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Audit Situations on API Manufacture – a scenario and suggested answer

Scenario 1
A firm has bought a new piece of equipment. It is similar but not identical to existing equipment however it is made of identical materials. The firm has decided it does not need to revalidate cleaning procedures when the new equipment is used for processes already carried out in the old one. Is this acceptable?

Suggested Answer

Please state the applicable GMP Regulations?

ICH Q7 section 12.7 and section 13 and ICH Q9, Annex II section II.6

The GMP topics pertaining to Cleaning validation, Change Control and risk management should be considered when answering this scenario.

Validation of cleaning procedures should reflect actual equipment usage patterns. If various APIs or intermediates are manufactured in the same equipment and the equipment is cleaned by the same process, a representative intermediate or API can be selected for cleaning validation. This should be based on the solubility and difficulty of cleaning and the calculation of residue limits based on potency, toxicity, and stability.

The potential impact of the proposed change on the Quality of the intermediate or API should be evaluated. A classification procedure may help in determining the level of testing, validation, and documentation required to justify changes to the validation process. Changes can be classified (e.g. as major or minor) depending on the nature and extent of the changes, and the effects these changes may have on the process. Scientific judgement should determine what additional testing and validation studies are appropriate to justify a change in a validated process.

What further investigations will you perform? 

It is not acceptable to avoid revalidating cleaning procedures when changing to a new piece of equipment. A risk assessment should be performed to evaluate the differences between the two similar pieces of equipment following the change control procedure. There should be some validation performed, for example design qualification based around equivalence of surface areas, pipe bends etc. However if differences are in the service lines, for example, then you would probably not need to revalidate the cleaning procedures.