Inspection
Inspection of drug distribution channels 3
Introductory note General
considerations Glossary 1. Drug inspectors
1.1 Qualifications 1.2 Organizational aspects
1.3 Methods of inspection 1.4
Reference/information sources 2. Inspection of establishments in
the drug distribution chain 2.1 Broad objectives
2.2 Establishments 2.3 Inspections
2.4 Special categories of drugs References
Selected further reading Appendix 1 Checklist for
inspection and the preparation of a report Appendix
2 Guidance on sampling Appendix 3 Guidance for inspection
when pharmaceutical products are suspected to be counterfeit,
spurious or substandard Appendix 4 Sample receipt form
Introductory note
The quality assurance of drugs at the
level of the manufacturer is outlined in the guidelines on good
manufacturing practices for pharmaceutical products (GMP) published
by WHO (1). Compliance with these guidelines will ensure that
products released for distribution are of the appropriate quality.
However, if this is to be realized in practice, it is essential that
an established drug regulatory authority exists in a Member State,
which complies at least with the "Guiding principles for small
national drug regulatory authorities" (2).
In addition, the holder of a marketing
authorization for a pharmaceutical product, or alternatively the
(legal) person responsible for the initial marketing of a product,
who ideally should be a pharmacist or a pharmaceutical company
authorized to practise in the Member State, should ensure that the
product is only released for distribution after it has been
established that it conforms with the product specification lodged
with the drug regulatory authority.
This level of quality should be
maintained throughout the pharmaceutical supply system or
distribution network. Basic principles of GMP are applicable to
wholesale operations and (to some extent) to retail outlets. These
principles may be summarized as follows:
— only authorized products are
distributed;
— a quality system is in place which
includes quality policy, quality management, appropriate
analytical controls, self-inspection;
— personnel are quality-conscious,
adequately trained and motivated;
— premises and equipment are suitable
for their intended use, and kept in a good sanitary condition;
— all products are received, stored and
handled appropriately (protected against contamination,
cross-contamination, mix-ups, environmental factors such as heat,
severe cold, moisture, light);
— all drug-related operations are
performed in accordance with written procedures, are properly
supervised and adequately documented; documentation ensures
complete traceability of receipt of all materials, quality testing
processes (if any) and shipping;
— adequate provisions exist to handle
complaints, recalls, and returned goods.
At the same time, many provisions of the
GMP guidelines published by WHO are clearly not addressed to
wholesalers and retail pharmacies where specific rules and
requirements apply. These rules are determined partly by
pharmaceutical science and common sense, and partly by national
(regional) regulations and standards. In this context reference is
made particularly to the guidelines entitled "Good pharmacy practice
in community and hospital pharmacy settings" (3). It follows
then that the "Provisional guidelines on the inspection of
pharmaceutical manufacturers" (4), which are directed to
government GMP inspectors, are not adequate to cover inspection in
the distribution system. The present document addresses this
specific issue.
These guidelines are intended for use by
pharmaceutical inspectors in national drug regulatory authorities.
They are therefore presented in a format that will allow for easy
reference in the field. They should, however, be adapted by national
drug regulatory authorities to suit their national legal
requirements and available resources.
This document discusses the "simplified"
situation when there is a single authority, the drug regulatory
authority, where all kinds of drug inspections are located, ranging
from those of drug manufacture to the inspections of pharmacies. In
reality, these tasks, requiring different inspection skills are
usually distributed among different (national and local)
authorities.
General considerations
A comprehensive system to assure the
safety, efficacy and quality of pharmaceutical products at a
national level has the following elements:
• Legal: drug
legislation
•
Administrative:
— drug regulatory authority with
functions of product registration, licensing of manufacturers,
importers and distributors (wholesale, retail and for
institutional supply), inspection and independent testing of
samples
— enforcement
• Technical:
— regulations
— standards and norms
— guidelines
— independent quality control
laboratory(ies)
This document focuses on one
element—inspection—and in particular on inspection in the
pharmaceutical supply system.
