Ask Not for Whom the Bell Tolls, it Tolls for Your LDT (Part II)

By Evan P. Phelps

In our prior posting, we provided a brief overview of the notification and adverse event reporting requirements that will apply to the vast majority of a subset of in vitro diagnostic devices known as Laboratory Developed Tests (LDTs), most likely in the not so distant future.  These requirements were detailed in the draft guidance documents published on October 3 of this year, outlining the agency’s proposed plan to begin actively regulating firms that produce LDTs.

The draft guidance documents may be found here: Draft Guidance for Industry, Food and Drug Administration Staff, and Clinical Laboratories: Framework for Oversight of Laboratory Developed Tests (LDTs); and here Draft Guidance for Industry, Food and Drug Administration Staff, and Clinical Laboratories: FDA Notification and Medical Device Reporting for Laboratory Developed Tests (LDTs).

This posting provides an overview of the remainder of the regulatory controls outlined in these guidance documents.


FDA will begin applying various levels of additional requirements to LDTs based on the agency’s view of the amount of risk posed by the test. These additional controls will include, among others, premarket review and compliance with manufacturing quality controls found in the Quality System Regulation (QSR).[1] These requirements will apply to both LDTs that are currently in clinical use and to those that a laboratory intends to introduce in the future. The draft guidance indicates that the agency will establish three classes of LDTs and apply varying levels of premarket scrutiny and QSR compliance to each according to the risk they present.

  1. Lowest Level of Scrutiny: No Premarket Review and No QSR Requirements

The lowest level of premarket scrutiny and QSR compliance will be applied to devices considered to be of the lowest risk. These will include “Traditional LDTs.” “LDTs Used for Rare Diseases,” and “LDTs for Unmet Needs.”  While notification and MDR requirements still apply, FDA intends to continue to exercise enforcement discretion regarding premarket review and QSR requirements for LDTs that fit into these categories.

  1. a) Traditional LDTs

Although the use of the term “Traditional LDTs” may appear promising, the agency defines the term in the guidance in a way that is likely to be far narrower than laboratories’ own definition of the term. As a consequence, many laboratories that believe they are offering traditional LDTs may not in fact be doing so under FDA’s definition and will not be eligible for this exemption from the premarket review and QSR requirements. Under FDA’s definition, only those IVDs intended for clinical use that are designed, manufactured, and used within a single laboratory and are of the type of LDTs that were available when FDA first opted to exercise enforcement discretion for LDTs in 1976 are considered to be “Traditional LDTs.”  FDA indicates that it will consider several factors in determining if an LDT meets its definition of a “Traditional LDT.” These factors include:

  • Whether the device meets the definition of LDT (a device designed, manufactured and used by a single laboratory);
  • Whether the LDT is both manufactured and used by a health care facility laboratory (such as one located in a hospital or clinic) for a patient that is being diagnosed and/or treated at that same health care facility or within the facility’s health care system;
  • Whether the LDT is comprised only of components and instruments that are legally marketed for clinical use (e.g., analyte specific reagents, general purpose reagents, and various regulated laboratory instruments); and
  • Whether the LDT is interpreted by qualified laboratory professionals, without the use of automated instrumentation or software for interpretation.

When such criteria are ultimately applied, many laboratories that presently believe that they are offering a “Traditional LDT” may, in fact, learn that they are not and face more significant FDA regulatory burdens.

  1. b) LDTs Used for Rare Diseases

Likewise, the term “LDTs Used for Rare Diseases” is also defined in a way that makes it less inclusive than may initially appear. Rather than basing the definition on the prevalence of a disease, the category is limited to instances where the number of persons that may be tested with the device is fewer than 4,000 per year. If there are more than 4,000 persons a year who would be tested with the LDT, it would not qualify as an “LDT Used for Rare Diseases.” Perhaps a better and more descriptive name than the one chosen by the agency for this category of tests might have been “Rarely Used LDTs.”

  1. c) LDTs for Unmet Needs

Generally, “LDTs for Unmet Needs” are those used to meet urgent health care needs where there is not a comparable FDA-cleared or approved alternative. FDA has published a number of factors it will use to determine if an LDT should be considered one that is “for unmet needs.” These factors include:

  • Whether the device meets the definition of LDT in this guidance (a device designed, manufactured and used by a single laboratory);
  • Whether there is no FDA-cleared or approved IVD available for that specific intended use; and
  • Whether the LDT is both manufactured and used by a health care facility laboratory (such as one located in a hospital or clinic) for a patient that is being diagnosed and/or treated at that same health care facility or within that facility’s health care system.
  1. Highest-Risk LDTs: Highest Level of Scrutiny 

LDT’s presenting the most risk (high-risk) will be considered Class III medical devices and will be subject to the highest level of regulatory control. The premarket review requirements for these LDTs will begin twelve months after the guidance is finalized. FDA considers the highest risk LDTs to include LDTs with the same intended use as a cleared or approved companion diagnostic (i.e., those that provide essential information for the safe and effective use of a corresponding therapeutic product), LDTs with the same intended use as an FDA-approved Class III medical device; and certain LDTs for determining the safety or efficacy of blood or blood products. In most instances, these LDTs generally will require a Premarket Approval Application (PMA) and may remain on the market during the twelve month period and during the pendency of their PMA (provided it is filed within the initial twelve month period following the publication of the finalized guidance). Enforcement of the premarket review requirement for other high-risk LDTs will be phased-in over four years after finalization of the guidance.

