Angie Drakulich was editorial director of Pharmaceutical Technology.

Angie Drakulich

This blog post was written by Ben Comer of 

	Recognizing that traditional market forces – namely incentives related to intellectual property and a steady demand for products – have failed in developing countries, the World Health Organization (WHO) asked a member state-nominated group to come up with ways to fund R&D and pay for the treatment of neglected diseases in the world’s poorest nations. The group’s proposals will be discussed at the 

sixty-fifth session of the World Health Assembly

, beginning today in Geneva. Dr. Paul Herrling, a member of the group and head of the Novartis Institute for Tropical Diseases, sat down with PharmExec to explain the group’s process, conclusions and next steps.

	Paul Herrling was a member of the previous WHO group [Expert Working Group on Research and Development: Coordination and Financing] asked to examine the problem of financing R&D and treatment in developing countries, which reported in 2010. However, disagreements among various constituents over the transparency of the process and the criteria for considering different proposals led to a stalemate, which this new group – the Consultative Expert Working Group on Research and Development: Financing and Coordination (CEWG) – was created to overcome. This time, member states appointed the members of the group, instead of WHO Director-General Margaret Chan. Herrling was selected to represent Switzerland.

: You were the only person from the drug industry appointed to the CEWG, and some other groups protested your inclusion.

: On principle they didn’t want to have the pharma industry in there, which is completely crazy because the pharma industry is a key stakeholder and part of the solution. It was decided that when discussions on my model – The Fund for R&D in Neglected Diseases (FRIND) – took place, I would step out of the room, and I would also not participate in written debates on the FRIND model. An that’s what I did. The whole group was roughly 20 people and I was the only one who had actually ever done R&D. There were a few medical people, but really doing drug discovery, I was the only one. But the overall mission – to find a way to bridge the R&D gap in funding for neglected diseases – was something that everybody around the table subscribed to, so we were able to work together. The chairman of the group, John-Arne Røttingen, deserves a lot of credit for that.

: On the positive side, we were able to avoid discussions about abolishing IP, which aren’t helpful. Instead, we talked about keeping IP in place where it works and concentrated on solutions for where IP doesn’t work, where there are not markets. Second, and this is positive from the industry’s point of view, we did not talk about just squeezing industry for funds and forcing industry to pay. This time, the primary responsibility is put on government. Commercial industries can only go so far, they aren’t not-for-profits or charities. And there’s also a limit on what charities can do, even the Gates Foundation.

: What criteria did you use to evaluate the various proposals?

: The criteria are published in our report [

]. The basic criteria were, does it contribute to the funding of neglected diseases, and does it delink the costs of R&D from the actual price of the medicine. And this is why we need the help of the governments because the delinking will be done by the noncommercial organizations: pay for the R&D so that we can make the drugs available at cost, or even for free to the patients that need them. Another aspect has to do with capacity building, because it doesn’t make sense to build up a scientific medicines pipeline and then send it to countries where nobody has a clue what that is or what to do with it. The [226 page] report is comprehensive; a lot of people had a lot of messages to pack in there. The stuff on data exclusivity I tried to get out, but I didn’t win that one. But I won others…the key thing is that the proposals are viable and everyone involved is content with it.

: Can you describe some of the most promising proposals?

: There’s one proposal called the Milestone Prizes, which is similar to mine [FRINDS], where you get funding only for one step in the process and if it fails, fine, it was paid. But if you reach the milestone, then you’re eligible for the next phase. The pooled funds, of which FRINDS is one of them, has a delinking component because of the exclusive license that you give to the fund. It meets the coordination part because you do it through a kind of portfolio management. [Herrling’s FRIND model would let a compound’s originators patent the molecules to be used under the auspices of FRIND, but in return for the money received, would give an exclusive license for the neglected disease (and the neglected disease only) indication to FRIND. The originators would maintain ownership for composition of matter and any other indications for which a commercial return might be expected.]

: How much will you ask governments to contribute?

: One way that we’re proposing is that governments pay a small portion of their GDP, as a guideline for how much to invest in R&D for neglected diseases. That way, the ones who can pay more, pay more, but everyone is part of it, so they can take ownership.

: Won’t it be difficult to get governments to vote on a commitment to give a percentage of GDP to neglected diseases?

: There are many different proposals so different governments could pick out the one they like most. But yes, some will go home and say we’re going to give 0.01% of our GDP [and no more] because it restricts our flexibility. Somebody likes to buy more guns. So that’s what we try to avoid. Developing countries, for example, would probably go for capacity building in their own countries, whereas developed countries that already have [R&D] capacity, would hopefully go for R&D financing through allocation of part of the development portfolio.

: The report will be discussed at the World Health Assembly, and they could say, like last time, that some countries oppose the fundamental position, so go away, and then maybe they’ll create a fourth working group. But they could say, okay, we’ll accept this report and we are going to set up whatever mechanisms are necessary to start the discussions around this type of treaty.

This interview was drastically condensed from the original.

