In April 2022, just five months after granting approval for use of Covaxin, a COVID-19 vaccine developed and manufactured in India, the World Health Organization (WHO) publicly warned United Nations agencies against procuring the vaccine. An inspection of a Covaxin production facility revealed deficiencies in what are called good manufacturing practices (GMP) – standards that must be met to ensure medicines are produced in hygienic conditions (sterile where necessary) and consistently of high quality. The nature of the deficiencies wasn’t disclosed, but they must be important for public health for the WHO to broadcast this shaming.
Why should this be of concern to Canadians? After all, Covaxin is not approved for use in Canada and is unlikely to ever be.
The concern is that many raw pharmaceutical materials are imported from India to manufacture drugs for use in Canada and many medicines used here are made entirely in India. India is a major exporter of active pharmaceutical ingredients. Canada’s trade data show the total value of these imports in 2021 was more than $13 billion – 84 percent coming from just 10 countries. A third of this total came from the United States, our largest trading partner by far.
All but one of the other nine countries were western European nations. The exception was India. Although pharmaceutical imports from the United States dwarfed those from India, the value from India increased over the last decade by 169 percent – only Belgium had a greater increase. This resulted in India moving from our 13th highest value import country in 2012 to our seventh in 2021.
Pharmaceutical products are sourced from India because they can be made more cheaply there than in Canada and other industrialized countries. But cheapness doesn’t guarantee quality or patient safety.
GMP violations are not new in India’s pharmaceutical industry. Warning letters from the US Food and Drug Administration (FDA) to Indian manufacturers document numerous GMP issues over the last decade. Health Canada has an inspection tracker of drug manufacturing establishments producing pharmaceuticals sold here which, in mid-April 2022, recorded 174 issues; 79 concerned facilities in India, twice the number in the United States. The primary reason for action in over 95 percent of the 174 issues was recorded ambiguously as “general GMP observations.”
Forty-seven issues also included data integrity violations with 26 (55 percent) involving Indian plants. Data integrity violations may sound trivial, but they include wilful deceit, such as making up data to be able to claim a facility is sterile without actually doing the required testing. FDA inspections between 2014 and 2019 show data falsification, destruction or backdating occurred twice as often in Indian drug manufacturing plants as in American and European facilities.
The FDA performs on-site inspections of manufacturing facilities in the United States and abroad. Inspections are unannounced at US plants but pre-arranged abroad, which can allow foreign plants time to remove any evidence of data manipulation, unsanitary conditions or other wrongdoing. In 2014, a pilot program gave Indian facilities short or no notice of inspections and found serious violations increased by almost 60 percent.
Health Canada’s inspection tracker records the source of information about GMP issues as “regulatory partner(s)” for all but one of the 174 issues. Only 11 had an additional source of information. An on-site inspection by Health Canada staff is recorded in just 15 issues, usually as a follow-up to evaluate whether a problem was resolved. On-site inspections are typically pre-announced whether here or abroad. In foreign countries, Health Canada “works in conjunction with international regulatory partners to conduct joint/concurrent inspections,” which is free-loading on other national agencies. The number of foreign inspections performed by Health Canada staff alone is not publicly documented. Domestic facilities are scheduled for inspection every two to four years. The regularity of foreign inspections is unspecified but unlikely to be more frequent.
Canadians rely on the quality of imported pharmaceuticals. If production facilities in other countries are careless or deliberately cut corners in their processes, this can negatively affect the health of Canadians by failing to provide the anticipated therapeutic benefit or causing a toxic effect. For patients, this can mean the difference between life and death.
Canadian patients taking prescription medicines and those prescribing should inform themselves about who inspects production facilities, how often and with what results. Health Canada can and should do more to inform patients and prescribers about the quality and safety safeguards in place in Canada and abroad.
Nigel Rawson is an independent researcher and a Senior Fellow at the Macdonald-Laurier Institute.
John Adams is cofounder and CEO of Canadian PKU and Allied Disorders Inc., a Senior Fellow at the Macdonald-Laurier Institute and volunteer board chair of Best Medicines Coalition. The views expressed are the authors’ own and do not necessarily represent those of organizations with which they collaborate