Consumer reporting of adverse drug reactions

79 Pages·2004·0.52 MB·English

W HO D R UG
INFORMATION
V O L U ME 14 • N U M B ER 4 • 2 0 00
P R O P O S ED I NN L I ST 84
I N T E R N A T I O N AL NONPROPRIETARY N A M ES
FOR P H A R M A C E U T I C AL S U B S T A N C ES
W O R LD HEALTH O R G A N I Z A T I ON • GENEVA
WHO Drug Information Vol. 14, No. 4, 2000
General Policy Issues
Consumer reporting of which is crucial to advancing the effective and safe
adverse drug reactions use of medicines. The sharing of information in a
public reporting system also encourages consum-
ers to help one another.
Effective use of medicines depends on the avail-
ability of reliable information. Where adverse reac-
3. The medical establishment can profit from the
tions and interactions of drugs are concerned,
discipline of consumer input since the standard of
existing systems of adverse drug reaction monitor-
practice can only benefit from an ongoing and
ing by health professionals are an important tool for
active encounter with consumer concerns. Con-
collecting, collating and analysing data as a means
sumers for their part need a willing ear and a chan-
of establishing new knowledge and generating early
nel through which to make their experiences and
signals of possible drug complications not reported
feelings known as they assume the risks and costs
through clinical trials. Output from such adverse
of using medicines. They are also exposed to the
drug reporting systems complements the informa-
relationship between benefits, harm, and costs of
tion appearing in the published literature and from
drug use, and can themselves contribute to knowl-
other studies. However, for a number of reasons
edge of that relationship.
these systems have important deficiencies and
limitations and they cannot stand alone. Adequate
Limitations of physician-based and
feedback is needed from users of medicines.
pharmacist-based reporting
Adverse reaction reporting systems have evolved
The following is an extract from a consensus docu-
ment developed during the First International considerably since their creation and play a signifi-
Conference on Consumer Reports on Medicines cant role in mobilizing data. However, they have
certain serious limitations. Foremost among these
(CRM) held from 29 September to 1 October 2000
in Sigtuna, Sweden*. The meeting was attended by is the fact that only a small proportion of practising
participants from the medical and pharmaceutical physicians (often less than 5%) and a relatively
small number of pharmacists (varying from country
professions, drug regulatory authorities, consumer
associations and the World Health Organization. to country) contribute data. Consequently, informa-
tion on suspected adverse reactions communicated
There are both general and specific reasons to by a patient to his physician stands a 95% chance
support the development of consumer reporting as of going no further and making no contribution to
an essential component of drug safety. It is also an adverse reaction reporting.
important mechanism for consumer empowerment
in health, which extends to processes such as There are various well-documented reasons why a
regulation and clinical trials. Consumer reporting health professional may fail to report to the system
promotes: an adverse effect communicated to them by the
patient. The effect may be sufficiently well-known
1. Consumer rights and equity, including fairness already, or conversely it may be dismisses as being
since it is the patient who assumes the risks and unlikely, vague or unrelated to the treatment. How-
the costs; the fundamental right to express oneself, ever it also seems clear that the prescriber may
to be listened to; and the right to informed consent. perceive risk and adverse events differently from
the patient. While, for instance, the doctor is likely
2. Consumers have unique perspectives and expe- to accept the existence of any tangible or visible
riences. They can provide information and insight physical reaction (e.g. a rash), he or she is less
* The First International Conference on Consumer Reports on Medicines (CRM) was organized by the Consumer
Institute for Medicines and Health (KILEN), Kammakargatan 7, SE-111 40 Stockholm Tel: [phone]. Fax:+46 8-
696 01 10. Website: www.kilen.org in collaboration with the Swedish International Development Cooperation Agency
(SIDA), The National Board of Health and Welfare, Sweden, Dag Hammarskjold Foundation, Health Action International
(HAI), People's Health Assembly, Uppsala Monitoring Centre, the Swedish Consumers Association and the Sigtuna
Foundation.
