Medical Device Development
Categories Preclinical Research

Medical Device Development: Design Validation and Preclinical Research

For medical device manufacturers, the preclinical testing of medical device development is most crucial. This is the stage in which they set the design of the product including its functionality and safety aspects and validate the selected materials.

However, their major dilemmas are “When to plan the preclinical stage of the device development?” and “What aspects to consider?”

So, here we answer these questions to help the medical device manufacturers in their preclinical research and design validation.

A Step-by-Step Guide:

1) Review the current industry standards to plan your preclinical research.

2) Consider the following aspects for your research:

a) Material selection: Carefully select the material to be used in the device keeping in mind the factors like its mechanical, physical, chemical, and toxicological properties. Review the current literature to get information about the standard tests, purity, and bio-compatibility studies of the raw material.

b) Manufacturing methods: Since manufacturing processes affect the safety and performance of the device, get as much information as possible on the manufacturing processes.

Evaluate any changes in the manufacturing methods made during the preclinical phase irrespective of whether it will or will not impact the timing of the testing of the device. The manufacturing methods can also change during the post-market phase of the device development. Thus, consider its possibility during the preclinical phase.

Factors such as packaging/sterilization, manufacturing storage instructions, shelf life, transport, and target population should also be considered.

c) Biocompatibility tests: If existing literature doesn’t give sufficient information about a product’s safety, then preclinical biocompatibility testing is also needed.

d) Preclinical study design: After considering the materials, manufacturing methods, and biocompatibility, the manufacturer must also test its performance. First, determine the purpose, aim, and endpoints of the study. The duration of the study is the next point of consideration as this will determine the number of termination intervals needed, which can range from a couple of weeks to several months.

If you only look at the device’s functionality, histopathology of the implant site is sufficient. But, if you plan to prove its safety, it will require body and organ weights, target organ pathology, and a statistical analysis of the data

e) Packaging and sterilization: Select the packaging material based on the product integrity, sterilization method, and product functionality. Your aim is to design a packaging system that is easy to access and protects the product from internal or external breaches in sterility.

It is important to consider packaging materials and sterilization methods early in the design process. Before validation, it’s important to identify the product packaging.  This will help you avoid choosing materials for the device that are incompatible with the packaging and sterilization, and thus, save time.

f) Sterilization validation: For devices that will be sold and used sterile, or cleaned between uses, it’s imperative to choose and validate their sterilization method. This is because sterilization methods can also affect the product’s safety and efficacy. Some of the common sterilization methods are:

  • Ethylene oxide
  • Steam
  • Dry heat
  • Irradiation (gamma, x-ray, or e-beam)

Different methods have different effects on the device material. For example, Ethylene oxide residuals can be toxic, gamma sterilisation can increase cross-linking in polymers, high temperatures may soften or oxidise the material.

Thus, while choosing the device materials, consider its sterilisation method also.

Finally, before planning your preclinical study, also plan out the following to avoid unnecessary delays:

  • Where to submit.
  • When to submit
  • Timelines for all activities like biocompatibility and preclinical studies, sterilisation validation, and written evaluation of existing materials.
  • Compilationof all documents and data

If you pay attention to all these aspects and plan well in advance, your preclinical design validation stage of medical device development will be a great success.

Preclinical Study
Categories Preclinical Research

How to Design a Preclinical Study that makes a Difference?

Many preclinical studies are conducted and thousands of research papers are published every year. However, these publications fail to provide clear information on how the study was designed, conducted, and analysed. They lack the standards of scientific rigour and transparency in their reports. As a result, they lose their value in informing future scientific studies, designing drugs and making policy decisions.

In such a scenario, you can be a role model and increase the potential of your preclinical research by designing robust preclinical studies.

You must plan your experiment before starting. So, here are the tips on how to design a powerful experiment and detect biologically important results.

1) Minimize bias

There’s always the potential for bias when assessing the results of your study, especially if a subjective element is involved.

Therefore, perform the experiment in such a way that the researchers are “blind” to the division of the animals to treatment groups and mouse genotypes.