Articles

Recognizing that traditional market forces – namely incentives related to intellectual property and a steady demand for products – have failed in developing countries, the World Health Organization (WHO) asked a member state-nominated group to come up with ways to fund R&D and pay for the treatment of neglected diseases in the world’s poorest nations. The group’s proposals will be discussed at the sixty-fifth session of the World Health Assembly, beginning today in Geneva.

Will WHO Member States Pony Up for Neglected Diseases?

The Pharmaceutical Research and Manufacturers of America (PhRMA) released a statement last week regarding the Senate’s vote to pass the Food and Drug Administration Safety and Innovation Act (

), which reauthorizes the Prescription Drug User Fee Act (PDUFA). PDUFA was created by Congress in 1992 and must be reauthorized every five years. The current program, known as PDUFA IV, will expire unless reauthorized by Congress on Sept. 30, 2012 (see back 

Said senior vice-president Matthew Bennett in the 

, “By reauthorizing PDUFA, members of both sides of the aisle have taken an important step forward toward providing the FDA with much-needed resources and management tools to support patient safety and to promote innovation through increased consistency and efficiency in FDA’s science-based human drug review program.”

The Senate vote also reauthorized permanently the Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA), which PhRMA applauded in its statement.

These programs “have encouraged increased research into the use of medicines in children, helping us make significant advances in the care that children receive. Permanent reauthorization of these patient-focused programs will help to continue the progress made in this field by providing more certainty to the sponsors of important pediatric clinical trials,” said Bennett.

The Biotechnology Industry Organization (BIO) issued a 

 in support of the Senate votes as well. “In particular, we appreciate the leadership shown by Chairman Tom Harkin (D-IA) and Ranking Member Mike Enzi (R-WY) to craft a bipartisan measure which will continue to ensure patient safety, access to the newest cures and therapies, and job growth in America,” said the BIO statement. 

BIO specifically commented on the inclusion of an enhanced Accelerated Approval pathway, crafted by Senator Kay Hagan (D-NC), in the Act, which “will help expedite the development of modern, targeted, and personalized therapies for patients suffering from serious and life-threatening diseases while preserving the FDA’s robust standards for safety and effectiveness.” The enhanced accelerated approval pathway goes beyond the current fast-track 

, to “enhance the authority of the FDA to consider appropriate scientific data, methods, and tools, and to expedite development and access to novel treatments for patients with a broad range of serious or life-threatening diseases or conditions,” says the Senate-passed legislation (S. 3187). Updated guidance would be required. 

BIO went further to say, “We greatly appreciate the Senate defeat of amendments which would have threatened final approval of FDASIA, including an amendment which would have slowed the FDA's consideration of genetically-modified salmon…. BIO also appreciates the Senate defeat of amendments pertaining to patent settlements, importation, and the elimination of innovator data protections.”

Read Washington Editor Jill Wechsler’s 

 on the Senate votes and what is needed next.

NOTE: On May 30, the House passed the FDA Reform Act also reauthorizing PFUDA. See PhRMA's 

The Pharmaceutical Research and Manufacturers of America and Biotechnology Industry Organization released statements last week regarding the Senate's vote to pass the Food and Drug Administration Safety and Innovation Act, which reauthorizes PDUFA.

Industry Comments on Senate Passage of PDUFA V

ICH Q11, the anticipated guideline from the International Conference on Harmonization (ICH), titled 

Development and Manufacture of Drug Substances

, has achieved international consensus. Q11 has been one of the fastest guidelines to move through the ICH harmonization process. Q11 was published as a draft in May 2011, and reached Step 4 this month, which means that the ICH steering committee members (representing regulatory and trade organizations in the US, Europe, and Japan), have reached scientific consensus and signed the guideline. At this point, each of the region’s regulatory agencies, including FDA, will publish the guideline as official guidance within their appropriate regions and implementation will begin. 

The Q11 guideline will be folded into the Quality trio which includes ICH Q8 

, which together detail quality-by-design (QbD) concepts for pharmaceutical development and manufacturing. Although the ICH Quality trio guidelines apply to drug substance as well as drug product, industry and regulators felt there was a need to clarify QbD or "enhanced" concepts for drug-substance manufacture. 

"There are fundamental scientific differences in the process for drug-substance manufacture and the process for drug-product manufacture, including impurity control and removal and chemical transformations," explained Pharmaceutical Research and Manufacturers Association (PhRMA) representatives of the ICH Q11 expert working group to PharmTech. These representatives, among others, talked to PharmTech earlier this year regarding the expected approval of Q11; their discussion of the guideline can be found in the February 2012 issue 

Q11 describes approaches to developing process and drug substance understanding and also provides recommendations to industry on what information should be provided in Common Technical Document sections 3.2.S.2.2–3.2.S.2.6. The guideline provides further clarification on the principles and concepts described in ICH Q8, Q9, and Q10 as well.

ICH Q11, the anticipated guideline from the International Conference on Harmonization, titled Development and Manufacture of Drug Substances, has achieved international consensus. Q11 has been one of the fastest guidelines to move through the ICH harmonization process.