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General Policy Issues WHO Drug Information Vol. 14, No. 4, 2000
likely to appreciate that a consumer’s description of one comparative study, consumer reports have
experiencing ill-defined malaise, unease or been found to cover a wider spectrum of organ
changes in mental state may equally constitute an systems and adverse reactions than reports enter-
early sign of drug complications. Some physicians ing a physician-based system.
appear particularly hesitant to report adverse
2. Direct reporting can provide exceptionally in-
reactions to a drug which they have prescribed for a
formative, vivid and more complete accounts of
non-approved indication (“off-label use”). In some
unwanted experiences which do not readily
countries, physicians have been more generally
lend themselves to classification in any rigid sys-
reluctant to submit adverse reaction reports to
tem. These may include mental reactions but also
official systems because of a fear that, particularly
adverse changes in the quality of life which can be
where a reaction is serious, the prescriber may be
very important, real and distressing to the medicine
blamed and accused of malpractice.
user yet are unlikely to be clear to a prescriber.
Above all, however, the physician who has no 3. Because consumer reporting can cover situa-
interest in communicating suspected adverse tions about which the physician is not informed and
reactions to a central system will take no action. about which he or she therefore cannot report, it is
What may be significant information then remains bound to provide information which is not normally
buried in the patient records. It should be added available to existing systems. Where, for example,
that there is also a problem relating to under- a patient discontinues a drug because of an ad-
reporting by patients to physicians, especially verse effect, and does not return to the prescriber,
where a patient is nervous about raising the issue. the latter will have no knowledge of the event.
This situation is regrettable, but it exists, and some Again, if patients experience a suspected reaction
consumers in this situation would be less reluctant to a self-medicated drug, or to a traditional, herbal
to report their experiences to a neutral consumer- or alternative medicine which they have taken at
based system. The prescriber could and should do their own initiative, no prescriber is likely to know
more than is usually done to alert a patient to the about it. It is clear that in much of the world there is
need to report suspected adverse reactions, what- extensive self-treatment involving drugs which
ever reporting channel is used. This is particularly formally are restricted to prescription sale, and
important where a new drug is prescribed, or an old these include new and potent products with still
drug is administered for a new or unusual indica- poorly defined risks.
tion.
Similarly, if a patient is being treated by two
A final problem with existing systems is that the physicians (e.g. a general practitioner and a spe-
input relates primarily to new drugs; reports of cialist) the one may not be aware of drugs pre-
adverse experiences with products which have scribed by the other, and adverse reactions or
been marketed for many years are relatively few, interactions will be missed. The onus of ensuring
despite the fact that new problems can emerge with proper collaboration and communication in this
such drugs even after decades of use and that old matter clearly lies with physicians and the health
drugs may be redeveloped for new indications (e.g. system, but where it fails, a consumer-based sys-
thalidomide for treatment of acute lepromatous tem may well provide important input.
reaction). The establishment of direct consumer-
based reporting of suspected unwanted events can Present barriers to consumer participation
compensate for these and other deficiencies in In addition to the above challenges, a series of
existing systems. reasons can be advanced as to why consumer
experience so far has not been mobilized as a tool
Benefits and challenges to develop new knowledge and monitor possible
of consumer reporting adverse reactions. The most obvious of these is the
Some positive and direct benefits of direct con- fact that in most countries, reports submitted di-
sumer reporting can be identified. rectly by patients or their representatives are not
accepted by the existing physician-based systems.
1. There is evidence from the field that direct con- They may be formally excluded, or those managing
sumer reporting can result in an earlier accumula- the systems may simply be reluctant to accept
tion of signals, some of which will point validly to them.
new and hitherto overlooked reactions. In at least
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WHO Drug Information Vol. 14, No. 4, 2000 General Policy Issues
In addition, however, consumers have not yet call upon independent experts, including pharma-
played an active role. Reasons for this include lack cists, pharmacologists and physicians with experi-
of knowledge regarding drugs and their reactions, a ence in assessing cause-effect relationships, but it
difficulty which is universal but especially severe in should also have expertise in consumer affairs and
countries where lack of education and illiteracy are patients’ rights.
widespread. In some countries medical mysticism is
still dominant, characterized by a desire to maintain Reporting channels
secrecy around medical facts and thinking. Im- Reports should be submitted through the most
proved public education and information services, appropriate route, depending on the current situa-
coupled with more modern attitudes on the part of tion in the country; the submission procedure
professionals, can do much to remedy this. should be as simple as possible. In some parts of
the world the Internet provides a widely available
The fact that drugs are often prescribed and used
means of reporting, whereas in others the mail,
irrationally creates other difficulties, for example
telephone or personal contact are more
where many drugs are given for a single condition
appropriate.
