Summary of Committee meetings held in 2021
Case No: 303-06-21 Hipra UK and Ireland Ltd / Zoetis UK Ltd; CircoMax® Myco.
Case 303-06-21 was brought by Hipra UK and Ireland Ltd against Zoetis UK Ltd and involved one item of Complaint relating to promotional claims made between March 2021 and May 2021 for Zoetis’ product CircoMax® Myco.
The Item of Complaint was that claims had been made by Zoetis that CircoMax® Myco provides broadest protection and broader coverage against PCV2. The promotional statements included phrases such as “Stay one step ahead with the broadest, longest-lasting combined PCV2 and M.hyo* protection” and “Protect your pigs with Europe’s first and only dual PCV2 genotype vaccine. Broader coverage – against multiple PCV2 genotype and Mycoplasma hyopneumoniae”
The clauses of the NOAH Code of Practice alleged to have been breached were as follows:
A Promotion of Animal Medicines must:
(i) be fair;
(ii) be balanced;
(iii) not be misleading (directly or by implication);
(iv) not directly or by implication disparage the products or services of other companies;
(vii) not state directly or by implication that an Animal Medicine, or an active ingredient, has some special merit, quality or property over other products unless this can be substantiated
Any information or claim in a Promotion of Animal Medicines must:
(i) be accurate;
(ii) be based on an up-to-date evaluation of all the evidence and must reflect this evidence accurately and clearly;
(iii) be capable of substantiation
Hipra presented their case to the Committee:
The key points in their arguments were as follows:
- The use of the terms “broader” and “broadest”, “protection” and coverage”, falsely implies that Zoetis’ product CircoMax® Myco provides protection against additional genotypes not protected by other products, including the Hipra product, Mhyosphere®.
- The claims on the Summary of Product Characteristics (SPC) must always be the primary reference point. Hipra argued that both the Zoetis product CircoMax® Myco and the Hipra product Mhyosphere® had similar wording on their SPC for the breadth of coverage offered by the vaccines against PCV2 types a, b and d. In their view, this meant that the Zoetis claim of broadest protection and broader coverage, could not be substantiated.
- Neither the Bandrick et al or Um et al studies considered the Hipra product Mhyosphere®. Whilst appreciating that Bandrick et al could not have included Mhyosphere® in their studies, as it was not marketed at the time, in Hipra’s view this clearly demonstrates why Zoetis cannot use this study to back up their claims of ‘broader’ or ‘broadest’ PCV2 protection/coverage.
Zoetis presented their response to the Committee:
The key points in their arguments were as follows:
- The phrase “broadest, longest-lasting combined PCV2 and M.Hyo protection” represents the fact that CircoMax® Myco offers protection against the fastest mutating ssDNA virus, PCV2.
- The Zoetis view was that because CircoMax® Myco contained PCV2a and PCV2b ORF2 proteins, CircoMax® Myco provided broader protection against PCV2 because it was the only trivalent vaccine on the marketplace.
- EpiVax® technology was used to compare the genetic sequences of PCV2 vaccine strains and field strains and to predict how well a vaccine would protect against strains on farm. A study by Um et al. applying EpiVax® technology found that the epitope coverage against the PCV2d field strain was 62.22% for a competitor product (which was not the Hipra product, Mhyosphere®) and 82.82% for CircoMax® Myco.
- A Bandrick et al (2020) in silico study compared CircoMax® Myco, with its PCV2a-PCVAb combination, and three other either PCV2a or PCV2b only vaccines and found that the combination PCV2a-PCV2b vaccine (i.e. CircoMax® Myco) “had, on average, the highest EpiCC score, thus the best potential to confer the broadest cross-reactive cell-mediated immunity and protection”
- Reference was made to statements in a draft European Public Assessment Report which is still in the process of being finalised by the European Medicines Agency (EMA) Committee for Veterinary Medicinal Products (CVMP)
- Zoetis stated they had previously offered to modify the wording of their promotions by replacing ‘Protection’ with ‘Coverage’. This modification would be supported by the statement ‘Coverage comparison based on epitope homology of PCV2a based vaccines and PCV2a/PCV2b vaccines against field strains, using EpiVax® methodology’. The claim ‘longest-lasting’ would be supported by the words ’23 week duration of immunity’ based on EpiVax® technology. Zoetis subsequently used this amended wording, although the modification was still not accepted by Hipra.