  1. Moderate-Risk LDTs: Moderate Level of Scrutiny

Once FDA has addressed the highest-risk Class III LDTs, it will turn to the enforcement of regulatory controls for moderate-risk LDTs which will be considered to be Class II devices by the agency. FDA has yet to identify which types of LDTs will fit into this category. Presumably, the information gathered as laboratories begin complying with the notification requirement will assist the agency in making this determination and the agency has announced that it will issue a guidance to describe what it considers to be Class I, Class II and Class III devices within two years after the guidance is finalized. Beginning five years after the guidance is finalized and continuing over the four subsequent years, FDA intends to begin enforcing the premarket review process for these moderate-risk LDTs and, in most instances, will require premarket notification (510(k) clearance) for their continued marketing.

  1. QSR Compliance for High-Risk and Moderate-Risk LDTs

Compliance with the QSR will be required for both high-risk and moderate-risk LDTs. The QSR sets forth the requirements for the methods used in, and the facilities and controls used for, the design, manufacture, packaging, storage, and installation of medical devices and also includes system requirements in areas of concern to all manufacturers of finished devices.  According to the draft guidance, FDA will continue to exercise its enforcement discretion with respect to QSR compliance for LDT manufacturers of moderate-risk devices until the time that the LDT is the subject of a cleared 510(k). For high-risk LDTs that require a PMA, enforcement discretion will end at the time that the PMA is submitted to the agency for review and approval.


The trigger for when FDA will begin enforcing controls is upon the publication of the final versions of these draft guidance documents. Potentially, this could occur as soon as April 2015.  For some laboratories, the shift from operating under FDA’s enforcement discretion to being fully-regulated as a medical device manufacturer is sure to be a significant and difficult challenge. Making such a change will require these laboratories to consider, plan for, and dedicate resources to achieve compliance with FDA requirements. Even for established medical device companies, doing so is no small effort. The key to success for these laboratories will be to begin assessing how FDA’s proposed requirements will apply to their LDTs now, the burdens that they will assume, and to establish a plan to be in compliance before FDA’s enforcement discretion comes to an end.

Until such time, however, FDA is accepting comments regarding these proposed guidances from members of the public. Accordingly, firms have an opportunity to make their voices heard before FDA’s regulatory scheme comes into effect. If you believe that your own organization will be unduly burdened by this proposed regulatory scheme, we would very much encourage you to have your say while there is still a chance that you can make a difference.

[1]               21 C.F.R. Part 820.

Celebrating 35 Years of Success: USDA Practice Team

By Brett T. Schwemer

Recently, Olsson Frank Weeda Terman Matz, P.C., otherwise known as “OFW Law,” celebrated 35 years of business with colleagues, family, friends and clients.  We were extremely proud to share this milestone with those who have helped make OFW Law one of the leading firms practicing USDA and FDA law today.

Although OFW Law has expanded in other areas of law, the origin of OFW Law began in agricultural law and these roots remain strong today. Indeed, OFW Law is one of the most comprehensive agriculture law firms in the country, representing large and small companies and trade associations on a myriad of legal issues, ranging from food safety and nutrition, animal welfare and forestry, to everything in between. Together, our USDA practice team, consisting of 17 attorneys and Senior Policy Advisors, are capable of representing clients before virtually every agency of the USDA.  Our most frequent interactions involve the USDA’s Food Safety and Inspection Service (FSIS), Food Nutrition Service (FNS), Agricultural Marketing Service (AMS), Animal and Plant Health Inspection Service (APHIS), Grain Inspection, Packers and Stockyard Administration (GIPSA), Risk Management Agency (RMA) and Federal Crop Insurance Corporation (FCIC).

One attribute that makes the USDA practice team unique among its peers is its experience.  Many of our professionals have served in high level agricultural positions in the government and/ or have a long history of working in or with the agriculture/food industry   This has allowed our professionals to not only apply real world experience and technical expertise to solve difficult problems, but to identify the right contacts at USDA should issues need to be resolved at the Department.

The experience and expertise of our professionals have allowed the USDA practice team to tally many successes over the last 35 years.  We are proud to share a few of our most notable ones, as follows:

  • Our professionals have assisted numerous meat, poultry and other food clients design, implement and assess food safety, sanitation and quality control programs. With in-plant experience and training in HACCP principles, our professionals have helped clients not only comply with food safety requirements, but exceed them.
  • Our professionals have successfully assisted clients in FSIS enforcement actions (e.g., Notice of Intended Enforcement Actions, Notice of Suspensions), providing advice which has allowed clients to avoid, or minimize the duration of, plant closures.
  • Our practice team has helped numerous clients facilitate the marketing of their food and agriculture products, by assisting in obtaining government approval for new label claims and/or new ingredients/processing aids, or by helping to remove regulatory impediments for marketing their products. For example, we successfully petitioned FSIS to eliminate the standard of identity for pizza, giving frozen pizza manufacturers the flexibility to make more innovative products so they can better compete with pizzeria restaurant chains.
  • Our practice team has successfully defended meat packers, poultry slaughterers, livestock dealers and market agencies in numerous GIPSA enforcements actions under the Packers and Stockyards Act. In one case, GIPSA filed a complaint seeking over $3 million in civil penalties against a packer for failing to notify livestock sellers, prior to purchasing livestock, of a more accurate formula used for grading pork carcasses.   As a result of our representation of the packer, the Administrative Law Judge and Judicial Officer of USDA issued no civil penalties in the case.
  • Following a successful multifaceted campaign by our team, AMS rewrote the Florida Tomato Marketing Order in 2005 to permit the nationwide distribution of the UglyRipe® tomato during the regulated Florida tomato season.
  • When the Congress considered amendments to, and perhaps even repeal of, the Perishable Agricultural Commodities Act (PACA), stakeholders turned to our professionals for counsel. The amendments resulted in preservation of the fair trade statute covering all fresh and frozen fruits and vegetables with more efficient reservation of PACA Trust benefits and a stabilized funding mechanism for USDA’s PACA Branch.
  • Puerto Rico attempted to impose specific labeling requirements for shell eggs imported from outside the Commonwealth, including on the eggs themselves.  We successfully challenged the regulations in federal court at both the district and appellate levels, with the First Circuit holding that Puerto Rico’s regulation violated the Dormant Commerce Clause of the U.S. Constitution.
  • On FCIC Federal crop insurance, we have represented players on every side of the fast-growing program: approved insurance providers (AIPs), agents, farmers, product developers, and grower associations. In just one area, new insurance policies, we assisted in the approval of Livestock Risk Protection (LRP) for cattle, hogs, and lamb, margin protection for wheat and rice, oysters, barley, biotech corn, and many others. This past year, we assisted drought-hit farmers in Oklahoma and Texas on controversial claims, helped two insurance companies address oversight issues with RMA, and successfully urged changes in rules on treatment of indebted farmers.