2) Housing and husbandry considerations

If you use mice with different genotypes in your study, generate similar housing conditions for all. This ensures comparable environment and maternal influences on your animal models.

3) Report your methods and results accurately

Check out Animal Research Reporting of In Vivo Experiments (ARRIVE) guidelines to report your animal research completely and accurately.

Take these fundamental steps to develop robust preclinical studies that use mouse models of human diseases and make a difference in the world of clinical research.

Common Barriers to Preclinical Studies
Categories Preclinical Research

Common Barriers to Preclinical Studies and How to Overcome Them

The scientists, physicians, and academicians who investigate the preclinical studies are busy individuals. They do not involve themselves in one study at a time but in multiple studies. Plus, they have their own clinical duties and responsibilities. This gives them little time to stay engaged in any of the preclinical studies. Thus, a preclinical research study suffers from a poor engagement by its investigators and its progress gets delayed. It can further impact the quality of the research results negatively.

So, how can you improve the investigator’s engagement in the preclinical studies?

Let us first see what are the common barriers to the investigator’s engagement in preclinical studies?

  1. Conflicting demands of multiple job duties
  2. Lack of enjoyment in preclinical studies
  3. Lack of a sound and supportive research infrastructure
  4. Complexities associated with the preclinical research

A comprehensive solution to preclinical research barriers

1) Outsource your lab services to a Contract Research Organization (CRO)

An experienced and a competent contract research organization have the necessary tools and resources to process your research study with accuracy and on time. Thus, investigators who are busy and unable to devote much time to their preclinical studies can avail the services offered by CRO.

However, choose an organisation which has a minimum of 10 years experience in handling scientific research in every domain, can strike a perfect balance between the quality of results and their timely delivery, and observe the best practices and ethics of research.

2) Use a mobile platform to access the research data

In the era of smartphones, investigators can use their personal mobile devices to access the research data and communicate with their team quickly and as per their convenience.

3) Take part in online study-specific communities

Online forums dedicated to your specific research area are available to discuss the research results, share ideas, and stay connected with other like-minded people. They are an excellent medium to share preclinical research data between the institutions and prevent duplicate research.

4) Hire a courier service to pick up study materials

Hire a courier service which can retrieve the study materials from your place and deliver it the off-site for professional processing. After the process is complete, the courier returns the materials to your facility along with a report of the study results. This can save yours and your team’s time so you can focus on your preclinical studies.

The best way to overcome the barriers of your preclinical research study is to take the help of the leading preclinical research services or CRO. Make a list of the services offered by the CRO in your area. By doing so, you can drive maximum engagement from the research investigators and improve your research results.

How Preclinical Gene Models Push Advance Anti Diabetic Research
Categories Preclinical Research

How Preclinical Gene Models Push Advance Anti Diabetic Research?

Ants always eat sweet food but none of them haven’t diabetes?- This could be the longing and despondent statement of any of the more than 300 million individuals worldwide affected by diabetes.

Diabetes is debatably the most critical health care concern that has ignited a global crisis on the fiscal and physical status of all nations of the world. With its intricate association with obesity, hypertension, cardiovascular diseases, cancers, Kidney and Eye disease, Stroke, Alzheimer?s disease and so on, it has become a giant octopus that ruthlessly extends it claws to drill dents in the socio-economic welfare and quality of life. Recently, with the ever increasing incidence of diabetes in children as well, it has become imperative for the health care sector to speed up research on diabetes and identify drug targets that in the long run would emerge as a possible cure for the presently incurable, but manageable disease.

#1 How does diabetic research progress?

Virtually every medical achievement of the last century has depended directly or indirectly on research with animals.?

The truth and weight of this statement can be realized from the Nobel Prize winning isolation of insulin from the pancreas of dogs. Eventually mice became the most preferred animal models that have significantly contributed to the progress in diabetes research as well as in research regarding other diseases. This is because the genome of mice and humans are 90% identical. The striking anatomical, genetic and physiological similarity, cost effectiveness, generation time and life span make them a highly efficient tool in the field of drug development.

#2 What are the most widely used Animal models for diabetes?

