Despite Reforms, WHO ‘Prequalification’ Program for Vital Medicines and Diagnostics Is Inconsistent and Full of Delays

Recent reforms to the World Health Organization “prequalification” program that certifies the safety and efficacy of health products procured in bulk by donors for low and middle-income countries have speeded up the process and thus accelerated access to lifesaving medicines and diagnostic tools in low- and middle-income countries.

However, long lead times for product approvals, averaging 17 months, as well as a lack of transparency and clarity about the process, can delay procurement of critical health products for countries in need.

The lack of clarity about certain steps in the process can also be confusing for manufacturers seeking WHO’s “PQ” label in order to sell their products in bulk procurement deals to global health agencies such as Gavi, the Vaccine Alliance or The Global Fund to Fight AIDS, Tuberculosis and Malaria. 

These are the key findings of a report released by the Global Health Technologies Coalition (GHTC) and the Duke Global Health Innovation Center (GHIC) that reviewed the WHO prequalification program. 

WHO Prequalification – a backbone of global health procurement

Since the late 1980s, WHO has managed its “Prequalification” programme for drugs, vaccines and certain diagnostics as an international seal of approval attesting that products meet acceptable standards for the way they are manufactured and how they function. The “PQ” label is the basis under which national governments and donor-based organizations such as the Global Fund can reliably procure the products in bulk from an approved list of manufacturers.   

“The WHO Prequalification Program certifies the safety, quality, and efficacy of drugs, vaccines, diagnostics, vector-control products, and devices to address a range of deadly diseases and conditions, ranging from HIV/AIDS, to newborn infections, to COVID-19,” said Elina Urli Hodges, assistant director of programs at Duke GHIC.

“Over the years,” she said, “the program has expanded in scope to respond to the changing needs and demands of WHO member states and UN procurement agencies and to support the response to public health emergencies.”

WHO’s recent reforms to the program have further helped to “speed access to health technologies through expedited reviews of safety and efficacy,” Jamie Bay Nishi, executive director of GHTC, said in a press release.But we also identified issues that can be confusing for product developers and thus impede approvals.”

These issues include uncertainties regarding WHO review timelines; high data and evidence standards data needs; and how prequalification is impacted by other WHO processes.

The report analyzed the review timelines for two dozen WHO prequalified products. Experts from GHTC and GHIC also conducted interviews with WHO staff, product developers and regulatory experts.

Market of $3.5 billion, over 1,125 products prequalified

Over 1,125 products have been prequalified by WHO, from 1987 to April 2022

WHO has prequalified more than 1,125 products since the assessment program began in 1987, according to the report. 

The programme has fostered a market of $US 3.5 billion worth of health products in low- and middle-income countries and “spurred the development of products that would not otherwise have been developed for LMIC settings, raised manufacturing standards in LMICs, and enabled access to significant procurement tenders from various aid agencies,” the report concludes.

And with drugs, vaccines and other medical innovations emerging from so many different countries today, Nishi noted that efforts to accelerate global access to them, which has been a critical feature of the COVID-19 pandemic, requires “a trusted authority” that can vet safety and efficacy.

“The WHO prequalification process gives aid agencies and governments in low- and middle-income countries confidence that they are purchasing quality products that have been carefully evaluated by independent experts,” said Nishi. “It removes a major barrier to getting health innovations to people who need them the most.” 

The PQ program focuses primarily on five products: vaccines and vaccine storage equipment; medicines; in vitro diagnostics (tests on blood or tissue); vector control products; and immunization devices.

Product types assessed by WHO prequalification.

Lack of transparency in parts of the process

Since 2010, an average of 47 medicines, 12 vaccines, and 8 in vitro diagnostics have been prequalified each year, according to the report. 

However, it is difficult to evaluate efficiency – since WHO doesn’t provide comparative data on how many applications are submitted and reviewed each year.  That, says the report, is just one example of the continuing lack of transparency in the process. 

There is also inconsistent interpretation and understanding of the types of assessments and their scope that WHO PQ undertakes.

In addition, the role of the PQ process, pathway to approval and eligibility is “not always clear to the broader product development community,” states the report. 

For instance, WHO pre-qualification is not a substitute for WHO expert approval of the safety and efficacy of a vaccine by WHO’s Strategic Advisory Group of Experts on Immunization or of a new drug, which typically must be reviewed and included in WHO Essential Medicines Listing

Rather, once the drug, vaccine or diagnostic has been approved by WHO as efficacious, the prequalification label acts as a mark of quality control of the specific manufacturer and product brand being sold. 

