First GCC Stakeholder Meeting on Approval Process, Interchangeability/Substitution and Safety of Biosimilars 2017 – Report

Generics and Biosimilars Initiative Journal (GaBI Journal). 2018;7(4):158-63.
DOI: 10.5639/gabij.2018.0704.032

Published in: Volume 7 / Year 2018 / Issue 4
Category: Meeting Report
Page: 158-63
Author(s): , , , , , , ,
Visits: 1340 total, 1 today
Keywords: biologicals, biosimilars, GCC, interchangeability, regulatory, Saudi Arabia

Author byline as per print journal: Gianluca Trifirò, MD, PhD; Meteb Al-Foheidi, MD, FRCPC; Ali M Alhomaidan, PhD; Ahmed H Aljedai, PharmD, MBA, BCPS, FCCP, FAST; Musaed Abdullah Alkholief, PhD; Mohammad A Alsenaidy, MSc, PhD; Aws Alshamsan, BPharm, RPh, PhD; Tore Kristian Kvien, MD, PhD

Introduction: A meeting was organized by the Generics and Biosimilars Initiative (GaBI) in collaboration with Saudi Pharmaceutical Society (SPS), to discuss the regulation, approval process, interchangeability/substitution, and post-marketing surveillance of biosimilars in Gulf Cooperation Council (GCC) countries. This ‘First GCC Stakeholder Meeting on Approval Process, Interchangeability/Substitution and Safety of Biosimilars’, took place on 20 November 2017, in Riyadh, Saudi Arabia and gave relevant stakeholders an opportunity to discuss these concepts between themselves and with experts from Saudi Arabia and abroad.
Methods: The meeting brought regulators from GCC countries and academics, medical specialists, and pharmacologists and pharmacists from Saudi Arabia together with experts from Italy, Norway, Saudi Arabia and the US, to share knowledge and exchange information. There were a number of expert speaker presentations with an interactive panel discussion. Following this, the audience was presented with data for two semi-fictional similar biotherapeutic products. The participants were divided into two discussion groups where they evaluated the fictional data supplied.
Results: The presentations were successful in conveying information about the current state of biosimilar regulation, approval, interchangeability/substitution, and post-marketing surveillance of effectiveness and safety. This resulted in a useful interactive discussion from which clearly defined action points could be extracted.
Conclusion: Biosimilar medicines are becoming increasingly available and used across GCC countries. The First GCC biosimilars stakeholder meeting was successful in bringing representatives from GCC nations together with those from Europe and the US, to discuss the best routes forward for successful biosimilar approval and regulation and enabled action points to facilitate biosimilar uptake with appropriate pharmacovigilance to be outlined.

Submitted: 22 November 2018; Revised: 27 November 2018; Accepted: 28 November 2018; Published online first: 11 December 2018

Introduction

Appropriate methods for the approval and regulation of similar biotherapeutic products (SBPs or biosimilars) are subject to global discussion [1, 2]. To ensure that biosimilars successfully enter markets and maintain the safety and efficacy achieved by originator products, approval and regulation guidelines need to be clearly outlined. In addition, it is important to define interchangeability/substitution so that products are used in a way that does not impact on safety and efficacy.

To discuss the regulation and approval of biosimilars in the Gulf Cooperation Council (GCC) countries such as Bahrain, Kuwait, Oman and Saudi Arabia, the First GCC Stakeholder Meeting on Approval Process, Interchangeability/Substitution and Safety of Biosimilars, took place on 20 November 2017, in Riyadh, Saudi Arabia. It was organized by the Generics and Biosimilars Initiative (GaBI) in collaboration with Saudi Pharmaceutical Society (SPS). Fifty-four participants, speakers included, attended the meeting.

This first GCC biosimilars stakeholder meeting was an interactive scientific meeting on the regulation, approval and use of biosimilars with a focus on their interchangeability/substitution and safety. It brought regulators from GCC countries, and academics, medical specialists, and pharmacologists and pharmacists (clinical, hospital) from Saudi Arabia; together with experts from Italy, Norway and the US, to share knowledge and exchange information.

The meeting aimed to address the issues of physicochemical characterization, analytical comparability, interchangeability/substitution and safety of biologicals/biosimilars. The participants engaged in active discussion concerning regulatory approval process, cell line development, hospital formulary selection, switching, and set out to identify future educational needs.

