Biopharmaceuticals, or biological medical products are the future of medical treatment both in Bangladesh and India and could become the core of the pharmaceutical industry here. Biological medical products as a class have had a profound impact on many medical fields like rheumatology, oncology, cardiology, dermatology, neurology, gastroenterology and many autoimmune diseases. Biologic medical products are major therapeutic options for treating many diseases, for which no effective therapies were available, and where previously existing therapies were inadequate.

There will be significant transformation in the laboratory technology, and operations and even in marketing strategies. Medical representatives will have to transform into knowledge workers and their upline too will have a redefined leadership role to play.

Over the next 15 to 20 years, you can expect pharma business models of today to be metamorphosed by biopharmaceuticals and biosimilars. Biopharma technologies will develop new ways to treat and cure a wide range of diseases. “The biotech industry is becoming the most active group for later-stage pipeline work. While Big Pharma sees its R&D share drop, emerging life science companies are better prepared to go it alone,” says a an interesting report from Fierce Biotech (1)

The report further says that 2018 was a bumper year for FDA approvals, with 59 new therapies getting the thumbs-up. But the report points out that large pharma’s were the filing companies for fewer than half of these launches. Emerging biopharma companies, however, were the originator of 38 of the 59 meds (64%). The importance of Big Pharma in originating molecules is decreasing,” but they “remain important partners” for biotech. The need for smaller biopharma’s to align with Big Pharma companies – and their large sales teams – is becoming less important. (2)

The five challenges facing biopharmaceuticals.

1. Unique challenges for biopharmaceutical scientists

Development of biologic therapies can present several unique challenges for formulation scientists. Unlike many small molecule products, most biologics require a parenteral route of administration. Formulators therefore must develop suitable means to deliver the product via injection. This entails addressing a variety of potentially complex challenges related to the unique properties of the biologic substance being delivered. Issues such as the stability of the biologic material in a solution state must be considered along with the overall practicality of a formulation in terms of manufacturing, storage, transport, and administration. (3)

Such obstacles open a window for a new ancillary industry – the prefilled syringes (PFS) industry for instance. PFS are ready to use disposable syringes containing premeasured dosage of the medicine. PFS’s reduce dosing errors and accuracy is high. And the biggest benefit? The usage of PFS can make the patients adhere to therapy and the caregivers at home can ensure better compliance. This will be a boon to patients who suffer from chronic diseases and opt for self-administration of drug.

In India there is currently only one company to manufacture and deliver sterile PFS and for the filling process. Imagine the potential for such an industry, as the demand for biological medical products bloom. 

2. Biopharmaceuticals are sophisticated

Biopharmaceutical products are among the most sophisticated achievements of modern science. The huge, complex structures of these drugs don’t just look extraordinary in the 3-D modelling systems used to design them; they also perform their jobs remarkably well, offering high efficacy and few side effects. 

Biopharmaceutical drugs have high specificity and potency compared to small molecules. With their low adverse effects, especially in the treatment of cancer and autoimmune diseases, they have huge benefits for patients. 

3. Biopharmaceuticals have large molecular weight

Chad Eichman, Ph.D. says, “Biologics are significantly larger and more complex than their small molecule counterpart. These large molecules range from 3,000-150,000 Da and their use as drugs require injections instead of the pill format. Insulin, for example, weighs 5,808 Da, whereas adalimumab weighs 144,190 Da. and susceptible to degradation, which makes it challenging to formulate and deliver them. Because of their large structure and complexity, biologics are not chemically synthesized, but are only recombinantly produced by engineered cells. Biopharmaceuticals are usually derivatives of natural human proteins, which make them ideal for targeted cellular therapy. Unlike small molecule drugs, which penetrate cell membranes including healthy cells, biopharmaceuticals act through external cellular binding to induce the desired cellular response. Moreover, the molecules are capable of site-specific cellular binding, which means they do not interfere with healthy cells, ultimately making them more attractive drugs”.(4) These therefore are generally administered through the parenteral route.

For the good of humanity scientists have accepted this challenge. Some advances in formulation and delivery strategies include the use of microsphere-based controlled-release technologies, protein modification methods that make use of polyethylene glycol and other polymers, and genetic manipulation of biopharmaceutical drugs. (5)

4. Biosimilars should be identical to the reference product

Biosimilar products should be identical to the reference product in terms of quality, stability, specification, efficacy, safety, preclinical attributes, clinical attributes, pharmacokinetics, pharmacodynamics, toxicity, and immunogenic studies. A key factor that will continue to have a strong negative effect on biopharma manufacturing is the global shortage of skilled labour. Although some of the problems surrounding labour shortages could be solved using automation, the fundamental issue will persist.

Employees in manufacturing will need core competencies in cell and molecular biology, bioprocess engineering, digital and data analysis using artificial intelligence. In addition, operational techniques including aseptic operations, cell culture, column chromatography, filtration, virus reduction and single-use systems remain vital.

Sales force will need to be transformed into knowledge workers. With customised or personalised medicines, patient centred approach in marketing will be the new model. Not just the marketing and sales personnel have to be trained, the mindset of trainers too have to change. Training the trainers will have to be geared up to meet the new challenges.  

