CMC: FDA publishes Guideline with questions on post-approval modification of single-use materials


Disposable materials are increasingly used in the production of biopharmaceutical medicinal products for human and veterinary use. As a rule, these materials are comprehensively tested for their suitability; this may concern the resistance of the materials, the issue of leachables and extractables or other properties. This also raises the question of what needs to be considered when such qualified materials become necessary. Particularly in the aftermath of the COVID-19 pandemic and under the impact of the Ukraine war on international supply chains, FDA has received a whole series of questions about the limited availability of single-use production materials in times of increased demand. The limited availability of single-use production materials, as is currently the case due to the increased demand for the required raw materials, starting materials and finished products by the healthcare sector, also affects the manufacture of sterile drugs and biological products. 

The Guideline

Therefore, the FDA has now issued a guidance document with questions and answers on changes in chemistry, manufacturing and controls (CMC) of single-use materials. This is aimed at holders of Biologics License Applications (BLAs), New Drug Applications (NDAs) or Abbreviated New Drug Applications (ANDAs) and also at holders of New Animal Drug Applications (NADAs) or Abbreviated New Animal Drug Applications (ANADAs).
However, the FDA makes it clear in the introduction that applicants should apply science-based and risk-based principles, following the currently applicable guidance documents for industry.  It makes clear that it expects all changes to be managed by a facility's pharmaceutical quality system in accordance with the requirements of the FD&C Act and the applicable current good manufacturing practice (CGMP) regulations in 21 CFR Part. FDA further clarifies that the ICH Guidelines.

  • Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients ,
  • Q9 Quality Risk Management,
  • Q10 Pharmaceutical Quality System and
  • Q12 Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management,

are to be considered.

FDA further writes:
"Changes to disposable manufacturing materials for application products should be communicated to FDA through postapproval submissions - such as prior approval supplements (PAS) or changes being effected (CBE) supplements - or in annual reports. Regulations describe types of postapproval changes and associated reporting categories. Under CGMP, any changes to disposable manufacturing materials should be documented within the pharmaceutical quality system and available upon request during an inspection, including when the element being changed is not specifically described in an application. Changes to drug products for administration to humans or animals must be approved by the quality unit. Changes to disposable manufacturing materials for nonapplication products, including nonprescription drug products, should be documented under the pharmaceutical quality system and must be approved by the quality unit."

Further details and the questions and answers can be found in the Guideline "Changes to Disposable Manufacturing Materials: Questions and Answers Guidance for Industry".

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