However, in the case of certain types of equipment, for which regulatory approvals don’t exist, e.g. vaccine refrigerators, the onus of approval lies with PQ. Similarly, some devices, e.g. vector control products like bednets, that may not be subject to regulatory review, may still be reviewed and approved by WHO PQ.  

Staff turnover and shortages impede efficiencies 

Along with confusion about PQ’s mission, there is a frequent mismatch between the programme’s goals and its ability to deliver on expectations, the report found. 

It cited continuing challenges for product manufacturers in navigating the PQ process— including inconsistencies in how dossiers are reviewed by consultants; sometimes excessively high data and evidence standards required for dossiers; as well as a lack of understanding of the process stages overall. 

WHO’s excessive use of consultants, in lieu of permanent staff, to support the various stages of PQ review may also result in inconsistent approaches  – due to the consultants’ lack of tenure and familiarity with PQ processes. 

The already short-staffed WHO team also is responsible for communication activities, which places additional strain on their activities.  

“The limited capacity of the staff to perform even essential duties for PQ is exacerbated by increased numbers of dossier submissions during the COVID-19 pandemic,” noted the report. 

This has led to more work, a large quantity of small grants to manage without a grants management team, and continued calls for communication improvements and transparency. 

Prequalification product streams and approval processes 

The WHO prequalification process has several common steps in four of its product streams.

Though the prequalification process varies by product stream, all four streams studied (medicines, vaccines, in vitro diagnostics, and vector control products) have several common steps: assessment of eligibility; dossier submission; dossier assessment; and prequalification listing. 

For a product to start the PQ process, it first has to be deemed eligible. But eligibility for PQ varies by product type and area. While each product type maintains its own criteria for eligibility, it is generally impacted by whether there is enough data and evidence to prove the safety and quality of the product. 

Product developers then submit a dossier with required product information and data to the relevant PQ product stream. Overall, each dossier contains evidence of quality, safety, and efficacy. 

The PQ product stream team assesses the dossier and conducts any other required activities, including manufacturing site inspections, laboratory tests, and field tests. 

Eligible product dossiers are typically prioritized for review in the order in which they were submitted — first come, first served — with exceptions for products needed for public health emergencies like the COVID-19 pandemic or polio resurgence.

Shorter pathways to approval have products prequalified faster 

Alternative pathways led to faster prequalification than full assessments.

Experts found that the health products that proceeded down shorter, alternate pathways (abridged assessments, abbreviated assessments, streamlined procedures) were prequalified in an average of six months.

That is just one-third of the time required for products going through complete, full-assessment pathways that take an average of 17 months to complete. 

Expedited reviews have been welcomed to speed up the process and cope with the needs of health emergencies like COVID-19, however, the normal review time remains too long, the report concludes. But the PQ process has led to knock-on benefits for developing countries. 

In particular, the WHO-led Collaborative Registration Procedure (CRP) helped accelerate the national regulatory approvals of health products in low- and middle-income countries by sharing confidential information from the WHO prequalification process with national regulators. Doing this removes duplication of efforts.  

Accelerated response times and more clarity about process  

The report identifies a series of needed improvements to the WHO PQ programme that it says would enhance communication, improve the clarity of processes, and accelerate request response times.  Those recommendations include: 

  • Transparency: Publicly release performance indicators and launching a public database with complete timeline information on all prequalified products. 
  • Expedited reviews: Support the expanded use of interim or “living” guidelines for novel products. The report notes that WHO recently relied on interim treatment guidelines for COVID-19 therapeutics and the treatment of drug-resistant tuberculosis. This, in turn, allowed for the products in question to be submitted more rapidly for WHO’s prequalification. 
  • Feedback: Provide opportunities for external stakeholders to inform prequalification processes and strategy, such as feedback from product developers, regulators and others, as well as expanding country and product developer participation in WHO’s CRP, given its success in speeding regulatory approvals.
  • Reduce reliance on consultants: Adopt a new policy enabling the prequalification program to hire additional permanent staff and reduce reliance on consultants. 

“Our research unearths important advances the WHO prequalification program has made in enabling greater access to lifesaving health products in low-income countries,” Hodges said.

“But by adopting additional stepwise changes to the way it communicates and engages with developers and regulators,” she said, “we believe the program can better deliver on its mission to make quality essential medical products available to all who urgently need them.”

Image Credits: Marco Verch/Flickr, GHTC.

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