Genetic disorders impact people from all over the world, for their entire lifetime. With extensive research and innovation and the dedication of patients, scientists, and communities, some genetic diseases can now be treated by approved gene therapies. As time goes on, research aims to develop even more therapies for a broader range of genetic diseases.

Problem 1 - Impact of Common Genetic Disorders:

Some of the common genetic disorders are listed below and see their impact to newborns, toddlers, and patients with severe disease management practices.

• Hemophilia A and Hemophilia B: Impact: Hemophilia is characterized by impaired blood clotting due to deficiencies in clotting factors. This can lead to prolonged bleeding after injuries or surgeries. Severe cases may result in spontaneous bleeding into joints, muscles, or other tissues, causing pain, swelling, and joint damage. Treatment: Gene therapies aim to introduce functional copies of the missing clotting factor genes, reducing the severity of bleeding episodes.
• Sickle Cell Disease: Impact: Sickle cell disease affects red blood cells, causing them to become rigid and take on a sickle shape. These abnormal cells can block blood vessels, leading to pain, organ damage, and anemia. Treatment: Gene therapies seek to correct or replace the faulty HBB gene responsible for abnormal hemoglobin production. This could potentially cure the disease.
• Beta Thalassemia:Impact: Beta thalassemia results in reduced or absent production of beta-globin chains in hemoglobin. This leads to severe anemia, fatigue, and other complications. Treatment: Gene therapy approaches aim to enhance beta-globin production by introducing functional copies of the HBB gene.
• Leber’s Congenital Amaurosis (LCA): Impact: LCA is an inherited retinal disease causing severe vision loss or blindness from an early age. Treatment: AAV-based gene therapy delivers functional copies of the RPE65 gene to retinal cells, potentially improving vision.
• Choroideremia: Impact: Choroideremia also affects vision, leading to progressive vision loss due to retinal degeneration. Treatment: AAV-based gene therapy aims to replace the defective CHM gene, slowing down vision deterioration.
• Severe Combined Immunodeficiency (SCID): Impact: SCID results in a severely compromised immune system, making individuals susceptible to infections.Treatment: Gene therapy corrects the faulty genes, allowing patients to develop a functional immune system.
• Adrenoleukodystrophy (ALD): Impact: ALD affects the nervous system and adrenal glands, leading to neurological symptoms and adrenal insufficiency. Treatment: Gene therapy introduces functional copies of the ABCD1 gene, which is mutated in ALD patients.
• Parkinson’s Disease: Impact: Parkinson’s disease is a neurodegenerative disorder affecting movement, balance, and coordination. Treatment: While not exclusively gene therapy, researchers explore approaches to enhance dopamine production and manage symptoms.

Biopharma Pioneers who produce therapeutic solutions to Gene Therapies:

The field of gene therapy is continually evolving, and collaborations between industry players, academic institutions, and research organizations are crucial for further progress.

Worldwide various Biopharma companies, along with scientific researchers, are driving advancements in gene therapy, personalized treatments, and precision medicine solutions. Their efforts are transforming the pharmaceutical industry on a global scale, offering hope to patients with genetic conditions.

The outcome of every gene therapy manufacturing solution is mass production of ATMP(Advance Therapeutic Medicinal Product) for every targetted genetic disorders

Problem 2: Challenges for ATMP Bulk liquid drug management systems:

The challenges for liquid control systems in biopharmaceutical manufacturing processes encompass not only meeting requirements in process logistics. To ensure the safety of biopharmaceutical products, the high demands of regulatory bodies must be met. In particular, biomanufacturing processes are generally performed under sterile or aseptic conditions to achieve bioburden levels conforming to the respective specifications, which is a crucial element of current good manufacturing practice (cGMP).

Traditional processes using stainless steel pipes require cleaning and sterilization steps (e.g. clean in place and/or sterilize in place) and respective validation before any contact with process liquids. Naturally, this limits scalability and cost efficiency, as resources (labor, time, plant footprint) are bound to these steps.

Solutions for Safe handling of bulk drug substances:

While one of the main goals of bulk drug substance management is to ensure quality control, safety during manufacturing, storage and transportation are of great importance. Nevertheless, the safe handling of bulk drug substances is a necessary measurement when dealing with sensitive and potentially hazardous drug substances.

Safe storage and transport of bulk drug substances:

Considering their considerable value and often great diligence, bulk drug substances have to be protected during storage and shipping to prevent spoilage and product loss. Single-use bags, protected by robust and safe secondary packaging,  do not take up much space and can be stored most efficiently. Further, smart secondary packagings allow for rapid and controlled freezing. Therefore, Single Use Support developed a protection system for single-use bags that absorbs external mechanical influences and reduces the tension on the single-use bag

Protected filling and freezing:

Filling of substances into bio containers bears its complications and product loss through handling failures can occur. Nevertheless, the most frequent filling errors are related to equipment failure, human error or consumable failure. To prevent product loss through manual intervention, Single Use Support has developed a fully automated filling and filtration system, for single-use bags . Additionally, they reduce the risk of exposure, since the process is performed within an enclosed system.  

Controlled freezing of drug substances helps to maintain product quality and to guarantee safe storage. As insufficient freezing can stress the protein and lead to damage of the product, Single Use Support uses freezing platform systems that prevent unwanted alterations in the product through plate freezing .

Minimizing risks during thawing and draining:

As the process of thawing and draining drug substances is as sensitive as the process of freezing, Single Use Support has developed a fully automated freeze/thaw platform that can be used for any batch size. The devices can carry out both the freezing and thawing process, delivering high product stability via controlled freeze-thaw rates.

Nevertheless, even small process deviations can have big consequences in the handling of bulk drug substances. For staff members, this means being on alert during every step of cold chain logistics, monitoring the different steps, and protecting themselves from safety risks caused by exposure. For patients, on the other hand, product loss can result in supply chain delays.

End-to-end solutions for the safe handling of bulk drug substances – with Single Use Support

Single Use Support has developed an entire product line-up suitable for the safe and adequate handling of bulk drug substances, based on single-use technologies. With automated filling systems, the loss of drug substances can be reduced significantly. This reduces the risk of contamination related to the exposure to potentially toxic substances. With solutions for controlled freeze/thaw processes as well as dedicated draining methods, spoilage and unwanted alterations of biopharmaceutical products can be prevented.

Single Use Support’s solutions are fully customizable and adaptable to small-scale and large-scale requirements. Due to their flexibility and effectiveness, Single Use Support’s end-to-end solutions are the ideal choice for various processes within bulk drug substance management.

Reference:

1. https://www.susupport.com/knowledge/end-to-end-solution/fluid-management
2. https://www.susupport.com/knowledge/end-to-end-solution/safe-handling-bulk-drug-substances
3. https://www.thegenehome.com/basics-of-genetics/disease-examples