when only a single drug is indicated. In much of the
world, the patient has only a brief interview with the
Form of reports
physician before receiving a prescription or thera-
Existing physician-based systems have shown that
peutic advice, and there is neither an opportunity
it is helpful to receive the essence of a report in a
nor a positive tradition favouring information and
standardized manner. Well-designed reporting
advice about the drug that has been prescribed or
forms should ideally be used. Reports received by
recommended.
telephone, letter or through personal contact should
be transferred to such forms, but with retention of a
A particular problem in some developing countries
complete description of the event which has been
is that a patient may not know with which drug he/
provided, e.g. by scanning a letter or recording the
she has been treated or which dose he/she has
description given by telephone. The data as re-
received. Not only are drugs sold under a multitude
corded on the standard form should be sufficiently
of names, but in some instances they are referred
exact to permit digital analysis, while a plain text
to anonymously (“take two of the blue tablets and
description of the complication should also be
three of the green ones every day”) or dispensed
provided since it can be valuable in recognizing
without labelling (in sachets containing a few loose
unusual events not readily amenable to coding. As
tablets, for example). In such situations, the active
in professional reporting systems, great care must
participation of users will be difficult to achieve for
be taken to ensure anonymity so that personal
many years to come.
medical data do not become common knowledge.
In industrialized countries, medicine users increas-
ingly report their experiences on internet-discussion Terminology
sites, or to patient and consumer organizations. As became clear at an early stage with professional
These reports however tend to be left as anecdotal reporting systems, there will be a need to standard-
experiences. They are not taken seriously as ize terminology, particularly bearing in mind the fact
consumer reporting. Even in countries where the that information will arrive from different cultures
above barriers are severe, a start can be made by and in different languages. It is possible that in this
mobilizing consumers in the more educated classes respect the system will be able to benefit from the
to take part in a limited venture which will subse- work carried out by the Uppsala Monitoring Centre.
quently extend into a wider movement.
Examination
A structure for consumer reporting Every adverse reaction report received should be
No single structure is likely to prove ideal for all examined and considered. As with existing physi-
countries. However, a number of firm impressions cian-based systems, it will be important to have
as to preferred structures can be recorded. adequate information about the user, the treatment
details, timing and course of the reaction itself. A
Responsible body causality analysis should then be attempted, recog-
The scheme should be handled by an independent nizing that there is no exact methodology to this
body at arm’s length from government and industry end. An attempt should be made to determine
as far as data gathering and interpretation of infor- whether the report is novel or whether it has previ-
mation are concerned. The body should be able to ously been described in existing systems or in the
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General Policy Issues WHO Drug Information Vol. 14, No. 4, 2000
literature. The methods of analysis will not differ reports and analyses of this worldwide material, as
greatly from those developed in the best existing well as conducting methodological research. Its
professional-based systems, but a consumer experience and advice could be of great value in
perspective (“how was this event experienced by developing consumer systems.
the user?”) should be included.
Action required
Direct feedback A careful distinction must be made between a
Experience with existing adverse drug reaction neutral system for collecting, analysing and dis-
reporting systems shows the great importance of seminating data and an institution taking positive
acknowledging promptly the receipt of every report, action in the light of emergent findings. While, as
and following this up in due course with a full reply noted above, the system can and should bring its
and, where possible, an explanation and reassur- findings to the attention of other parties and agen-
ance. cies, it is likely to gain greatest respect if it concen-
trates single-mindedly on the most balanced possi-
Information to others ble analysis of data and the generation of signals. It
The individual report is essentially confidential and would be more appropriate for bodies primarily
under no circumstances should the name of the concerned with the active promotion of patient and
reporter, or any data on the basis of which the consumer interests to take whatever action seems
reporter might be identified, be transmitted to other justified in the light of such findings.
parties. However, general information on the nature
of reports received on a particular drug should be Hospital reports
made available, together with the relevant assess- Appropriate arrangements may be made to
ment, to all interested parties. These are likely to enable hospitalized patients to report directly to the
include the national professional- based adverse proposed scheme when they experience the need
reaction reporting scheme, the official drug regula- to do so, either during their hospital stay or later.