Expert speaker presentations

The format of the GCC meeting was similar to that followed in previous educational workshops and scientific meetings as reported in the GaBI Journal [35]. There were a number of expert speaker presentations followed by Q&A and an in-depth panel discussion. The presentations are downloadable from the GaBI website [6].

The GCC meeting began with a welcome from Professor Yousif A Asiri, Vice Rector of Planning and Development and Professor of Clinical Pharmacy at King Saud University (KSU), Saudi Arabia. This was followed by an introduction by Abdulaziz Alhossan, Assistant Professor at KSU, and then a series of presentations given by expert speakers [6].

The false myths of biosimilars
Clinical Pharmacologist and Professor Gianluca Trifirò, of the University of Messina, Italy gave a presentation during which he discussed and dispelled various ‘false myths’ surrounding biosimilar products. These were outlined as follows:

– Biosimilars are not identical but only similar to the reference product, thus they should be considered as different drugs
– Pre-marketing evidence on biosimilars are much more limited than what is available for the reference product at the time the drug is marketed
– Biosimilars are less safe than reference product in routine care
– Interchangeability of biosimilars and reference product should never be considered due to serious immunogenicity risks potentially associated with switching among therapeutic proteins

In each case, Professor Trifirò provided appropriate evidence and explanation as to why these myths should not be considered a concern.

Challenges related to physicochemical characterization and analytical comparability of biologicals/biosimilars
Mohammad A Alsenaidy, Assistant Professor at KSU, described biologicals/biosimilars as structurally complex, highly specific macromolecules used therapeutically to compensate for body deficiencies, e.g. hormones and clotting factors; and to treat diseases, e.g. cytokines and monoclonal antibodies; and to prevent illnesses, e.g. polyclonal antiserum and certain vaccines. He noted that the structural complexity of proteins makes it challenging to preserve their conformational integrity, biological activity and stability throughout manufacturing, storage and distribution. Professor Alsenaidy then discussed how physiochemical characterizations, stability and degradation profiles of protein-based drugs can be carried out. These are key exercises for the development of protein-based drugs, whether originator or biosimilar. He also noted that, the ability to establish high quality analytical profiles determines the extent for additional animal and/or clinical evaluations such as pharmacokinetics (PK), pharmacodynamics (PD), and/or immunogenicity studies.

Biosimilar cell line development
Musaed Abdullah Alkholief, Assistant Professor at KSU, outlined the key factors necessary for successful biosimilar cell line development. He noted that during the upstream development of these molecules, cell line selection and cell culture processing represents the most critical step in biosimilar development and as such should be carefully evaluated. When developing a biosimilar the slightest variability between the originator cell line and the biosimilar cell line may significantly affect the characteristics of the product, consequently limiting its utilization. It is anticipated that by 2022 the global market size of cell line development will reach US$6 billion. In conclusion, Professor Alkholief noted that a better understanding of the current status and future directions of cell line development is needed to fully exploit biosimilar development processes.

Biosimilar regulations in Saudi Arabia
The Executive Director for Pharmaceutical Products Evaluation of the Saudi Food and Drug Administration (SFDA), Dr Ali M Alhomaidan, gave a talk in which he described the biosimilar approval pathway in Saudi Arabia, quality, safety and efficacy considerations surrounding biosimilars, and their pricing and interchangeability. Background on the pricing of biosimilars in Saudi Arabia and the system used for pricing these products is explained in the paper by Alhomaidan et al. [7]. Further information can be found in the summary of discussions of this meeting below.

Interchangeability for biosimilars: considerations and concerns
Aws Alshamsan, Associate Professor at KSU, discussed the concepts of interchangeability, switching and substitution of biosimilars, and how they differ across Europe, Saudi Arabia and the US. He highlighted that a number of concerns surround the regulatory authority definitions and the differences between them. In addition, he highlighted four key challenges that need to be overcome to facilitate interchangeability that is safe and efficacious. These include: the extrapolation to indications only studied for the reference product; ethical and medical–legal aspects of approval; developing strategies for adequate post-marketing pharmacovigilance; and developing effective pricing policy that distinguishes high quality products.

