Trick not Treat

Thanks to the crack editorial team at the newsletter, FierceBiotech, I learned of a recent publication by several USFDA officials on a topic of interest to me- the strengthening of regulatory authorities in the low- and mid-income countries (FB article).  In their paper (Preston et al. 2012 ), the authors argue that strengthening regulation should be a “global health priority” for two reasons, to prevent injury to the US public by poor quality medicines made in these countries (self-serving but understandable) and to assure the quality of much-needed medicines including those purchased by global health programs.  They noted that improved monitoring is needed starting with manufacturing through trials and approval and into the marketplace and that there are on-going efforts (e.g., African Medicines Regulatory Harmonization Initiative) and the multiple challenges to be met.  Noticeably however, the authors do not cite nor propose any specific efforts by the FDA or other parts of the US government.

The points of Preston et al. were reinforced by two papers published in July 2012 and cited in the FB article as well as in a press release (FB press release).  In the first (Bates et al. 2012a), the authors reported that a study of the quality of anti-infective medicines in 17 low- and mid-income countries in cities such as Bangkok, Istanbul, Sao Paulo, Moscow, and Beijing found that only one-third had been approved by a national regulatory authority and/or WHO and a good percentage failed to have required level of active ingredient (4% of approved and 13% of unapproved).  Further, products made (or allegedly made since some could be total counterfeits) in three regions had high failure rates:  26% from Africa, 16% from China, and 4% from India.  In the second paper (Bates et al. 2012b), the authors reported the analysis of antimalarial drugs obtained from pharmacies in four African countries.  The drugs, which contain artemisinin in combination with other drugs, are called ACTs and are promoted by the Global Fund to Fight AIDS, Tuberculosis and Malaria and approved by its Affordable Medicines Facility- malaria (AMFm) as better alternatives to the artemisinin-only drugs to which the malaria parasite has evolved resistance.  Of concern, they found that 40% of the nonAMFm drugs were substandard (not enough active ingredient) and that, also worrying, 8% of the AMFm drugs were substandard.  While some of the loss of quality may have been due to degradation due to storage conditions, the degree of loss (more that 25%) suggested poor manufacture, possibly deliberate.  In addition to these substandard drugs possibly resulting in the death of malarial patients, they may also induce more ACT-resistant malaria and reduce the efficacy of the full-strength products.  As noted by the authors, with more than 100 million ACT treatment ordered through the AMFm for Ghana and Nigeria this year alone, a possible 7 million ineffective treatments is a serious problem.

So much better monitoring of the quality of drugs used against global diseases is needed.  One approach is to strengthen the testing and monitoring abilities of individual countries’ regulatory authorities.  Bates et al 2012a mentioned one US government program, the Promoting the Quality of Medicines in Developing Countries project (PQM) sponsored by the USAID under a five-year, $35 million contract to the US Pharmacopeial Convention (USP) that was granted in 2009 (PQM).  The USP is a non-profit group that sets standards for medicines, food ingredients, and supplements and is self-funded through the sales of those standards to manufacturers around the world.  The PQM’s mission is to work with countries to ensure the quality of medicines essential to USAID priority diseases, particularly malaria, HIV/AIDS, and tuberculosis, but, based on my read of the February 2012 progress report (PQM report), I thought the PQM hasn’t made much progress in the past three years.  Highlights were:  setting up web-based forum for information exchange; helping four national drug-testing labs get international certification; running a communication campaign in Senegal; holding two workshops; and helping the Global Fund set up antimalaria medicine monitoring sites in the southeast Asia.

A WHO-based program seems to be making more progress.  As some readers may remember from a post I did in the summer (“Bottleneckrophobia”), the Prequalification of Medicines Programme (PQP) evaluates generic drugs for the “big three” global diseases for purchase by international agencies like UNICEF, and it also inspects manufacturers and clinical trial companies and certifies national quality control laboratories (PQP Fact Sheet).  In 2011, in addition to approving 35 products, the PQP conducted 90 inspections in 18 countries, ran 32 training courses, and certified six labs, all with a budget of about $10 million per year provided by UNITAID, the global health drug purchase financing group (UNITAID Programs).  In my post I suggested strengthening the PQP approval process with donated expertise from wealthy nations’ regulatory agencies, like the FDA, and the multi-national pharma companies, and generating revenue through “user fees,” like the FDA does, to paid by companies seeking to avoid the expense of country-by-country registration in that with the PQP-approved products would be eligible for purchase by PQP-approved buyers, which would be any government or group able to commit to negotiated volumes and prices.  Clearly my scheme could be extended to include the PQP’s efforts to improve quality assurance in companies and in the marketplace which for honest manufacturers is in their best interest.  As I noted in my previous post, substantial funding and political will are needed to strengthen the PQP and that the WHO has been successful in setting up a similar system for the pre-approval of vaccines for UN supply (WHO vaccine program).  Of course, some backing from the US government and specifically the FDA (Preston et al.?) would likely help.

I’d be remiss if I didn’t mention a neat technological lever that is being applied to the problem.  As I mentioned in my post, “Counter Counterfeiting”, the UK-based non-profit, the Global Pharma Health Fund (GPHF), has designed and is distributing for free “mini-labs,” each of which is a complete set of equipment and reagents for testing 1000 samples of 58 drugs for potency, all packed into two large suitcase-type carriers (GPHF Minilab).  The GPHF reports that it has sent more than 500 mini-labs to customers in 80 countries, but, as far as I can tell, is not collecting data on their use.  In exchange for the free mini-lab, the GPHF should require users to report data.  It could be done through smart phones or web-based programs and would be useful in validating and documenting their utility.  Such data will be helpful should the GPHF decide to market the kits as the worldwide standard approach to verifying drug quality.  Just an idea.

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