1 MEETING SUMMARY

Meeting with Registrants: EPA Evaluation of Pet Spot-on Products Analysis and Mitigation Plan

March 17, 2010, 9:30 am to 11:00 am

Room N-4830, One Potomac Yard 2777 S. Crystal Drive Arlington, VA 22202

Meeting Attendees (see also attached signin sheet):

- Summit Vet Pharm, LLC

- Central Life Sciences

- Consumer Specialty Products

Association

- The Hartz Mountain Corporation

- Technology Sciences Group Inc.

- Exponent, Inc.

- Bayer Healthcare LLC, Animal

Health Division

- Sergeant’s Pet Care Products, Inc.

- SafetyCall International

- Merial Limited

- Animal Health Institute

- Pillsbury Winthrom Shaw Pittman

LLP

- Pfizer Inc.

- The Accord Group

Via Telephone

- Canada’s Pest Management Regulatory Agency Representatives from EPA:

Office of Pesticide Programs

- Julie Chao, RD

- Venus Eagle, RD

- Kit Farwell, HED

- Claire Geselman, FEAD

- Samantha Hulkower, RD

- Meredith Laws, RD

- Rosanna Louie, RD

- Mary Manibusan, HED

- Autumn Metzger, RD

- Kimberly Nesci, RD

- Lois Rossi, RD

- Kevin Sweeney, RD

Office of General Counsel

- Michele Knorr

- Erin Koch2 Meeting Summary

The above-listed representatives from indus try, EPA, and Canada’s Pest Management Regulatory Authority (PMRA) me t on March 17, 2010, to discuss the Agency’s analysis of the enhanced adverse incident pet reports, the Agen cy’s conclusions, and a mitigation action plan needed to minimize adverse effects to pets.

The Agency presented background information a bout the increase in th e number of reported

adverse incidents seen between 2007 and 2008 asso ciated with the use of spot-on dog and cat products to control fleas and tic ks. As part of that summar y, the Agency described the information received from the registrants of pet spot-on pet products after holding a meeting on May 5, 2009. EPA explained that that informa tion was analyzed by EPA’s expert internal veterinarian team and the resulting Technical Re view Document was peer reviewed by the Food and Drug Administration’s (USFDA) Center for Veterinary Medici ne (CVM) and Canada’s Pest Management Regulatory Authority (PMRA).

The Agency shared the following regarding the an alysis of the enhanced incident reporting:

- The Agency explained that its obj ective in its analysis was to describe the nature of the incidents, and to identify susceptible subpopula tions or other trends associated with the use of the spot-on products;

- The Agency described the types of detailed in formation received in the enhanced incident
reports;

- The Agency described additional sources of data and methods to analyze and corroborate

the received enhanced incident reports, including toxicologi cal studies and literature by expert veterinarians;

- The Agency described its review process, in cluding the methods used to standardize the incident data in order to comp are and evaluate the data; and,

- The Agency shared its key findings from the analysis, as follows:

o Most incidents were minor, but unfortuna tely there were some pet deaths and “major incidents” reported. The Agency le arned that the most commonly affected organ systems were dermal, ga strointestinal, and nervous.

o Dog Findings

 small breed dogs were affected more th an larger breeds for some products

 the amount of product in a single dose needed to vary more for small to large dogs – that is, how much the dog weighs matters a lot in deciding how much of a product should be used.

o Cat Findings

 misuse or accidental exposure of cats to dog products was an important problem; cats can be harm ed by dog products; and

 label warnings against use of dog products on other animals, especially cats, are not working well enough and this appears to be a global concern.

o Safety Testing: The team also found that the data we now require to determine the safety of these products for pets do not accurately predict the toxicity seen in the incidents that took place.

The Agency concluded that, based on its peer-reviewed analysis, mitigation is necessary to prevent adverse effects to pets. The Agency then presented a regulatory ac tion plan that is being3 pursued that will include immedi ate further restrictions on products, tighter regulations, and a public outreach campaign. Specifically, the Agency is pursuing the following actions:

• Further Restrictions on Products

o Dosing. To address concerns about dosing, th e Agency is pursuing requiring label and/or packaging changes that would result in more narrow pet weight ranges per

vial size. This means there will be more categories for the weights of pets so that small, medium, and large dogs get the righ t amount of product. Pet owners should always be aware of the weight of thei r pet and purchase and use the correct product for their pet’s weight.

