Evidence-based Medicine For Animal Supplements – Part 2
Everyone remembers the issue with melamine contamination in pet food in 2007. It resulted in Senate hearings during which three areas of concern for pet food safety were identified:
1. Manufacturing practice standards, such as those found in the current Good Manufacturing Practices (cGMPs) for human dietary supplements, are inadequate for pet products.
2. There is no early warning system in the event something unforeseen occurs.
3. Verification mechanisms are not in place to help ensure the industry is implementing and following proper conduct.
Legislation was subsequently passed to help maximize animal safety by providing additional authority to FDA and increasing requirements for the pet food industry.
Representing 90% of the industry, the National Animal Supplement Council (NASC), a non-profit industry trade association, has driven this process through cooperative efforts with FDA-CVM and state agencies and associations that recommend regulatory policy like the Association of American Feed Control Officials (AAFCO). In every case, the requirements for NASC members have exceeded those mandated by federal legislation.
In 2001, NASC submitted a proposal called Compliance Plus to FDA-CVM defining key action steps that would be implemented within the animal supplement industry to help deal with safety concerns and egregious product claims for efficacy. Our organization committed to dates and specific action items to address the concerns of the regulators while serving the best interests of all stakeholders. Compliance Plus considers the following:
1. Safety – Demonstrating safety by conducting toxicology studies in the target species and microbiological tests on every animal supplement sold is not an economically viable option. For an effective and consistent approach, NASC committed to developing and implementing the most comprehensive adverse event reporting system in the industry. In August 2004, it launched the NASC Adverse Event Reporting System (NAERS), and compliance with NAERS became a requirement for all NASC members.
Each member company is required to enter information into the NAERS database listing individual ingredients in all products they sell, as well as the quantity of each ingredient per unit of administration (e.g., tablet, capsule or scoop) as specified on the product label. NASC members are also required to submit a monthly report of all adverse events to NAERS, and a quarterly report of sales data in number of units sold of each product listed in the NAERS database.
NAERS is accessible by FDA-CVM and the system currently monitors more than 5,000 products with over 1,400 individual ingredients. Ingredient Risk Reports are generated by analyzing data for each ingredient to determine dosage information for each species (dogs, cats or horses) and the adverse event report rate per administrations of products sold containing all ingredients in the marketplace from member companies. An example of an Ingredient Risk Report for glucosamine is found in Exhibit 1. Adverse events for different forms of glucosamine, such as hydrochloride and sulfate, are all tracked individually or can be combined in a consolidated report on all forms of glucosamine, as shown by individual species with adverse events being very broadly defined to include transient events like vomiting, diarrhea, accidental ingestion, etc.
Similar reports for any ingredient in the NAERS database are available to NASC members, professional veterinary organizations (e.g., AVMA, AHVMA, VBMA, ACVS, ACVIM) and regulatory agencies. Ingredient Risk Reports for garlic, lutein and evening primrose oil were provided to a scientific committee established by the National Research Council of the National Academies for consideration in their 2009 report, Safety of Dietary Supplements for Horses, Dogs, and Cats.
Does the NAERS system prove products are safe? No, but it does provide a very good system of monitoring risk and is consistent with current risk-based approaches utilized by the regulatory agencies in the US and other countries.
2. Current good manufacturing practices (cGMPs) – Good manufacturing practice standards are currently being developed by FDA-CVM for animal feed. The FDA website states:
“Animal Feed Safety System (AFSS) – The Food and Drug Administration announced in August 2003 its intention to make its animal feed safety program more risk-based and comprehensive. When completed, the modernized Animal Feed Safety System (AFSS) will incorporate risk-based, preventive control measures for ensuring the safety of animal feed. FDA, with State assistance, has developed an AFSS framework document that identifies the current major processes, guidance, regulations and policy documents that address feed safety and the documents that should be developed to make the Agency’s feed safety program comprehensive and risk-based. Public meetings were held in September 2003, April 2005, September 2006 and May 2007 to share draft plans and documents, and to solicit comments.”
Note the references to “risk-based” approaches specifically discussed by FDA in considering regulatory policy.
In the Compliance Plus proposal to FDA-CVM and AAFCO, NASC committed to define and implement manufacturing standards to help ensure production process controls for animal products that are similar to human dietary supplements. The first guidelines were published in 2005 and have since been revised and updated numerous times. When cGMPs for Human Dietary Supplements were officially published in 2007 , NASC reviewed these requirements and incorporated applicable standards into the requirements for NASC members as appropriate to the animal industry. Although not specifically related to evidence-based medicine, other accomplishments of NASC include:
3. Labeling claims guidance consistent with regulatory approaches
4. Scientific Advisory Committee review of ingredients
5. NASC independent quality audit program
6. Registration of products and facilities with FDA-CVM
7. Random testing of finished products
8. Verification of adverse event report entry
9. Continuing Education programs for the animal supplement industry
10. Cooperative, transparent programs with federal and state regulatory agencies
In the United States, consumers spend approximately $1.4 billion annually on supplements for dogs, cats and horses. These products offer two things to veterinary practitioners. First and foremost, they provide the ability to coordinate care and make proper recommendations to the client, which may include complementary natural products. Whether or not the veterinarian recommends supplements, demand indicates that pet owners are purchasing these types of products for their animals. Secondly, animal supplements are a source of revenue for the veterinary clinic as part of a comprehensive care program.
Everyone would like more “evidence” in the form of clinical studies to verify the safety and efficacy of currently available animal supplements. There are some very valid reasons why the ability and willingness of the industry to sponsor clinical research is challenging. These reasons primarily involve the limited ability to recover the substantial investment required to conduct randomized double-blind, placebo-controlled studies that satisfy the rigors of the scientific community. Furthermore, companies are limited in the claims they are allowed to make under current federal and state laws for any clinical studies yielding positive results.
The majority of stakeholders, especially veterinarians, would be well served to at least fairly consider how these products compare to current drugs and medical devices which are utilized every day in practice. This is not to say the animal supplement industry is perfect and certainly some fair scrutiny is very reasonable. Don’t be afraid to call supplement companies and ask some tough questions about their quality programs, adverse event reporting systems and registrations with the various regulatory agencies. However, to simply dismiss the potential value and benefit of animal supplements because of the lack of evidence-based data is not to ask the right questions, especially when the same criteria is not applied to literally hundreds of other products utilized every day in veterinary medicine. Good science is always fair and open-minded. If it wasn’t, where would the veterinary profession be today?