This is a small snapshot of the long record that our group has assembled over the past 35 years, and we are very proud of it.

FDA Tweaks Its Guidance on Food Facility Registration

By Robert A. Hahn

FDA has released a revised guidance document on food facility registration: Guidance for Industry: Questions and Answers Regarding Food Facility Registration (Sixth Edition).  The revised guidance adds only one new question and answer to the 34-page guidance:

1.3 Q: [Added November 2014] Under the supplemental notice of proposed rulemaking for preventive controls for human food, FDA has proposed changing the farm definition for registration and other purposes.  Under the proposed change, a farm would no longer be required to register as a food facility solely because it packs or holds raw agricultural commodities grown on a farm under different ownership.  While the rulemaking is still ongoing, what is FDA’s policy regarding farms that also pack or hold raw agricultural commodities grown on a farm under different ownership?

A: FDA does not intend to prioritize enforcing the registration requirement in this circumstance.

This change is intended to reflect a proposed change in the definition of “farm” in FDA’s supplemental proposed rule on Preventive Controls for Human Food.  FDA is proposing that a farm that also packs or holds raw agricultural commodities (RACs) grown on another farm not under the same ownership is still a “farm” exempt from FDA registration.  This change in FDA’s position was urged by several stakeholders in the produce industry.

According to the Federal Register notice announcing the revised guidance, “FDA intends to make further updates to this guidance once certain FSMA rulemakings are final…”  If the supplemental proposed rule on Preventive Controls for Human Food is finalized as proposed, it would change the rules on FDA registration in a number of other ways.  For example, it would expand the definition of what is a “farm” exempt from FDA registration by expanding the activities by farms that would be considered “packing” or “holding” to include activities incidental to the packing of RACs (such as sorting, culling, grading, packaging, and labeling of RACs) and activities incidental to the storage of RACs (such as blending lots of the same RAC, fumigating RACs).  Again, these changes have been sought by stakeholders in the produce industry.

The revised guidance is effective immediately, but FDA accepts comments on guidance documents at any time.

Consumer-Directed Promotions About Prescription Drugs: A Look Back at Print and TV Communications

OFW Law Celebrates 35 Years of Successes in Drug/Healthcare Privacy Practices (Part VI)

By Tish Eggleston Pahl

In celebrating 35 years of practice, OFW Law’s Drugs, Biologics, and Controlled Substances and Healthcare Privacy practice groups are taking a look back to share some highlights throughout the years.  Parts I, II, III, IV and V focus on Hatch-Waxman, medical privacy laws, FDA’s user fees, prescription drug traceability and GMPs.  Today’s blog looks back at changes in the regulation of drug promotion.

As we celebrate anniversaries at OFW Law this month (the firm’s 35th and my 21st), any retrospective on the drug practice would be incomplete without recognizing our work on, and the changes to, how entities communicate with patients and consumers about prescription drugs.

We could go back to Lydia E. Pinkham’s Pills Vegetable Compound and earlier for evidence of “patent” drug promotion directly to consumers.  However, this retrospective begins in 1962, when Congress enacted the Kefauver-Harris Amendments to the FDC Act.  In addition to expanding FDA’s authority over prescription drugs, and requiring proof of safety and efficacy prior to approval and marketing, Congress also transferred from the FTC to FDA the authority over the advertising of prescription drugs.

Pursuant to that authority, in 1963, FDA initiated and finalized the rulemaking that would eventually become the familiar § 202.1 – Prescription-drug Advertisements (28 Fed. Reg. 1448 (Feb. 14, 1963); 28 Fed. Reg. 6375 (June 20, 1963).  The requirements that a prescription drug promotion be fairly balanced and accompanied by appropriate information (the full prescribing information (“PI”) for promotional labeling and a brief summary of that PI for advertising) have been with us – seemingly forever – and without substantial change.  If it seems that existing regulations don’t fit modern healthcare communications very well, look no farther than the fact that the regulations are older than both today’s popular technologies and most of the people who use them for prescription drug information.

FDA cites the early 1980′s as the point when prescription drug sponsors first began targeting patients and consumers directly – what became known as “direct-to-consumer” or “DTC” promotion.  FDA requested a voluntary moratorium on DTC prescription drug promotion on September 2, 1983 and, thereafter, undertook a series of public meetings and research.  The agency lifted the moratorium two years later (56 Fed. Reg. 36,677 (Sept. 9, 1985)), stating that it believed current regulations provided “sufficient safeguards” for consumers.

(Keep in mind, just getting copies of regulatory documents was an adventure in those days.  Paralegals with rolls of nickels and good contacts would traverse from the downtown Federal Register office to Fishers Lane and back, scrounging for documents put on public display.)

