Medication Residues Validation Testing Procedures for Equipment Cleanout Procedures

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Introduction

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 performance of control measures
  • scientifically valid experimental trials that document the adequacy of control measures
  • collection of data obtained during normal operating conditions in the processing facility
  • statistically designed surveys
  • mathematical modelling

Should in-house data be utilized, the validation study will be conducted initially to prove the mill's processing methods are performing as expected and will be repeated (re-validated) should any changes be made to the process, product or equipment.

From a Hazard Analysis Critical Control Point (HACCP) standpoint, monitoring and verification are the tools used to check whether the control measures (at each process step) are being adhered to and are operating as intended. Validation involves measuring performance against a desired food safety outcome or target.

In the case of medication residues in feed, the desired food safety outcome is clearly specified in Section 14 (b) of the Feeds Regulations. From a risk perspective, the desired outcome is associated with final feed product and as a result, validation on the final processing step(s) would be required to ensure that the feed product produced meets the applicable regulatory requirements.

The likelihood is high that any loss of control associated with processing steps prior to the final step(s) will influence the desired outcome in the final feed product. Therefore, if the desired outcome has been met, the risk that any previous processing steps are not providing the necessary control is minimal.

Acceptable Validation Methodology

Where applicable, written equipment cleanout validation testing procedures must indicate the drug carryover management strategy (other than production sequencing) used for each piece of cross-utilized equipment or each processing stream.

For facilities that receive medications or medicated feeds through a common receiving pit, the effectiveness of the clean-out procedures used after receiving medicated products must be validated as close to the discharge as possible. For medicated feeds manufactured in the facility, rather than validation of cleanout procedures for each piece of cross utilized equipment, effectiveness of cleanout procedures can be verified at the end of each processing stream (e.g., processing stream 1 = mixer to pellet mill to bagger; processing stream 2 = mixer to bagger; processing stream 3 = mixer to loadout; processing stream 4 = mixer to pellet mill to loadout).

The effectiveness of equipment cleanout procedures need only be validated once unless significant changes are made to the equipment cleanout procedures (e.g., changes to the amount and type of flush material used are made) or major changes or repairs to manufacturing equipment are made.

Validation of the equipment cleanout procedures does not have to be completed for each medication used in a facility. Where possible, a higher risk scenario typical for the facility should be evaluated to ensure that drug carryover is adequately controlled. Higher risk scenarios include drugs requiring withdrawal, drugs where there are known manufacturing (drug handling characteristics) or toxicity issues, and situations where a variety of drug concentrations are manufactured (e.g., making a complete feed after a medicated feed requiring further mixing such as a medicated premix that has 20-40 times the level of the medication in a complete feed). Additionally, consideration needs to be given to the detection level of medications used in the facility or the use of tracers.

The following principles should be used when assessing the effectiveness of equipment clean out procedures:

  • 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.
  • Samples to validate equipment cleanout procedures must be obtained from the initial portion (first 50 - 100 kg) of the batch immediately following the use of the clean-out procedure. Composite samples representing the entire batch manufactured will not be accepted as evidence that such procedures were effective. Refer to Appendix I for information on drug interferences which should be taken into consideration when choosing feeds to sample for drug residue testing.
  • Appropriate analytical methodologies for determination of the level of drug carryover present must be used. Samples should be sent to an accredited laboratory for analysis where available. The laboratory must use an approved method.
  • As the purpose of these equipment cleanout procedures is to eliminate drug carryover in a high risk situation, the target is no detectable residue. However, as detection methods become more precise, it may be adequate to ensure that any detected carryover remains below the residue method limit of quantification (rLoQ) or action limit (which ever is higher) for drug residues as indicated in Appendix IA of the National Feed Inspection Programs (I-3-93).

Appendix I - Substances Causing Interference for Drug 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 by the Ottawa Laboratory (Carling).

Substances Causing Interference for Drug Residue Testing
Target Drugs

Interference (do not sample if present)

Chlortetracycline

Any other tetracycline

Penicillin

Lincomycin, tylosin and virginamycin

Tylosin

Lincomycin, urea, virginiamycin

Low level antibiotics

Mineral premixes and high levels of other antibiotics

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