ICH Q11 Drug Substance Guideline Has Gained Global Approval

	ICH Q11, the anticipated guideline from the International Conference on Harmonization (ICH) titled 

, has achieved international consensus. Q11 has been one of the fastest guidelines to move through the ICH harmonization process. Q11 was published as a draft in May 2011 and reached Step 4 this month, which means that the ICH steering committee members (representing regulatory and trade organizations in the US, Europe, and Japan), have reached scientific consensus and signed the guideline. At this point, each of the region’s regulatory agencies, including FDA, will publish the guideline as official guidance within their appropriate regions and implementation will begin.

	The Q11 guideline will be folded into the Quality trio which includes ICH Q8 

, which together detail quality-by-design (QbD) concepts for pharmaceutical development and manufacturing. Although the ICH Quality trio guidelines apply to drug substance as well as drug product, industry and regulators felt there was a need to clarify QbD or “enhanced” concepts for drug-substance manufacture.

	“There are fundamental scientific differences in the process for drug-substance manufacture and the process for drug-product manufacture, including impurity control and removal and chemical transformations,” explained Pharmaceutical Research and Manufacturers Association (PhRMA) representatives of the ICH Q11 expert working group to PharmTech. These representatives, among others, talked to PharmTech earlier this year regarding the expected approval of Q11; their discussion of the guideline can be found in the February 2012 issue 

	Q11 describes approaches to developing process and drug substance understanding and also provides recommendations to industry on what information should be provided in Common Technical Document sections 3.2.S.2.2 – 3.2.S.2.6. The guideline provides further clarification on the principles and concepts described in ICH Q8, Q9, and Q10 as well.

ICH Q11, the anticipated guideline from the International Conference on Harmonization (ICH) titled Development and Manufacture of Drug Substances, has achieved international consensus.

ICH Q11 Reaches Harmonization, Implementation is Next

	During the past two years, FDA has been looking more closely at enforcing Part 11 of the Title 21 Code of Federal Regulations regarding electronic records and signatures (see back 

). As a result, digital signatures are becoming more commonplace throughout laboratories, manufacturing sites, and offices as companies search for ways to track and file processes, SOPs, approvals, supply chain movement, drug applications, and more. Quality management systems, much like our personal lives, are becoming far more digital and far less paper-based.

	PharmTech discusses this issue and related compliance issues in a recent webcast, available 

During the past two years, FDA has been looking more closely at enforcing Part 11 of the Title 21 Code of Federal Regulations regarding electronic records and signatures (see back story).

Digital Signatures Growing as a Result of Part 11

FDA issued a final rule on sterility testing on May 3, 2012, that amends the requirements for most licensed biological products and aims to provide manufacturers with the flexibility, as appropriate, to keep pace with technological and scientific advances. The rule is in response to President Obama’s Executive 

 13563 which called for improving regulation and regulatory review.

 revises sterility requirements under Title 21 of the Code of Federal Regulations (CFR), subchapter F, parts 600 through 680 as follows: 

“Eliminates specified sterility test methods, culture media formulae (or formulation), and culture media test requirements

Eliminates specified membrane filtration procedure requirements for certain products

Eliminates specified sterility test requirements for most bulk material

Modifies the repeat sterility test requirements, so that repeat tests will occur only once for each lot

Replaces the storage and maintenance requirements for cultures of test organisms used to determine the “growth-promoting qualities” of culture media with validation requirements specifying that any sterility test used is able to consistently detect the presence of viable contaminating microorganisms, and with verification of “growth-promoting properties” or microorganism-detection capabilities of test and test components

Replaces the sample size or amount requirement with a requirement that the sample be appropriate to the material being tested

 section under § 610.12(c) with a requirement that manufacturers establish, implement, and follow written procedures for sterility testing that describe, at a minimum, the test method used, the method of sampling, and the written specifications for acceptance or rejection of each lot

Identifies the Director of CDER as one of the two Center directors authorized to grant an exemption under the exception provision at § 610.12(h)(2). In the proposed rule, the Center for Devices and Radiological Health was erroneously identified in this exception, instead of the Center for Drug Evaluation and Research

Revises the definition of the term “sterility” under § 600.3(q). 

Eliminates certain exceptions for allergenic products related to sterility testing under § 680.3(c).” 

Companies will not have long to implement the changes as the rule takes effect June 4, 2012. The proposed rule received several comments from industry and the final rule includes the agency’s response to those recommendations. Overall, FDA “recognizes the role innovation plays in bringing safe and effective products to market in a timely and cost-efficient manner,” according to an FDA announcement of the rule. “This action reflects the agency’s efforts to review and, as necessary, update biologics regulations, to keep pace with technological developments and to boost regulatory science.”

FDA issued a final rule on sterility testing on May 3, 2012, which amends the requirements for most licensed biological products and aims to provide manufacturers with the flexibility, as appropriate, to keep pace with technological and scientific advances. Many steps are changed or eliminated.