The usefulness of drugs in the treatment
of ailments, diseases and disorders is well recognized and
appreciated. It is also recognized that the inappropriate use of
drugs can produce severe toxic effects, some of which may be fatal.
National drug laws have therefore been introduced to reduce risks
associated with the use, misuse and abuse of pharmaceutical
preparations.
Drugs differ in the severity of their
side-effects and toxicity and these differences are taken into
consideration in the classification of drugs in national drug laws.
Drugs may be classified into four types as follows: over-the-counter
drugs, pharmacy-only drugs, prescription-only drugs and prohibited
drugs.
The distribution, supply, import, export,
sale, storage, advertisement and dispensing of drugs are normally
regulated by national drug laws, which provide for a system of
licences to be issued by a drug regulatory authority for such
drug-related activities. The drug laws may identify a
ministry/department/agency that would function as the drug
regulatory authority as well as provide for the enforcement of the
drug laws, using a system of inspections organized through an
inspectorate(s).
The inspectorate advises on whether
applicants and premises should be issued licences to engage in
drug-related activities. The inspectorate ensures that counterfeit,
spurious and substandard pharmaceutical products are not found in
the national pharmaceutical supply system or outside it, and that
licensed premises and authorized persons adhere to existing laws and
regulations. To do this, the inspectorate gathers information on the
working of the drug laws by liaising with other law enforcement
agencies and health institutions, including health-care professional
associations.
Glossary
The definitions given below apply to the
terms used in these guidelines. They may have different meanings in
other contexts.
batch A defined quantity
of any drug product processed in a single process or series of
processes such that it can reasonably be expected to be uniform in
character and quality.
batch number 4 A distinctive combination of numbers and/or letters which
specifically identifies a batch on the labels, the batch records,
the certificate of analysis, etc.
controlled drugs Narcotic
drugs and psychotropic substances regulated by provisions of
national drug laws.
counterfeit pharmaceutical
product A pharmaceutical product which is
deliberately and fraudulently mislabelled with respect to identity
and/or source. Counterfeiting can apply to both branded and generic
products and counterfeit products may include products with the
correct ingredients, with the wrong ingredients, without active
ingredients, with an insufficient quantity of active ingredient or
with fake packaging.
drug (pharmaceutical product) Any substance or mixture of substances that is manufactured
for sale or distribution, sold, supplied, offered for sale or
presented for use in:
(i) the treatment, mitigation, cure,
prevention or diagnosis of disease, an abnormal physical state or
the symptoms thereof and abnormal physiological conditions in
human or animal; or
(ii) the restoration, correction or
modification of organic functions in human or
animal.
finished pharmaceutical product A pharmaceutical product that has undergone all stages of
production and quality control, including being packaged in its
final container and labelled.
good manufacturing practice
4 Good manufacturing practice is that part of
quality assurance which ensures that products are consistently
produced and controlled to the quality standards appropriate to
their intended use and as required by the marketing
authorization.
good pharmacy practice
The practice of
pharmacy aimed at providing and promoting the best use of drugs and
other health care services and products, by patients and members of
the public. It requires that the welfare of the patient is the
pharmacist's prime concern at all times.
over-the-counter drugs
These are drugs
that can be sold from licensed dealers without professional
supervision and without prescriptions. These drugs are suitable for
self-medication for minor diseases and symptoms.
pharmacist A pharmacist is a holder of a degree or diploma in pharmacy
from a recognized higher institution of learning and is registered
or licensed to practise pharmacy.
pharmacy-only drugs These are drugs authorized to be sold only in
licensed pharmacies under the supervision of licensed and registered
pharmacists; they may be sold without a prescription.
poison A preparation or substance defined by a national drug law as
a poison.
prescription-only
drugs These are drugs supplied
only in licensed pharmacies on the presentation of signed
prescriptions issued by a licensed and registered medical
practitioner, licensed and/or registered dentist (for dental
treatment only), and/or licensed and/or registered veterinarian (for
animal treatment only), and the supply and dispensing of these drugs
must be carried out by a pharmacist or under the supervision of a
pharmacist. Prescription drugs are further subdivided into
controlled drugs (narcotic drugs and psychotropic substances) and
non-controlled drugs.
