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Regulatory Approval Testing of Hydroxyapatite – The Benefits of Using One Supplier

Author: Gemma Budd

This work by Ceram is licensed under a Creative Commons AttributionNonCommercial-ShareAlike 3.0 Unported License

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Gaining and maintaining regulatory approval of medical devices and materials, such as Hydroxyapatite (HA) can be a fraught, lengthy and complex process. Submission of data to regulatory bodies, for example the FDA (Food and Drug Administration), has to be credible and fully documented in order to ensure success. Post-regulatory approval testing is also important, not only to confirm that regulatory standards are continuing to be kept but also that consistency, quality and performance are being maintained. In this white paper, Gemma Budd, Product Manager – Healthcare at Ceram, argues the case for using one supplier for regulatory approval testing, using the example of HA testing.

What is HA?
Hydroxyapatite (HA) is a porous form of calcium phosphate present in natural bone. Synthetic HA is widely used as a replacement bone material, mainly for bone fillers, dental repair and metallic implant coatings due to its biocompatibility and bioactivity.

Why Does HA Need to be Tested?
Firstly, different processing techniques, such as chemical synthesis, sintering and thermal or plasma spraying will alter the properties of medical grade calcium phosphates including HA, altering its crystallinity, solubility and/or bioactivity. Moreover, the ability to easily modify its chemical structure means its properties can be tailored to meet specific needs; for example, to form a resorbable network into which bone can grow, or to form an intermediate structure to encourage bone growth onto the surface of an implant. In synthetic products, the calcium to phosphorous (Ca:P) ratio and the processing conditions may result in production of other components, such as alpha- and beta-tricalcium phosphate. These forms of calcium phosphate are both significantly more soluble than HA and need to be carefully controlled. Crystalline must be monitored as non-crystalline material behaves differently and affects the performance and suitability of the material for its purpose. Accordingly, the characterisation requirements of the HA material being used will depend on its application for use, and which properties will affect performance. Characterisation of HA is therefore necessary to ensure that critical parameters are maintained between batches, with tailoring of additional tests to be determined by the product. Similarly, if there is a change to a material or process, ensuring equivalence of the final product compared to the previous batch criteria is required. For regulatory approval in the USA (FDA) or Europe (CE marking), a comprehensive portfolio of accurate, quality controlled data is essential. Therefore, a full validation with a predefined protocol and acceptance criteria is required to confidently show that new products are equivalent to previously accepted products, and importantly, that the risk to the end user is minimal.

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What are the Benefits of Outsourcing to One Supplier?
Perhaps the most obvious benefit is that a tailored package can be designed to show consistency of processing and materials between batches. With all analytical capabilities under one roof, the testing package can cover all testing requirements, from toxicity to performance standards and diagnostic tests. Carrying out all the testing in a package does, of course, bring the added benefit of being able to cross-reference results to refine the testing programme and to facilitate fault diagnosis which will ensure quality control accuracy for data sets. It is one thing to individually quantify the mineralogy, chemistry, crystallinity and particle size, but these all affect the reactivity of HA, and predicting the overall effect of these factors is more difficult. There are standardised methods to assess this, but performing these at different testing houses may offer the potential for variation in methods and therefore in results - and thus invalidate any data. For example, solubility product (defining the Ksp at equilibrium in a defined medium in a defined environment), dissolution rates (techniques described in ASTM F1926 and ISO 10993-14) and bioactivity measurements (technique described in ISO 23317) are all susceptible to variation, and thus performing all testing procedures in one house will minimise the margin for variation and further validate any data generated for regulatory approval purposes. It is imperative that properties of a material, in this case HA, are monitored from batch to batch to ensure the product not only performs to its potential, but also to minimise any risk to the end user. Although the different tests can be performed individually, in different environments, the key to ensuring data is precise and accurate is to collect sufficient results and replicate specific conditions; performing all testing requirements in one place will minimise result variation and allow complete and reliable integration of all data. Having all the testing done under one roof should not only improve the accuracy of the data but, importantly, it should also improve the speed and cost-effectiveness of the process; there is no shipping of multiple sample sets to multiple suppliers or dealing with multiple orders, which also means no having to coordinate communications or generation of samples. Likewise, if there is a query, contact is with one person or one lab only rather than with multiple people across different locations. Finally, third party involvement in the validation of the materials adds credibility to any submission and will ultimately speed up the whole process, getting product to market with minimal delay.

Summary
Bringing new products, materials and technologies to market can be a timeconsuming and costly process. The final hurdle of gaining regulatory approval need not be such a process; outsourcing to one supplier improves efficiency and a costeffective solution with the supplier becoming a necessary adjunct to a manufacturer’s product development team. Furthermore, with the recent issues regarding the safety and quality of medical devices, in particular implants, having reliable and credible data is not only important, it is critical, not only to a product’s performance and safety but also to a manufacturer’s reputation and credibility.

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About Ceram
Ceram is an independent expert in innovation, sustainability and quality assurance of materials. With a long history in the ceramics industry, Ceram has diversified into other materials and other markets including aerospace and defence, medical and healthcare, minerals, electronics and energy and environment. Partnership is central to how we do business; we work with our clients to understand their needs so that we can help them overcome materials challenges, develop new products, processes and technologies and gain real, tangible results. Headquartered in Staffordshire, UK, Ceram has approved laboratories around the world.

About the Author
Gemma Budd Product Manager/Healthcare Gemma Budd has a BSc (Hons) Biomedical Sciences (First Class Honours) from Durham University and has previously worked at AstraZeneca. Splitting her time between the US and the UK, Gemma focuses on identifying new services to help Ceram’s clients differentiate themselves. She helps to ensure that Ceram is at the forefront of new technologies and that it has an in-depth understanding of its markets, thus helping its clients to grow and prosper.

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by Ceram