o Improve labeling to avoid confusion between dog and cat products. Because there were problems reported with cats exposed to dog products, the Agency needs to address this problem and is pursuing the following actions:

 Label changes that prohibit the use of the same brand names on cat and dog products; and

 Requiring appropriate, clear label statements to address concerns with cat exposure to dog products as a result of direct application or interactions between cats and dogs in multi-pet house holds after the application of dog products.

o Make labels more understandable. To improve label clarity, EPA will pursue changes such as larger fonts and pictograms.

o Make other label changes as needed. EPA will meet with companies individually to review thei r products and discuss additi onal changes to labels or ingredients that the Agency feels are n eeded. These actions may include anything from adding a more complete list of poten tial side effects to product labels to canceling products.

o Inert Ingredients. To address uncertainties a bout the “inert” (non-active) ingredients in these products and how th ey might contribute to toxicity, EPA will be pursuing the following actions:

 No longer allow the interchangeable use of inert ingredients in these formulations;

 Determine whether additional information is needed and, if so, require that information to evaluate certain inert ingredients; and

 Disallow inerts that have suspected toxic effects when and if these are

identified.

• Tighter Regulation

o Standardized reporting . To be able to monitor these products better, EPA is pursuing more standardized reporting on adverse effects and sales. This will allow the Agency to more effectively review inci dents, and if concer ns are raised, give

EPA information to act.

o Pre-market clinical trials and post-market surveillance. The Agency is taking steps to bring data requirements in li ne with FDA’s requirements for similar products. This will allow EPA to be more consistent with how FDA regulates similar animal drugs, which includes pre-ma rket clinical trials and a formal postmarket surveillance program, and will allow the Agency to more thoroughly assess the safety of the products.4 o Grant conditional registrations for new products. Future pet spot-on registrations and amendments to new registrations will be restricted by appropriate conditions and time-limitations to allow EPA to continue to ensure the safety of these products after they are available to the public.

After the Agency presented their findings and the regulatory action pla n, there was a question

and answer session.

Questions and Answers:

Registrants asked many questions about the process by which th e Agency is releasing the information, the analysis conducted, and the miti gation plan being pursued. The summary below describes the types of questions asked and the Ag ency’s responses, but is not a transcript. The meeting was not recorded therefore a transcript is not available.

1. The registrants had logistical questions about the schedule for the release of the findings and the rationale for the rigorous schedule. The registrant had questions about the timing for making the Agency’s reviews and decisions available to the public.

The Agency described the following process: the data evaluation records (DERs) are being made available for each registrant imme diately after the 9:30 am briefing and that the total set of DERs is being posted fo r public access at 2:00 pm along with the Technical Review Document and the Agency’s mitigation plan. The Agency explained

that it was criticized for th e May 2009 meeting with the re gistrants and, as such, it is releasing to the public as soon as possible after the re gistrant meeting the same information provided to the registrants to he lp eliminate doubts that the public may have about the impartiality of the Agency decisions.

2. Registrants asked questions about how the information from the enhanced incident reporting was analyzed.

The Agency stated that its analysis, which includes a description of the methods, will be available at the end of this meeting and will be made available to the public at about 2:00 pm. The Agency noted that the Technical Review Document was peer reviewed by PMRA and US FDA’s CVM. The Agency st ated that the data evaluation records (DERs) for each individual product describe/s ummarize the enhanced incident data after the Agency standardized the format of the information to more appropriately compare

similar incidents. With the standardized incident information, the team was able to determine for each product the relative ratios of the number and severity of each type of

incident.

3. Registrants asked questions about the facto rs EPA considered in its decision to impose additional restrictions on products.

The Agency responded that the Agency’s expe rt veterinary team concluded from its intensive analyses of the enhanced reporti ng information that mitigation measures are necessary to avoid preventable adverse effects to pets. Th e Agency explained that the

factors considered are described in detail in the DERs and the Technical Review5 Document. The Agency stated that there ar e a number of mitigation measures that the Agency is pursuing in order to minimize future adverse incidents to pets. The Agency

stated that it feels these incidents are avoidable.

4. Registrants had questions about the mitigation measures the Agency seeks to implement immediately, including what are the additi onal reporting requirements and new labeling requirements for the spot-on products.

The Agency responded that further, product-spec ific discussions will need to take place in order to finalize details of the mitigation measures. Some of the immediate requirements can include disallowing alternat e formulations, requiring the submission of additional information for inert ingredients if there are suspected potential toxic effects, time-limited conditional registrations of new products, and product labeling clarity improvements.

