Solving the Puzzle of Single-Use Consumables

Although the FDA’s regulatory requirements for acceptance of vendor test results in lieu of testing is clearly specified in 21 CFR 211.84 for incoming raw materials and container closures, the FDA has not put forth specific regulations for the acceptance of single-use consumables. Biologics manufacturers may use dozens or even hundreds of different single-use consumables in manufacture of products, but manufacturer standards for qualification of vendors, testing of materials, and acceptance of vendor test results for consumables may have gaps. The FDA has issued observations to manufacturers for accepting vendor test results without adequately qualifying the vendors testing.

A program for qualification and acceptance of single-use consumables is necessary. The components of the program should include, at a minimum:

• Development of meaningful user requirements (based on the product, identified during product development):
  • functional requirements, compendial requirements, specific test requirements such as endotoxin, extractables and leachables, sterility, etc.)
• Risk assessments:
  • criticality of the component based on expected use in manufacturing
  • quality attributes required based on use
  • availability of information on quality attributes from the vendor during audit or other documentation from vendor
• Meaningful release specifications (based on the product and the use of the consumable in the manufacturing process), based on:
  • process needs
  • risk assessment
  • compendial/regulatory requirements
• Audit program for qualification and periodic requalification of the vendor. In addition to typical audit requirements such as quality systems and controls, also include:
  • Validation of the manufacturing process for the consumable
  • Validation of sterilization, reduction of bioburden
  • Periodic verification of the above
  • If a vendor utilizes a third-party testing laboratory, records related to qualification of third-party laboratory
  • Validation of test methods used for testing consumable

Once the program is established, a company can decide which tests are critical for a consumable, which tests will be performed by the company itself (if any), and which tests will be accepted from the vendor. A risk assessment and justification of the tests and testing program underpins each material specification.

Which requirements should be considered when determining critical tests? Here are some regulatory considerations:

• Product contact surfaces must be clean and free of surface solids, leachable contaminants, and materials that might hasten deterioration. (21 CFR 600.11)
• Verification of sterility assurance should be performed as part of the supplier qualification and evidence of sterilization of each unit should be checked on receipt. (Annex 1)
• Adsorption and reactivity of the product with product contact surfaces should be evaluated under process conditions. (Annex 1)
• Extractable and leachable profile of the single-use consumable and impact on product quality should be evaluated. (Annex 1)
• Single-use consumable should maintain integrity through intended processing, with consideration of exposure to extreme conditions during routine processing. (Annex 1)
• Acceptance criteria should be established corresponding to the risk to the product. (Annex 1)
• Each piece should be checked to ensure they have been manufactured in accordance with approved specification, including a review of documentation and a visual inspection. (Annex 1)

Unsure of how to develop your consumables program? Lachman can help! Reach out to us at LCS@LachmanConsultants.com for a consultation.