Formulary considerations for biosimilars for health systems
According to Professor Ahmed Al-jedai of Alfaisal University, Saudi Arabia, global spending on medicinal products is expected to reach Euros 1.3 trillion by 2020 and that, with price reductions of 20%–40% with respect to reference products, biosimilars could create an estimated cumulative savings of Euros 50–100 billion during this timeframe. He highlighted the differences in biosimilar approval approaches between Europe and the US and noted that SFDA and the GCC have adopted the European Medicines Agency’s (EMA) approach. Currently, only five biosimilars are available in the Saudi markets. He also outlined the cost analysis of the biosimilars already approved in Saudi Arabia and discussed the role that pharmacists can play in increasing biosimilar adoption.

Switching from originator product to biosimilars in rheumatology, dermatology and gastroenterology: clinical evidence
The keynote presentation was delivered by Tore Kvien, Professor of Medicine and Rheumatology at Diakonhjemmet Hospital in Norway. This presentation outlined the current need for biosimilar products that are less expensive and as such, can increase patient access to biological medicines. The details of a randomized clinical trial that compared the tumour necrosis factor (TNF) inhibitor infliximab with the less expensive biosimilar CT-P13, also known as the NOR-SWITCH study [8], were presented. This study addressed questions surrounding the efficacy, safety and immunogenicity of switching from an originator to its biosimilar for the first time and showed that switching is not inferior to remaining with the originator product, and that switching can be considered for non-medical reasons.

During a 6-month extension study, patients on the reference infliximab were switched to CT-P13 and compared to the group whose treatment with CT-P13 was maintained. Results from the switch group was not inferior to the maintenance group. The point estimates were actually generally in favour of the switch group and this extension study supported the results of the primary study published in The Lancet 2017.

Oncologist perspective – the use of biosimilar trastuzumab in breast cancer: clinical experience
Assistant Professor Meteb Al-Foheidi of King Saud Bin Abdulaziz University for Health Science in Saudi Arabia discussed the need for oncology biosimilars, noting that they could lead to cancer treatment savings of up to 30%. However, there is currently no consensus on which endpoints to use in oncology biosimilar studies and long-term endpoints are often not feasible in these studies.

Professor Al-Foheidi also described the case of biosimilar trastuzumab in breast cancer treatment and noted that there had been no issues or safety concerns regarding its use in the EU.

Summary of the discussions that followed the expert presentations

After the presentations, there was the opportunity for discussion about the topics covered. The key discussion points are summarized below.

Biosimilar variability
The presentation on ‘Biosimilar cell line development’ prompted a number of questions about biosimilar product variability. Assistant Professor Alkholief stressed that when developing a biosimilar the most critical step is choosing the initial cell line. Having the right components and conditions for growth is also very important in reducing variability, but these are all dependent on the cell line chosen to begin with.

It was suggested that a ‘cell line bank’ could be used as a reservoir of standard cell lines. However, he noted that cell lines are already available to buy and that this is not the critical issue affecting variability. Instead, pharmaceutical companies develop their own processes and set the conditions to grow the biologicals/biosimilars as required and the pharmaceutical companies are not required to share this information at any point, even after patent expiry. As such, variability is inevitable for biosimilars as cell lines and conditions will likely differ from those used to produce the reference products. Despite this, Professor Aws Alshamsan informed that the World Health Organization (WHO) is starting a programme to create a master cell line of bevacizumab so that it can be distributed to manufacturers in order to harmonize biosimilar product outcomes. Dr Ibrahim Aljuffali from the Ministry of Health Saudi Arabia advised that this was done in an attempt to reduce the cost of biosimilars and lessen the burden on national healthcare budgets. He also stated that this, and other similar cell lines, are likely to have a significant impact on the biosimilar landscape in the future.

The cell line bank approach could be rolled out to produce other biologicals after their patents have expired. Such banks would enable governmental agencies to harmonize globally by providing the starting material. However, such an initiative is the responsibility of the government regulators and not private companies.

Global harmonization of biosimilar regulatory approval procedures
Across the globe, biosimilar approval processes differ and harmonizing these processes could reduce the number of clinical studies carried out and make biosimilars more accessible. However, achieving global harmonization of regulation and approval procedures for biosimilars is likely to be complicated and lengthy.

