Leftover Biosamples: ICMR Guidelines Fall Short
S Krishnaswamy
THE Ministry of Health and Family Welfare (MoHFW) has unveiled the Indian Council of Medical Research’s (ICMR) guidelines for the ethical use of leftover de-identified/anonymous biosamples for commercial purposes. Initially issued via a hastily prepared office memorandum on December 15, 2023, and published without amendments on June 19, 2024, these guidelines detail how leftover biological samples collected for testing can be utilised by commercial entities to develop diagnostics, following the signing of a memorandum of understanding (MoU) with the hospitals or clinics.
The ICMR guidelines ostensibly aim to leverage leftover biosamples for affordable healthcare solutions in India, but they also unfortunately adopt a more lenient approach compared to the stringent US FDA guidelines. This contrast between these regulatory frameworks highlights the need for careful consideration of ethical implications, patient rights, and the potential for exploitation in using leftover biological samples.
Leftover biological samples are the unused portions of specimens collected and analysed for medical reasons that would normally be thrown away if not repurposed. However, portions of biological samples that need to be preserved for legal or technical purposes are not classified as leftover until the required storage duration has elapsed. These biological samples may also be referred to as remnant bio-samples or residual biological materials. Portions of samples that must be retained for legal or technical requirements are not regarded as leftover until the obligatory storage duration has finished.
Leftover specimens are frequently utilised in feasibility studies and for evaluating the performance of new in vitro diagnostic devices. These evaluations typically require specimens with specific laboratory characteristics, such as being positive or negative for a particular disease marker, to meet study inclusion criteria. Routine clinical testing provides information about these characteristics, allowing investigators to quickly determine if a specimen meets the necessary criteria. Consequently, these remnant specimens become valuable for research once they are no longer needed by the patient and are ready to be discarded. The lower cost of these specimens, compared to those collected prospectively for research, makes studies more affordable, enabling manufacturers to conduct research that might otherwise be unviable. Additionally, banked leftover specimens can provide unique and rare biosamples in ample quantities, enabling the swift completion of investigations that would otherwise be difficult.
ANONYMISATION
In medical laboratories, biological samples are frequently associated with different forms of personal data, such as identifiers and health-related information. The nature and accessibility of this data are critical in determining the ethical requirements for sample use. De-identification means the removal of personal identifiers from biological specimens to ensure that the identity of any study participant remains confidential. This process may not require the complete removal of information: in some instances, a coded link to the personal data can be retained. However, this necessitates stringent procedures to ensure that the laboratory does not share the decryption key with the investigator, and the investigator must not have the intention to re-identify the samples. Therefore, leftover biosamples must be entirely anonymous, with no way to trace them back to the original patient.
The ICMR guidelines are designed to advance research and development in diagnostics and treatments by encouraging the use of leftover biosamples, ensuring they are not wasted but instead used to benefit future patients. They also stress the importance of safeguarding patient privacy through strict anonymisation of biosamples. Utilising leftover samples supports research progress, especially in translational and personalised medicine, by providing more representative data and minimising selection bias.
Despite the benefits, the ICMR guidelines have been criticised for lacking punitive measures or fines for misuse. The lack of strict consequences raises concerns that companies might overlook ethical considerations, as they face no financial or legal penalties for violations. The guidelines only specify that products developed must be offered at a low cost, but this requirement is vague and open to interpretation, which could result in inadequate enforcement.
CONCERNS
Although the argument for secondary research on leftover biological samples is compelling, their utilisation must be approached with caution. Individuals visit medical laboratories with the expectation of receiving clinically relevant results, and there are significant ethical concerns about repurposing their biosamples for other uses. The guidelines specifically pertain to leftover biosamples that are irreversibly anonymised and not intended for further research. Hospitals and clinics must ensure robust data security, and companies using these biosamples must maintain transparent communication with these institutions while ensuring that the resulting technologies remain affordable for patients in India. Notably, informed consent is not required for anonymised leftover biosamples, as patients cannot be identified.
There is a risk that the sample could be lost or compromised due to secondary use, which must be avoided to maintain the integrity of clinically relevant tests. For instance, the quality of the clinical test should not be sacrificed to reserve sufficient material for future research. Another associated risk is the inclination to collect more samples—such as drawing extra blood—than what is necessary for the diagnostic procedure. Therefore, it is considered best practice in the laboratory to determine the necessary sample volume before extraction, rather than deciding during the process, which regrettably the guidelines do not explicitly define.
Ethical considerations regarding the use of leftover biological samples can be analysed through the principles of respect for autonomy, beneficence, and justice. The primary concern involves respecting the autonomy of individuals who provide biosamples, as their consent is usually limited to the specific clinical test they sought. Although obtaining informed consent for secondary use of biosamples may not always be practical, efforts should be made to secure it whenever possible.
The story of the HeLa cell line, so named because it was obtained from one Henrietta Lacks without her knowledge or consent, underscores the critical need for ethical considerations in the use of bio specimens. While HeLa cells have made invaluable contributions to biomedical research, the absence of informed consent and the subsequent exploitation of the Lacks family's legacy have ignited continuing debates about patient rights and compensation.
Special care is essential when conducting investigations that generate genomic data, as re-identification of subjects has been demonstrated in genetic studies. While not all information needs to be hidden from the investigator, retaining certain demographic details can heighten the risk of re-identification and potentially expose vulnerable populations. A historical example is the legal battle of the North American Indian Havasupai tribe over the use of their blood samples. Originally collected to test if their Type 2 diabetes was linked to a gene also implicated in another North American tribe, the leftover samples were used in multiple genetic studies without the Havasupai's consent or permission. The publication of these results led to protests from the Havasupai, who felt stigmatised. This case highlights the ethical complexities involved in using leftover biological samples.
The ICMR guidelines' vagueness regarding the requirement for low-cost products, combined with the lack of robust oversight mechanisms, raises concerns about potential misuse driven by profit motives. Without rigorous monitoring, there is a risk of exploiting leftover biosamples in ways that may not adhere to principles designed to protect patient rights and ensure affordability.
or reload the browser