5. Registrants had questions about the effecti veness of label changes, considering that current warnings are being disregarded by consumers.

As stated above, the Agency responded that th at further, product-specific discussions will need to take place in order to finalize deta ils of the mitigation measures. The Agency

wishes to continue discussions about the inci dent report findings th at indicate that, in some cases, current warnings are not working. A possibility that registrants may wish to consider is the availability of market-research information on consumer products. Companies with that data may have informa tion to better inform labeling decisions. EPA

also believes that consumer education about both proper use and potential side effects is

crucial.

6. Registrants asked about additional requireme nts that the Agency anticipates needing from the registrants in the future t hat would require long-term collaboration.

The Agency responded that as part of the move to become more similar with FDA requirements for similar topical animal drugs , EPA is looking into additional detailed reporting requirements; clinical trials similar to FDA’s clinical trials; and a formalized post-market surveillance process. The interi m, the Agency will pursue enhanced adverse event reporting to allow EPA to efficientl y continue post-market surveillance and analysis of any incidents associated with the use of these products.

7. Registrant had questions about how the Ag ency’s plan compares to the FDA’s current regulatory processes. Registrants also asked questions about how EPA intends to streamline regulations between the two Agen cies and whether changes to guidelines will be subject to rulemaking.

With regards to the questi ons about how the Agency’s plan compares to FDA requirements, the Agency stated that it is looking into streamlini ng current regulations and requirements with those of FDA in orde r to address the information gaps in the information we currently obtain. The Agency explained that it w ill follow usual, public procedures in order to revise its guidelines.6 8. Registrants had questions on the Agency’s plans for public outreach and publicity of the

issue to consumers.

The Agency responded that to maintain tran sparency to all stakeholders, including the public, EPA has taken steps to keep all interest ed parties informed as the information and reviews become available. The Agency stated that it recognizes the importance of these flea and tick products and the importance of their availability to a wide range of consumers, but also the importance for cons umers to have full understanding of the proper use and potential impacts of thes e products. In addition to the press announcements and the release of the Agency’s Technical Review Document and Data Evaluation Records, part of the public outreach campaign is to inform the public of steps they can take to ensure safe use of pet fl ea and tick products. The Agency stated that although specific details have not been finalized, some ex amples could include label clarity improvements, information bulle tins and videos, and additional product

information made available at the stores where these products ar e purchased. Based on the current product labeling and the Agency’s analysis of the in cident reporting, it appears that consumers are not aware of the full spectrum of potential toxicity to pets, such as the possible different e ffects seen between a dog and cat.

9 The registrants had logistical questions about the timing of implementing these mitigation measures, to ensure a le vel-playing field for all companies.

The Agency acknowledged that the implement ation of these mitigation measures will begin as soon as possible, and will be addressed on a case-by-case basis depending on the characteristics of the product in question. In addition, the Agency acknowledged that a proposed (new) product applicati on may be handled differently than an amendment to an existing product and that individual compa ny meetings are needed. The Agency also acknowledged that there are othe r influencing factors that may need to be considered as part of these decisions, such as how a speci fic product is market to targeted consumer

groups.

10. The registrants had logistical question about cl inical trials for pesticide products; e.g., how unregistered product can be distributed and whether EPA will accept clinical trials conducted for submission to the European Union.

The Agency responded that there are many que stions to address and consider when changing any regulation and that additional discussions and public comment will be needed in the future to address these ques tions. The extensive collaboration with FDA and the resulting mitigation proposals are unprece dented. By taking the time and effort to make these changes and consider public i nput as well as input from external experts, the overall credibility and safety of these products will be enhanced.

With regards to clinical trials conducted fo r the EU, the Agency is open to the possibility of considering these trials and wi lling to discuss this further.

11. The registrants had questions about the Agency’ s plan to better dist inguish between cat and dog products (including changes in brand na mes or other means); specifically, whether we were going to re quire that distinction in cases where a formulated dog product could be safely used on cats.7 The Agency explained that the rational e behind distinguishing between cat and dog products is because the average consumer ma y not know the differen ces between active ingredients and the Agency would like the message that consumers should never use dog products on cats to be more universal. Cons umers are typically not aware of the full spectrum of potential toxicity to a pet and curent label warnings do not appear to be adequate. In addition, part of the issue is dosing in that, even if an active i ngredient could be safely used on cats, generally the dose for cats would be very different than the dose for dogs. The Agency also reiterated that this would be addressed on a case-by-case

basis.