Professor Trifirò highlighted that EMA and the US Food and Drug Administration (FDA), who have differing policies, regularly communicate regarding approval of biosimilar products. However, having different policies in different countries can reduce the credibility of biosimilars and the amount of trust practitioners and patients have in these products. For example, in the case of infliximab, which underwent studies verifying its use as a treatment option for rheumatology indications, the biosimilar drug product was also approved for treatment of inflammatory bowel disease (IBD) in Europe based on extrapolation of indication. Nevertheless, this extrapolation was not accepted by Health Canada and these contradicting policies may lead physicians to have a lack of confidence in the biosimilar product.

A lack of harmonization does not only cause a lack of trust in biosimilar products, but it also creates an increased workload for pharmaceutical manufacturers. They have to submit applications to different regulatory authorities worldwide which have different requirements and this means separate bioequivalence studies and applications are needed. This is expensive for producers in terms of both time and money.

Currently, there is no global harmonization for the regulation and approval of generic drug products. ‘These are far simpler than biologicals/biosimilars and as such, consensus is that we will not see global harmonization of biosimilars for some time. However, biosimilar regulation development is at an early stage in some countries and there are still only relatively few products approved globally, which means that regulatory processes can still be altered and developed to allow for harmonization’, said Professor Trifirò.

Biosimilar pricing
Biosimilars are designed to be lower-cost alternatives to originator products and facilitate access to biological medicines worldwide. Professor Kvien advised that in most markets, the cost reduction for the biosimilar infliximab is 30%. In Norway, when Remsima was approved it was initially 39% less expensive than the originator Remicade, in its second year it was 69% less expensive (possibly the highest cost reduction seen so far), and it is currently about 60% cheaper. This large cost reduction was largely achievable due to the Norwegian national tender system.

In Saudi Arabia, the price of each registered product is accessible through the SFDA website. Dr Alhomaidan described how biosimilar prices are set in Saudi Arabia according to three approaches and each product is priced on a case-by-case basis. The first pricing approach is based on reference pricing, where the price is set relative to its price in 30 reference countries. The second approach requires pharmacoeconomic evaluation and the price is set according to the results of this. And, the third is based on recommendations from the company/manufacturer. In the latter case, the company recommendation may be applied if it offers a product at a significantly lower price than reference product prices.

Professor Kvien added that the pricing transparency in Saudi Arabia is positive. In Europe, pricing can be concealed, but he believes that patients should be aware of the magnitude of saving that is achieved when choosing to switch to a biosimilar product.

The discussion highlighted that in some cases, a reference product manufacturer will gain biosimilar market access after originator patent expiry through production and marketing of a subsidiary’s biosimilar. In these cases, Professor Al-jedai believes that it is highly likely that some biosimilars will come from the same cell line as the reference products as several major pharmaceutical companies have started producing biosimilars of their own biological products. It would cost pharmaceutical companies and its subsidiaries a lot in terms of time and money, to start from scratch and create a new biosimilar when they know they already have a functioning and effective cell line that produces the already approved medicine. Under these circumstances, Professor Kvien believes the product is the same as the originator but re-packaged to be able to take a share of the biosimilar market. Here, the biosimilar must still undergo the same process of evaluation and approval of any other biosimilar product.

Biosimilar nomenclature
Much debate has surrounded the nomenclature of biosimilars in recent years. Across the globe, different approaches have been adopted. With respect to this, Professor Trifirò emphasized that traceability is key for any biological/biosimilar/chemical drug product. It should be possible to achieve this through product naming or identification via batch number. If products can be traced back to the batch level or at least brand name, adequate pharmacovigilance will be achieved so that the source of any adverse reactions/effects can be immediately identified.

In Europe, legislation has been passed to improve pharmacovigilance. In the event of an adverse event, the brand name must be evident (this differs for each biosimilar version of a reference product); and in the absence of a brand name, the manufacturer and non-proprietary name, plus batch level information, must be available. This is very important if a quality investigation is required.

In the US, the situation is slightly different. All biosimilar versions of a reference product currently have the same non-proprietary name which makes them indistinguishable from one another. With respect to this, it is also noted that if one company’s biosimilar product is flagged as a concern, this affects the credibility of all biosimilars with the same non-proprietary name, even if they are made by different manufacturers.

