Harper's most recent remarks on the trade talks have created uncertainty for Canadian egg, poultry and dairy producers, Mulcair writes in a letter to the prime minister.
Supply management relies on marketing boards to control domestic production of eggs, milk, cheese and poultry and high import tariffs to protect against foreign producers.
"I am urging you to commit to defending supply management in its entirety and reassure Canadians that it will be protected in all future negotiations," Mulcair writes in the letter, sent late last week.
"Concessions in supply management sectors could have profoundly negative effects on our regional economies."
Mulcair also stressed the importance of the policy in his home province.
"In Quebec alone, nearly 7,000 family farms exist and prosper thanks to supply management, which also accounts for 92,000 jobs and 43 per cent of total agricultural revenue."
Last Thursday, Harper said Canada is "working to protect" the supply management system while it participates in the trade talks.
"I believe these negotiations are going to establish what will become the basis of the international trading network in the Asia Pacific. It is essential in my view that Canada be part of that — that the Canadian economy be part of that," Harper said.
"At the same time, we are working to protect our system of supply management and our farmers in other sectors."
Max Moncaster, a spokesman for Trade Minister Ed Fast, denied media reports from last week that said the government was prepared to make concessions on supply management.
"Our government is committed to defending our system of supply management," he said in a statement.
"Unlike Thomas Mulcair, who has consistently opposed Canada's free trade agreements and advocated against Canada's economic interests on the world stage, our government will continue to promote Canadian trade interests across all sectors of our economy, including supply management."
The TPP is currently being negotiated by 12 countries including Canada, Australia, Brunei, Chile, Japan, Malaysia, Mexico, New Zealand, Peru, Singapore, the United States and Vietnam.
The government says TPP countries represent 792 million people and a combined GDP of $28.1 trillion, which is about 40 per cent of the global economy.
One of the central complaints from opposition parties has been the secrecy surrounding the talks, which have gone on behind closed doors.
The government has also faced strong opposition from dairy and poultry farmers who want supply management preserved.
Some groups, including the Dairy Farmers of Canada, have expressed concerns about how the trade deal could increase access to the Canadian dairy market.
In a 2014 report, the Conference Board of Canada said supply management "effectively transfers resources from poorer Canadians to wealthier Canadians" and called for the policy to be dismantled or dramatically retooled.
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