tory authorities, the health professions, agencies
responsible for rational drug use policies and Reports from trials
programmes, the manufacturer, consumer and It would be very desirable for patients and volun-
patient organizations and others likely to need the teers taking part in clinical drug trials to report
data. The media should have full access to the adverse reactions when they so wish to a central
analysed data. system. It is well known that many adverse reac-
tions occurring in trials provide early pointers to
When providing information, disclaimers similar to drug injury, and that the data in question sometimes
those employed by existing spontaneous reporting fail to become generally known either in a timely
systems should be added, so as to reduce any risk manner or at all. In particular, adverse reactions
of over-interpretation or unnecessary alarm. In experienced by subjects dropping out of a trial may
many instances periodic reporting on data input be lost to the records despite the fact that these
(e.g. quarterly) will be adequate, but it will be appro- events may provide the first indications of a serious
priate to disseminate groups of related reports that problem. The principle of the subject’s freedom to
suggest the emergence of a hitherto unrecognized report should be laid down in guidelines such as
problem more urgently. those for Good Clinical Practice.
Collaboration The same principles should be incorporated in
At the very least, there should be an exchange of clinical trial protocols subject to approval by ethics
data between public reporting schemes in different committees and analogous bodies. Confidentiality
countries to strengthen systems and a further agreements concluded between an industrial
acceleration in the identification of new data. There sponsor and a clinical investigator should never be
is strong interest in establishing a global centre for allowed to impede reporting of adverse reactions by
consumer reports, analogous to that existing for participants.
professional reporting to The Uppsala Monitoring
Centre but separate from the latter. The Uppsala Active reporting
Centre is, however, open for an input of data from Over the years, there have been several
the consumer system, which could form a separate successful ventures into “intensive monitoring” or
data base. The Centre currently holds the data from “active reporting”, seeking to obtain integral regis-
59 national physician-based schemes and provides tration of all adverse events from a particular pa-
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WHO Drug Information Vol. 14, No. 4, 2000 General Policy Issues
tient group or at a particular location. Such efforts could in due course perform a useful role by peri-
are justified, where there is a special reason to odically sampling the relevant content of the Inter-
anticipate certain problems and to quantify them net and disseminating selected data that appear
within a short period. significant.
System monitoring Pitfalls and problems
The functioning of all aspects of a system of this Past reasons for rejecting the principle of direct
type should be monitored internally and its useful- consumer reporting need to be borne in mind since
ness should be evaluated periodically so that they can provide pointers to necessary action. The
modifications can be introduced as necessary. opinion that information emanating directly from
Field trials of modified procedures may be called consumers is less reliable than that communicated
for. by way of physicians (or pharmacists) is only valid
insofar as the professional reporter may provide
Secondary services preliminary screening and useful background
It seems clear from experience that once consum- information when submitting the report. Provided
ers have established contact with the proposed there is proper feedback and careful expert analysis
system they will seek supplementary services from of reports, it will not necessarily be more difficult to
it, in particular requesting advice and information. eliminate mischievous, misleading or ambiguous
While the system should refer requests for medical reports than has been the case in professional-
advice to the most appropriate body (generally the based systems, where entirely similar problems
patient’s own physician) sympathetic assistance arise. A problem deserving particular attention,
should be given where factual information or especially in international collaboration between
reassurance is sought. Such information may also systems, is that of translation and interpretation.
need to be communicated to other bodies, espe- Concepts regarding drug safety and subjective
cially where it points to a problem which, though it experiences (e.g. concerning the quality of life) may
may not concern adverse reactions, demands prove difficult to translate from one language to
attention and correction. Finally, much information another, and plain text accounts of experiences
regarding adverse drug reactions is now to be may simply be difficult to comprehend when read in
found on the Internet, although it is scattered and of a different environment. These are intercultural as
variable reliability. Consumer reporting systems well as linguistic challenges.
WHO Drug Information
is now available at:
http://www.who.int/druginformation
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WHO Drug Information Vol. 14, No. 4, 2000
Vaccines and Biomedicines
Quality assurance Recommendations for Oral Polio Vaccine. How-
ever, it would be necessary for laboratories intend-
and safety of biologicals
ing to use the alternative assay to follow standard
training and implementation procedures. A pro-
Because of their unique origin, biological products gramme of training and staged implementation has
derived from normal or genetically-modified living therefore been developed by WHO, with the col-
organisms offer particular challenges concerning laboration of the Center for Biologics Evaluation
requirements for quality, safety and efficacy. Bio- and Research (CBER), Food and Drug Administra-
logical products are used in the diagnosis, treat- tion, USA, and the National Institute for Biological
ment or prevention of disease, and include vac- Standards and Control (NIBSC), United Kingdom,
cines, blood, blood products, hormones, cytokines in order to facilitate the introduction of the new
and a range of cellular technologies. To ensure the assays.
quality, safety and efficacy of these products,
regulatory guidance, the provision of standards,
Inactivated polio vaccine
and the design of appropriate tests must be pro-
Updated Recommendations for Inactivated Polio
vided which are in line with latest developments.
