A very interesting and not widely known document on drug safety was released in 2010/2011 on Good PV Practices for the Americas. It was prepared by a Working Group in the Pan American Health Organization which is a regional office of the WHO. It was prepared between 2005 and 2008 and “validated” in 2010 and published in English in June 2011. It also exists in Spanish and Portuguese.
The committee members who prepared the document were from Colombia, Cuba, Canada, Barbados, and Uruguay with additional expertise from Brazil, Guatemala, Spain and Argentina. All of the members appear to be either academics or members of the government health authorities. There appear to be no industry or public representatives nor do there appear to be any members from the US or Mexico. The references cited are largely WHO/UMC documents, publications in the literature and a few FDA regulations including the 2005 risk documents from FDA. There do not seem to be any EU references.
The document runs some 85 pages and it covers good PV practices with particular attention aimed at setting up national PV systems and centers in the Americas, record management, identification and quantification of risks, generation of signals and further information on risk management, communication and risk prevention. The bulk of the document relates to the governmental agencies, a little on hospitals, universities and other health institutions and there is less than one page devoted to the industry.
Although the document is a bit old, limited in its scope and stakeholder representation, it is still worth reviewing.
The first part of the document is aimed at setting up a government PV system and center but this is somewhat applicable to companies, CROs and other institutions if they want a primer on setting up such a system.
It covers the basics including contacting health authorities, national institutions in medicine, pharmacology and toxicology. Get money and office space and draft a plan. Here are some of the other getting started items needed:
- Setting up the center: main office, technical staff, other locales, telephones, word processors, database management capacity, bibliography, etc.
- Designing a reporting form and beginning the data collection process by distributing the form to hospitals, clinics, family doctors in primary health care, and pharmacies;
- Designing a reporting form and beginning the data collection process by distributing the form to hospitals, clinics, family doctors in primary health care and pharmacies;
- Preparing printed materials to inform health professionals about the definitions, objectives and methods of the pharmacovigilance system;
- Training pharmacovigilance personnel in the following tasks:
– Collecting and verifying data;
– Interpreting and coding descriptions of adverse reactions;
– Coding medicines;
– Assessing causal relationships;
– Detecting signals;
– Managing risks;
- Installing a database—that is, a data storage and retrieval system;
- Holding meetings in hospitals, universities, and professional associations to inform professionals about
the principles and demands of PV and the importance of reporting;
- Stressing the importance of reporting adverse medicine reactions in medical journals and other specialized publications.
- The resources can be obtained from registration fees or by imposing a special compulsory PV fee. Both can be included in the budget of the medicine regulatory authority.
- In addition to basic resources, the center can obtain additional funds from other entities with an interest in PV. The following institutions are examples of those that can be contacted:
– Government departments concerned with medicine safety;
– Health insurance companies and funds
– University departments
– Professional associations
- Staff: a pharmacist, doctor or pharmacoepidemiologist, administrative staff, a programmer or systems analyst, a data processor, experts or consultants and “new professionals from the health sector that are beginning their training in the specialty” advisory committees, an information service and more.
Next they describe the characteristics of reports. They use text to describe what is essentially a MedWatch/CIOMS I form or an E2B transmission but without reference to either of these two standard forms. They next discuss good documentation practices, record keeping, a quality manual, a manual of SOPs and then they list the minimum SOPs that should be in place.
There is a description of basic safety computer systems and how to manage reports, coding and data entry, dictionaries (they suggest either WHO-ART or MedDRA) and the WHO Drug Dictionary. Note that this is not surprising given the heavy WHO input. It must be said though that the state of the art these days really is MedDRA for coding by major health agencies and most companies. They recommend the WHO definitions and the Naranjo and FDA algorithms for causality determination. There is a discussion on how to assess reports.
There is next a brief discussion of Good Risk Analysis and Risk Management Practices including looking isolated cases, medical literature, spontaneous reports, trials, case series etc. Data mining is briefly discussed as is signaling and the quantification, assessment, management and prevention of risk. A risk management plan is suggested using more or less the ICH E2E document as a base. Risk communication, periodic reporting, publications and crisis management are also discussed.
There is a large section relating to how the government should review and track and analyze its PV system. They suggest setting up national and regional PV centers such as is done in France and elsewhere. The responsibilities of physicians and other health care practitioners are discussed.
The pharma companies’ obligations are next discussed and these can be summarized as:
- Reporting all suspected serious adverse reactions received from a health professional through the pharmacovigilance system within the period stipulated by the authority in each country (generally, within 15 days of receipt of the report);
- Keeping detailed records on all suspected adverse reactions that it has learned of, which should be reported to the national regulatory authority;
- Designating a qualified professional to take charge of PV tasks on a continuous and on-going basis, providing adequate means to exercise his or her functions; this professional will also serve as the liaison with the regulatory authority and should be the only spokesperson recognized by the competent public health authorities when it comes to pharmacovigilance;
- Proposing timely changes to the fact sheet file, labeling and package insert when adverse reactions not listed in the material occur;
- Ensuring that all laboratory technical staff receive the training required for the exercise of their PV functions;
- Transferring some or all of its functions and responsibilities to another company, but not the ultimate pharmacovigilance responsibility for monitoring the medicines it is authorized to market;
- Establishing agreements on PV issues in cases where a joint marketing agreement among several companies has been negotiated. Any transfer of pharmacovigilance functions and responsibilities must be documented through a written agreement signed by company representatives. Functions not transferred under this agreement remain the responsibility of the marketing authorization holder. Any transfer of functions and responsibilities must be reported to the respective health authorities;
- Facilitating the designated professional’s access to the fact sheet and basic safety information for each pharmaceutical product approved, ensuring that they are properly updated;
- Ensuring that appropriate standardized work procedures are adopted and followed;
- Guaranteeing a filing system which permits the preservation of all documentation on PV responsibilities and activities. The responsibilities for managing the files must be stated in writing;
- Establishing an audit program to ensure that the pharmacovigilance system follows good practices.
There are extensive appendices with definitions (many are non-standard, unfortunately) as well as sample forms and templates.
This is a very interesting and informative document that really is a primer on how to set up a drug safety unit either in a government, university, company or other entity. The point of view is primarily that of the WHO and a lot of the suggestions are now either outdated or “non-standard” as much of the world has adopted ICH/CIOMS standards.
There is no mention of the internet, electronic transmission, social media and much of the other rapidly developing technology now impacting on drug safety and pharmacovigilance. It seems to be aimed at beginners in the field, institutions that are newly created and those that have limited resources.
It is worth a read and, as noted, is available in Spanish and Portuguese. But the reader should be aware that it presents a particular point of view, is somewhat out-of-date and uses some non-standard definitions and procedures. Much has occurred since this was written and it seems that the document could now use a revised, second edition. Still worth looking at though.
For governments and health authorities, this document should be used as a starting point in setting up a PV system or center but it should not be considered to really represent the state of the art. Reference should be made, in particular to CIOMS and ICH guidelines, as well as how major agencies (FDA, EMA, MHRA, Australia, Canada, Spain and others) handle drug safety. EudraVigilance should be looked at as well as FDA’s FAERS and commercial databases which several health agencies now use (e.g. France, Canada). Note that many agencies (FDA, EMA and others) have their SOPs on-line.