In August 1995, FDA announced the first of several public hearings on DTC-related issues (60 Fed. Reg. 42,581 (Aug. 16, 1995)).  Two questions FDA posed were of special interest: what information should accompany print promotion; and how to satisfy the disclosure requirements for broadcast advertisements.  Nearly 20 years later, these issues continue to vex prescription drug communications.

Accompanying Information in DTC Print Communications

Under 21 U.S.C. § 352(n), any print advertisement must be accompanied by “information in brief summary relating to side effect, contraindications, and effectiveness,” which FDA had interpreted in 21 C.F.R. § 202.1(e)(3)(iii) to mean “each specific side effect and contraindication” in the drug’s PI.

This meant that magazine and newspaper ads would include a page or more of solid text that reprinted most or all of the PI in a tiny font.  At the 1995 public hearing, then-FDA Associate Director for Medical Policy, Dr. Robert Temple, bluntly acknowledged that this approach for consumer-directed communications was an oxymoron:

Let’s say we all agree for the sake of argument that the current brief summary, which is neither brief nor a summary – like the Holy Roman Empire was neither holy nor an empire – isn’t very helpful.  I think you won’t find a great deal of disagreement about that among FDA staff either.

Unanimous condemnation of the PI-based brief summary in DTC promotion would continue through several more rounds of comments and FDA research that showed, unsurprisingly, that consumers found it no more useful than FDA staff did.

In 2004, FDA released the Brief Summary Draft Guidance which expressed the agency’s decision to exercise enforcement discretion and, the requirements of 21 C.F.R. § 202.1(e)(3)(iii) notwithstanding, permit and encourage abbreviated, consumer-friendly brief summaries with DTC print advertising.  Marketers implemented the draft guidance, hugely improving DTC print promotions.

Unfortunately, the agency never addressed what has, in the last 10 years, become an enormous problem in other patient-directed communications.  The Brief Summary Draft Guidance only helps DTC print advertising (e.g., magazines and newspapers) – media that are in significant decline.  The Draft Guidance does not apply to patient-directed labeling, like refill reminders and compliance and adherence communications given to patients to support their prescribed and dispensed therapy. FDA still interprets its requirements as mandating patient-directed labeling to be accompanied by the full PI, even though the agency has long acknowledged (and has the data to prove) that the PI isn’t helpful to patients.

Keeping patients compliant is an enormous, costly, and deadly public health problem and everything that can be done should be done to make these communications easier, better, and more accessible.  Since the release of the Brief Summary Draft Guidance in 2004, the agency has been urged, repeatedly, to do for patient-directed labeling what it did for DTC print advertising.  It never has.

In February, there was cause for hope when FDA’s Center for Drug Evaluation and Research (CDER) published its proposed Guidance Agenda and announced it would finalize the 2004 Brief Summary Draft Guidance.  This was good news, even if it would have little impact as so little DTC advertising remains in traditional print media and anyone still in that space adopted the consumer-friendly brief summaries years ago.  More exciting was the new title of the Guidance:

Brief Summary and Adequate Information for Use: Disclosing Risk Information in Consumer-Directed Print Advertisements and Promotional Labeling for Prescription Drugs.

(Emphasis added.)  It appears that FDA may take the opportunity the guidance provides to address the heavy disclosure burden placed upon patient-directed promotional labeling that the DTC advertising does not have to meet.  Maybe, hopefully, compliance and adherence communications patients need for the safe and effective use of their prescribed and dispensed drugs can finally be accompanied by a useful, brief summary of the PI rather than the full PI.

“Adequate Provision” for DTC Broadcast Advertisements

That seminal 1995 DTC hearing also addressed the dilemma § 202.1 posed for prescription-drug broadcast advertising.  Under 21 C.F.R. § 202.1(e)(1), sponsors of broadcast advertisements are, among other things, required to present a brief summary in the advertisement or, alternatively, must make “adequate provision … for dissemination of the approved or permitted package labeling in connection with the broadcast presentation.”

This requirement made it impossible for manufacturers to promote DTC prescription drugs in regular broadcasts.  No one knew what “adequate provision” of the PI meant.  The brief summary was too long for the typical broadcast commercial, though advertisers would scroll through a drug’s brief summary or PI at the end of video presentations made at medical conferences – a measure that was as technically compliant as it was utterly useless.

In 1997, FDA issued a Draft Guidance on Consumer-Directed Broadcast Advertisements that explained how manufacturers could make “adequate provision” for the PI in a broadcast ad.  62 Fed. Reg. 43,171 (Aug. 12, 1997).  To satisfy adequate provision requirements, a prescription drug advertisement needed to identify several mechanisms describing where a consumer could obtain the product’s PI.  These included a toll-free number, a concurrent advertisement in a print publication, and an Internet URL.  The agency finalized the Guidance in 1999.

With this new clarity, TV prescription drug ads blossomed and have been highly controversial ever since.  FDA’s Office of Prescription Drug Promotion now has an extensive procedure for voluntary, pre-dissemination advisory review of both DTC TV ads and other materials.  In March 2012, FDA issued a draft guidance addressing when and how it would use its statutory authority under the FDA Amendments Act of 2007 to review prescription drug television advertisements prior to dissemination.  The guidance was highly controversial and FDA stated it would not begin pre-dissemination review until the guidance was final.  According to CDER’s agenda discussed above, this guidance is also slated to be released in final in 2014.

* * *

As we draw to the end of the year and continue celebrating OFW Law’s anniversary, we’re still waiting on the Brief Summary Guidance that will – we hope – resolve a problem that has vexed patient-directed compliance communications for decades.  If we do see the final guidance on pre-dissemination review of DTC TV ads in 2014, it should make for interesting reading given the vociferous objections to the draft guidance.  With so many marketers turning away from traditional media, we do wonder how much it will matter.  We’ll look at that next generation – prescription drug promotion in social media – in another retrospective coming soon.

