TWN Info Service on Health Issues (May19/08)
23 May 2019
Third World Network

16th May 2019

Dr. Tedros Adhanom Ghebreyesus
Director General
World Health Organisation

Re: Revision of the WHO Guideline on the Evaluation of Similar Biotherapeutic Products (SBPs)

Dear Dr. Tedros,

We, the undersigned Civil Society Organisations (CSOs) are writing to request the updating of WHO Guideline on the Evaluation of Similar Biotherapeutic Products (SBPs) (SBP Guideline) as mandated by the World Health Assembly (WHA) resolution.

In 2014 WHA adopted resolution titled “Access to biotherapeutic products including similar biotherapeutic products and ensuring their quality, safety and efficacy” (WHA 67.21). It requests the Director-General: “to convene the WHO Expert Committee on Biological Standardization to update the 2009 guidelines, taking into account the technological advances for the characterization of biotherapeutic products and considering national regulatory needs and capacities and to report on the update to the Executive Board”. However, till date, the Secretariat has not updated the SBP Guideline.

Instead of updating the SBP Guideline the Expert Committee on Biologic Standardisation (ECBS) decided to publish questions and answers (Q&A) on SBPs to complement the SBP Guidelines. The Q&A states: “In April 2015, an informal consultation was organized during which participants from NRAs of both developing and developed countries, as well as from industry, recognized and agreed that the evaluation principles described in the Guidelines were still valid, valuable and applicable in facilitating the harmonization of SBP regulatory requirements globally. It was therefore concluded that there was no need to revise the main body of the existing Guidelines.” We would like to point out that this statement goes against WHA67.21, which explicitly requests the Director General to convene ECBS “to update” the SBP Guideline. It did not require the ECBS to assess whether to update it. In addition, neither the ECBS nor the WHO has given any scientific reasons for the decision to not update the SBP Guideline.

The current SBP Guidelines insists on head to head comparison of non-originator biotherapeutic product with the originator product with the goal of establishing similarity in quality, safety, and efficacy. This insistence of comparative clinical trials makes development of non-originator biotherapeutic products expensive and time consuming. In addition, increasingly there is robust scientific evidence that calls into question the need for comparative clinical trials for the approval of non-originator biotherapeutic products (biosimilar). The Q&A approved by the ECBS merely restates the content of SBP Guideline in the form of a Q&A form. It does not take into consideration the currently available scientific evidence. Apart from insisting on comparative clinical trials, the Q&A also does not adequately address extrapolation and interchangeability.

We would like to draw your attention to a Memo signed by 8 scientists calling for Revision of the SBP Guidelines.[1] We request you to initiate the revision of the SBP Guidelines as required by WHA67.21, based on the following principles mentioned in the Memo:

– Demonstration of similarity in quality is sufficient to assure the safety and efficacy of most products.
– Emphasis on quality testing should focus on impurity profiles and potency.
– Well-designed pharmacokinetic/pharmacodynamic (PK/PD) studies will be sufficient if clinical studies are needed.
– Immunogenicity studies are only needed if SBP does not match the critical quality attributes related to manufacturing.
– Interchangeability and extrapolation to all indications should be the default unless there are scientific reasons to deny extrapolation.

Failure of the ECBS and WHO Secretariat to update the SBP Guidelines to reflect current scientific evidence and technological advancements, compromises access to affordable biotherapeutic products, as the unnecessary requirements of the SBP Guidelines hinders the prompt availability and accessibility of affordable SBPs with grave consequences for the realization of the right to health and the right to enjoy scientific progress and its applications (right to science).

In the light of the above-mentioned concerns, we request WHO as the directing and coordinating authority on international health work in the interest of public health:

  • To promptly publish in verbatim records of the informal meeting of national regulatory authorities which decided not to update the Guideline mandated by WHA 67.21;
  • To promptly make public the scientific reasons for insisting on comparative clinical trials for the approval of SBP;
  • To urgently take measures to update the SBP Guidelines in light of new scientific evidence as mandated by WHA 67.21 with a focus on clinical trials requirements for marketing approval, default extrapolation as well as requirements regarding interchangeability to facilitate switching to SBPs;
  • To urgently hold public consultations to review the scientific evidence with respect to the need for comparative clinical trials and the possibility of default extrapolation and interchangeability issues.