product recall Product recall is a process for withdrawing or
removing a pharmaceutical product from the pharmaceutical
distribution chain because of defects in the product or complaints
of serious adverse reactions to the product. The recall might be
initiated by the manufacturer/importer/ distributor or a responsible
agency.
prohibited drugs These are drugs with toxicity or
side-effects that outweigh their therapeutic usefulness, so that
public health and welfare are protected by prohibiting their
production, manufacture, export, import, trade, distribution,
supply, possession or use, except in amounts required for medical
and scientific research. Prohibited drugs are normally determined by
the national or supranational registration/licensing
authority.
quality assurance 4 Quality assurance is a wide-ranging concept covering all
matters that individually or collectively influence the quality of a
product. It is the totality of the arrangements made with the object
of ensuring that pharmaceutical products are of the quality required
for their intended use.
quality control Quality control covers all
measures taken, including the setting of specifications, sampling,
testing and analytical clearance, to ensure that raw materials,
intermediates, packaging materials and finished pharmaceutical
products conform with established specifications for identity,
strength, purity and other characteristics.
unauthorized market (in some countries
called parallel market) The unauthorized market
consists of wholesale establishments and retail outlets distributing
or selling drugs without authorization from a competent
authority.
1. Drug inspectors
1.1 Qualifications
Inspectors should normally be pharmacists
who have working experience in community and/or hospital pharmacy.
Where persons other than pharmacists are employed as drug
inspectors, they should be adequately experienced in drug control
affairs and suitably trained in inspectorate functions. The
possibility of having part-time inspectors with specialist knowledge
as part of inspection teams should also be considered.
The inspector should possess the
following attributes:
- good knowledge of pharmacy, drugs, and
poisons
- good knowledge of the laws and
regulations to be enforced
- good command of technical terms and
excellent communication skills
- awareness of the probable methods of
using forged or false documents for transactions in pharmaceutical
preparations and skill in determining the genuineness of documents
presented for examination
- maturity, honesty and integrity
- responsible conduct which commands
respect
- willingness to accept challenges
- ability to organize their own work
with minimum supervision
- ability to assess facts quickly and
take rational and sound decisions without delay
- ability to assess character and
honesty of persons being interviewed
- good public relations image with key
personnel/pharmacists in charge of premises while remaining firm,
fair and resolute
- ability to hold discussions with
company management at the completion of inspection
- ability to motivate others
- commitment to hard work and long hours
- ethical approach to any potential
conflict of interest.
1.2 Organizational aspects
Inspectors should be embedded in an
organization, usually called an inspectorate, which ensures the
following aspects:
• A job
description which describes the duties of the inspector.
• Proper
reporting: inspectors should report either to the drug regulatory
authority or to the pharmaceutical department (chief pharmacist)
of the Ministry of Health.
• Uniformity
of approach:
(a) Regular meetings of inspectors, in
which experiences on the job are exchanged, will help promote a
uniform approach to inspection as well as enhance the performance
of the inspectors.
(b) Inspectors should work according to
a work plan and to Standard Operating Procedures (SOPs).
(c) Inspection reports should
preferably be in three or four parts:
(i) date of inspection and general
information on the establishment inspected,
(ii) description of the inspection
activities undertaken, including analytical data of samples
taken,
(iii) observations and
recommendations,
(iv) conclusions.
(d) Inspectors should be encouraged to
submit weekly reports of work to
headquarters.
• Total
coverage of the country. This can be achieved by:
(a) dividing the country into defined
areas for the purpose of inspection and placing an inspector in
charge of a defined area for the purpose of inspecting wholesale,
community and hospital pharmacies, and clinics,
(b) inspection of ports and border
posts in a defined area.