Hipra responded as follows to some of the points made by Zoetis:
- Coverage is widely understood, by the target audience (i.e. vets and farmers) to be a synonym for protection when referring to vaccines, therefore the overall messaging of the promotions would have, and did, remain the same. This was the key reason Hipra still had concerns in spite of the proposed amendments to the Zoetis promotions.
- Zoetis rely on the EpiVax® technology to substantiate their claims but that model has not been tested in vivo.
- The Bandrick et al study was in silico, and therefore an extrapolation to real life on farm conditions should not be made.
Following comprehensive presentations from both Parties and detailed analysis of the scientific and technical background, the Committee unanimously found that Zoetis had breached Clauses 4.3(i), 4.3(iii), 4.3(vii), 4.4(i) and 4.4(iii).
In reaching this decision, the Committee first considered the use of the terms ‘broader’ and ‘broadest’ in the context of the promotions and concluded that by using ‘broader’ and ‘broadest’ in relation to either protection or coverage in promoting their CircoMax® Myco vaccine Zoetis had implied that the CircoMax® Myco vaccine provides respectively the best and broadest protection of all vaccines for PCV2 or better and broader protection than other vaccines on the market, including Mhyosphere®.
The Committee then considered whether Zoetis had substantiated this claim.
At the heart of Zoetis’ defence was that CircoMax® Myco vaccine was the only trivalent vaccine on the marketplace (PCV2a, 2b and M.hyo). No other vaccine included the PCV2b protein in it. However, it was common ground that no field trials or in vivo trials had been carried out between it and all other PCV2 vaccines, including, in particular, Hipra’s Mhyosphere® vaccine. Zoetis relied upon (i) Bandrick et al (2020) paper (ii) Um et al (2021) paper and (iii) a short statement in a redacted draft and not yet published CVMP Public Assessment Report produced by the European Medicines Agency (EMA) that the inclusion of the PCV2b antigen provided broader immune coverage than vaccines based on a single PCV2 type.
In reference to the Bandrick et al (2020) paper, the Committee noted that it was an in silico study and not a field or in vivo trial. Furthermore, the Mhyosphere® vaccine was not considered by the authors. Moreover, counterbalancing the above, the Franzo/Segales paper (2020) indicated that all vaccines in the market had shown great efficacy in reducing clinical signs caused by PCV2 regardless of the genotype and the authors considered that there was thus but one serotype in PCV2. It is the serotype that provokes an immune response in the pig’s body.
In reference to the Um et al (2021) paper, the Committee noted that the authors carried out a field trial with CircoMax® Myco and a PCV2a only vaccine, but again it was not a field study of all vaccines on the marketplace now, and importantly did not compare Mhyosphere®, which is a recent entry to the market. Therefore, the Committee felt that the paper could not be relied upon to justify a claim that CircoMax® Myco provides better or broader (or the best or broadest) protection against PCV2.
In reference to the draft CVMP Public Assessment report, the Committee did not consider that it substantiated the claims and it was accepted by Zoetis that the statements made by the EMA in the report were not based on in vivo studies.
Therefore, the Committee considered that the above did not substantiate the claims.
Moreover, as said above, the Committee noted that the SPC for the Hipra product Mhyosphere® had shown efficacy in field studies against PCV2 types a, b and d notwithstanding that the Mhyosphere® vaccine did not have the PCV2b protein in it.
In summary, the Committee found that in their promotional statements, Zoetis has promoted its CircoMax® Myco vaccine as providing better and broader protection against the PCV2 virus than other vaccines on the market and that the evidence presented was not sufficient to substantiate such claims. As a result, Zoetis were found to be in breach of clauses 4.3(i), 4.3(iii), 4.3(vii), 4.4(i) and 4.4(iii) of the NOAH Code of Practice.
Zoetis were issued with the following undertaking, which the Committee noted should reflect the current position with regard to the Respondent’s ability to substantiate these promotional statements made in this campaign:
Case No. 303/06/21
- We acknowledge and accept the decision of the Committee in Case 303/06/21 as set out in the NOAH Code of Practice Committee Decision Notice provided by email on 18 June 2021.
- We undertake not to make statements whether in circulars, advertisements, leaflets or otherwise which expressly or impliedly claim that CircoMax® Myco provides the broadest, best, broader or better protection (including through the use of the word “coverage”) for pigs infected with the PCV2 virus than other licensed PCV2 vaccines unless such claims are substantiated through in vivo or field trials.
- We hereby give an assurance that we will take all possible steps to avoid a breach of the above undertaking.