Feed the Future: A Bipartisan Opportunity

By Marshall L. Matz, as published in Agri-Pulse

The “Feed the Future” initiative is aimed at improving agriculture productivity and economic development around the world. Bipartisan legislation has been introduced in the both the House and Senate to make this discretionary program permanent. The legislation (H.R. 5656; S.2909) has the support of private sector corporations as well as non-profit public interest organizations.  To use an old phrase, the initiative teaches people how to fish rather than just distributing fish. It deserves our attention.

For generations, the United States has been a leader in providing agriculture development assistance across the globe to alleviate suffering and build shared progress and prosperity. But global food price spikes and resulting instability in 2007 and 2008 were a wake-up call that more needed to be done.

Feed the Future was borne out of President Obama’s pledge at the 2009 G-8 Summit in L’Aquila to mobilize at least $3.5 billion towards global food security—spurring commitments of $18.5 billion from other donors. But the United States has, in fact, thanks to tremendous bipartisan support, surpassed its goal and committed $5 billion in the fight to end hunger and malnutrition.

In 2010, the Administration launched “Feed the Future” (FTF), an initiative designed to expand and better coordinate the United States’ investments in improving global food security. Feed the Future is a whole-of-government approach from USDA to AID and State. It focuses on the dual objectives of improving farmer productivity, income, and livelihoods in developing countries while fighting hunger with a special focus on women and children in particular.

On September 18, 2014 Chairman Chris Smith with Rep. Betty McCollum in the House introduced the Global Food Security Act of 2014 in the House. In the Senate, the legislation was introduced by Senators Casey and Johanns with Senators Coons, Isakson, Cardin and Boozman.

The Global Food Security Act is based on the premise that global food insecurity impacts not only the economies of developing nations but also the international economy and U.S. national security. The bill recognizes the key role that agriculture development plays in economic growth.

There is broad bipartisan support for sustaining Feed the Future due in large part to tremendous gains made over the past few years—

WORLDWIDE: Last year, Feed the Future helped more than 7 million smallholder farmers’ access new tools and technologies to help them improve yields and boost incomes. Feed the Future also reached 12.5 million children with nutrition interventions.

ZAMBIA: Feed the Future played a key role in the record maize harvest for the 2013/14 cropping season (3.4 million metric tons – a 32 percent increase over the previous year’s total) through policy advocacy and by helping smallholder farmers’ access agricultural inputs such as improved seeds and fertilizers through private sector providers.

ETHIOPIA: Feed the Future and other U.S. Government programs are making progress toward achieving real reductions in stunting in Ethiopia. A recent nationwide survey shows stunting rates declined by over 9 percent over the past three years, even as the population grew, resulting in 160,000 fewer stunted children.

HONDURAS: More than 4,300 families are now well above the $1.25-per-day poverty line, thanks in part to Feed the Future’s efforts, which increased horticulture sales by 125 percent last year.

BANGLADESH: Feed the Future reached 3.3 million smallholder farmers with improved seed, fertilizer and farm management practices, helping farmers increase rice yields by as much as 20 percent and creating additional rice sales of $25 million.

SENEGAL: Feed the Future introduced a new breed of high-yielding, high-protein rice that helps smallholder farmers’ triple yields in a single year.

TANZANIA: Feed the Future helped increase horticulture yields by 44 percent and rice yields by more than 50 percent among farmers. The initiative assisted the Government of Tanzania in its efforts to turn the nation’s fertile south into a breadbasket.

Dr. Raj Shah, AID Administrator

Dr. Raj Shah, AID Administrator

“Through Feed the Future, we are harnessing the power of science, technology and innovation to unlock opportunities in agriculture for the world’s most vulnerable people,” said USAID Administrator Dr. Rajiv Shah. “By creating and scaling cutting-edge solutions to our most pressing agricultural challenges, we can help the world’s most vulnerable people move from dependency to self-sufficiency—and out of the tragic cycle of extreme poverty.”

USDA’s expertise is also critical in this effort. From research and extension to market development and trade, USDA must play a central role for Feed the Future to be successful.

Secretary Vilsack has executed a Memorandum of Understanding with the Alliance for a Green Revolution in Africa to help transfer research and extension expertise and that is a building block for Feed the Future.

Feed the Future is not just a commitment of money, it is a new multi-department approach. Instead of merely providing food aid in times of crises, it establishes a new model to turn agriculture into a business—one that especially works for women.

In short, the Global Food Security Act of 2014, the Smith (R-NJ) -Casey (D-PA) -Johanns (R-NE) legislation, compliments the successful PEPFAR program initiated by President Bush and uses our expertise in agriculture as the best possible foreign policy. The Global Food Security Act of 2014 presents an excellent opportunity to come together behind a piece of bipartisan legislation that puts our best foot forward as a country.

Marshall Matz, formerly Counsel to the Senate Committee on Agriculture, specializes in global food security at OFW Law. He serves on the Board of Directors of the World Food Program—USA; the Congressional Hunger Center; and the Food Research Action Center (FRAC).

Family Farms in Africa

By Marshall L. Matz and Peter B. Matz, as published by the National Farmers Union

Kudos to National Farmers Union for recognizing the link between family farming and meeting the challenge of global food security. Family farms are indeed the key to ending world hunger.

First, for purposes of this blog, let’s define a smallholder farmer as anyone tilling less than two hectares, or 5 acres. In most of the world, family farming means smallholder farming, usually by women.

Africa is an important case in point. Let’s look at some numbers—

  • Half of all the underutilized and unused agriculture land in the world is in Africa;
  • 65% of all Africans are involved in farming and food production;
  • 70% of disposable income is spent on food;
  • Most of the smallholder farmers are women using a hoe; and
  • Yields for maize are 20 bushels per acre, or one ton per hectare.

