**7. Role of healthcare systems**

*Advances in Hematologic Malignancies*

parameters define quality of generics.

**5. Challenges for switch and adoption**

and substitution with generics and biosimilars.

**6. Efforts by companies and physicians**

**4.4 Quality**

real-world settings with these products. Economic efficiency is not solely determined by the relative costs of generics and comparators. It is ideally defined by the attainable levels of efficiency and safety with the use of lower-priced options. This eventually constitutes the quality of the generics and biosimilars [30]. In a cost minimization study in Colombia, use of generic equivalents of bortezomib, decitabine and capecitabine resulted in substantial savings of 63% (USD 4.68 million), 26%

Quality is a key parameter that impacts the utilization of generics. It is important to understand the perceptions about quality of generics and also define what

The regulatory standards for approval of generics and biosimilars are guided by the principles of quality by design (QbD) [32]. This implies that science-driven and risk-based concepts underlie the development, scale-up, and manufacturing of generics and biosimilars. The yield of this approach is a high-quality generic product or biosimilar molecule with an implied clinical equivalence which may be validated in research studies and clinical experience. Quality is not alone limited to structural and chemical similarities during development; it also spans to the similarities of generic drugs to comparators in final formulations and packaging. Quality is also defined by testing for stability, sterility, and impurities. These data are an important and mandatory component of abbreviated new drug applications (ANDAs) [33]. The WHO has defined standards for good manufacturing practices

(GMP) as a guide to the quality assurance of pharmaceutical products [34].

With the prevalent perceptions about generics, there are several likely challenges that physicians and patients can confront for the adoption of these drugs. Observational studies have confirmed doubts and unfavorable attitudes in physicians, pharmacists, and lay people for the effectiveness, safety, and quality of generic medicines [27]. There may be questions regarding the dependable and acceptable evidence for the effectiveness and safety of generics and biosimilars. There may be uncertainties regarding the acceptance of bioequivalence as a marker of similarity. These uncertainties may lead to cohesive discussions in media and scientific platforms which in turn may influence the decision-making for switch

Physicians may want to go for facility visits to understand and inspect the development and manufacturing of generics. This can build trust in the products and facilitate their early and easy adoption. Consistent product supply may be taken as a proxy to dependable quality and this can safeguard the trust in the product of a particular supplier. On the other hand, physicians may feel reassured regarding safety if the generic or biosimilar has been approved in a regulated market with

Physicians should make sustained efforts to discuss the most cost-effective therapeutic options with patients and help them to achieve desired outcomes at lower costs [35, 36]. This may be an important aspect of therapy in low income

clear guidance for development and approval of these products.

(USD 0.29 million), and 46% (USD 1.50 million), respectively [31].

**142**

Healthcare systems should prepare for increased adoption of generics and biosimilars by procurement and formulary management, continued safety surveillance, and transformational reforms for mitigating the economic and operational challenges. A healthcare system should aim to allow an equitable access to essential medicines of assured quality, efficacy, and safety [39]. Policies and programs should aim to not only improve access but also build trust in medicine quality and healthcare systems [40].

Procurement of high-quality generics is the first and key step that acts as a gatekeeper to the access and adoption of generics and biosimilars in a particular country. These practices need to be standardized and implemented as nation-wide initiatives for successful utilization of generics. Efforts should be made to develop and design a prequalification scheme to assist countries lacking strong regulations in procurement of anticancer generics and biosimilars of assured quality [13].

Regulators are making constant efforts to improve the knowledge and understanding for the development and clinical use of biosimilars. In collaboration with the European Commission, the EMA has formulated an information guide for healthcare professionals to educate them about the development, approval, effectiveness, safety, switch, substitution, and interchangeability of biosimilars [8]. Such efforts need to be replicated by the healthcare systems in countries with poor regulations. Manufacturers can collaborate with the healthcare systems to plan and implement educational programs for physicians, pharmacists, and patients. Physicians should be educated for the criteria of equivalence, safety and vigilance, and manufacturing processes adopted for developing high-quality generics and biosimilars.

There is lack of unawareness for the costs of pharmaceutical therapies in physicians [41]. Educational programs should aim to improve understanding for the lower costs of generics and biosimilars and the implications of this on overall cost of therapy.

Payers should be encouraged to develop appropriate reimbursement policies that will encourage the use of generic medicines in routine clinical practice. Further, a pool of generic suppliers should be identified to ensure an uninterrupted availability of these medicines [13]. Generic medicines and biosimilars should be included in the national lists of essential medicines and should be part of national formularies. The integrity of supply chains should be maintained and circulation of counterfeit or substandard products should be discouraged. Lack of constant drug supplies can lead to mistrust in patients and lack of confidence in physicians and healthcare systems. All these factors compromise clinical care in oncology where treatments are phased and last longer.

#### **8. Recommendations**

Most experience about the knowledge and perceptions regarding generics comes from interviews and surveys conducted in cross sections of populations in various

countries [12, 27, 42, 43]. There is lack of a standard approach for the assessment of knowledge, attitudes, and perceptions about generics. In addition, factors impacting the utilization of generics have not been precisely determined. Sustained and collaborative efforts should be made to understand the perceptions for generic medicines and mitigate the same.

Educational initiatives should be introduced by manufacturers of generics and biosimilars and healthcare systems to improve knowledge about these drugs and develop positive attitudes towards their adoption. This will empower physicians, patients, and pharmacists to make rational choices in therapy and improve outcomes of cancer care.

Uniform standards should be developed for high-quality generics and these need to be implemented at global levels. Maiden efforts in this direction include tools like the generic dRug adoption framework (GRAF) (**Figure 1**). This framework, comprising a 20-item questionnaire, has been developed to enable physicians and pharmacists to make decisions to identify and differentiate high quality generics and facilitate interchangeability. Currently available in three languages (English, Spanish, and Portuguese), the framework has successfully been implemented in Brazil and Colombia. More and more countries should adopt such objective measures to evaluate the perceptions and adoption of high-quality generics. Insights gained from the experience of such frameworks can help to make further reforms to allow the identification, procurement, and prescription of high-quality generic medicines. This can advance the use of cost-effective solutions in cancer care.