To address this problem and improve traceability of biosimilars, FDA implements a non-proprietary name policy with a four-lowercase letter suffix [9]. This aims to improve and facilitate pharmacovigilance in a multi-source environment which will prevent adverse event data collection that cannot be disaggregated. It should be possible to disaggregate all data and have product-level traceability that allows manufacturers to be held accountable and to develop product safety signalling. In addition to this, FDA’s new naming approach hopes to prevent inadvertent substitutions occurring as a result of product names being the same. This can occur at the pharmacy, rather than prescriber level, if non-proprietary names are shared by different products. At present, when two products have the same non-proprietary name, they can be perceived as being therapeutically equivalents. However, for biologicals and biosimilars, healthcare professionals need to examine the trial data to confirm that they are therapeutically similar and ensure a switch is acceptable.

Dr Aljuffali noted that the new naming guideline issued by FDA is likely to cause chaos and confusion. The idea is that approved products will be named retrospectively and as such, there will be significant impact on electronic health records, utilization of products, existing national drug codification, and finances. Dr Hajer Almudaiheem of the Ministry of Health Saudi Arabia agrees that the new US naming guideline will cause confusion. She also added that if products have different names this could create an artificial barrier to interchangeability due to the misperceptions of prescribers/practitioners.

Professor Trifirò emphasized that it is important to reach a balance in which nomenclature allows the traceability of products and also facilitates the interchangeability of drug products to ensure effective pharmacovigilance.

There are various other naming approaches being adopted around the world. Overall, this makes it difficult to assemble adverse event data in a manner that can be used and accessed internationally. A globally harmonized naming approach for biologicals/biosimilars would facilitate universal pharmacovigilance.

Patient choice, nocebo effect and education on biosimilars
In the future, it is hoped that patients will have a far greater role when it comes to decisions made about their treatment. However, ‘In Saudi Arabia, patients do not yet have this level of autonomy regarding their treatment and their physician makes most of the treatment decisions on their behalf’, said Professor Alshamsan. He stressed that this is likely a cultural issue governed by patient attitudes in GCC countries that are different to those seen in the west.

Professor Al-Foheidi reiterated that in Saudi Arabia the healthcare provider is generally in charge of treatment and switching. Here, both the practitioner and pharmacist have a say in the ultimate treatment decision. Clinicians weigh up the benefits and risks of treatment options based on the information available to them and although they may discuss this with patients, ultimately clinicians make the decision.

‘Patients should always be fully informed about their treatment options and decisions made by their clinicians. Through adequate patient education, the nocebo effect can be dramatically reduced’, said Professor Kvien.

This final comment was supported by Dr Nabila Al Lawati who noted that generally, patients are either educated or non-educated with respect to biosimilars and it is relatively easy to persuade the educated patients to take biosimilars. However, non-educated patients, particularly those who are older, often believe that the most expensive medication is the best and in such cases; it may be beneficial to leave the decision in the hands of the clinician. Professor Al-Foheidi commented that it can be more effective to make a general rather than an individual decision regarding biosimilars and patient advocacies can play an important role here.

Biological/biosimilar switching
The issue of switching between biologicals and biosimilars and the safety of multi-switching was raised. Professor Trifirò advised that the pre- and post-marketing evidence gathered so far, with respect to switching from different sources, had not identified any clinical issues. In Europe, a lot of data have been accumulated which allow for the assessment of the long-term effects of switching, however, this is difficult to investigate in a post-marketing setting. He added that ideally, studies similar to the NOR-SWITCH study [8] for each biosimilar would be carried out, but in reality performing such expensive RCT (randomized clinical trials) to explore all possible reference product/biosimilar switches is impossible. So, efforts need to be made to investigate the effects on long-term switching especially for drugs that have long-term effects, such as rituximab in real-world settings. He noted that healthcare databases including claims databases and electronic medical records as well as drug registries have the potential to help here. Understanding the long-term effects of switching and multi-switching between biosimilars is one of the key challenges that needs to be addressed and this requires an international concerted effort to develop the best methodological approach.

Professor Kvien informed about the Norwegian disease-modifying antirheumatic drugs (DMARD) registry established in 2000. The registry continues to enrol patients who are switching to a biosimilar and those starting treatment with a biosimilar. He estimates that 80% of patients using biosimilars enrol with the registry. However, more data are needed to conduct analysis of biosimilars in a way similar to that carried out in the NOR-SWITCH trial [8]. This registry will soon merge with other registries, such as the death and cancer registries, so that there is more robust data on safety.

