nnanomedicines workshop 7 Flashcards
what is. nano medicine?
nanomedicines are purposely designed systems for clinical applications,with at least one component at the nanoscale, resulting in reproducible properties and characteristics
- Enhanced solubility and dissolution - Because of the high surface are to volume ratio offered by nanoparticles, the solubility and rate of dissolution can be increased.
- Enhanced drug delivery - The small particle size can prolong a drug’s residence in the systemic circulation, it can modify drug distribution and it may permit drug targeting and transport across biological barriers.
what dies MHRA advise about formulations ?
MHRA reminds healthcare professionals that lipsomes, pegylated-liposomas, lipid-complex and conventional formulations containing the same drug substance are not interchangeable. take care when dispensing nd prescribing. product name and dose should be verified before admin and ma dose shout not be exceeded
What does similar mean in terms of nanomedicines?
A generic should offer the same attributes in terms of quality and efficacy to the reference product
The assessment of equivalence to a reference product for complex formulations is difficult
The use of this approach for nanomedicines have proved to be ineffective
The understanding of how to correctly use, interchange or substitute such medical products in daily practice and clinical route is key (and you need to be able to recognise the complex formulations).
can nanosimailrs be substituted?
No – they can not be interchangeable
Nanosimilars approved by the generic pathway have been shown to be clinically different.
Clinically meaningful quality attributes are not known
Decisions are often made based on drug and not formulation considerations
Often nanoparticle structures cannot be fully quantified and characterised by physicochemical analytical means. A well-controlled robust manufacturing process is fundamental to ensure quality, safety and efficacy.
What is the issue with Nanosimiliars/follow-ons
Like biologicals, nanosimiliars consist of different (closely related) structures that cannot be fully quantitated, characterized or described by physicochemical analytical tools.
The composition and quality of nanosimiliars is dependent on the manufacturing process and controls – just as is the case with biologicals.
Compare of small molecule drugs, biologicals and nanomedicines
small meolcuel are simple well defied whereas nanaomediciens and biologics Complex heterogeneous, defined by manufacturing process
small molecules are well defined whereas biologics and nanaomdeciens are Produced by living cells or organisms and Synthetic technology
small molecule drugs are stable, biologics and nanomdeiciens Generally unstable, sensitive to external conditions
small meocluel - Identical copies can be made
egress nanomedicines Difficult to ensure identical copy versions
what is a critical quality attribute ?
A CQA addresses a physical, chemical, biological or microbiological property or characteristic that should be in an appropriate limit, range, or distribution to ensure the desired product quality.
what are factors that can impact a pharmaceutical quality of a nano medicine?
Chemical composition
Pharmacopoial specifications
*Particle size and distribution
*Particle surface characteristics
*Uncaptured/unencapsulated drug fraction
Storage stability
*nanomedicine-specific criteria
how can quality impact a pharmaceutical nano medicine ?
Particle size and size distribution: influences cell uptake, biodistribution and degradation of nanomedicines and drug PK profile
Particle surface characterisation: morphology and surface can influence cell uptake, biodistribution, clinical efficacy and safety. Pegylation is an important attribute and influences PK.
Unentrapped/uncaptured drug fraction: the PK/PD of the particle vs the drug will be different. We are using the Nanomedicines to control this, so the relationship is important. (important to also consider in terms of stability on storage).
Discuss the risks of interchanging nanosimiliars
Complexity in Replication: Nanosimilars are highly complex structures, and even minor differences in manufacturing processes can lead to variations in efficacy and safety profiles compared to the original product.
Immunogenicity: Any slight alteration in the composition or structure of nanosimilars could potentially be more immunogenic, leading to adverse immune reactions.
Regulatory Pathways: Many regulatory agencies have strict guidelines for approving biosimilars, and these might be even more stringent for nanosimilars due to their complexity, making interchangeability a challenging regulatory hurdle.
Pharmacovigilance: Continuous post-marketing surveillance is crucial to ensure that any unforeseen risks are identified and managed, but this can be more complex with nanosimilars due to their novel properties.
Patient Safety: Without adequate testing and evidence, switching patients from an original nanomedicine to a nanosimilar could compromise safety and effectiveness.
