A Look Ahead at Manufacturing and Regulation - Pharmaceutical Technology

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PharmTech Europe

A Look Ahead at Manufacturing and Regulation
FDA talks about the changing scope of regulatory science and its effect on drug reviews, site inspections, overall approaches.

Pharmaceutical Technology Europe

Foreign inspections/imports

PTE: Part of FDASIA helps to fund FDA foreign inspections through new user fees (i.e., the Generic Drug User Fee Amendments of 2012 [GDUFA]). Starting in 2014, inspections will use risk-based methodologies. What factors will the agency use to determine whether and when to inspect a foreign facility?

FDA: We have yet to finalise the revised risk-based approach although FDASIA Section 705 outlines the factors relevant to evaluating risk. All facilities will be inspected sooner or later. Firms new to FDA will be a priority as would be firms that are seeking approval for a type of manufacturing operation that is new to that site. FDA will consider establishing different frequencies for active ingredient and finished-dosage form production facilities. Facilities that make sterile drugs will likely be a higher priority than other types of production. GDUFA expects the frequency and rigor of domestic and foreign facility inspections to be equitable, which makes good sense for all drugs, so the risk-based model will have to ensure this is achieved.

PTE: FDASIA calls for the agency to issue guidance by July 2013 that defines when an inspection may be denied or limited. What is the status?

FDA: As required by Section 707 of FDASIA, FDA is currently working on a draft guidance that will address the scope of actions or inactions that constitute a delay, denial, refusal or limitation of an inspection. Section 707 deems a drug misbranded if it is produced in a facility for which an inspection is delayed, denied, refused or limited. This provision is important because it creates a strong incentive for all facilities, including foreign facilities, to allow FDA to conduct timely and complete inspections. If a domestic facility delays, denies, refuses or limits an inspection, FDA has jurisdiction to obtain an inspectional warrant. Prior to FDASIA, however, FDA did not have an effective tool to facilitate the cooperation of foreign facilities with inspections. Now, if a foreign facility delays, denies, limits or refuses an inspection, FDA may refuse entry for all drug products produced in that facility. This will save FDA time and resources and help ensure the safety of our drug supply.

PTE: FDASIA allows for FDA to use inspection information from other governments and agencies. Can you elaborate on this and other information-sharing?

FDA: FDA inspection reports are generally detailed accounts of each inspection that include the purpose, description of the breadth and depth of coverage, findings and significant discussions with a firm's staff. FDA would be able to make use of comparably detailed reports from our counterparts and, under FDASIA Section 712, FDA would be able to recognise a foreign government's inspections once a review and audit of its system verifies its inspections to the satisfaction of FDA. FDA currently shares inspection reports, as well as data-systems access with counterpart national regulatory agencies that often use these reports or inspection findings in lieu of their own inspection. Fortunately, there now exists an organisation of pharmaceutical inspectorates that harmonises drug-regulatory practices: the Pharmaceutical Inspection Co-operation Scheme (PIC/S). FDA became a member of PIC/S approximately two years ago. Membership gives FDA an opportunity to work with fellow PIC/S member authorities to ensure that inspection standards are robust and followed.

PTE: Regarding imports, FDASIA notes that foreign manufacturers must demonstrate the regulatory status of their drug as well as cGMP compliance and prove facility registration within the US; otherwise, the agency has the right to destroy noncompliant imported drugs under a $2500 value. These rules are set to take place in July 2014 after further regulations are developed. How will the new standards differ from current import and foreign registration requirements?

FDA: FDASIA provides FDA clear authority to require information about drugs offered for import and to refuse admission if it is not provided, which strengthens FDA's ability to monitor imported drugs for compliance with applicable laws. Similar to many other countries, FDASIA places the burden on the importer or product owner to prove its drug complies with applicable US requirements. These import authorities strengthen FDA's ability to evaluate imported drugs for compliance with US laws and regulations. The authorities also enable FDA to better target higher risk products and prevent violative products from entering the US.

FDASIA also grants FDA explicit authority to destroy violative drugs refused admission to the US if they are valued at $2500 or less. Before FDASIA's enactment, FDA had no independent administrative destruction authority. Instead, FDA could only issue a 'notice of refusal of admission' for noncompliant drugs offered for import. Once FDA issued a 'notice of refusal of admission', FDA had to rely on Customs and Border Protection (CBP) to either export or destroy the noncompliant import under the Tariff Act (19 U.S.C. 1595). By granting FDA administrative destruction authority after adequate notice and hearing, for violative drugs valued at $2500 or less, these new FDASIA authorities will not only create efficiencies and transparency in the import process, but also strengthen FDA's ability to protect public health.

PTE: How will these new requirements affect the supply chain and drug shortages?

FDA: The new drug-safety authorities FDASIA grants FDA reflect a more comprehensive and transparent view of the drug supply chain. For instance, FDASIA Section 714 requires that commercial importers register with FDA and Section 703 requires that drug-product listings identify excipient information. By granting FDA new authorities that more accurately reflect the entire drug lifecycle, FDASIA better equips the agency to protect public health and minimise consumer exposure to unsafe, ineffective and poor quality drugs in today's globalised supply chain. FDA will continue all efforts to address and prevent drug shortages while implementing these new requirements, which are anticipated to further strengthen efforts to assure the safety and quality of drugs for US patients.


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