Biosimilars in Saudi Arabia
Dr Alhomaidan confirmed that in Saudi Arabia there are guidelines on the quality requirements for biosimilars and there is a pricing system in development for biosimilars, but this is not well established yet. The safety and efficacy requirements are the same as those adopted by EMA. In both Europe and Saudi Arabia, guidelines do not aim to promote biosimilar usage, but instead promote the dissemination of the correct information about them to ensure their quality, safety and efficacy.

In Saudi Arabia, biosimilar products are evaluated during registration, with the first consignment, and then are continually assessed by taking random market samples. When it comes to manufacturer inspections, each manufacturer is inspected by a team of three inspectors before biosimilar production is initiated. He added that Saudi Arabia is in the process of setting up a centre that will enable phase I clinical trials to be carried out by an approved, licensed clinical trials team. These will subsequently be reviewed by the benefit-risk assessment team to facilitate the safe and efficacious entry of biosimilars to the market.

Action points highlighted in the discussions
The key findings from the discussions of the stakeholder meeting are summarized as below:

  • Further research and investment into ‘master cell bank’ could enable further cost reductions in biosimilar products and reduce variability between products and batches.
  • Action needs to be taken to achieve global harmonization of biosimilar approval and regulation procedures. This should be done in the near future, while currently there are only few products approved in the global market.
  • Biosimilar pricing transparency is positive and should continue.
  • Action should be taken to ensure that all biosimilar products globally are traceable to batch level to ensure adequate pharmacovigilance is upheld.
  • Global consistency, transferability and/or harmonization of biosimilar nomenclature needs to be achieved.
  • Strong governmental regulations should be in place to ensure drug products can be tracked without necessarily having to initiate new biosimilar nomenclature.
  • The long-term effects of switching and multi-switching between biosimilars and/or reference products need to be addressed. This requires an international concerted effort to develop an optimal methodological approach.
  • Electronic healthcare records need to be developed and implemented to facilitate pharmacovigilance and gather further data on switching.
  • Biosimilar patient registries could be established and implemented to gather further data on switching.

Parallel case study working sessions

After the formal presentations and discussions, the audience was presented with data for two semi-fictional SBPs, both are a trastuzumab monoclonal antibody. The participants were divided into two discussion groups where they evaluated the fictional data supplied. This was carried out in a similar way to that which occurred at previous GaBI meetings [2].

Summary discussion of case study of therapeutic protein monoclonal antibody – candidate 1
Based on the information the two groups received, Dr Nabila Jawad Al Lawati and Associate Professor Khalid Alsaleh agreed that the first candidate, monoclonal antibody IgG1, did qualify as a biosimilar of the reference product. Dr Al Lawati noted that, with respect to the physiochemical attributes, the charge profile acidity and deamination were not similar to the originator, but this did not affect the products activity or quality attributes. In terms of biological attributes, all is within predefined limits, so the candidate does qualify as a biosimilar from a quality perspective. Professor Alsaleh noted that his discussion group was aware that there are some differences between the candidate and the reference product, but these were not major.

To remediate the differences between the IgG1 candidate and the biosimilar, Dr Al Lawati’s group thought that the product applicant could be asked to alter the charge profile to ensure it is more acidic. Professor Alsaleh’s group said the chemical structure of the candidate could be altered but this would then need further biosimilarity studies to be carried out on it which would negate the point in developing a biosimilar as it would cost a lot in terms of time and money.

To address the ‘residual uncertainty’ in the preclinical and/or clinical studies, Dr Al Lawati’s group suggested that the PK/PD parameters be obtained in clinical studies. Professor Alsaleh’s group said that the bio-immunogenicity could be addressed through clinical studies. Here, the group noted that there was a hard endpoint observable when using the biosimilar. This was seen in the complete initial pathological response when treatment was given, and in the follow-up studies carried out in the year after initial treatment. The overall response to the treatment was good – 46% for the candidate versus 48% for the reference product.