• Total coverage of
the field. The inspector will be expected to inspect establishments
such as:
(a) pharmaceutical manufacturers in
respect of drug distribution,
(b) pharmaceutical importers/exporters,
(c) pharmaceutical wholesalers and
retailers,
(d) hospital pharmacies/clinics,
(e) ports and international border
posts,
(f) drug warehouses, stores and
unauthorized markets.
(Note: The existence of
unauthorized markets for the distribution of drugs poses
considerable health hazards. The inspectors should, with the
assistance of task forces if necessary, investigate the extent of
the unauthorized market, the types of drugs distributed and
supplied, and the sources of the drugs. Where possible,
unauthorized markets for drugs should be prohibited through
effective inspectorate activities. Inspectors should also
investigate the sources of supply of suspect counterfeit or
substandard pharmaceutical products.)
• Cooperation with
other agencies. The inspector will be expected to interact and
cooperate with other interested parties such as:
(a) industrial, community and hospital
pharmacists,
(b) management and supervisory staff of
pharmaceutical establishments and hospitals,
(c) medical practitioners, dentists,
veterinarians, nurses and midwives and other health workers,
(d) public analysts,
(e) ministry of justice officials and
court officials,
(f) drug law enforcement officers
including the police and customs,
(g) officers of port authorities,
clearing agents at the ports, importers and exporters,
(h) members of the public,
(i) staff of faculties of
medicine/pharmacy,
(j) foreign drug regulatory
authorities.
• Independence.
Inspectors should, for example, have the use of official vehicles.
• Adherence to a code
of inspection.
1.3 Methods of inspection
The inspector uses different methods to
check compliance with the national, supranational or international
drug laws and regulations. Among these methods are:
•
Comprehensive/routine inspection. This form of inspection
is generally reserved for a new pharmaceutical establishment, when
an establishment is applying for permit to extend its scope of
operations beyond that for which it was originally licensed, has
made important changes in key personnel or is changing premises,
has not been inspected for a long time (3–5 years), or when there
is information (even of an informal nature) of serious lapses.
Where the inspection is for a new establishment or for extension
of scope of operation or because of changes in key personnel, the
inspection should be announced.
• Concise
inspection. This is reserved for establishments that have
previously been inspected with a view to assessing standards of
good pharmacy practice. The outcome of the inspection will help in
the proper assessment of the establishment. The inspection may be
unannounced.
•
Follow-up inspection. This is normally carried out to
ensure that corrective measures have been undertaken following
advice and notice given during a previous inspection. Where a time
limit was given for applying the corrective measures, the
inspection may be unannounced.
• Special
inspection. This is undertaken to deal with specific
complaints received about lapses or non-compliance with standards
of professional practice. The inspection should preferably be
unannounced.
•
Investigative inspection. This type of inspection is used
to assess the per- formance of a new establishment whose scope of
operation was previously unknown.
Any of these methods may be applied with
or without prior announcement. Normally inspections should be
announced but it serves a useful purpose to undertake some
unannounced inspections. Follow-up, special and investigative
inspections should preferably be unannounced.
Inspections should be held regularly.
Premises should be inspected at least once every 12–18 months. Where
contravention is often noticed, the inspection should be more
frequent (e.g. every six months). For premises with a good record,
less frequent inspections may be needed.
1.4 Reference/information sources
The reference/information sources of an
inspector should include:
• Existing national
and international drug laws and regulations, covering such aspects
as:
— licensing — GMP — good
distribution practice — good pharmacy practice — promotion
of pharmaceutical products — controlled drugs — counterfeit,
spurious or substandard pharmaceutical products.
• Codes of
inspection (national and regional), where in existence.
• Codes of
professional ethics.
• Health
consequences of drug abuse and misuse.
•
Available data on imports/exports/prohibited
drugs.
2. Inspection of establishments in the
drug distribution chain
2.1 Broad objectives
The welfare of patients and other members
of the public is of prime concern in the distribution chain of
drugs, either manufactured within the country or imported.
