FDA Lawyers Blog

by Brian Malkin

On March 15, FDA announced the availability of a new guidance, Planning for the Effects of High Absenteeism to Ensure Availability of Medically Necessary Drug Products. The guidance is intended to encourage manufacturers of medically necessary drug products ("MNPs") and their components to develop contingency plans for use when emergencies cause high absenteeism in their production facilities.

According to the guidance, a MNP is "Any drug that is used to treat or prevent a serious disease or medical condition for which there is no other adequately available drug product that is judged by medical staff to be an appropriate substitute." FDA indicated that high absenteeism may be associated with the emergency situation for which the MNP is indicated, e.g., influenza pandemic, where widespread illness outbreaks could result in production stoppages.

FDA recommends that the contingency plans include mechanisms to attempt to anticipate emergencies that can result in high rates of absenteeism and encourage by increasing inventory of MPNs and components to manufacture MPNs, increase cross-training of employees so they may be reassigned to manufacture MPNs if necessary, performing routine maintenance of equipment to manufacture MPNs and provisions for alternate suppliers of resources and goods to manufacture MPNs. In addition, contingency plans should include mechanisms to activate and deactivate the contingency plans and drills should be run internally to ensure that employees are familiar with the plans and when and how to implement them.

FDA requests that the guidance be provided to all suppliers and contractors associate with MNPs. The guidance provides that it expires on January 31, 2014.

by Brian Malkin

On September 7, FDA announced a public meeting and opening of a docket to a draft guidance related to the development of medical countermeasures to combat chemical, biological, radiological, or nuclear threats under a 2002 "Animal Rule".

The Animal Rule permits, when it is neither ethical nor feasible to conduct human efficacy studies, FDA to grant a marketing approval based on adequate and well-controlled animal efficacy studies as well as human safety studies. The animal studies, however, must establish that it is reasonably likely to produce benefit in humans, preferably in multiple animal models where the toxicity of the threat and the mechanism for treatment is well understood.

While at FDA, this author worked on developing and implementing the Animal Rule, following an initial assessment of multiple biological threats, focusing on recommending medical countermeasures for then contemplated stockpiles in the event of a threat. One of FDA's responses to ongoing criticism of its stringent regulatory processes for approving new medical countermeasures was the Animal Rule.

Despite FDA's effort to produce draft guidance for the Animal Rule, reviews under the Public Health Emergency Medical Enterprise continued to cite the Animal Rule and its implementation as hurdles for developing new and effective medical countermeasures. In response, FDA decided to open the docket for comment and conduct this public meeting.

FDA will conduct the meeting on November 5. Comments on the draft guidance may be submitted up to January 5, 2011. The original draft guidance was dated January 2009 with comments closing on March 23, 2009.

by Brian J. Malkin

On August 19, the President's Council of Advisors on Science and Technology (PCAST) recommended a targeted federal investment of $1 billion per year until certain key areas in flu vaccine development and production are improved to develop a more rapid response to flu outbreaks. Significant delays during the 2009-2010 H1N1 pandemic flu outbreak catalyzed the President to request this review.

PCAST's report identifies five key areas that could lead to a faster response time: (1) surveillance - Centers for Disease Control to identify emerging pandemic viruses earlier, so vaccine production may begin earlier; (2) seed viruses - National Institutes of Allergy and Infectious Diseases (NIAID) and the Biomedical Advanced Research and Development Authority (BARDA) to develop a collection of stock viral "backbones" to facilitate developing vaccine strains; (3) sterility testing - FDA and BARDA to develop faster and more reliable vaccine sterility tests; (4) potency test reagents FDA and BARDA to develop faster and more reliable vaccine potency tests; and (5) FDA and other federal agencies in collaboration with industry to enlarge capacity and modernize equipment used in final vaccine production including vial filling.

In addition, PCAST's report recommends encouraging industry to develop more technologically-advanced vaccines. PCAST recommends that HHS, NIAID, and BARD work with industry to develop methods for making flu viruses using mammalian cell culture systems rather than chicken eggs. Currently, chicken eggs are the only approved method in the U.S. for making inactivated or live attenuated flu viruses, yet cell cultured and recombinant DNA methods are used to make other vaccines more rapidly and with less chance of contamination or allergies.

by Brian Malkin

On August 19, Health and Human Services (HHS) Secretary Kathleen Sebelius announced a long-term plan to infuse $1.9 million into the public health infrastructure to help develop medical countermeasures to combat medical threats caused by both naturally-occurring and terrorism-driven events. Sebelius acknowledged that despite an increased awareness of new or potentially weaponized medical threats, the public health system has been slow to respond with new products and rapid manufacturing capabilities. For example, during a two-stage outbreak of H1N1 pandemic flu in 2009-2010, it took 26 weeks to develop the initial vaccine doses and 38-weeks to have sufficient doses for half of the population, when the second wave occurred already at 18 weeks.

HHS's medical countermeasures focus on five key areas: (1) strengthening regulatory science at FDA, so it has the resources to create clear regulatory pathways and analyze new technologies faster by developing action teams for high priority products; (2) developing flexible manufacturing, so domestic facilities can change current manufacturing platforms to manufacture surge capacity for medical countermeasures; (3) utilizing the National Institutes of Health's (NIH's) resources to identify and nurture promising countermeasure technologies; (4) upgrading the current flu vaccine manufacturing process to include live attenuated strains, cell culture, and other technologies for more rapid vaccine development and production (see related blog); and (5) continue developing incentives for strategic partners to invest in new countermeasure technologies, such as more flexible contracting procedures.

Initial funding for the countermeasures comes from funding for the H1N1 flu pandemic and amount to: (1) $170 million for improving FDA's regulatory science; (2) $678 million to set up at least one private facility to work under government contract with small firms to make new products, develop new manufacturing processes, and help to produce vaccines during peak demand periods; (3) $33 million for new teams at NIH to identify promising research; (4) $822 for upgrades top speed development of pandemic flu vaccine; and (5) $200 million fund to invest in small companies that develop promising technologies.