Vaccine (IPV) were also adopted by the ECBS. The
Recommendations (formerly requirements) for
WHO, through its Expert Committee on Biological
Inactivated Polio Vaccine were last revised in 1985
Standardization (ECBS), plays a key role in review-
and there have been several advances in vaccine
ing scientific progress and in establishing Interna-
production technology and quality control since that
tional Reference Preparations and Recommenda-
time. Furthermore, as the goal of eradicating polio-
tions on production and control of biological prod-
myelitis due to wild-type polio viruses is in sight,
ucts. The report of its Fifty-first meeting, held in
laboratories that use wild polio viruses will become
November 2000, is summarized below.
an important potential source of accidental reintro-
duction of wild virus into the community. To mini-
Oral polio vaccine
mize this risk, WHO has developed a global action
WHO Recommendations (formerly requirements) plan that requires increased biosafety containment
for Oral Polio Vaccine (OPV) were revised at the of wild polio viruses (1). This applies to parts of the
Fiftieth meeting of the ECBS in1999, and new production process for IPV where wild polio viruses
quality control procedures introduced. These in- are used. For these reasons, it was essential for the
cluded the use of transgenic mice as an alternative IPV Recommendations to be urgently updated. The
to the neurovirulence test in primates for type 3 oral ECBS reviewed a draft which had already under-
polio vaccine, as well as a test for the molecular gone considerable international consultation and,
consistency of production of the live virus vaccine after making some comments, adopted the draft as
(MAPREC assay). the new Recommendations for Inactivated Polio
Vaccine.
At the Fifty-first ECBS meeting, data concerning the
use of the transgenic mice model for testing the
Production and control of Japanese
neurovirulence of types 1 and 2 were reviewed. The
encephalitis vaccine
ECBS concluded that the mouse model provided an
Japanese encephalitis is a major cause of viral
alternative neurovirulence assay also for types 1
encephalitis in the Asia-Pacific region. A live-
and 2 oral polio vaccines and agreed to include this
attenuated vaccine has been developed in China
recommendation as an addendum to the updated
* The Expert Committee included members from Belgium, Canada, China, the Netherlands, Mexico, the Russian Federation,
United Kingdom, and the United States of America. Experts were invited from Austria, Canada, China, Denmark, Finland,
France, Germany, Japan, Republic of Korea, the Netherlands, Switzerland, United Kingdom, and the United States of
America. with representatives of the Council of Europe, European Plasma Fractionation Association, International
Association for Biologicals, International Federation of Pharmaceutical Manufacturers Associations (IFPMA), International
Society on Thrombosis and Haemostatis, and the Plasma Protein Therapeutics Association.
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WHO Drug Information Vol. 14, No. 4, 2000 Vaccines and Biomedicines
where it has also been licensed and used for a Transmissible spongiform
number of years as an alternative to existing inacti- encephalopathies
vated vaccines. Several countries are interested in The ECBS attaches considerable importance to
using the live attenuated vaccine. measures undertaken to ensure the safety of
vaccines and blood products with respect to trans-
Guidelines for the Production and Control of Japa- missible spongiform encephalopathies (TSEs).
nese Encephalitis (JE) Vaccine (live) for Human
Use were adopted by the ECBS. The document At its Fifty-first meeting, the ECBS discussed the
provides information and guidance concerning the current situation regarding measures taken to
history, characteristics, production and control of exclude materials possibly carrying bovine spongi-
live attenuated Japanese encephalitis vaccine and form encephalopathy (BSE) from the production of
is designed to facilitate progress towards the even- vaccines and other biologicals, including issues
tual international licensing of the vaccine. The text related to the use of bovine serum and other bovine
is written in the form of guidelines rather than derived materials. Recent risk assessments, carried
Recommendations since further work is needed to out in the USA and European Union, agree that any
develop and standardize appropriate methods and risk from vaccines and other biologicals is theoreti-
criteria for certain tests, such as the neurovirulence cal and negligible.
test.
