• Increasing prices, quality, and efficacy of alternative brand affect patients

In the battle against cancer, access to life-saving medications is paramount. However, for many patients in Sri Lanka, obtaining crucial medicines like trastuzumab has become a harrowing ordeal, marred by scarcity and exorbitant prices.

In Sri Lanka, trastuzumab, a vital treatment for HER2-positive breast cancer, has become a symbol of the challenges faced by cancer patients in the country. With a staggering price tag of approximately Rs. 95,000 for a 440 mg vial in the local market, this essential medication is financially out of reach for many.

What is more concerning is the scarcity of the original brand of trastuzumab. According to a pharmacist based in Colombo, the available brand in the market is sourced from India and is not the original brand previously accessible to Sri Lankan patients. This substitution raises questions about the quality and efficacy of the alternative medication.

The pharmacist revealed broader issues plaguing cancer care in Sri Lanka, such as the lack of proper procedures to import essential medicines, particularly those needed in relatively low quantities. Trastuzumab, like many other cancer medications, is subject to these logistical challenges, resulting in its classification as a ‘baggage medicine’.

Shockingly, trastuzumab has found its way into the illicit networks of the black market, where prices soar even higher, exacerbating the financial burden on patients already grappling with the challenges of battling cancer.

“There’s a huge difference between the prices of these medicines when purchased through the open market and the black market,” lamented the pharmacist. 

Elaborating further on the need for Government involvement in uncommon medicines such as cancer medications, the pharmacist emphasised that many cancer patients were in desperate need of specific medicines. When these medications are not available in the open market, patients tend to resort to purchasing them on the black market at any given rate. This has been exploited by the black market, the pharmacist stressed.

Concerns regarding procurement process

Trastuzumab is a monoclonal antibody designed to target and neutralise the Human Epidermal Growth Factor Receptor 2 (HER2)/neu receptor, which is often overexpressed in certain types of cancers, particularly HER2-positive (HER2+) breast cancers. This overexpression can lead to uncontrolled cell proliferation.

The original product, Herceptin (trastuzumab), was developed by Roche and received approval from the US Food and Drug Administration (FDA) in September 1998 and from the European Medicines Agency (EMA) in August 2000. Herceptin has been a significant commercial success, with worldwide sales reaching CHF 7 billion ($ 7.5 billion) in 2018.

Despite being a highly-sensitive and costly medicine, concerns have been raised regarding the approval process for bringing trastuzumab to Sri Lanka.

The National Audit Office (NAO) in its audit of the State Pharmaceuticals Corporation (SPC) in 2019 highlighted several concerns regarding the procurement process for trastuzumab. The audit revealed that the SPC had purchased 8,945 trastuzumab injections from a local supplier, under the trade name Herticad, in 440 mg vials with solvent in 20 ml vials on 14 instances between 2018 and 2019, totalling a staggering sum of Rs. 891.18 million.

One major issue highlighted was the composition of the Technical Evaluation Committee responsible for assessing the procurement. Despite regulations stipulating the appointment of a committee with five members, including two consultants, due to the procurement value exceeding Rs. 50 million in 13 out of the 14 instances, the SPC had appointed a committee with only three members. 

Furthermore, only one consultant, nominated by the Chairman of the SPC, had provided technical assistance to the committee for all 13 procurements, which raised concerns about impartiality and expertise.

The audit also revealed that bids had been rejected based on the recommendation of the consultant, citing the lack of prior experience with the specific pharmaceutical products of the lowest bidder. This had resulted in an additional cost of Rs. 230.86 million to the corporation.

Moreover, despite the maximum control price set for trastuzumab injections at Rs. 95,000 per unit, payment had been made for 500 units at Rs. 135,900 per unit in a purchase order issued on 4 September 2018, resulting in an excess payment of Rs. 20.45 million.

