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Q1. Can human and animal drugs be manufactured on the same manufacturing line?
Q2. Can penicillin and cephalosporin animal drugs be manufactured in the same facility or on the same manufacturing line as other animal drugs?
Q3. Does the CDER draft guidance for industry “Non-Penicillin Beta-Lactam Drugs: A CGMP Framework for Preventing Cross-Contamination Guidance for Industry” apply to animal drug manufacturing?
Q4. Why are there differences in the requirements for human and animal drug products regarding penicillin and cephalosporin manufacturing?

Q1. Can human and animal drugs be manufactured on the same manufacturing line?

A: Yes, human and animal drugs can be manufactured on the same lines. They must be manufactured to the same quality standard (e.g., must meet current good manufacturing practice (CGMP) standards). The exception to this is non-penicillin drug products intended for human use, which must be manufactured on a line that is physically separated from the manufacturing line used for penicillin, (see 21 CFR 211.42(d) and 211.46(d)). The CDER draft guidance for industry “Non-Penicillin Beta-Lactam Drugs: A CGMP Framework for Preventing Cross-Contamination Guidance for Industry” includes background on the issue.

Q2. Can penicillin and cephalosporin animal drugs be manufactured in the same facility or on the same manufacturing line as other animal drugs? 

A: Animal penicillin and cephalosporin drugs can be manufactured in the same facility as non-penicillin and non-cephalosporin animal drugs. Operations should be performed in dedicated production areas, which can include separate facilities, separate air handling equipment and/or separate process equipment, unless cleaning procedures are established, implemented, and maintained to prevent cross-contamination. Dedicated manufacturing lines within the facility reduce the risk of cross contamination. Risks for cross-contamination are assessed during preapproval inspections (when applicable) and during routine surveillance current good manufacturing practice (CGMP) inspections of the facility.

Q3. Does the CDER draft guidance for industry “Non-Penicillin Beta-Lactam Drugs: A CGMP Framework for Preventing Cross-Contamination Guidance for Industry” apply to animal drug manufacturing?

A: The CDER draft guidance directly applies to all facilities that manufacture human drugs and “with operations that include one or more beta-lactam compounds.” This includes facilities where human drugs are made and where an animal drug manufacturing operation involves a beta-lactam compound. The guidance explains what controls may be appropriate to prevent cross contamination affecting human drugs based on the risks to humans.  Regarding controls to prevent cross-contamination affecting the animal drugs, if penicillin or cephalosporin products will be manufactured on the same line or in the same facility with any other drug products, there should, at minimum, be procedures in place to prevent cross-contamination affecting animal drugs, as well as any relevant cleaning validations and ongoing monitoring. The CDER draft GFI contains useful information (e.g., recommendations on cross-contamination prevention strategies) that you can apply to your facility to mitigate the risk for cross-contamination affecting the animal drugs, regardless of whether the facility is a mixed facility or only produces animal drugs. Additionally, as part of the risk evaluation for animal drugs, the classes of animals that will receive the drugs that will be manufactured on the same lines should be determined and incorporated into any relevant risk assessments. If the drugs are intended for food animals, this may increase the risk from FDA’s perspective and adjustments to any cleaning or cross-contamination procedures may be needed. In this case, the sponsor should request a meeting with CVM to discuss any concerns.

Q4. Why are there differences in the GMP requirements for human and animal drugs regarding penicillin and cephalosporin manufacturing?

A: The regulations regarding penicillin are specific to the manufacture of human drugs (21 CFR 211.42(d) and 211.46(d)). In response to comments submitted during the rulemaking for 21 CFR Part 211, FDA determined that, although hypersensitivity reactions to penicillin occur in animals, the prohibition against the use of common facilities and air-handling systems in the production of veterinary drugs was not warranted based on the information available at the time. See Comment 140, 43 Fed. Reg. 45038 (Sept. 29, 1978).