Validating equipment cleanout procedures for medication or unapproved ingredient residues

Summary of policy

To prevent cross-contamination of feeds that may negatively impact human or animal health, the Canadian Food Inspection Agency (CFIA) requires feed manufacturers that cross utilize equipment for handling medications or unapproved feed ingredients, to have equipment cleanout procedures in place where appropriate feed sequencing is not an option.

The purpose of equipment cleanout procedures (for example flush or physical cleanout) is to eliminate carryover of unintended residues during the manufacture of livestock feeds. The policy below provides guidance to feed manufacturers related to validating their equipment cleanout procedures for the following unintended residues:

• medicating ingredients having withdrawal requirements or considered unapproved for a species
• unapproved feed ingredients in livestock feeds 

Facilities that are considered to be low risk for Transmissible Spongiform Encephalopathies (TSEs) are only required to validate their equipment cleanout procedures at the exit of each processing stream. This is conducted once, initially, and repeated when there are changes in equipment, manufacturing procedures or equipment cleanout procedures, by verifying that the level of residue carryover does not exceed regulatory requirements in the batch^{Footnote 1} immediately following the feed for which the cleanout is being validated.

Samples taken to validate the equipment cleanout procedures must be representative of the whole batch (that is, a composite sample consisting of sub-samples taken at regular intervals over the entire batch). 

A detailed description of the cleanout procedures used for each production stream and the data supporting their effectiveness must be available at the facility for assessment by CFIA feed inspectors.

Introduction

To prevent the carryover of unintended residues while manufacturing feeds, facilities may use equipment cleanout procedures as a control measure. Validation is the process of demonstrating that the feed processing steps, if operated as designed, can adequately control identified hazards to produce a safe feed product.

Validation will provide documented scientific or technical justification to prove that mill processing will result in an end product which meets the company standard and applicable regulations.

Validation documentation can consist of:

• existing scientific or technical literature
• previously completed validation studies
• historical knowledge of the control measures performance
• valid experimental trials documenting that the control measures are effective
• data collected during normal operating conditions in the facility
• statistically designed surveys
• mathematical modelling

A facility may use in-house data to prove their equipment cleanout procedures are performing as expected. However, the process must be repeated (re-validated) should any changes be made to equipment, manufacturing procedures or equipment clean out procedures.

Monitoring and verification activities are used to check whether the control measures are being followed and are effective (at each process stream). Validation involves measuring performance against a desired feed safety outcome or target. 

In the case of medication or unapproved ingredient residues in feed, the desired feed safety outcome is clearly specified in Section 14 of the Feeds Regulations: 

Section 14 of the Feeds Regulations states:
A mixed feed shall not contain

1. ingredients other than those listed in Schedule IV or V
2. medicating ingredients of a brand, at a level or for a purpose or species other than as set out in the Compendium of Medicating Ingredient Brochures unless the feed is a veterinary prescription feed

From a risk perspective, the desired outcome is associated with the final feed product and as a result, the final processing step(s) would require validation to make sure that the feed produced meets the applicable regulatory requirements.

Acceptable Validation Methodology

Equipment cleanout validation testing procedures must indicate the carryover management strategy (other than production sequencing) used for each processing stream.

The following details must be considered by all facilities identified as low risk for Transmissible Spongiform Encephalopathies (TSEs) (that is, don't manufacture ruminant feeds and feeds containing prohibited material using the same equipment):

• Procedures identify that the flushing or physical cleanout procedures used to prevent cross-contamination must be validated for effectiveness
• Validation procedures must meet the following standards:
  • Validation of equipment cleanout procedures at the exit of each processing stream is necessary, for example:
    • Processing stream 1 = mixer > pellet mill > bagger
    • Processing stream 2 = mixer > bagger
    • Processing stream 3 = mixer > loadout
    • Processing stream 4 = mixer > pellet mill àloadout
  • Samples taken must be representative of the whole batch (that is, a composite sample consisting of sub-samples taken at regular intervals over the entire batch) 
  • Be conducted once initially and repeated when there are changes in equipment, manufacturing procedures or equipment clean out procedures by verifying that the level of residue carryover does not exceed regulatory requirements in the batch immediately following the feed for which the cleanout is being validated

In addition, ingredient-receiving equipment should be validated as close to the discharge as possible where medicated feeds, medicated feed ingredients or unapproved feed ingredients (including returned feeds) are received in bulk at the facility.

Validation of the equipment cleanout procedures does not have to be completed for each medication and unapproved feed ingredient used in a facility. For example, a facility which uses the same equipment to manufacture livestock feed using three different medicating ingredients and pet food which contains unapproved ingredients, would only be required to validate the equipment cleanout procedure for one of those scenarios. Where possible, a higher-risk scenario typical for the facility should be evaluated to ensure that any carryover is adequately controlled.

Higher-risk scenarios include:

• drugs requiring withdrawal
• drugs where there are known manufacturing (medicating ingredient handling characteristics) or toxicity issues
• situations where a variety of medicating ingredient concentrations are manufactured (for example, making a complete feed after a medicated feed requiring further mixing such as a medicated premix that has 20 to 40 times the level of the medication in a complete feed), or
• unapproved ingredients 

Additionally, consideration needs to be given to the detection level of medications used in the facility or the use of tracers.

Facilities identified as low risk for TSEs may choose to use the validation procedures required for facilities identified as high risk for TSEs (that is, facilities that manufacture ruminant feeds and feeds containing prohibited material using the same equipment) in lieu of the validation procedure identified above.

Refer to Appendix I for information on medicating ingredient interferences which should be taken into consideration if choosing a medicating ingredient as the test substance to validate equipment clean out procedures.

Appropriate analytical methodologies for determination of the level of medicating ingredient carryover present must be used. Samples should be sent for analysis to an accredited laboratory, where available, which must use an approved method.

As the purpose of these equipment cleanout procedures is to eliminate carryover in a high risk situation, the target is no detectable residue. Refer to Appendix II for more information related to use of medicating ingredients as test substances when validating in equipment clean out procedures.

Appendix I - Substances Causing Interference for medicating ingredient residue testing

Interactions between medicating ingredients often affect the capability of the laboratory to accurately analyze the feed. To help clarify which tests cannot be done due to interferences, the following list has been prepared (Table 1).

Appendix II: Cleanout validation targets

If a medicating ingredient is used to validate equipment clean out procedures, it is important to verify that the laboratory conducting the analysis has the appropriate methodology and detection limit. Table 2 (below) outlines the medicating ingredients and their validation target levels for which residue testing is available at the CFIA.