Educational Seminar “Introduction to Bioprocessing and Biologic Medicines”
(“Introduction to Bioprocessing and Biologic Medicines”)
13 September 2014
Dublin, Ireland
National Institute for Bioprocessing Research and Training

On 13 September 2014, the Educational Seminar “Introduction to Bioprocessing and Biologic Medicines” was held in Dublin, Ireland, at the National Institute for Bioprocessing Research and Training (NIBRT). CYCCA was represented by the Association’s Assistant Secretary, Ms. Natassa-Revekka Theodosiou. The objectives of this educational seminar were: :contentReference[oaicite:0]{index=0}

• To provide information and education on the methods and stages involved in the production of biologic medicines.
• To introduce biosimilar medicines.
• To understand the regulations governing biologic and biosimilar medicines.

The seminar also included a guided tour of the biologic medicines production and processing facilities.

Speakers: Dr. John Milne BSc, PhD and Dr. Darine Dempsey, PhD, Senior Regulatory Consultant, The Compliance Group.

Biotechnology is the technological application that uses biological systems, living organisms, or their derivatives to produce or modify products or processes.

The production of biologic medicines is complex, time-consuming, and costly. However, biologic medicines offer significant advantages over traditional medicines. For example, therapeutic proteins can interact more effectively with a large number of target receptors, something traditional medicines cannot achieve due to their smaller molecular structure. In addition, biologic therapies target specific malfunctioning cells (targeted therapy), unlike conventional chemical medicines that affect both healthy and diseased cells.

The cost of biologic medicines is high because they are produced from living organisms that require careful handling, as they are fragile and highly sensitive to environmental conditions. Any mistake or omission during production can destroy an entire batch and result in losses worth millions of euros for the manufacturer.

According to the World Health Organization (WHO, 2009), biosimilars are biotherapeutic products that are similar in quality, safety, and efficacy to an already licensed reference biotherapeutic product.

For any medicine to receive approval, it must satisfy four key criteria:

1. Quality
2. Stability
3. Efficacy
4. Multidisciplinary evaluation

Biosimilar Medicines (Biosimilars):

1. They share similarities with reference biologic medicines but are not generic medicines.
2. They are similar, but not identical, to the original biologic medicines.
3. It is impossible for them to be exact copies of the reference biologic products.
4. Manufacturers of biosimilars do not have access to the proprietary production processes used to manufacture the original biologic medicines.
5. They are not required to independently demonstrate patient benefit, as this has already been established for the reference biologic medicine.

The European Medicines Agency (EMA) notes that the biologic medicine Remicade was approved for the treatment of rheumatoid arthritis, Crohn’s disease, ulcerative colitis, ankylosing spondylitis, psoriatic arthritis, and psoriasis.

Its biosimilar versions, Remsima and Inflectra, were approved following studies in ankylosing spondylitis and rheumatoid arthritis. Their use was also approved for Crohn’s disease and ulcerative colitis; however, broader use requires additional clinical studies and supporting evidence.

By contrast, the U.S. Food and Drug Administration (FDA) stated that:

“…it could not be recommended due to differences between Inflectra and the reference product that may affect clinical safety and efficacy.”

The FDA therefore requested further research and evidence before approving its use in inflammatory bowel diseases.

Figures 1 and 2 compare the approval pathways for biologic and biosimilar medicines in Europe and the United States. In Europe, as illustrated in Figure 1, fewer clinical and non-clinical studies are required for biosimilars. Specifically, biosimilars must demonstrate that there are no clinically meaningful differences compared with the reference product, although a limited degree of variation is accepted.

This approach is based on demonstrating similarity to an already approved product rather than re-establishing safety and efficacy from the beginning.

Particular attention was drawn to the fact that significant pathophysiological differences exist between rheumatologic diseases and inflammatory bowel diseases, as well as differences in their safety profiles.

Figure 3 illustrates the concept of a biosimilar medicine: a product that resembles the original biologic medicine in many respects but is not identical.

Regarding interchangeability between biologic medicines and their biosimilars, the European Medicines Agency (EMA) has not issued specific guidelines and leaves decisions to individual member states. Each European Union country must establish its own policies on this matter.

More than twelve European countries have already introduced regulations preventing the automatic substitution of biologic medicines with biosimilars.

It should also be noted that the FDA has stated that biosimilarity alone does not make two medicinal products interchangeable.

The substitution of biologic medicines with biosimilars:

a) is generally not permitted in Europe;

b) is not widely recommended; and

c) is considered a separate issue from interchangeability.

Conclusions:

1. Biologic medicines have a highly complex production process involving multiple stages and large molecular structures.
2. The cost of biologic medicines is substantial because they are produced from living organisms that require careful handling due to their fragility and sensitivity to environmental conditions. Any error during production may destroy an entire batch and result in losses worth millions of euros.
3. Biosimilar medicines differ significantly from the original biologic medicines in both structure and manufacturing process. Concerns have been raised regarding their similarity, comparability, and potential short- and long-term complications.
4. Manufacturers of biosimilars face considerable challenges in reproducing the complex manufacturing processes of original biologic medicines, particularly because they only have access to the final product and not the earlier stages of production.
5. At present, biosimilar medicines do not offer the same level of cost reduction as traditional generic medicines.
6. The issue of interchangeability between biologic medicines and biosimilars remains the responsibility of each individual country according to EMA guidance. Every European Union member state must establish its own rules on this matter.

CYCCA, based on the educational workshop organized in Dublin by the European Federation of Crohn’s & Ulcerative Colitis Associations (EFCCA) and on its forthcoming meeting with the Cyprus Gastroenterology Society, will determine its official position regarding biosimilar medicines.

* Biosimilars = biosimilar or biological equivalent medicines

** Reference biologics = original biologic medicines

References

1. Educational Seminar “Introduction to Bioprocessing and Biologic Medicines,” 13 September 2014, Dublin, Ireland – National Institute for Bioprocessing Research and Training (NIBRT).
2. “The Impact of Biosimilars Entry in the EU Market,” Andalusian School of Public Health, January 2011.
3. Simon D. Roger & Ashraf Mikhail (2007). “Biosimilars: Opportunity or Cause for Concern?” J Pharm Pharmaceut Sci 10(3):405–410.

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Natassa-Revekka Theodosiou
Assistant Secretary, CYCCA Board of Directors