These numbers paint the picture of a significant challenge, but they also demonstrate a major opportunity. African farming is on the cusp of great change and its own unique green revolution. African farmers can double production in the next five years and triple production in the next ten.

The technology is coming on line. Seeds are being created for Africa’s climate and soil. Markets are developing and iPhones are being used for extension services (Africa is very advanced in communication technology).  Soil health is a priority. And the African Union, with the support of the G-7 and G-20, has made agriculture a priority for all African nations. Several African nations are very close to being self sufficient in food production.

U.S.-Africa Ag ComparisonIn the U.S., technology is a modern tractor with GPS and an air-conditioned cab, which is connected to the Chicago Board of Trade. In Africa, “technology” is a rope that shows farmers how far to space out rows and seeds, and how far from the seeds to put the fertilizer. The biggest challenge in Africa is getting the new technology to smallholder farmers and teaching them what to do with it.

That is where the “agro-dealer” has stepped in. Agro-dealers are private sector businesses located in rural villages that sell hybrid seeds, fertilizers and other inputs to smallholder farmers. They also conduct classes for the farmers…the African extension service. There are now some 20,000 agro-dealers in the key countries that comprise Africa’s two major bread baskets. We need 200,000 agro-dealers.

Much of the progress in Africa is being coordinated by the Alliance for a Green Revolution in Africa (AGRA). AGRA was started less than ten years ago by the Gates and Rockefeller Foundations, and was originally chaired by former United Nations Secretary General Kofi Annan. Mr. Annan is now the Chair Emeritus and the current chairman is Strive Masiyiwa. Mr. Masiyiwa is also chairman of the telecommunications giant Econet, but is the first to say that agriculture is the key to Africa’s economic development.

And that brings us to the last point: Increasing production for smallholder farmers is the way to eliminate hunger, but it is also the way for Africa to grow itself out of poverty. Six of the ten fastest growing countries in the world are in Africa. Africa holds the key to the future on many levels. It is important for the U.S. to recognize this and continue establishing/improving economic and political relations with Africa’s 54 countries—which comprise 25% of all the votes in the United Nations. African farmers are on the rise, and so is Africa.

GMPs Have Long History That Precedes Application In Medical Products 1

OFW Law Celebrates 35 Years of Successes in Drug/Healthcare Privacy Practices (Part V)

By Neil P. Di Spirito

In celebrating 35 years of practice, OFW Law’s Drugs, Biologics, and Controlled Substances and Healthcare Privacy practice groups are taking a look back to share some highlights throughout the years.  Parts I, II, III, and IV focused on Hatch-Waxman, medical privacy laws, FDA’s user fees, and prescription drug traceability.  Today’s blog looks back at changes in drug GMPs over time.

After the Second World War, a group of young veterans developed a method to mix, process, and package bovine intestines in a manner that allowed surgeons to pack organs and stop bleeding.  The product, developed under a $1,500 government grant, proved useful beyond the veterans’ imagination.  From battlefield surgery to bloody noses sustained on college and playground football fields, the specific surface area configuration or form of the product stopped the blood from cuts and contusions.

When the veterans retired in the 1970’s, fading into the collective memories of history, this revolutionary medical advance almost faded with them.  Why?  How could an important medical product simply fade away with the inventors’ lives?  The art of making the product could not be replicated by the scientists and engineers who followed.  The inventors knew how to make the product, but the process had never been reduced to a verifiable and repeatable procedure.

Good Manufacturing Practices (“GMPs”) were developed in other industries prior to the FDA requiring their use in safe production of medical products.  The automotive, aviation, defense, and multiple other manufacturing industries all used GMP’s rigorous procedures with quality systems to assure their products performed as intended, according to specifications, 100% of the time.

To achieve this goal, manufacturing processes are “design-reviewed,” meaning they are formulated with subject matter expert and operational implementation personnel input, to maximize efficiencies in achieving product specification goals.  All materials and equipment are pre-qualified prior to their introduction into the assembly or service process, and point-of-process completion quality systems assure the product meets specifications prior to completion.

Medical products, both drugs and devices, did not initially require GMP production documentation, with the resultant failure to meet expected performance.

The well documented, inadvertent contamination of sulfa drugs with phenobarbital in 1941 (resulting in approximately 300 patient deaths), and failure to totally inactivate polio viruses in one vaccine batch in 1955 (resulting in approximately 60 inoculated patients developing the disease), led to the establishment of Federal GMPs Regulations for drugs (21 CFR Parts 210 and 211) and medical devices (21 CFR 820). In 1978, GMPs developed into the most rigorous of Good Manufacturing Practices.

The meticulous design-reviewed processes are only effective because they are required to be conducted under point-of-process completion quality systems by the entity utilizing the process, to assure the processes are completed as intended. Pre-qualification/validation of raw materials and required services before either are entered into the process, with review of the data at the time is acquired, provide control over the outcome quality.

*Certain parts of this blog were adapted from a Policy Forum article written by Neil DiSpirito and Anton Usala.

26 Years, With 9 To Go…. 35 Years to Prescription Drug Traceability 2

OFW Law Celebrates 35 Years of Successes in Drug/Healthcare Privacy Practices (Part IV)

By Tish Eggleston Pahl

In celebrating 35 years of practice, OFW Law’s Drugs, Biologics, and Controlled Substances and Healthcare Privacy practice groups are taking a look back to share some highlights throughout the years.  Parts I, II, and III focused on Hatch-Waxman, medical privacy laws, and FDA’s user fees, respectively.  Today’s blog looks at the evolution of prescription drug traceability and tomorrow’s blog will discuss drug GMP requirements.