Inspections of establishments are therefore undertaken to ensure:
• Protection
of patients and members of the public from malpractice by
distributors and suppliers of drugs.
• Adherence
to the drug laws and regulations governing compounding,
distribution, importation, export and storage of drugs.
• High
ethical and professional standards of pharmaceutical practice.
2.2 Establishments
In the drug distribution chain several
kinds of establishments can be distinguished:
— production sites
— storage or warehouse facilities
— establishments for the supply, sale,
dispensing and distribution of drugs, such as pharmacies,
hospitals, clinics, ports and stores.
2.3 Inspections
When inspecting these establishments the
inspector uses the appropriate references. The method of inspection
should be laid down in a SOP which also contains the requirements
for a specific type of establishment. The inspection SOP may be in
the format of a checklist (see Appendix 1 for an example applicable
to most drug distribution establishments). When sampling is part of
the inspection procedure, the SOP should contain detailed guidance
for the inspector; an example of this guidance is to be found in
Appendix 2.
2.4 Special categories of drugs
When special categories of drugs are
present the inspector may require a modified SOP. This situation is
likely to occur with controlled drugs, pharmaceutical products
moving in international commerce, or with counterfeit, spurious or
substandard pharmaceutical products. For this last category an
example of extra guidance is given in Appendix 3.
References
1. Good manufacturing practices for
pharmaceutical products. In: WHO Expert Committee on
Specifications for Pharmaceutical Preparations. Thirty-second
report. Geneva, World Health Organization, 1992, Annex 1 (WHO
Technical Report Series, No. 823).
2. Guiding principles for small
national drug regulatory authorities. In: WHO Expert Committee
on Specifications for Pharmaceutical Preparations. Thirty-first
report. Geneva, World Health Organization, 1990, Annex 6 (WHO
Technical Report Series No. 790).
3. Good pharmacy practice in community
and hospital pharmacy settings. In: WHO Expert Committee on
Specifications for Pharmaceutical Preparations. Thirty-fifth
report. Geneva, World Health Organization, 1998, Annex 7 (WHO
Technical Report Series, No. 885).
4. Provisional guidelines on the
inspection of pharmaceutical manufacturers. In: WHO Expert
Committee on Specifications for Pharmaceutical Preparations.
Thirty-second report. Geneva, World Health Organization, 1992,
Annex 2 (WHO Technical Report Series, No.
823).
Selected further reading
ASEAN good manufacturing practices
guidelines, 2nd ed. Jakarta,
Technical Cooperation on Pharmaceuticals, 1988.
Basic tests for pharmaceutical
substances. Geneva, World Health
Organization, 1986.
Basic tests for pharmaceutical dosage
forms. Geneva, World Health
Organization, 1991.
Bulk pharmaceutical
chemicals. London, Institute of
Quality Assurance, 1992 (Pharmaceutical Quality Group
Monograph).
Code of ethics. Pharmaceutical
journal, 1992, 248:545–556.
Convention on Psychotropic Substances,
1971. New York, United Nations,
1977.
Ethical criteria for medicinal drug
promotion. Geneva, World Health
Organization, 1988.
Hayes P, Kayne S, Martin T, McMurdo A.
Use of professional self audit in pharmacy practice.
Pharmaceutical journal, 1992, 249:650–652.
International nonproprietary names (INN)
for pharmaceutical substances: Lists 1–73 of proposed INN and lists
1–35 of recommended INN; cumulative list no. 9. Geneva, World Health Organization,
1996.
Sampling procedures for industrially
manufactured pharmaceuticals. In: WHO Expert Committee on
Specifications for Pharmaceutical Preparations. Thirty-first
report. Geneva, World Health Organization, 1990, Annex 2 (WHO
Technical Report Series, No. 790).
Single Convention on Narcotic Drugs,
1961, as amended by the 1972 Protocol. New York, United Nations, 1977.
Statutory Committee: professional
conduct. Pharmaceutical journal, 1969, 203:472.
Statutory Committee: three names to be
removed from register. Pharmaceutical journal, 1973,
210:212.