In research involving animals, scientists attempt to induce the identical disease features into the mice. In case of the diabetes, the mice are rendered completely devoid of insulin by treating them with chemicals like streptozotocin and alloxan that destroy pancreas, the production house of insulin. Injecting streptozotocin releases toxic levels of nitric oxide that cause DNA damage of the insulin secreting pancreatic beta cells and subsequently kills them. On the other hand, alloxan treatment releases highly reactive and toxic ?free radicals? that ameliorate the pancreas and induce experimental diabetes

#3 Are the currently used models of diabetes research robust?

The applicability of the results of drug testing done on mice models to humans depends on whether the diabetes induced in mice exactly resembles that of the diabetes occurring in humans. So naturally, the question of whether the alloxan and streptozotocin induced diabetes is similar to the human equivalent of diabetes arises. The answer to this question is unfortunately No! Following are disadvantages of using alloxan and streptozotocin induced mice.

  • Hyperglycemia develops due to the killing of insulin producing beta cells of pancreas. However, another major pathogenic feature of diabetes is insulin resistance- the inability of liver, muscle and other cells to properly use the secreted insulin. This core feature of type 2 diabetes mellitus is not captured by these animal models.
  • The FDA has directed that streptozotocin induced diabetes model should not be used in preclinical studies involving drug targets aimed at the immune system in type 1 diabetes. This is because type 1 diabetes involves the autoimmune destruction of pancreatic beta cells which is not reflected in the streptozotocin model of diabetes.
  • Diabetes induced by chemicals is reversible because of the development of insulinoma and spontaneous beta cell regeneration which poses a big problem during long term studies
  • The results of experiments done on chemically induced diabetes models show high variability in terms of hyperglycemia development
  • There is a high incidence of liver and kidney tumors in these animals
  • The dose and time of streptozotocin required to induce diabetes is still not standardized
  • A high degree of lethality is found in case of alloxan induced diabetes mellitus.

#4 What alternatives does preclinical research provide?

Hence an animal model with pathologic features resembling type 2 diabetes is highly important. A proven strategy superior to chemically induced models to study both type 1 and type 2 diabetes is the use of genetic mouse models.The following genetic animal models are invaluable in pre-clinical diabetes research.

NOD (Non-obese diabetic) mice: These mice have the characteristic features of autoimmune type 1 diabetes like the infiltration of pancreatic cells by leukocytes and insulitis development. These mice are produced by mutating the CTLA-4 gene that play an important role in suppressing the immune response of the T cells. Without a functional CTLA gene T cells attack the insulin producing cells resulting in type 1 diabetes. This mice could provide important data on the pathogenesis of type 1 diabetes.

ob/ob mice: Developed by introducing a mutation in the leptin gene, these mice are a highly useful model to study type 2 diabetes as they display hyperphagia, hyperinsulinemia, hyperglycemia, hyperlipidaemia, insulin resistance and so on that mimic a type 2 diabetic individual.

db/db mice: These mice harbor a mutation in the leptin receptor gene and are the best model to study obesity induced insulin resistance as they display increased body weight, insulin resistance, hyperphagia, hyperinsulinemia, hyperlipidemia and so on.

The Zucker rats (fa/fa): These are excellent rat models in obesity research which demonstrate hyperlipidaemia and hypertension apart from increased body weight. Additional features like hypertrophy and hyperplasia of the adipose tissue shown by these rats makes them outstanding models for obesity and diabetes research.

Apart from these sophisticated invivo animal models, cutting edge biomedical research could be done with the additional support of invitro and ex-vivo models. Interesting research questions on diabetes associated complications can be addressed using high end facilities designed for thrombosis, orthopaedic, vascular and macular degeneration research. Further liver, adipocyte, PBMC cell lines facilitate the invitro confirmation of the results of animal experiments in diabetes and vice versa. Other cell lines like chondrocytes, glial cells, spleenocytes, and Caco2 could be used to study a variety of other metabolic disorders. The world of animal research is expanding in leaps and bounds every day and the successful outcome of a Diabetic NCE is highly dependent on the use of genetically engineered animal models.