The safety of vaccines and other biologicals with
Diphtheria, tetanus, pertussis respect to BSE is considered to be assured by a
and combined vaccines combination of sourcing of materials used in manu-
A WHO Working Group recommended the develop- facture from safe sources with respect to country/
ment of a simple, robust and standardized assay to herd/ animal and by employing only tissues with no
demonstrate consistency of immunological charac- demonstrable infectivity. Furthermore, in relation to
teristics suitable for lot release of vaccines contain- the safety of vaccines and other biologicals pre-
ing diphtheria and/or tetanus toxoid. The ECBS pared from mammalian cells there is no evidence
therefore discussed a proposal to amend the that the transmissible agent of BSE is capable of
present requirements for diphtheria, tetanus, per- amplification in cultures of the non-neuronal cells
tussis and combined vaccines to permit the use of a that are currently used as substrates for production.
test procedure based on serological assay for this Nevertheless, in view of rapid developments in this
purpose. The ECBS endorsed the need to work area the ECBS recommended that WHO should
towards a common model acceptable by all parties, review the situation and update its report on Medi-
provided that new problems were not created. The cal and Other Products in relation to Human and
ECBS welcomed the steps already taken, but Animal Transmissible Spongiform Encephalopa-
concluded that further work was necessary before thies (2).
any changes could be made to the present Recom-
mendations. Further work on this issue is in In addition, the ECBS noted that progress is being
progress. made by the Working Group on International Refer-
ence Materials for Diagnosis and Study of TSEs in
A range of single component and combined acellu- the development and evaluation of essential hu-
lar pertussis vaccines are now available. However, man-derived reference materials. Efforts of the
ethical considerations prevent clinical protection Working Group are aimed at the standardization of
studies of new vaccines or vaccine combinations diagnostic procedures under development. The
and so the need exists for a suitable animal model need for international reference reagents and
to evaluate vaccine potency. The immunogenicity of panels to compare new diagnostic procedures for
these vaccines does not necessarily reflect clinical TSEs was considered to be a priority. Reports of
efficacy. Studies of appropriate animal models to these developments are published on the WHO
assess the protective activity of acellular pertussis Website at the following address: http://
vaccines are under way, and a respiratory chal- www.who.int/technology/biological.html.
lenge model appears to offer a good prospect for
product characterization. Further studies of this International standards
model are planned as well as studies to assess the The ECBS established 6 new or replacement
value of the modified intracerebral challenge assay International Standards and Reference Reagents
of acellular pertussis vaccine as a discriminatory lot covering a range of products (Table 1, page 220).
release assay.
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Vaccines and Biomedicines WHO Drug Information Vol. 14, No. 4, 2000
Additionally, one International Reference Material In October 1999 in the United Kingdom, a sero-
is no longer needed and was discontinued following group C conjugate vaccine became the first novel
a public consultative process (3), (See Table 2, vaccine to be licensed for use in infants for which
page 220). Also, due to a decrease in use or protective efficacy was not determined by a phase
following a change in international requirements, III study, but inferred from immunogenicity data.
the ECBS proposed to discontinue a number of The ECBS was informed of an expert panel set up
reference materials at its next meeting subject to to assess current methodologies for measuring
public comment to this notice. The materials pro- immune responses to meningococcal A/C conju-
posed for discontinuation are listed in Table 3 (page gate vaccines and agreed with its recommendation
221). The WHO Catalogue has been updated that either human or rabbit serum could be used as
appropriately (4). the source of complement for the serum bacteri-
cidal assay. It also agreed with the criteria pro-
Other activities posed to indicate protective human immune re-
The ECBS was informed of discussions that had sponses. However, the ECBS emphasized the
taken place at a WHO Consultation on International need to review these criteria in the light of clinical
Biological Standards for in vitro Diagnostic Proce- protection data now emerging from the United
dures held in September 2000. International biologi- Kingdom following the introduction of meningococ-
cal standardization is becoming increasingly impor- cal C conjugate vaccine, especially in relation to the
tant for the regulation of clinical diagnostic proce- demonstration of immunological memory.
