FDA Continues to Solicit Comments on Drug Supply Chain Issues

By James E. Valentine* & Anne K. Walsh –

Despite Congress giving FDA new powers to regulate the integrity of the drug supply chain, the globalization of the pharmaceutical market continues to present clear challenges for the Food and Drug Administration (“FDA”).  FDA’s new authorities are outlined in Title VII of the Food and Drug Administration Safety and Innovation Act of 2012 (“FDASIA”). (A comprehensive overview of Title VII can be found in our detailed summary and analysis of FDASIA here). 

FDA held a meeting last Friday as part of the process for implementing FDASIA.  During the first portion of the meeting, FDA updated the public on the progress it has made to date.  Commissioner Hamburg and other FDA officials touted the recent release of two documents related to enforcement under Title VII:

• A proposed rule that details the procedures FDA will employ to prevent distribution or subsequent use of potentially adulterated or misbranded drugs encountered during inspections, until the Agency has had time to consider what action it should take concerning the drugs, and to initiate legal action, if appropriate.   
• A draft guidance that defines the types of actions, inaction, and circumstances that FDA considers to constitute delaying, denying, or limiting inspection, or refusing to permit entry or inspection. 

John Taylor III, Acting Deputy Commissioner for Global Regulatory Operations and Policy, explained the need for these enforcement tools in the face of the “staggering” increases in FDA-regulated shipments into U.S. ports in the recent decade. 

During the second portion of the meeting, FDA solicited input on how to implement two sections of Title VII, both of which amend Section 801 of the Federal Food, Drug, and Cosmetic Act (“FD&C Act”):

• Section 713 – FDA may now require importers to demonstrate that the drug does not violate the FD&C Act by submitting certain information, such as evidence of compliance with current Good Manufacturing Practices and a satisfactory inspection.   
• Section 714 – FDA may now require a commercial drug importer to register with the Agency and include with their registration a unique identifier for the principle place of business at the time of registration.  As part of this scheme, FDA must establish good importer practices with specific directives for importers to follow to avoid importing products in violation of the FD&C Act and the Public Health Service Act. 

The comprehensive list of questions FDA posed about these sections can be found in the meeting notice.  Following is a summary of the top, and most interesting, points of discussion.

Industry Wants FDA to Level the Global Playing Field.

Martin Van Trieste, Senior Vice President, Quality, Amgen Inc., spoke on behalf of Rx-360 Consortium, a nonprofit international supply chain organization led by volunteers from the pharmaceutical and biotech industry.  According to him, traditional pharmaceutical and biotech manufacturers and suppliers want standards for importation, registration of importers, and good importer practices (“GIPs”), that would differentiate them from the “criminals” that affect the drug supply chain.  For law-abiding industry players, companies that either intentionally or negligently supply counterfeit or adulterated drugs are undermining the industry, especially when these unsafe products are priced more competitively than legitimate products (e.g., as seen with the supply of counterfeit Avastin distributed to U.S. oncology practices a year ago).

Overall, manufacturers appreciated the risk-based framework in these sections because FDA can impose lesser requirements on “highly compliant importers” by allowing for a streamlined import process for those importers with validated compliance histories.

Excipient Manufacturers Hope to Be Exempted from Importer Regulations.

Pleading its case to FDA, David Schoneker from IPEC-Americas, the trade association for excipient manufacturers, distributors, and users, said that while excipients are “drugs” under the FD&C Act, they are different from active ingredients in important ways.  The trade group argued that, because there is already a burden on the end user of an excipient to provide oversight, putting standards on excipient manufacturers for importing under Section 713 would create a redundant regulatory scheme. 

Excipient manufacturers also commented that it is unnecessary to impose on them importer registration requirements and GIPs under Section 714 because the industry is already held to facility registration requirements, as well as current Good Manufacturing Practices and Good Distributor Practices. 

Importers Should Provide CoAs and Evidence of Compliance with USP Standards.

Multiple public stakeholders (such as the Certified Importer Program Coalition, United States Pharmacopeia Convention (“USP”), and Six Degree Counterfeit Prevention LLC) supported requiring drug importers to supply the Certificates of Analysis (“CoA”) for their products.  While most stakeholders believed the CoA would be a useful tool to determine compliance, both FDA and stakeholders shared a concern regarding their authenticity.  Many cited the 2007 global tragedy of counterfeit glycerin that resulted in poisonings and deaths (see related FDA MedWatch Safety Alert).  In that case, the CoA was falsified to attest to its purity, and the name of the manufacturer and previous owner were removed.  Reid Graves, Manager, Global Master Data Management, Pfizer, spoke on behalf of Six Degrees Counterfeit Prevention LLC, regarding the use of “a non-mathematical polymorphic encryption technology” to prevent forgery or falsification of CoAs, which would allow FDA to decrypt the CoAs and authenticate them. 

In addition, Ben Firschein, Director of Government Affairs and Policy, USP, suggested that it should be a critical requirement of Section 713 to require evidence demonstrating compliance with compendial standards.  He emphasized that many of the compounds included in the USP would allow for some import oversight for special categories of drugs, such as compounding ingredients.

Conclusion

Unfortunately, the meeting revealed no concrete answers about how to implement these FDASIA sections, especially concerning the sufficiency of evidence necessary to demonstrate compliance with the FD&C Act.  FDA continues to struggle with the variability of evidence based on level of risk posed by a specific imported product.  At the meeting, however, FDA seemed very eager for industry and other external input as it navigates these questions.  The public comment period is open for these dockets until August 12, 2013 (see here).  FDASIA requires the Agency to promulgate regulations within three years, and to provide a “reasonable period of time” for an importer of a drug to comply with good importer practices. 

The transcript and slides from the meeting should be available for review at the FDA Division of Dockets Management and http://www.regulations.gov approximately 30 days from July 12, 2013, the date of the meeting.

* Law student