FSMA Implementation Enters a New Phase

The Food and Drug Administration hosted a public meeting in Chicago on October 20, 2015 to discuss the recently released final rules on preventive controls for human and animal food, along with plans for the next phase of FSMA implementation. This was a substantive meeting and I encourage you to view the six slide presentations on FDA’s FSMA website.

The first phase of FSMA implementation – the release of final FSMA regulations and related guidance and policies – is moving swiftly forward. FDA released final rules on preventive controls for human and animal foods on September 17 and the agency is now developing numerous guidance documents.

FDA was under a court-imposed October 31, 2015 deadline for releasing three additional final rules – on produce, foreign supplier verification and accreditation of third-party auditors (These are not yet available as I prepare this article). Under the consent decree, FDA must issue final rules on sanitary transportation and on intentional adulteration by May 31, 2016.

The second FSMA implementation phase focuses on “gaining and maintaining industry compliance,” with the final rules and identifying metrics for measuring success. The third phase involves actually using those measuring tools and making any needed adjustments.

Many elements of the complex rules will require further explanation and guidance. In the October 20 meeting, Dan McChesney, director of the Office of Surveillance and Compliance in FDA’s Center for Veterinary Medicine, presented an overview of the animal food final rule and explained, for example, that feed mills may or may not be required to comply.

Mills that are not part of a farm and are required to register as a food facility are subject to the new rule. Examples include an independent feed mill, a feed mill that makes food for contract farms, an on-farm feed mill that makes food for animals under different management than the farm, he said.

Feed mills that are part of a farm are exempt from registering as a food facility and are not subject to the new rule, he explained. For the feed mill to be considered part of the farm, the raising of animals and the feed mill must be under the same management in one general location, and animal food made at the mill must only be fed to animals under the farm’s management, he said.

The agency is currently working on several guidance documents relating to the animal food rule, including guidance on current good manufacturing practices, on human food by-products for use as animal food, and on hazard analysis and preventive controls. It is also developing a compliance guide for small or very small businesses. Under the rule, a very small business is defined as one with an average of less than $2.5 million in annual sales of animal food, plus the market value of animal food held without sale. A small business is defined as one with fewer than 500 full-time equivalent employees.

Provided the three final rules on produce, foreign supplier verification and accreditation of third-party auditors are available, I will offer my perspective on those in the next EAS-e-News issue.

New Drug Development in the 21st Century

Most people who work in the pharmaceutical industry know that drug development comprises of pharmaceutical development, animal pharmacology and toxicology studies, and clinical research; many also know that there are quality standards applied to manufacturing and controls that become more and more stringent as the development process evolves. Similarly, the quality standards for animal pharmacology, safety pharmacology and toxicology are implemented in a tiered manner. Clinical research, the most time consuming and costly part of the process, is also controlled by quality practices.

Many more drugs fail during development than make it to market. The Pharmaceutical Research and Manufacturers of America estimates that it requires more than 10 years and $2.6 billion dollars for a drug to be approved for marketing. And only 12% of drugs that enter the development process make it to market. The discovery of clinical lead compounds requires many more potential drugs to be discarded prior to IND development.

This means that FDA holds many more pre-IND meetings than end-of phase 2 or pre-NDA meetings.

Many people hold that “regulatory efficiency” is an oxymoron. The only efficient path to market is to do it right in the first place. FDA provides consultation to pharmaceutical manufacturers throughout the development process. Using the opportunities offered by standard development, pre-IND, end of Phase 2, and pre-NDA meetings with the agency gives sponsors access to the wealth of information FDA has gained from review of previous applications as well as up-to-the minute advice on how to comply with current regulations and standards. There are published guidance documents on how to prepare for and hold these meetings; however, often, a sponsor requires the assistance of consultants who are experts in the various aspects of development that pertain directly to their product (e.g. a new nanotech formulation). Most sponsors also benefit from the assistance of regulatory experts for defining the topics and detailed questions to discuss, preparation of documents, regulatory protocol, and the conduct of the meeting itself.

Today, global drug development is coordinated mainly through the International Conference on Harmonization (ICH) process. The beauty of this system is that when a drug is developed according to ICH Guidelines, the research portfolio will be accepted in all the countries that have incorporated those guidelines into their own regulatory system. For example, the group of toxicology studies required before starting clinical studies is agreed and accepted by all the countries that participate in this process. This allows one body of technical information to be accepted by health regulatory authorities in Europe, Japan, Canada and many other countries.

Because the development of a novel compound into a marketable drug is so costly and time consuming, other regulatory routes to market are available. Perhaps the best known is the Abbreviated New Drug Application, a copy of a previously approved drug, which is available after all patents and marketing exclusivity options have expired. Recently, the 505(b)(2) process has become a popular means of short-circuiting part of the drug development process; it relies, as does the ANDA process, on FDA’s previous finding of Safety and Effectiveness for a drug product.

In summary, this brief overview illustrates that there is no simple route when introducing a new drug and there is more than one possible path to success.