Confidence Beyond Compliance

Pharmaceutical batch sizes manufactured to support the NDA or ANDA license application are typically scaled up to larger batch sizes after approval.

FDA Scale-up and Post Approval Changes (SUPAC) guidance provides recommendations to product license holders on scale-up of the process and making a change to the site of manufacture or testing post NDA or ANDA approval. Scale-up activities should be managed under the Pharmaceutical Quality System (ICH Q10).

Also, current regulations and FDA Technology Transfer best practice standards demand that any transfer of a technology as required to support SUPAC to the CMC documentation, is managed under the Pharmaceutical Quality System.

PharmaLex’s team of experts, which includes a number of former EU regulators, have the experience and expertise to provide support services to your scale-up operations, including:

  • Working with Technical Services, Validation, Manufacturing Operations and Regulatory to
    • identify changes to the manufacturing process, equipment, or site of manufacturing or testing to scale-up the batch size
    • assess the changes required as Major, Moderate or Minor, in accordance with regulatory guidance
    • advise on regulatory filing procedures based on the category of the changes, i.e. For US, Prior Approval supplement, Changes Being Affected supplement or Annual reportable; for EU Type 1 or Type 2 variation
    • advise your SMEs on validations and/or release testing to be performed in order to confirm successful scale-up (or down) of batch size, and any Technical Transfer activities employed as part of the scale-up process.
  • Providing guidance and support on preparation of scale-up documentation, including protocols which
    • define the scale-up activities
    • assign roles and responsibilities
    • document performance of validations and/or release testing to confirm successful scale-up (or down) of batch size, and any Technology Transfer activities employed as part of the scale-up process
    • apply Risk Management principles to the scale-up operation
    • describe performing the scale-up under the management of the Pharmaceutical Quality System, including management of documentation, change control, deviation investigations and CAPA management
    • require appropriate sign off/approval by relevant parties and by Quality on completion of the scale-up protocol
    • and scale-up reports, including associated records of actions taken or conclusions reached as part of the Scale-up activities
  • Providing support in the management of scale-up projects, whether within-site or inter-site, and incorporating Technology Transfer activities, to
    • ensure that the key milestones of the project are identified
    • ensure that the challenges to the scale-up process are identified
    • ensure the application of Quality Risk Management to the process
    • ensure that the scale-up process is completed effectively, efficiently and meets regulatory expectations and compliance.

Providing training on scale-up activities in compliance with GMP and regulatory guidance.