Drugs

Container Closure System Guidance Comments

David McFarland

— 2 min read
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Pharmaceutical Research and Manufacturers of America (PhRMA) says it appreciates FDA’s attention to container closure systems in light of the significant technological advances that have emerged in material science and drug delivery systems since the agency’s 1999 guidance on the same topic. In a comment letter on an FDA draft guidance, PhRMA asks FDA to clarify certain aspects of scope and bring it into alignment with various International Council for Harmonization (ICH) guidelines. It also asks that some consideration be given to implications for combination products, and to certain aspects of container closure integrity testing (CCIT), shipping studies, and studies at extreme temperatures.

PhRMA says FDA should:

  • clarify the scope of the guidance in a way that reflects a science and risk basis;
  • ensure the final guidance aligns with ICH and other international standards;
  • ensure the guidance is appropriately tailored to combination products;
  • clarify expectations for CCIT assessments including in-process testing, routine controls, and sterility assurance;
  • clarify expectations on shipping studies and studies at extreme temperatures; and
  • revise its position on using recycled plastics in primary packaging components.

The PhRMA letter also provides line-by-line specific comments, as does the American Association of Pharmaceutical Scientists.

In addition to its specific comments, the Parenteral Drug Association recommends that FDA define and consistently use container closure system and packaging components throughout the guidance. “The definitions should clarify the relationship between these terms, distinguish primary, secondary, and other packaging components, and provide representative examples, including how non-product-contact device parts are classified,” it says.

In its response, the Combination Products Coalition makes these overarching comments:

  • the draft guidance should state that expectations differ across early clinical and commercial stages, and should recognize that qualification data from a platform or an established device constituent part may be leveraged with appropriate scientific rationale;
  • recommendations in the draft that read as fixed requirements should be reworded to preserve risk-based flexibility, consistent with current agency precedent;
  • well-established, FDA-recognized consensus standards should be recognized alongside the U.S. Pharmacopeia;
  • the draft’s use of “container closure system” and “packaging component” interchangeably and lack of definition of “assembled container closure system” is a concern for combination products because sponsors cannot tell how to classify a component that never contacts the drug directly but performs a function;
  • misalignment in the guidance tables has practical consequences for sponsors because examples are frequently treated as requirements; and
  • when related draft guidances are referenced to provide context, material revisions to the referenced document before finalization could affect the accuracy or applicability of those cross-references in the present guidance, creating uncertainty for stakeholders navigating concurrent guidance.

 The association also includes specific line-by-line comments.

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