The ability to track the commercial life of a finished prescription drug, from the point at which it leaves the manufacturer to the point at which it is dispensed or administered to a patient, has proven elusive.  Congress intended for The Prescription Drug Marketing Act (PDMA) to reduce the risk of counterfeit, adulterated, misbranded, subpotent, or expired drugs being sold to patients.  President Reagan signed the PDMA into law on April 22, 1988; yet, twenty-five years later, the PDMA was never fully implemented and it is only with last year’s passage of Title II of the Drug Quality and Security Act, the Drug Supply Chain Security Act (DSCSA), that the goals of the PDMA will, eventually, be realized.

The PDMA sought to achieve its lofty, public health goals through a variety of means.  It provided for FDA’s establishment of minimum standards for the licensing by State authorities of wholesale distributors of prescription drugs.  The State wholesale distributor licensing provisions of the PDMA were implemented in a final rule, 21 C.F.R. Part 205.

The PDMA also banned the sale, purchase, or trading of drug samples and established requirements for drug sample distribution, storage and handling.  It further restricted the re-importation of prescription drugs and prohibited, with certain exceptions, the sale, purchase, and trade of prescription drugs purchased by hospitals or other health care entities, or donated or supplied at a reduced price to charities.  FDA promulgated final regulations to implement these provisions of the PDMA.  21 C.F.R. Part 203, Subparts B, C, and D.

The PDMA also sought to require unauthorized wholesale distributors – frequently referred to as “secondary wholesalers” – to provide purchasers with a statement (a “pedigree”) that identified each prior sale of the drug.

It was here that the PDMA floundered.

FDA promulgated a final rule, codified at 21 C.F.R. § 203.50(a), that implemented these requirements.  64 Fed. Reg. 67,720 (Dec. 3, 1999).  Amid public outcry, FDA stayed the rule until October 1, 2001, and then, until April 1, 2002 . . . and several more times thereafter.  Finally, in June 2006, FDA announced it would not further delay implementation and § 203.50(a) would go into effect on December 1, 2006.  71 Fed. Reg. 34,249 (June 14, 2006).

On September 20, 2006, a group of unauthorized wholesaler distributors sued FDA seeking, among other things, a declaratory judgment that § 203.50(a) erroneously interpreted the PDMA’s pedigree requirement.  RxUSA Wholesale, Inc. v. HHS, 467 F. Supp.2d 285 (E.D.N.Y. 2006).  The plaintiffs eventually prevailed and halted FDA’s implementation of 203.50(a).  In 2011, FDA withdrew the regulation.  76 Fed. Reg. 41,434 (July 14, 2011).

In the Federal Register notice announcing the withdrawal, FDA reiterated that it wasn’t giving up:

[We] will continue to move forward, working with the private and public sectors to improve the security of the drug supply chain and implement measures to further protect Americans from counterfeit and diverted drugs.

[S]uch measures include implementation of tracking and tracing, which would help secure the integrity of the supply chain by providing an accurate electronic record of transactions in the drug supply chain. Such electronic records documenting the movement of a drug product from the manufacturer to the dispenser would be an important step in preventing counterfeit and diverted drugs from entering the drug supply chain.

76 Fed. Reg. at 41437.

In November 2013, a coalition of drug supply chain stakeholders, working closely with FDA and Congressional staff, achieved the passage of the next stage of the PDMA, the DSCSA.  Over the next ten years (now nine), FDA along with manufacturers, distributors, dispensers, repackagers, and third-party logistics providers, will work to develop an electronic system for the exchange of information about individual packages of prescription drugs.  The system that will allow for the identification and tracking of where a drug has been in the supply chain.  Important provisions of the law include:

  • Affixing a unique, machine-readable identifier on each prescription drug package;
  • The exchange of information between trading partners about the drug each time it changes ownership in the supply chain;
  • Establishment of systems for the verification of product identifiers;
  • Establishment of systems for identification of, responding to, and notifications regarding, suspect and illegitimate product in the supply chain;
  • Wholesale distributor reporting of licensure status; and
  • Licensing of third-party logistics providers.

The first significant DSCSA milestone arrives January 1, 2015, when manufacturers must provide data about each product transaction and wholesale distributors must receive and be able to transmit that data.

For those of us who have been with this from the beginning, the path to product traceability has been rife with false starts and delays.  Now, the DSCSA gives the supply chain and FDA a roadmap to achieving that goal.  It will be a 35-year journey, but the end is in sight.

John Block Reports: Dietary Guidelines for Americans 2015 Edition – Losing It’s Way on Sugars (Part II)

OFW Law founding principal Richard L. Frank fills in for former USDA Secretary John R. Block

There are a variety of disturbing questions surrounding the Dietary Guidelines for Americans now being drafted for release in 2015. The questions relate to whether the Dietary Guidelines Advisory Committee should focus its review and recommendations on the current science on nutrition and diet, or whether it should be working to ensure the guidelines fit a policy agenda.  Part I of this mini-series focused on what the Advisory Committee has called “high dose caffeine” products.

USDA and HHS have jointly published the Dietary Guidelines for Americans every five years since 1980. The American public is best served when federal dietary guidance is based on the totality of scientific evidence. In 1990, Congress mandated that the Dietary Guidelines “shall be based on the preponderance of scientific and medical knowledge…current at the time of the report.” Despite these clear instructions and limitations, the 2015 Dietary Guidelines Advisory Committee, at multiple levels, appears to be crafting its recommendations to support government policy and political initiatives, such as placing limits on the amount of “added sugars” in the diet despite the fact there is absolutely no scientific justification for differentiating between added sugars and naturally occurring sugars.

