Drugs

Clarify Draft on FDA-483 Responses: Comments

David McFarland

— 2 min read
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Pharmaceutical Research and Manufacturers of America (PhRMA) says it is concerned that an FDA draft guidance on responding to form FDA-483 observations at the end of a drug CGMP inspection “could be interpreted to go beyond the topic … and to suggest new substantive CGMP expectations.” The comment letter asks the agency to clarify, provide further guidance, or revise its substantive and format and content recommendations to better align with FDA’s authorities under the Federal Food, Drug, and Cosmetic Act.

PhRMA asks for these clarifications:

 

  • emphasize the voluntary and non-binding nature of FDA-483 responses and acknowledge that approaches not described in the draft guidance may meet FDA requirements;
  • not all FDA -483 observations necessarily constitute CGMP deficiencies or deviations;
  • establishments may contest observations on regulatory grounds in addition to scientific and technical grounds;
  • align the recommendations on management responsibility with existing CGMP regulations;
  • acknowledge that evaluating the effectiveness of a corrective and preventive action depends on its scope and complexity;
  • how to respond when deviations may require more than 15 days to resolve;
  • align recommendations for risk assessments with existing authorities;
  • establishments are not required to disclose the identity of consultants or legal counsel when submitting an FDA-483 response;
  • reduce the administrative burden on establishments;
  • only the relevant information in attachments must be translated into English and provide guidance on what qualifications are necessary for a translator; and
  • the timeline and use of follow-up responses submitted by establishments and FDA’s timeline for issuing a final inspection classification.

 

The Association for Accessible Medicines (AAM) says the draft would benefit from additional clarity on FDA processes following the submission of a form FDA-483 response, especially since both surveillance inspections and pre-approval/pre-license inspections can affect pending marketing applications. AAM suggests that the guidance outline opportunities for communication during the period after issuance of an FDA-483 but before inspection classification or an application action, such as through acknowledgement of receipt, clarification questions, or other mechanisms for dialog to support timely resolution of outstanding issues. The association asks that the guidance address how observations arising from remote regulatory assessments (RRAs) will be communicated and how firms should respond, as this process may differ from traditional on-site inspections.

The Parenteral Drug Association (PDA) recommends that the guidance either specifically state that remote regulatory assessments are out of scope of this guidance document or clarify expectations on how to respond to observation letters received from RRAs that require a response to FDA. Additionally, it requests that FDA clarify how firms should respond to an observation letter issued as part of RRAs. “While the FDA Guidance ‘Conducting Remote Regulatory Assessments Questions and Answers’ does highlight responding back to RRAs, it is not as detailed as this draft guidance,” PDA says. “As FDA use of RRAs is expected to increase, additional clarity would be valuable to industry.”

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