Training and continuously updating employees on modern technologies can have a significant impact on the speed, reach and effectiveness of upskilling programmes. Immersive technologies, (meaning integrating virtual content with the physical environment in a manner that allows a user to engage naturally with a blended reality) such as virtual reality (VR) and augmented reality (AR), have also been gaining momentum.

To meet demand and provide a sustainable talent pool, collaboration between industry, government and academia is a must, as is implementing multiple programmes, leveraging a broad array of learning modes across all levels and demographics. Much depends on the skills, training and attitudes of the personnel involved. (6)

5. Cost of treatment doubles the trouble

Double the trouble! This is what exactly happens when a middleclass, a lower-middle class, or those below poverty line human falls ill in Bangladesh and India – the trouble caused by the disease is doubled by the cost of treatment. What about biological medical products? Let’s hear what Favour Danladi Makurvet has to say. “Though much progress in healthcare has been made with biologics, end-user access to these innovative drugs is gradually being ignored or, at least, seldom prioritized,” she writes. She continues, “A balance between the efficacy of wonder-performing drugs and the patient’s financial ability to access them must be established to obliterate the crippling effect of the high costs of drugs on the poor majority of patients – those who cannot afford them.” (7)

An analysis of ten pharmaceutical companies by Boston Consulting Group revealed the average production cost per pack was ca. $5 for small molecules and ca. $60 for biologics. What a huge difference ca.$55! Why? Let us take the example of a drug like aspirin. Only five ingredients are required to produce aspirin. Insulin manufacture, on the other hand, requires genetic modifications in living microorganisms. This complex manufacturing typical of all biologics production, in addition to its nondisclosure in patents, makes their characterization by prospective competitors a near-impossible task. (8, 9)

Gary Owens says it upfront: “Some of the therapies range from $10,000 to $40,000 a year, and if patients do not have adequate coverage, they may find that access to them is limited.” (10) The poor majority naturally resort to the cheaper small molecules to “manage” conditions that are curable by the more expensive and unaffordable biologics; often, a cheaper drug is not as effective.

The pharma industry in both these countries must collaborate with their respective governments to have something similar to National Health Scheme (NHS) of UK or the Sistema Único de Saúde (SUS) of Brazil. Both are publicly funded healthcare systems. SUS virtually covers 100% of the Brazilian population of 220 million people. These systems are entirely free of any cost at the point of service. The cost is borne by the taxpayers.

What does the Constitution of Brazil say? “Health is a right of all and an obligation of the State, guaranteed by socioeconomic policies which seek to the reduction of the risk of disease and of other grievances and to the universal and equal access to the actions and services in its promotion, protection and recuperation”. (11)

Till such a scheme is introduced, the industry and healthcare systems can collaborate with financial institutions like the SBI, HDFC or Grameen Bank to provide loans at nominal rate of interests repayable at EMI’s.  

Summary:

• Pharma leaders in Bangladesh and India should develop strategies to take advantage of the short- and long-term opportunities that emerge in the changing environment and there is quick shift towards biological medical products.
• F&D of this industry should also seriously look at delivery routes that provide alternatives to the parenteral route. F&D can work on transdermal, oral, and pulmonary delivery systems. Microsphere-based controlled-release technologies is another delivery method that could be investigated.
• Modern methods of learning and development like Continuous Pharma Education (CPhE) should be considered. The obsolete methods of sales training should be replaced by newer methods like using the phygital medium, videos and podcasts.
• The industry in collaboration with their governments or WHO should adopt altruism for the poor who cannot afford biopharmaceutical products, yet they need it. They should start with the end in mind i.e., better patient outcomes.

References

1.    Biotechs getting bigger in late-stage R&D, leaving Big Pharmas behind: report | Fierce Biotech). Accessed on 3rd January 2023

2.    Biologic Processing & Manufacturing Challenges & Strategies (singota.com) Accessed on 28 November 2022

3.    Large vs Small Organic Molecules in Biopharmaceuticals (phenomenex.blog) Accessed on 14 April 2023

4.    Overcoming the challenges in administering biopharmaceuticals: formulation and delivery strategies – PubMed (nih.gov) [Accessed 10 June 2022]

5.    The weakest link – biopharma workforce development (europeanpharmaceuticalreview.com)

6.    Biologics vs. small molecules: Drug costs and patient access – ScienceDirect [[Accessed 14 October 2020]

7.    J. Gooch, F. Cordes, F. Bressau, P. Berk. What does- and does not- drive Biopharma cost performance The Boston Consulting Group (2017) [Accessed 14 October 2020]

8.    International Aspirin Foundation. The Chemistry of Aspirin (acetylsalicylic acid)(2020) [https://www.aspirin- [Accessed 13 December 2020]

9.    New York Times How to decrease prices for an expensive class of drugs https://www.nytimes.com/2015/11/17/upshot/how-to-decrease-prices-for-an-expensive-class-of-drugs.html (2015) [Accessed 14 April 2020]

10. American Health and Drug Benefits. The value of Biologics (2008), pp. 20-28 [Accessed 5 August 2020]

11. https://www.gov.br/saude/pt-br/assuntos/saude-de-a-a-z/s/sus  [Accessed 12 May 2022]