The audit report raised concerns about the transparency, efficiency, and adherence to procurement guidelines in the purchasing process of trastuzumab. It emphasised on the need for proper oversight, adherence to procurement regulations, and accountability to prevent wastage of public funds and ensure the availability of essential medications for patients in need.

More discrepancies revealed

Meanwhile, in the 2022 audit report, the NAO revealed further discrepancies in the procurement process related to the purchase of 500 units of trastuzumab (440 mg) injections worth Rs. 26.225 million for the medical supply sector.

According to the report, the selected bidder had submitted a registration certificate issued by the Secretary to the State Ministry of Pharmaceutical Production, Supply, and Regulation instead of the required certificate from the National Medicines Regulatory Authority (NMRA). Furthermore, the certificate submitted had expired, indicating a lapse in compliance with regulatory requirements.

Despite the recommendation of the Technical Evaluation Committee to award the bid to the lowest bidder contingent upon the submission of a valid registration certificate from the NMRA, the ministry Procurement Committee had decided to award it to a bidder who did not fulfil this requirement.

When contacted by The Sunday Morning, NMRA Chairman Dr. Ananda Wijewickrama stated that there were four brands of the medicine registered in Sri Lanka, each under different companies. He emphasised that the quality of the brands was equal and that there had been no complaints regarding medicine quality recorded with the NMRA yet.

“Four different companies have registered to import four different brands. NMRA approval has been granted following the quality checks of the four brands,” Dr. Wijewickrama said.

When contacted, All-Island Private Pharmacy Owners’ Association (AIPPOA) Secretary Manjula Jayawardena informed The Sunday Morning that the association had repeatedly raised concerns with the authorities over the lack of proper procedures for importing specialised cancer medications. However, the authorities are yet to respond.

“Besides trastuzumab, there are a number of other cancer medications that require a proper mechanism to enter the country. Most of these low-quantity medicines are not appealing to pharmaceutical companies as they are profit-oriented. Therefore, there needs to be a system within the Government to facilitate the importation of these medicines,” he stressed.

A matter of patents

Patents protecting Herceptin have expired in Europe as of July 2014 and were set to expire in the US in June 2019. This has paved the way for the development and approval of biosimilar versions of trastuzumab. Several trastuzumab biosimilars have been approved or are in various stages of development by different pharmaceutical companies.

Several pharmaceutical companies have developed biosimilar versions of trastuzumab, a monoclonal antibody used to treat HER2-positive breast cancer. 

Actavis/Amgen submitted an application for approval of Kanjinti to the FDA, but faced rejection in June 2018, citing the need for additional technical information. However, Kanjinti received approval from Health Canada in October 2020. 

Biocad’s trastuzumab biosimilar, Herticad, obtained approval in Bosnia and Herzegovina in March 2020. 

Biocon/Mylan encountered challenges with their application process in Europe. Initially submitted to the EMA in August 2016, their application was withdrawn due to procedural requirements. After addressing these issues, they resubmitted their application in December 2017 and eventually received a positive recommendation from the CHMP for their trastuzumab biosimilar, Ogivri, in October 2018. Ogivri received approval from the FDA and Brazil’s ANVISA in December 2017 and from the EMA in October 2018. 

Celltrion’s trastuzumab biosimilar, Herzuma, gained approval from the Korean Ministry of Food and Drug Safety (MFDS) in January 2014, followed by approvals from the EMA in December 2017 and the FDA in December 2018. 

Pfizer’s trastuzumab biosimilar, Trazimera, received approval from the EC in July 2018, Japan’s MHLW in September 2018, the FDA in March 2019, and Australia’s TGA in August 2019. 

Samsung Bioepis’ Ontruzant was approved by the EMA in November 2017 and by the FDA in January 2019, while Samfenet (SB3) gained approval from MFDS Korea in November 2017. Ontruzant was launched in the US in April 2020 and in Brazil in September 2020. 

Shanghai Henlius’ Zercepac received approval from the EC in July 2020.

(Source: US National Library of Medicine)