FDA Talks about Supply Chain Challenges

Globalization's impact

-Janet Woodcock, director, Center for Drug Evaluation and Research (CDER)

"Heparin was a wakeup call," demonstrating that we "need vigilance throughout the supply chain," said Woodcock. Solving these issues is "going to take a lot of harmonization" given the challenges. These challenges include: an explosion of global manufacturing, increased complexity of the supply chain, greater potential for exploitation, a global regulatory system that is still fragmented, US erosion of inspectional coverage, and a lack of modern information technology systems.

"Globalization is taking over as the standard of the day....," added Woodcock. To move forward from here, we need "seamless, effective global regulatory collaboration" with a worldwide safety net and increased effectiveness of inspectorates in developing countries. We also need fully harmonized quality standards in ICH (International Conference on Harmonization) and non-ICH regions, manufacturing modernization, harmonization of pharmacopeial stands, agreed-upon methods for supply-chain security, and better information technology, including better automation and standardization of global inventory.

In terms of responsibility, Woodcock discussed the fact that manufacturers must take responsibility for pharmaceutical quality of their products and for the integrity of their own supply chains. Regulators must adopt standards that ensure a safety net and take actions against poor quality, while enabling continuous improvement. Standards and technical organizations need to reach consensus on technical standards. Professional and technical societies must develop and update standards and disseminate them to industry via educational opportunities.

For its part, said Woodcock, FDA is continuing with its Pharmaceutical Quality for the 21st Century initiative, intensifying its international outreach with programs such as Beyond our Borders, and keeping track of inventory of manufacturing establishments as well as movement of product. More efforts may crystallize after the upcoming presidential election with regard to legislation currently circulating within Congress.

Import safety

-Jeffrey Shuren, associate commissioner for policy and planning, Office of the Commissioner

The Interagency Working Group on Import Safety, established by executive order in July 2007, issued a strategic framework for an Import Safety Action Plan last November. We no longer want a "snapshot at the border, but rather a streaming video feed" of when risk arrives and how we can rapidly respond, said Shuren. The goal is to have a level playing field regarding standards, corporate responsibility, and global partnerships. Companies who are outsourcing or contracting out services need to "trust the 'good actors' but verify their compliance and impose stiff penalties on 'bad actors,'" he said.

According to Shuren, FDA is continuing to work on "good importer practices" guidance, which will be available for comment. Guidance may involve certification of compliance with FDA standards before imports are allowed into the United States.

Supplier audits and certification

-Joe Famulare, deputy director, Office of Compliance, CDER

"There are many initiatives on the table regarding third-party certification of suppliers, including parts of the Import Safety Action Plan and proposals on Capitol Hill," said Famulare. [The action plan calls for FDA to have the authority to require that producers of certain high-risk products in a particular country, under an agreement with that country, certify that their products meet FDA standards in order to export to the US.] "Other types of possible legislation changes may mandate that companies audit their suppliers," he added. "The main effort in this area is within ICH Q7: Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients (APIs), and the voluntary standards of the International Pharmaceutical Excipients Council and International Pharmaceutical Excipients Auditing," he said.

Table I: Supply chain changes since 2001.

In another conference session, Famulare discussed supply chain qualification. "We have a task force within CDER compliance and there could be a guidance in that area forthcoming. We also enhanced ICH Q10: Pharmaceutical Quality System Section 2.7 regarding outsourcing to lay out a basic form of supply chain control by industry," said Famulare. "We're still studying the lessons learned from heparin and how to prevent it from happening again, but really, industry has to have the intelligence on their own supply chains."

External quality systems

-Joe Famulare

"For external supplier quality systems, whether you contract out or are getting supply, the regulations are specific regarding the testing to do to receive those materials and validate them," explained Famulare. "Now, with ICH Q10, having a program to audit that system and facility supplying you is very important—it goes beyond testing.... Having the intelligence to understand what may adversely impact that supply is also important. We don't expect the external supplier to have a mirror image of your quality system but we do expect it to mesh...and work with your quality system."

Future goals

-Deborah Autor, director, Office of Compliance, CDER

"We all share these new challenges and we all need to give serious thought to what we do.... It's not as simple as more inspections. We need to change the system," said Autor. "The old system was directed toward a domestic industry; that's not what we have anymore. Regulators and industry need to do more....

"We need more corporate responsibility. We're not in the shoe business. People are relying on these products to protect their health. We need to know where a product has been, where it was made, its integrity..." and so forth, she explained. "Management needs to be able to vouch for its products.... We can no longer say, 'FDA has to prove a drug product is bad.... We have to know a drug is 'good.'"

Autor also talked about how industy needs to shift to international cooperation in the longterm. "The job is simply too big for one regulator to do," she said. The European Medicines Agency/FDA joint inspection pilot is ongoing for information-sharing on European Union and US sites, and on API sites in third countries.

Author closed with the following: "In a global economy, manufacturers must bear clear responsibility for the integrity and quality of all ingredients. If you disagree with that, please let me know. Regulators must work together to adopt a worldwide approach. Together, we have to ensure that drugs are what we want ourselves and our families to take and to feel good about."