Since 2010, the Dietary Guidelines Advisory Committee has relied on the Nutrition Evidence Library to assist in evaluating new science and developing its recommendations. The NEL provides a standardized and systematic way to evaluate new research which has emerged since the previous Guidelines.

The 2010 Dietary Guidelines recognized that the human body does not differentiate between added sugars and naturally occurring sugars. Unfortunately, the 2015 Advisory Committee is deviating from the Nutrition Evidence Library approach and selectively looking at only those studies and recommendations which support establishing limits on “added sugars.”

Examples of this type of “politically motivated” activity include:

1. Efforts to provide support for the Food and Drug Administration’s controversial proposal to disclose “added sugars” on food product labels, in addition to total sugars, calories, and carbs which are already required.

2. Recommending punitive taxes on certain foods and beverages; and

3. Relying heavily on the controversial USDA Food Pattern Modeling in an effort to support actual limits on “added sugars” consumption.

These limits have not been accepted by the Institute of Medicine or the Food and Drug Administration when it recently refused to set a daily value or intake limit for added sugars.

The Dietary Guidelines should be a practical and achievable set of recommendations based on balance, variety, and moderation. The process should not become a political circus used to impose an agenda without a sound scientific basis or Congressional authority. Hopefully, the Secretaries of Agriculture and Health and Human Services will ensure the Dietary Guidelines recommendations continue to be based solely on the preponderance of scientific evidence, as required by its Congressional mandate.

The Realized Benefits of User Fees 3

OFW Law Celebrates 35 Years of Successes in Drug/Healthcare Privacy Practices (Part III)

By Mason Weeda

In celebrating 35 years of practice, OFW Law’s Drugs, Biologics, and Controlled Substances and Healthcare Privacy practice groups are taking a look back to share some highlights throughout the years. Parts I and II focused on Hatch-Waxman and medical privacy laws, while today’s blog looks at how user fees transformed the FDA. Please stay tuned for Part IV, which will provide a review of the changes in prescription drug supply chain requirements.

One important shift at FDA over the past 35 years is the substantial decrease in FDA review time of new drug applications (NDAs), biologic license applications (BLAs), and abbreviated new drug applications (ANDAs). This improvement, of course, did not come cheap.

Since the 1950s, FDA entertained the mechanism of user fees to provide additional resources for rapid review of pending applications; but industry resisted. Over the years, FDA’s time to review NDAs stretched ever longer. By 1987, the average time for FDA to make a decision was a staggering 29 months. With applications stuck in never-ending review, industry began to see the potential benefit of user fees in order to get products through FDA and onto the market faster.

Congress also came to see the potential harm to public health in the lengthy NDA and BLA approval process that delayed the availability of life-saving therapies. In 1992, Congress passed the Prescription Drug User Fee Act (PDUFA) and so the bargain was struck. NDA sponsors would pay considerable fees to the agency and, in exchange, FDA committed to reviewing the applications on set timetables. By the time PDUFA was up for its first reauthorization in 1997, NDA median approval time for NDAs and BLAs dropped significantly to 12.5 months for standard applications and 7.8 months for priority applications.

PDUFA has been reauthorized four times since 1992, most recently in 2012 with PDUFA V. PDUFA V will sunset in October 2017. With each authorization, FDA has been required to provide annual reports on progress in meeting targeted review times.   The most recent reports indicate that the program continues to do well, meeting review time goals nearly 100% of the time.

Delays in the review of ANDAs began to creep up in the 1990s and 2000s, ultimately creating a significant back-log of pending applications for generic drugs. As of 2011, ANDA review took approximately 31 months (or 2.5 years) on average. Relying upon the same premise as PDUFA, Congress passed the Generic Drug User Fee Act (GDUFA) and Biosimilar User Fee Act (BSUFA) in 2012 to expedite the approval process for generic drugs and biosimilars. Though FDA has committed to reviewing 90% of ANDAs within 10 months, there remains a significant backlog of pending applications. In 2013 there remained a backlog of 2,866 original ANDAs and 1883 supplements. In year 2013, FDA was able to provide 45% of the backlog with first action.

User fees have resulted in a huge budget increase for FDA. By 2013, FDA had collected $729 million in user fees since the inception of PDUFA. Drugs are getting to market faster – FDA met its 2013 goal to review 90 percent of standard NDAs and BLAs within 10 months. FDA’s 2013-2017 user fee performance goals are very aggressive. By 2017, FDA aims to:

  • Review ninety percent (90%) of standard new molecular entities (which are the most complex NDA) within 10 months of filing acceptance and 90% of priority applications within 6 months of acceptance;
  • Review ninety percent (90%) of complete electronic ANDAs within 10 months; and
  • Review and act on ninety percent (90%) of biosimilar applications (applications under §351(a)) within 10 months.

Fees are set annually based upon the agency’s actual costs and vary by program. For fiscal year 2015, the application fee for NDAs with clinical data are $2,335,200, ANDAs are $58,730, and Biosimilar Product Application Fees are $110,370 (other user fees for supplements, reviews with and without clinical data, manufacturing sites, and products may also apply).

Despite the reduced backlogs and faster reviews of lifesaving drugs and their generic equivalents, the user fee programs have been roundly criticized as well. FDA is, after all, receiving direct and substantial financial support from the entities it regulates. While we can appreciate that critique, in our experience, it is unfounded. Over our 35 years of observing the drug approvals, user fees are making the process faster and more predictable but have definitely not impacted the quality and rigor of FDA’s review. Indeed, we have found that review standards have significantly tightened over the years and applications that would have slid through the review process 30 years might not even be accepted for review today.

In our view, user fees have helped industry and the agency, with benefits to patients who more expeditiously receive critical drug therapies.