dures and the consultation was the first occasion
when participants from the various disciplines had Draft Guidelines for the production and control of
met together to discuss issues associated with the inactivated oral cholera vaccines were in the pre-
provision of international reference materials in this liminary stages of development and were intended
area. to reflect the needs for production and control of the
new inactivated oral vaccines, even though further
Discussion centred on a standardization process, development work will be required. The ECBS
the Draft ISO document 17511, that involves the recognized that this is a rapidly evolving field of
use of a reference system consisting of a reference great importance in developing countries. It wel-
material, a reference method and a reference comed and endorsed the action taken by the Secre-
laboratory. The ECBS considered that the draft ISO tariat.
standard 17511 as presently written may not be
entirely applicable to the measurement of complex A proposed Guidance Document on Viral Inactiva-
biological substances in clinical samples, and it tion Procedures for Plasma and Plasma-derived
recommended WHO collaborate closely with the Medicinal Products, intended to assure the viral
ISO and other scientific bodies involved in the in safety of plasma-derived products, was discussed.
vitro diagnostics field. Issues should be resolved The document will be circulated to national regula-
whereby the principles of ISO 17511 are main- tory authorities less familiar with decontamination
tained as far as possible, while the distinct charac- processes and will be widely reviewed at a WHO
teristics and difficulties of biological substances are Consultation. A Guide for Good Manufacturing
clearly recognized. Practices for the Collection of Source Materials for
the Production of Plasma Derivatives will be devel-
The ECBS endorsed Recommendations arising oped to complement the above guidance docu-
from a meeting on the standardization and control ment, aiming to strengthen the technical capacity
of serogroup B meningococcal vaccines and and expertise of the national regulatory authorities
agreed that guidelines for outer membrane vesi- in the evaluation and control of blood plasma-
cles-based meningococcal vaccines should now be derived medicinal products.
developed. The ECBS also recommended a review
of evidence concerning immune responses to these The ECBS also supported the initiative to develop
vaccines and to consider how the assays could guidelines on preclinical and clinical testing of
best be standardized and reliable immunological vaccines — a project already in progress — and
correlates of protection established. Finally, it agreed that these Guidelines would be of consider-
agreed that it would be useful for WHO to set up a able benefit in supporting national regulations and
working group to consider all aspects of clinical would serve as guidance for national regulatory
management of meningococcal disease and possi- authorities and industry, especially in developing
bly draft suitable guidance. countries, and for ethical committees.
218
WHO Drug Information Vol. 14, No. 4, 2000 Vaccines and Biomedicines
References 2. World Health Organization. Report of a WHO Consulta-
tion on medicinal and other products in relation to human
1. World Health Organization. WHO Vaccine Assessment
and animal transmissible spongiform encephalopathies.
and monitoring. WHO global action plan for laboratory
WHO/BLG/97.2
containment of wild polioviruses. Document WHO/V&B/
99.32, Geneva, 1999. http://www.who.int/vaccines- 3. WHO Drug Information, 13: 234 (1999).
documents/DocsPDF99/www9956.pdf
4. World Health Organization. WHO Catalogue on Interna-
tional Biological Reference Preparations. http://
www.who.int/technology/biological.html
Table 1
International biological standards and reference reagents established
by the Fifty-first WHO Expert Committee on Biological Standardization
ADDITIONS
Antigens
tetanus toxoid (adsorbed) Third International Standard 2000
Blood products
fibrinogen concentrate, human First International Standard 2000
Parvovirus B19 DNA, human First International Standard 2000
Cytokines, growth factors and endocrinological substances
follicle-stimulating hormone and
luteinising hormone, human, urinary, for bioassay Fourth International Standard 2000
somatropin Second International Standard 2000
inhibin B First Reference Reagent 2000
RE-ESTABLISHMENT
insulin-like growth factor 1 for immunoassay First Reference Reagent 1988
CHANGE OF NAME
From: To:
insulin-like growth factor 1 insulin-like growth factor 1 for bioassay
(First International Standard 1994) (First International Standard 1994)
inhibin, human, recombinant inhibin A, human, recombinant
(First International Standard 1994) (First International Standard 1994)
alteplase (recombinant tissue plasminogen tissue plasminogen activator (TPA), human,
activator) (First International Standard 1999) recombinant (Third International Standard) 1999
These substances are held and distributed by the International Laboratory for Biological Standards,
National Institute for Biological Standards and Control (NIBSC), Potters Bar, Herts. EN6 3QG, England.
Table 2
Reference materials discontinued by
the Fifty-first WHO Expert Committee on Biological Standardization
protamine First International Reference Preparation 1954
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