LAGOS, Nigeria — In the past few years alone, money and expertise have been invested into overcoming Nigeria’s position as the second largest contributor to maternal mortality worldwide, through initiatives such as the World Bank-supported Saving One Million Lives Initiative Program-for-Results project and the United Kingdom government-funded Maternal, Newborn and Child Health Programme.
While increasing the capacity of health care workers and facilities are sure to have helped, one often-overlooked factor in health programming could be hindering progress: The quality of medicines such as life-saving oxytocin. Recognizing this, Nigeria’s health community is now taking huge steps to tackle poor-quality oxytocin and advance maternal health.
What is oxytocin?
Recommended by the World Health Organization as the most effective and safest drug of choice for the control, prevention, and management of postpartum hemorrhage — the leading cause of maternal mortality globally, particularly in Nigeria and other low- and middle-income countries — oxytocin is a life-saving commodity. When oxytocin is not effective, women can die during childbirth from uncontrolled bleeding or experience an unnecessarily prolonged labor.
The current likelihood of a woman receiving poor-quality oxytocin during labor in Nigeria is extremely high, according to Dr. Chimezie Anyakora, chief of party in Nigeria for the Promoting the Quality of Medicines, or PQM, program, funded by the U.S. Agency for International Development and implemented by USP, a global health organization.
How can Nigeria improve oxytocin quality?
In 2016, the PQM program — which aims to improve regulatory and quality assurance systems and manufacturing while ensuring the quality of medicines in low- and middle-income countries according to international quality standards — in collaboration with Nigeria’s National Agency for Food and Drug Administration and Control conducted a survey analyzing oxytocin at different points in the supply chain. The NAFDAC/PQM survey found that almost 75 percent of oxytocin was of substandard quality in Nigeria. This could be due to poor manufacturing, storage, and distribution, including a lack of accountability and general awareness about how to store oxytocin.
Unlike other medicines, injectable oxytocin needs to be stored below 8 degrees Celsius. Exceeding this temperature at any point in the supply chain can reduce its quality or render it ineffective. Therefore any efforts to improve maternal health care are impeded if the cold chain of this commonly used medicine is not maintained.
For Nigerians, the main sources of oxytocin are from overseas manufacturers, meaning there are ample opportunities for the cold chain to be broken from manufacturer to mother.
Professor Osato Giwa-Osagie, founder of the Omni Medical Centre and Advanced Fertility Clinic and renowned gynecologist in Nigeria, recounted such a story from his examination room in Lagos.
“There was a patient here in a small private hospital where, on a Sunday afternoon, I had to go and look for genuine oxytocin because the one they had bought from their supplier was not working,” he said. “The woman was not bleeding, but she had a prolonged labor. Once the good [quality] oxytocin was put in, the baby was delivered in two to three hours, so we potentially saved the baby and the mother’s life.”
Having identified the scope of the problem, USP's PQM project, alongside NAFDAC, began a number of actions to tackle the issue.
1. Working with a local manufacturer to produce quality oxytocin
By having a manufacturer closer to the patient to supply oxytocin, the time required for intercontinental travel and time the medication subsequently sits at Nigeria’s ports or airports is eliminated, as is the risk of degradation. It also assures a predictable supply of oxytocin.
The likelihood of high-quality is further increased together with NAFDAC’s work conducting postmarketing surveillance, taking regulatory actions when needed, monitoring threats to quality, and applying resources to high-risk areas within the supply chain. A Nigerian manufacturer can also be held more accountable should substandard medicines enter the system, Giwa-Osagie noted, given that affected patients and health care staff can directly contact the factory, or indeed NAFDAC, to request further testing.
The prefilled syringe machines needed to manufacture such a product come at a high cost, which is why very few African manufacturers have produced oxytocin. However, following the research, USP, through the PQM program, supported local manufacturer Juhel in building its capacity to produce oxytocin. According to good manufacturing practices, Juhel is the first local manufacturer to obtain NAFDAC approval to market oxytocin to the African continent and beyond. In May, Juhel launched its own oxytocin injection business.
“We manufacture them [oxytocin] in Nigeria, we keep them at the required temperature, we follow up with distributors and consumers, and follow up with the patient,” said Dr. Ifeanyi Okoye, chief executive officer of Juhel.
“We keep regular monitoring of temperatures wherever our oxytocin goes, and we believe, with this, Nigerians will receive the right quality of oxytocin at the right time.”
