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Indian Journal of Pharmacology, Vol. 43, No. 3, May-June, 2011, pp. 362-363 Letter to the Editor Biogenerics: Are we ready to take safety challenges in India? Salil Budhiraja, Raghuram Akinapel Department of Pharmacovigilance and Drug Safety, Makro Care, Hyderabad, India Correspondence Address: Salil Budhiraja, Department of Pharmacovigilance and Drug Safety, Makro Care, Hyderabad, India, salil_budhi@yahoo.co.in Code Number: ph11098 DOI: 10.4103/0253-7613.81493 Sir, Biogenerics are biological products manufactured after expiry of the patent of innovator biopharmaceuticals. Biogenerics, also known as Biosimilars (in Europe), Follow-on-biologics (in the US), and subsequent entry biologicals (in Japan) are effective treatment for a number of serious and life-threatening illness because of their high specificity and activity. India is growing in the arena of developing and marketing biogeneric products. In 2008, the Indian market was estimated to be $200 million for biogenerics, which is likely to increase to approximately $600 million by 2012. [1] Although the use of biogenerics has increased sharply in India, are we really ready to answer their safety concerns? Biogenerics are more complex compared to small molecule drugs. Their quality and safety are highly dependent on the process of production (choice of the cell type, development of the genetically modified cell for production, etc), purification, and formulation. Small changes can have significant effect on the safety and efficacy parameters of biogenerics as shown by a few instances in which manufacturing changes in the innovator process of biologicals have led to unforeseen adverse events. For instance, more than expected cases of pure red cell aplasia were seen after administration of different formulations of epotein sold outside the US. [2] Although Indian pharmaceutical industries have good state-of-the-art buildings and manufacturing processes, it is also obvious that the USFDA has identified several irregularities in manufacturing plants of some of the top pharmaceutical industries during inspection and has issued letters and taken regulatory actions. [3] As production process plays an important role in the safety of biogenerics, it is really a concern for the safety profile of biogenerics in India. Biogenerics are higher-rewarded but higher-risk products when compared to classic generic drugs. Experiences related to biogenerics and regulatory guidelines in a regulated market are not as old as compared to conventional drugs. Currently, regulatory bodies insist on additional pharmacovigilance and risk management plans (medication guide, patient package insert, communication plan to health care provider, special certified health care provider, pharmacies and healthcare settings for dispensing and prescription, certain monitoring of patients, enrolling patients in registry and timely assessment at 1.5, 3, and 7 years, and submission of details of these activities) along with routine pharmacovigilance activities (spontaneous adverse drug reactions reporting and periodic safety update reporting) [4] to establish their potential risks, safety, and missing information. Although safety information is collected in different phases of clinical research, because of constraints of limited exposure, time, non-inclusion of vulnerable population, etc, energetic and proactive plans are required for safety monitoring post marketing. India is still in infancy in the area of pharmacovigilance. Pharmacovigilance system is handled by the Drug Controller General of India (DCGI), which manages regulatory approval of drugs and clinical trials. A well developed pharmacovigilance system is also lacking in most Indian pharmaceutical companies. Basic understanding about pharmacovigilance by healthcare professionals and consumers and motivation is almost negligible. Also, there is a scarcity of pharmacovigilance experts in India. For a product′s safety we rely on data from the other countries. Recently, sibutramine, R-sibutramine and rosiglitazone were withdrawn from the Indian market based on foreign data. [5],[6] Although we have experienced human resources, proper infrastructure and funding are lacking and under reporting exists. [7] By definition, biogenerics will only be similar, but not identical, to the product they seek to replicate. So, switching patients from one product to a similar but "not quite identical" product may have undesirable consequences. When faced with the possibility of substituting an originator product with a biogeneric product, it is important to carefully consider the potential risks to the patient, such as that of an immunogenic response to a different molecule. A classic example to illustrate that the safety profile of a biosimilar will not be identical to that of the reference product is the biosimilar growth hormone - Valtropine - that has different precautions and warnings than its reference product Humatrope. This is a likely consequence of the different cell lines. [8] Shifting between biopharmaceuticals with the same active substance may further complicate the causality assessment, especially in case of ADRs with a long latency period between exposure and occurrence of the ADR. Hence, physicians need to regularly update their knowledge for different safety concerns over biogenerics and must closely supervise patients while switching over to these. In India, physicians are not able to spend quality time with patients, which results in a compromise on the safety concerns with an increased frequency of litigation against healthcare professionals and outcry in newspapers. [9] The effects of biogenerics depend on their structural integrity, and any factors causing physical and chemical instability alters the three-dimensional structure and folding pattern of proteins, which may lead to severe immunogenicity reactions. The chemical instability is caused by numerous chemical reactions and the physical instability by improper storage and handling factors. [10] Hence, maintaining and manufacturing instructions should be followed strictly to maintain their safety, purity, and potency. In India, stability and storage specifications to be followed for biogenerics may be a big challenge because of insufficient power supply and storage conditions. Also, it has been observed that market for resale of expired drugs with compromised safety and efficacy is mushrooming in India. This may be a safety concern for biogenerics. The biogenerics market is continuously growing in India at astronomical rate due to its important treatment options for a number of chronic and drug-resistant illnesses with their high specificity and activity. As discussed earlier, this can lead to serious safety problems unless adequate care in the drug development and manufacturing is taken. Hence, while using biogenerics we should keep in mind that - "first do no harm". References
Copyright 2011 - Indian Journal of Pharmacology |
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