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Regulatory Focus™ > News Articles > 2021 > 3 > COVID-19: FDA offers guidance on container closure switches

COVID-19: FDA offers guidance on container closure switches

Posted 04 March 2021 | By Michael Mezher 

COVID-19: FDA offers guidance on container closure switches

The COVID-19 pandemic has created unprecedented global demand for raw materials and components of products used in the response to the virus. Supply chains for critical materials such as reagents, test swabs and now the glass vials and stoppers used to hold vaccines and therapeutics have been impacted, necessitating workarounds to keep pace with demand.
 
With COVID-19 vaccines and several therapeutics using glass vials and stoppers for their container closure systems (CCS), the US Food and Drug Administration (FDA) on Thursday issued an immediately effective guidance to facilitate changes to those systems “to mitigate the disruptive effect of the COVID-19 pandemic.”
 
“The supply of CCS components for FDA-regulated products generally may become constrained as manufacturers respond to the public health emergency related to COVID-19. As a result, manufacturers of FDA-regulated products may need to update their approved applications to make changes to CCS components to meet current product demand or increase supply resilience,” FDA says.
 
In the guidance, FDA details its regulatory approach to chemistry, manufacturing and controls (CMC) changes, discusses common changes related to glass vials and stoppers and outlines a risk-based approach to facilitate changes to CCS components. The appendix to the guidance also features a set of tables describing CCS changes for products approved under new drug applications (NDAs), abbreviated new drug applications (ANDAs) and biologics license applications (BLAs) outlining the recommended information to support each type of change, the reporting category such a change would require and considerations for alternative reporting categories.
 
Some of the changes covered in the appendix include changes from glass to another material; changes in glass composition or type; changes between molded and tubing glass; changes in vial dimension; switching from amber to clear glass; changes in stopper material and dimensions; changes to the source or site of manufacture of vials and stoppers; and manufacturing and processing changes.
 
The reporting category required to gain approval for or to notify FDA of a change to an approved application depends on the potential of the change to have an adverse effect on a product that could impact its safety or effectiveness. Depending on the change, an application holder may need to submit a prior approval supplement (PAS), a changes being effected in 30 days (CBE-30) supplement, a changes being effected (CBE) supplement or include the change in an annual report.
 
“Applicants must validate the effects of the change prior to distribution of the drug, and, as appropriate, conduct additional qualification tests or submit information to address product-specific risks as part of that assessment,” FDA writes. For instance, FDA says applicants may need to assess the effect of formulation attributes such as high pH or the effect of factors that increase the potential for glass delamination, particulate matter, leachables or interactions of labile molecules with leachables.
 
FDA also says that applicable tests and studies called for in United States Pharmacopoeia (USP) chapters “should be conducted to demonstrate the suitability of the glass vial following a change; such tests must be conducted where needed to ensure continued compliance with compendial standards for strength, quality, or purity of the drug.”
 
While FDA says it encourages applicants to submit the appropriate postapproval supplement type as recommended in existing guidance, the agency will also consider allowing lower reporting categories to be used for specific changes.
 
“FDA may expedite the assessment of a supplement or determine that a different reporting category is appropriate, taking into account public health priorities and the applicant’s rationale and associated risk assessment and mitigation strategy for the proposed change,” FDA writes.
 
FDA explains that it will consider requests to submit certain changes to CCS with a lower reporting category than set out in existing guidance if the applicant is facing a supply shortfall of CCS or CCS components if the product is used for the treatment or prevention of COVID-19 or is otherwise in shortage.
 
Companies looking to make a change to their CCS that wish to request a lower supplement reporting category are instructed to provide FDA with their rationale, supporting information and risk mitigation approaches.
 
FDA also instructs applicants seeking a lower reporting category than is normally required to contact it for feedback first.
 
Additionally, the guidance explains how comparability protocols can be used to prospectively facilitate changes to CCS. “[Comparability protocols] allow FDA to review a description of one or more proposed CMC postapproval changes, supporting information (including any analysis and risk assessment activities), the plan for implementing the change(s), and, if appropriate, the proposed reduced reporting category for the change(s). By delineating the specific approach to be used to evaluate one or more future changes and the rationale for that approach, the applicant can gain the Agency’s approval of the plan well in advance of the need to implement the change(s). This process can facilitate a more efficient submission process for the applicant and review process for FDA,” the agency writes.
 
Once an application or PAS containing a comparability protocol is approved, FDA says that changes can typically be implemented using a lower reporting category. Comparability protocols can also be used to support one-time changes, multiple changes over the lifecycle of a product or for identical changes to multiple applications.
 
“[A comparability protocol] is a well-suited tool for making changes to glass vials and stoppers, because a change to one component can be implemented to many products sharing that container or closure, and the protocol could be used multiple times as the need arises for additional changes to accommodate the dynamic supply chain evolution in reaction to COVID-19,” FDA writes.
 
FD

 

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