1. Affordable Trastuzumab Campaign, India
2. Alianza LAC – Global por el Acceso a Medicamentos (Global)
3. Acción Internacional para la Salud – Perú (Health Action International- Perú)
4. Act Up-Basel, Switzerland
5. Access, France
6. Agora Society Malaysia
7. All India Drug Action Network, India
8. Asia Pacific Council of AIDS Service Organizations (Regional)
9. Asia Pacific Network of People Living with HIV/AIDS (Regional)
10. Associação Brasileira Interdisciplinar de AIDS (ABIA), Brazil
11. Asociación por un Acceso Justo al Medicamento, Spain
12. Canadian HIV/AIDS Legal Network, Canada
13. Cancer Alliance, South Africa
14. Cancer Patients Aid Association, India
15. Caritas Latinoamerica y el Caribe (Regional)
16. Centro de Pensamiento Medicamentos, Información y Poder, Universidad Nacional de Colombia
17. CIMUN, Universidad Nacional del Colombia
18. Comité de Veeduría y Cooperación en Salud (Committee of Oversight and Cooperation in Health), Colombia
19. Conferencia Episcopal de Colombia (Colombian Council of Bishops), Colombia
20. Consumer Association Penang, Malaysia
21. CureSMA Foundation of India
22. Delhi Network of Positive People (DNP+), India
23. Federación Médica Colombiana (Colombian Medical Federation), Colombia
24. Fundación IFARMA, Colombia
25. Foundation for Research in Science Technology and Ecology, India
26. Fundación Grupo Efecto Positivo (GEP), Argentina
27. Global Humanitarian Progress Corporation, Colombia
28. Grupo de Trabalho sobre Propiedade Intelectual (GTPI), Brazil
29. Hemophilia Society Mumbai Chapter, India
30. Health GAP (Global Access Project)
31. Health Innovation in Practice (HIP)
32. Initiative for Health and Equity in Society, India
33. International Treatment Preparedness Coalition South Asia (Regional)
34. International Treatment Preparedness Coalition – Latin America and The Caribbean (Regional)
35. Just Treatment, UK
36. Kenya Legal and Ethical Issues Network, (KELIN), Kenya
37. Kenyan Network of Cancer Organizations, Kenya
38. Knowledge Ecology International, USA
39. Labor Education and Research Network (LEARN), Philippines
40. Lawyers Collective, India
41. Misión Salud, Colombia
42. OBSERVAMED, Colombia
43. NO GRACIAS, Spain
44. People’s Alternative Study Center for Research & Education in Social Development (PASCRES), Philippines
45. Pan-African Treatment Access Movement (PATAM), Zimbabwe
46. Peoples’ Health Movement (Global)
47. Políticas Farmacéuticas, Chile
48. Positive Malaysian Treatment Access & Advocacy Group (MTAAG+), Malaysia
49. PT Foundation, Malaysia
50. Public Eye, Switzerland
51. Red Latinoamericana por el Acceso a Medicamentos (RedLAM)
52. Salud y Farmacos, USA
53. Salud Por Derecho (right to health foundation), Spain
54. Salud Visible, Universidad de los Andes, Colombia
55. SDG Center for Latin America and the Caribbean (Regional)
56. SECTION 27, South Africa
57. Sentro (Sentro ng mga Nagkakaisa at Progresibong Manggagawa), Philippines
58. Treatment Action Group, USA
59. Third World Network, Malaysia
60. Treatment Action Campaign, South Africa
61. Vietnam Network of People living with HIV (VNP+), Vietnam
62. Women’s Coalition Against Cancer (WOCACA), Malawi
63. WomanHealth, Philippines
64. Yolse, Switzerland