Control Log (CFU/g) Log (CFU/g) Log (CFU/g) Log (CFU/g) Lot Number 5 Lot Number Lot Number Lot Number

21 Microbial Distribution Routine sampling plans assume random distribution Non-random distribution is common for microbial contamination Wide variation in contamination rates Start up issues with inadequate sanitization Multiple lane processing equipment Growth during extended run time Environmental sources Recognize that you may not always have to test for microorganisms to ensure their control

22 22 Process Control, examples Process = Produce flume with antimicrobial substance Hazard = Cross-contaminants Control = Antimicrobial substance at the right concentration Considerations for Validation What is range of expected microbial load? How does concentration vary at different places in flume close to point of delivery and further away? What is the impact of organic matter, ph, and turbidity? Does temperature affect it? Other critical factors? Key = Identification of relevant critical factors and assuring their control

23 Further example: Pathogen-Specific Intervention Technologies Bacteriophages Modified R-type pyocins Vaccines Others?

24 Potential Benefits of Pathogen-Specific Interventions No/low impact on food quality Natural, organic More effective pathogen control Environmental and employee safety No impact on friendly microorganisms

25 In-Plant Validation Challenge Interventions are often introduced to control specific pathogens; however, many also affect non-pathogens (broad-spectrum activity) Broad-spectrum activity is convenient for initial validation: Allows measurement of indicator organisms instead of (low prevalence) pathogens Same approach not possible with pathogen-specific interventions

26 Ways to overcome this challenge Determine critical parameters that correlate to pathogenspecific intervention E.g., for bacteriophage Concentration (PFU/ml) - Results from manufacturer on lot specific COA How much to apply? - Volume applied per standard surface area surface area, weight Others as appropriate

27 27 Determine appropriate indicators for the active agent Physical characteristic Meat piece size Turbidity Chemical characteristic ph Temperature Concentration Other as appropriate

28 28 Chemical Hazard Example Food allergens present risks to a significant portion of consumers Incumbent on food manufacturers to effectively manage this hazard and validate their controls

29 29 Typical Food Allergen Controls Effective cleaning between formulations with different allergen profiles to prevent carryover of allergen Must demonstrate that cleaning is effective! Other techniques also need to be shown to be effective E.g., Push through method

30 30 Validating allergen controls Method of choice = Qualitative allergen-specific ELISA tests for cleaning Take samples before and after cleaning or other method Record whether there is visible soil present Guard against cross-transfer between samples Swab all crevices and potential niches before equipment reassembly Use kit, specific to expected allergen type and food matrix Make sure you know how to react to the result May consider testing product made after a validated cleaning process with a quantitative allergen-specific ELISA

31 Ice Cream Study Objective: Compare 2 detergents for CIP cleaning of stainless steel ice cream equipment Soil: Two premium, high protein (2.6 4%) & high fat content ice cream mixes Factors Detergent concentration Cycle run time Water temperature Pressure

32 Ice Cream Study Results: Detergent Protein Stain ELISA Test Soiled Surface Control ug/cm 2 Water only Control ug/cm 2 Cl-Alk 4000 ppm - < ug/cm ppm - < ug/cm ppm + < ug/cm 2 Enzyme 900 ppm - < ug/cm ppm Slight + < ug/cm ppm + < ug/cm 2

33 33 Considerations - Proper Validation Product is designed for its intended use Preventative controls address identified hazards Control must work effectively Need documented, legitimate results to provide evidence Scientific support and in-plant Consider periodic re-validation to confirm consistent application of controls

34 34 Parting comments Key factors Proper design of product and process Demonstrating that the needed preventative controls can be effectively applied in plant There s a lot out of our control that can affect safety and need to be considered in validation discussion Raw materials Transportation Distribution Retail & Consumer Handling Make use of available data or generate what you don t have

35 Questions? 35