Turner JL. The implementation of European
Community directives concerning GMP. Drug information
journal, 1991, 25:537–544.
United Nations Convention against Illicit
Traffic in Narcotic Drugs and Psychotropic Substances,
1988. New York, United Nations,
1991.
Wingfield J. Misconduct and the
pharmacist. Pharmaceutical journal, 1990, 245:531–533.
Appendix 1
Checklist for inspection and the preparation of a
report
Inspection applicable to all drug
distribution establishments
1. General information
(a) name of establishment inspected
(b) date of inspection
(c) name(s) of the inspector(s)
(d) date of last inspection.
2. Type of inspection
Comprehensive, concise, follow-up,
special, investigative, announced, unannounced.
3. Licensing
(a) licensing of premises
(b) person with supervisory role in
establishments handling prescriptions and pharmacy sale-only drugs
(is normally a registered pharmacist or a person so prescribed by
national legislation)
(c) personnel authorized to sell only
over-the-counter drugs (licensed, where such licensing is
required)
(d) adherence to licensing provisions.
4. Activities undertaken on premises
Manufacturing, wholesale, importation,
export, retail, hospital pharmacy, clinic, nursing and maternity
homes.
5. Adequacy and suitability of premises
(a) premises clean, tidy and in good
state of repair
(b) premises secure
(c) floor durable and easily cleaned
(d) premises constructed to prevent
infestation by vermin and pests
(e) clean shelves in retail pharmacy
and premises for sale of over-the-counter drugs
(f) changing rooms and toilet available
(g) adequacy of lighting and
ventilation
(h) appropriate layout of premises.
6. Warehouse/store
(a) adequacy and suitability of
warehouse/store
(b) warehouse/store clean and
uncluttered
(c) warehouse/store inaccessible to
unauthorized persons
(d) temperature and humidity control
(e) enforcement of stock rotation
(f) adequacy of shelving
(g) existence of areas for returned
drugs, recalled drugs, expired drugs, and drugs in quarantine
(h) warehouse/store free from vermin
and insects.
7. Special storage
(a) availability of cold room storage
or refrigerator for vaccines and biological products
(b) suitability of the cold storage
facilities
(c) standard written procedure prepared
by an appropriate national regulatory agency for the maintenance
of cold chain
(d) special storage area for controlled
drugs and other prescription drugs
(e) suitable and secure storage
facility for controlled drugs and poisons.
8. Record-keeping
(a) name and address of supplier of
each drug product with date
(b) name and address of purchaser of
each drug product with date
(c) supplier or purchaser licensed
(d) retention of order forms, copy of
delivery notes, stores receipt, and issue vouchers, and book of
records (controlled drugs book/prescription drugs book) on the
premises as provided for in the drug laws
(e) accuracy of records kept.
9. Conditions for sale and supply
(a) sale and supply of prescription and
pharmacy sale-only drugs under the control of a registered
pharmacist
(b) sale and supply of prescription and
pharmacy sale-only drugs effected from registered/licensed
premises
(c) sale of prescription drugs on the
basis of valid prescription
(d) sale and supply of over-the-counter
drugs undertaken in registered premises under the supervision of a
pharmacist or premises licensed for the purpose of sale and supply
of over-the-counter drugs only, where such registration or licence
is required by law.
10. Diversion of controlled drugs
Diversion of controlled drugs prevented
by examining the records and by physical examination of stock.
11. Returned and expired drugs
Procedures in place for handling returned
and time-expired drugs.
12. Product recall
Procedures in place for recall of drugs
and handling recalled drugs.
13. Product complaints
Procedures in place for dealing with
complaints about drugs.
14. Promotional activities
Assess promotional materials for
compliance with drug laws.
15. Personnel
(a) person responsible for supervising
sale in a wholesale/retail pharmacy is a registered/licensed
pharmacist
(b) name of the pharmacist in
continuous personal control noted
(c) personnel wear clean protective
clothing.