Nigeria’s Ministry of Health director of family health, Dr. Adebimpe Olugbeminiyi Adebiyi, agreed: “It’s actually the way to go because you cannot rely on another country for something that is a life-saving commodity for your country,” she said at a press conference to mark Juhel’s oxytocin release last month. “It’s better to source it locally so that you can be sure of availability and assure affordability.”
That’s just one part of the problem, however. Once leaving the factory gates, oxytocin then faces a challenge in reaching the patient in optimal condition.
2. Securing the supply chains
“When it’s not stored properly, it’s not going to be effective. There’s no magic about it, it’s what happens and we all understand the chain of events that could happen if it’s not effective,” said Dr. Chioma Ejekam, a public health medicine specialist at Lagos University Teaching Hospital.
Giwa-Osagie also outlined the country’s so-called “fake pharmacies” as contributors to the problem.
“The shop itself is not even air-conditioned and they bring out the unrefrigerated product from some box under the table,” he said, and while a person with at least some medical training should be running a pharmacy, this often isn’t the case. “Nothing is being done. They don’t store the medicine at the right temperature.”
To ensure a quality product, Juhel — again with NAFDAC and PQM’s help — adopted a strict auditing process for their distributors, along with the medical facilities and pharmacies it supplies, before allowing them to stock oxytocin.
“Where they don’t have facilities to store, we don’t sell. We advise them on what to do — you get a generator, we buy a chiller, and then we supply you our oxytocin,” explained Juhel’s Okoye.
Juhel buys chillers and mini generators for facilities believed to be committed to maintaining the medicine’s low temperature. The manufacturer also trains health care practitioners at these sites on cold storage techniques, given that health care practitioners often don’t realize this medicine requires specific storage conditions. A recent study found that only 52 percent of health care providers in Lagos State know the proper storage procedures for oxytocin.
And although health care workers in hospitals understand storage requirements, Ejekam, the lead researcher on the study, said that workers don’t typically question the medicine’s quality when it isn’t effective.
This presents a challenge if Juhel wishes to expand its supply zone beyond Nigeria to neighboring countries.
3. Providing guidelines for reporting suspected poor quality
Health care providers “need continued training on drug safety monitoring and a line of reporting so that if, when we are using medicines and we are not getting results, we begin to ask questions,” Ejekam explained, citing that 64 percent of health care workers believed they had no way of reporting the perceived ineffectiveness of the drug.
If no one reports when oxytocin is failing, that same batch could continue to be used — instead of being replaced — leading to more unnecessary deaths. This is why NAFDAC released guidelines on how to report suspected poor quality and therapeutic ineffectiveness.
“If there isn’t a guideline, people won’t be held accountable so there is need for a unified guideline, continuous training, supervision of manufacturers, and improving adherence to good manufacturing practices,” continued Ejekam.
“Most people rarely attribute treatment failure to poor-quality medicines, yet it is a significant contributor particularly in low- and middle-income countries. The importance of medicine quality cannot be overemphasized. Whatever we are doing in the health sector, addressing medicine quality is an imperative.”— Dr. Chimezie Anyakora, chief of party at PQM
4. Strengthening medicines regulation
“Good medicines regulation translates to quality-assured medicines for the patients,” said Ejekam, adding that by making quality oxytocin a responsibility — not just for the manufacturers but for all — the likelihood of a patient receiving an ineffective dosage is reduced.
The PQM program has been working to advance national policies for quality assurance of medical products. It has contributed to Nigeria’s first documented quality assurance policy, which mandates testing, sampling, and other safeguards along the pharmaceutical supply chain. The program is also improving awareness and capacity to detect substandard, falsified, and unapproved medical products in Nigeria’s quality control laboratories, so NAFDAC can then recall poor-quality products from the market.
“Most people said you can only guarantee the quality of the cold chain at the point when they send to the distributors. But the government said ‘no, going forward we need to protect the product,’” said PQM’s Anyakora. “You cannot expect a patient or doctor to test every medicine. With government, we are developing a system of quality medicine.”
Introduced in 2015, the national policy combined with the actions taken by the USP, USAID, and NAFDAC, are expected to have long-term benefits says the ministry’s Adebiyi.
And PQM’s advice to other countries with poor maternal mortality rates?
“Take steps to assure medicine quality,” said Anyakora, explaining that the importance of medicine quality cannot be overemphasized.
“Some people spend time in tough terrains trying to solve tough problems but get negative results. I always ask, have you checked medicine quality? Most people rarely attribute treatment failure to poor-quality medicines, yet it is a significant contributor particularly in low- and middle-income countries. Whatever we are doing in the health sector, addressing medicine quality is an imperative.”