Dr Al Lawati’s group said that, for extrapolation to be recommended, the applicant would need to submit more information about the mechanism of action and site of action. Only with this additional information could a decision be made. On the other hand, Professor Alsaleh’s group said that the IgG1 candidate could be extrapolated but only if there was no other choice. However, if the reference product was available this would be used in preference to the biosimilar for extrapolated indications. He explained that for the reference product trastuzumab, there is a combination indication for metastatic settings which makes extrapolation complicated. He noted that, if a trastuzumab, biosimilar were to be used in such a situation, a combination study should be required, not just clinical data.

Summary discussion of case study of therapeutic protein monoclonal antibody – candidate 2
Based on the information the two groups received, Dr Al Lawati and Professor Alsaleh agreed that the second candidate did not qualify as a biosimilar of the reference product as there8 were many differences in the physiochemical properties of the candidate and the originator. Dr Al Lawati noted that there were particularly significant differences in the total protein content which is an important parameter. The charge profile and deamination also differed. In addition, there were differences in the aggregates and particulates which are important factors when considering the immunogenicity.

Dr Al Lawati said that the physiochemical data need to be a closer match to those of the reference product before further steps are taken towards candidate approval. According to Professor Alsaleh, there is a very soft endpoint to the study that should not generally be used as a primary endpoint and this needs to be amended. Based on the physiochemical data, both groups agreed that the candidate should not undergo preclinical/clinical trials at this point. As the candidate is not a suitable biosimilar, it cannot be extrapolated for any indications.

Conclusion

Biosimilar medicines are being increasingly used and available across GCC countries. The first GCC meeting was successful in bringing representatives from GCC nations together with experts from Europe, Saudi Arabia and the US, to discuss the best routes forward for successful biosimilar approval and regulation and enabled action points to facilitate biosimilar uptake with appropriate pharmacovigilance to be outlined.

Speaker Faculty and Moderators

Speakers
Assistant Professor Meteb Al-Foheidi, MD, FRCPC, Saudi Arabia
Assistant Professor Khalid A Alburikan, PharmD, BCPS, Saudi Arabia
Ali M Alhomaidan, PhD, Saudi Arabia
Assistant Professor Abdulaziz Alhossan, PharmD, MPH, BCPS, Saudi Arabia
Professor Ahmed H Al-jedai, PharmD, MBA, BCPS, FCCP, FAST, Saudi Arabia
Assistant Professor Musaed Abdullah Alkholief, PhD, Saudi Arabia
Assistant Professor Mohammad A Alsenaidy, MSc, PhD, Saudi Arabia
Professor Aws Alshamsan, BPharm, RPh, PhD, Saudi Arabia
Thomas Felix, MD, USA
John Bradley Jordan, PhD, USA
Professor Tore Kristian Kvien, MD, PhD, Norway
Professor Gianluca Trifirò, MD, PhD, Italy

Moderators
Nabila Jawad Al Lawati, PhD, Oman
Associate Professor Khalid Alsaleh, MD, Saudi Arabia

Editor’s comment

All moderators had provided the discussion/conclusion of the group discussion, read the report and revised the content of the summary discussion of the case study.

Acknowledgements

The Generics and Biosimilars Initiative (GaBI) wishes to thank Assistant Professor Abdulaziz Alhossan, for his support through the offering of advice and information during the preparation of this scientific meeting; as well as Professor Gianluca Trifirò, chair of the 2017 GCC stakeholder meeting; for his strong support in facilitating the discussion in the scientific meeting.

The authors and speakers would like to acknowledge the help of all the meeting speaker faculty and participants, each of whom contributed to the success of the meeting and the content of this report, as well as the support of the moderators: Dr Nabila Jawad Al Lawati and Associate Professor Khalid Alsaleh in facilitating meaningful discussion during the parallel case study working sessions, presenting the discussion findings at the meeting and contributing in the finalization of this Meeting Report.

Lastly, the authors wish to thank Ms Alice Rolandini Jensen, GaBI Journal Editor, in preparing and finalizing this meeting report manuscript and providing English editing support on the group summaries.

Competing interests: The scientific meeting was sponsored by an unrestricted educational grant to GaBI from Amgen Inc.

Provenance and peer review: Not commissioned; externally peer reviewed.

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Author for correspondence: Professor Gianluca Trifirò, MD, PhD, Policlinico ‘G Martino’, Dipartimento di Medicina, Clinica e Sperimentale, 1 Via Consolare Valeria, IT-98125 Messina, Italy.

Disclosure of Conflict of Interest Statement is available upon request.

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