16. Labelling of drug products and
package inserts
Check adequacy of labelling of drug and
information on package inserts.
17. Physical examination and sampling of
drugs
Conduct physical examination of drugs in
stock and take samples of drugs for quality assessment.
18. Reference books
Check existence of reference books on
premises, where they are required.
Specific inspection applicable to
individual establishments
19. Importer
(a) all drugs accompanied by import
documents such as bill of lading, export authorization, product
licence and batch certificate
(b) controlled drugs also accompanied
by export authorization certificate or export declaration,
whichever is applicable
(c) imported drugs are in original
packs, except for drugs imported in bulk for repackaging and/or
manufacturing drug formulations.
20. Retail and hospital
pharmacy
(a) compounding of drugs carried out by
or under the supervision of a pharmacist
(b) quality of raw materials used in
compounding complies with pharmacopoeial specifications
(c) dispensing of prescription drugs
carried out by or under the supervision of a pharmacist
(d) entries of dispensed prescription
drugs made in prescription book and for controlled drugs in
controlled drugs book
(e) prescriptions for prescription
drugs retained on premises for periods provided in the drug
laws
(f) dispensed drugs labelled
appropriately with name of drug, name of patient, name and address
of pharmacy, clinic or hospital, instructions for using the drugs
and, where appropriate, warning labels
(g) counselling of patients on use of
dispensed drugs
(h) adequacy of containers for
dispensed drugs
(i) personnel observe high standard of
personal hygiene and wear clean protective clothing
(j) dispensing area clean, adequate and
has necessary equipment
(k) walls in dispensing area easily
cleaned
(l) quality of extemporaneous
preparations
(m) sources of drugs sold and supplied
from the pharmacy
(n) suitable cabinets for storage of
controlled drugs and poisons.
21. Clinics, nursing and maternity
homes
(a) sources of drugs used, supplied and
administered
(b) records of controlled drugs used,
supplied and administered
(c) storage facilities and security for
controlled drugs.
22. Unauthorized markets
(a) investigate sources of drugs in the
unauthorized market
(b) sample drugs for quality
assessment
(c) seize drugs in the unauthorized
market.
Appendix 2
Guidance on sampling
This guidance is applicable to collecting
samples of drugs to be tested by the official quality control
laboratory. The collection may be aimed either at assessing the
quality of products on the market, in which case adequate sampling
plans should apply (see, for example, "Sampling procedures for
industrially manufactured pharmaceuticals" (1, 2)), or
at detecting substandard, spurious and counterfeit pharmaceutical
products. In this case sampling shall be based on information and
may involve confiscation of entire stocks to prevent further
distribution. Compliance with legal procedures for sample
collection, analysis and documentation is obligatory.
(a) Check that the sample is properly
labelled with the following:
(i) name of sampled pharmaceutical
preparation
(ii) batch number
(iii) date and source of sample; the
original manufacturer's label may be
helpful.
(b) Check that the records contain the
following:
(i) number of samples
(ii) types of packaging and storage
conditions
(iii) circumstances of sampling that
may include suspected quality defects.
(c) Place seals on containers of the
samples.
(d) Hand over one-third of the samples
to the representative of the inspected establishment.
(e) Confirm in writing that samples
were taken from the premises and have the confirmation
countersigned by an appropriate official of the inspected
establishment (see, for example, the sample receipt form in
Appendix 4).
References
1. WHO Expert Committee on
Specifications for Pharmaceutical Preparations. Thirty-first
report. Geneva, World Health Organization, 1990, Annex 2 (WHO
Technical Report Series, No. 790).
2. Quality assurance of
pharmaceuticals. A compendium of guidelines and related materials,
Volume 1. Geneva, World Health Organization, 1997.
Appendix 3
Guidance for inspection when pharmaceutical products are
suspected to be counterfeit, spurious or substandard
This section addresses specifically the
situation in which the inspector suspects counterfeit, spurious or
substandard pharmaceutical products to be present during an
inspection. This may be during either a regular inspection or an
investigation aimed at detecting such products.
1. Broad objective
The presence of counterfeit, substandard
and spurious pharmaceutical products in the drug distribution
channels may present a danger to public health, and it is imperative
that suspect products are effectively and rapidly taken out of the
distribution channels and quarantined. In order to facilitate the
work of the inspector, the help of capable and experienced persons
involved in the distribution of products should be obtained on a
proactive basis to help identify such products.
2. Standard operating procedures
(a) A written SOP for inspectors should
be drawn up and made available to them.
This SOP should include at least the
following information:
(i) how the suspect product should be
isolated to prevent its further distribution
(ii) the size of the samples required
for testing purposes
(iii) the manner in which the samples
should be taken
(iv) the record-keeping procedure to
be followed in recording the details of the action
taken
(v) the details which should be
recorded on the receipt issued for the embargoed product and/or
samples taken
(vi) the type of materials which
should be used for sealing samples or for embargoing or
confiscating suspect products
(vii) the names, addresses and
telephone numbers of persons who should be contacted to report
on the action taken
(viii) special precautions to be
noted by the person initiating the sampling or seizure
procedure, with particular reference to correct legal procedures
to be followed
(ix) where appropriate, the manner in
which the suspect product should be
destroyed.
(b) Where other persons are involved in
the detection of counterfeit pharmaceutical products they shall
operate on the basis of a suitable SOP. In any case of suspicion
of counterfeit pharmaceutical products an inspector shall be
notified immediately.
3. Counterfeit products
The following applies specifically to
counterfeit products:
(a) When examining a possible
counterfeit pharmaceutical product the inspector shall first
screen the product by looking, smelling, touching and listening to
the sound of the packing and its contents. The inspector shall
look for anything, in particular its labelling and packing, that
makes the product look different from an original reference
sample. A SOP may assist in examining the product in this
way.
(b) When the organoleptic examination
does not give conclusive evidence the inspector shall have a
sample tested using appropriate simple screening methods, such as
the basic tests recommended by WHO or a suitable thin-layer
chromatography method.
(c) In addition to any full analytical
testing, the drug regulatory authority of the country of origin
stated on the label of the product may be asked to establish
whether the product is counterfeit.
(d) Proven cases of counterfeit
pharmaceutical products shall be fully documented and communicated
to all other inspectors, to increase their level of expertise.
Information on counterfeit products shall also immediately be made
available to drug regulatory authorities of other countries
concerned and to WHO.
Appendix 4
Sample receipt form
Institution/company (under inspection) .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
.
Address . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . .
. . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . .
Date of inspection . . . . . . . . . . .
. . . . . .
Name of representative of the inspected
establishment . . . . . . . . . . . . . . . . . . . .
Name of inspector . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . .
Name of the drug and description of
sample . . . . . . . . . . . . . . . . . . . . . . . . . . .
.
. . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . .
Dosage form . . . . . . . . . . . . . . .
. . . . .
Batch no. . . . . . . . . . . . . . . . .
. . . . . .
Place sampled (warehouse, production
line, packaging section, etc.)
. . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . .
No. of samples taken (tins, packets,
etc.) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
.
. . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . .
Signature Signature
Inspector Representative of the
inspected establishment
Footnotes
1 Provisional guidelines on the inspection of pharmaceutical
manufacturers. In: WHO Expert Committee on Specifications for
Pharmaceutical Preparations. Thirty-second report. Geneva, World
Health Organization, 1992, Annex 2 (WHO Technical Report Series,
No. 823).
2 Extracted (with permission and minor changes) from an
unpublished document (PH 6/91) prepared for the Pharmaceutical
Inspection Convention, November 1991.
3 Guidelines for inspection of drug distribution channels. In:
WHO Expert Committee on Specifications for Pharmaceutical
Preparations. Thirty-fifth report. Geneva, World Health
Organization, 1999, Annex 6 (WHO Technical Report Series, No.
885).
4 As defined in "Good manufacturing practices for
pharmaceutical products"
(1).
|